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- Do not distribute without permission from WHO Draft WHO guidelines for comments, August 2016 -

- WHO guidelines on good herbal processing practices (GHPP) for herbal medicines -

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1 WHO/SDS/TCM 2

Draft WHO guidelines for comments 3 August 2016 4

Distribution: Restricted 5

Draft: 6

WHO guidelines on good herbal processing practices (GHPP) 7

for herbal medicines 8

9

DRAFT FOR COMMENTS 10

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Please address any comments on this draft guidelines by 20 February 2017, to:

Ms Yukiko Maruyama, Scientist, Traditional and Complementary Medicine, Service Delivery and

Safety Department, World Health Organization, 1211 Geneva 27, Switzerland, at the email address

below:

E-mail: [email protected]

12 Traditional and Complementary Medicine (TCM) 13

Service Delivery and Safety Department (SDS) 14

World Health Organization (WHO) 15 16

TITLE: Draft: WHO guidelines on good herbal processing practices (GHPP) for herbal medicines - Draft 17 for comments, August 2016 18

19 © World Health Organization 2016 20 21 All rights reserved. 22 23 This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft 24 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in 25 any form or by any means outside these individuals and organizations (including the organizations’ concerned staff and 26 member organizations) without the permission of WHO. The draft should not be displayed on any web site. 27 28 Please send any request for permission to: 29 30 Ms Yukiko Maruyama, Scientist, Traditional and Complementary Medicine, Service Delivery and Safety Department, World 31 Health Organization, 1211 Geneva 27, Switzerland. E-mail: [email protected] 32 33 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 34 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or 35 of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate 36 border lines for which there may not yet be full agreement. 37 38 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or 39 recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and 40 omissions excepted, the names of proprietary products are distinguished by initial capital letters. 41 42 The World Health Organization does not warrant that the information contained in this draft is complete and correct and shall 43 not be liable for any damages incurred as a result of its use. 44

mailto:[email protected]



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SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DRAFTDOCUMENT: 45

WHO GUIDELINES FOR GOOD HERBAL PROCESSING PRACTICES FOR HERBAL 46

MEDICINES 47

Need for a WHO technical guidance on processing to produce herbal

materials, and to produce herbal preparations for quality control of herbal

medicines at different stages of their production, was stated during the

WHO informal meeting on methodologies for quality control of finished

herbal products (Ottawa, Canada) as a recommendation to WHO for

development/action.

July 2001

Reported to the 37th session of the WHO Expert Committee on

Specifications for Pharmaceutical Preparations (ECSPP), Geneva, on the

output of the WHO informal meeting (July 2001) and informed the

Committee that WHO planned to develop new technical guidelines on

processing of herbal medicines; the Committee noted the proposal.

22-26 October 2001

Needs for good processing practices for herbal medicines were also stated

during the International Conferences of Drug Regulatory Authorities

(ICDRAs)

Hong Kong SAR, China,

November 2002

Madrid, Spain, February 2004

Drafting of the proposal on the development of WHO guiding document

on good processing practices for medicinal plant materials

2003

Obtained WHO’s internal approval in developing a WHO guiding

document on good processing practices for medicinal plant materials

(title: tentative)

November 2003

Identification, collection, collation and compilation of technical

information and reference materials for formulating draft synopsis and

annotated content table

2008

Development of concept paper on scope and background as well as the

document development plan

2008

Further identification, collection, collation and compilation of technical

information and reference materials for revising draft synopsis and

annotated content table.

2012

Revision of draft concept paper on scope and background as well as the

document development plan

2012-2013

Revision and elaboration of the draft synopsis and content table for

drafting the first working draft guidelines

2012-2013

Meeting proposal development and search for potential host of the

meeting (2nd WHO consultation on quality control of herbal medicines) 2012-2013

Further collection and collation of technical information and reference

materials for the preparation of the first working draft guidelines

2013-2014

Formulating the first working draft WHO guidelines on good processing

practices for herbal medicines

2014

Formation of initial drafting group 2014

Reported on the progress to the 49th session of the WHO ECSPP,

Geneva, October 2014

October 2014



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48

Distribution of the first working draft WHO guidelines to the participants

of the 2nd WHO consultation on quality control of herbal medicines for

discussion at the 2nd WHO consultation meeting

October – November 2014

Reported on the progress to the 37th Annual meetings of national centres

participating in the WHO international drug monitoring programme,

Tianjin, China, October 2014

October 2014

At the 2nd WHO consultation meeting held in Hong Kong SAR, China, in

November 2014, the first working draft WHO guidelines on good

processing practices for herbal medicines were reviewed and discussed;

and the objectives, scope and proposed contents were discussed

intensively, and agreed. The draft synopsis and table of content of the

proposed guidelines were further refined and agreed; it was also agreed to

revise the first working draft WHO guidelines based on the discussion

and agreed guidelines’ objectives, scope, and contents at the 2nd WHO

consultation meeting.

17-19 November 2014

Reported on the progress of the guidelines development at the 7th annual

meeting of International Regulatory Cooperation for Herbal Medicines

(IRCH), Lisbon, Portugal, December 2014

December 2014

Further identification, collection and collation of relevant technical

information for revision of the first working draft guidelines

2015-2016

Revision of the first working draft WHO guidelines 2015-2016

Reported on the progress at the 8th annual meeting of IRCH, Riyadh,

Saudi Arabia, December 2015

8-10 December 2015

Formulation of the draft WHO guidelines on good herbal processing

practices for herbal medicines for a global review

2016

Reported on the progress to the 51st session of the WHO ECSPP, Geneva,

October 2016

17-21 October 2016

Reported on the progress at the 9th annual meeting of IRCH, New Delhi,

India, November 2016

9-11 November 2016

First global review on the draft WHO guidelines on good herbal

processing practices for herbal medicines

December 2016 - February

2017

Meeting proposal development and search for potential host of the

meeting (3rd WHO consultation on quality control of herbal medicines) December 2016 – February

2017

Compilation of comments received and revision of the draft February – April 2017

The second global review on the revised draft May-June 2017

Compilation of comments received and revision of the revised draft June- July 2017

Review and discussion of feedback received at the 3rd WHO consultation

on quality control of herbal medicines

Date to be decided

Finalization of the manuscript based on the discussion at the 3rd WHO

consultation meeting

Date to be identified

Update to the 10th annual meeting of IRCH September 2017

Update to the 52nd session of the WHO ECSPP, Geneva, October 2017 October 2017

Any follow-up action, as needed



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Table of Contents 49 50

1. INTRODUCTION…………………………………………………………………...………………6 51 1.1 Background of guidelines development………………………………………………...…6 52 1.2 Scope………………………………………………………………...…………………….753 1.2.1 Processing of herbs into herbal materials……………………………………...….8 54 1.2.2 Processing of herbal materials into herbal preparations…………………...……8 55 1.2.3 Processing of herbal materials or herbal preparations into herbal dosage forms…8 56 1.3 Objectives of guidelines………………………………………………………...…………9 57 1.4 Glossary/definitions of terms………………………………………………..…….……10 58 1.4.1 Terms relating to herbal medicines…………………………………..….………10 59 1.4.2 Terms related to herbal processing practices……………………….……….…..11 60 1.4.3 Terms related to herbal preparations……………………………………….……12 61 1.4.4 Terms relating to quality control……………………………………………..….13 62 63 2. GOOD HERBAL PROCESSING PRACTICES FOR THE PRODUCTION OF HERBAL 64

MATERIALS…………………………………………………………………………………...….14 65 2.1 General information………………………………………………………………….…..14 66 2.2 Purposes and functions of processing……………………………………………….…...15 67 2.3 Processing techniques and procedures……………………………………………….…..16 68 2.3.1 Preparation of harvested/collected medicinal plant part for processing……...….17 69 2.3.2 Primary processing procedures……………………….…………………………17 70 2.3.3 Secondary processing procedures………………………………….……………20 71 2.3.3.1 Selection of processing method…………………………….…………22 72 2.3.3.2 Temperature…………………………………………………………..23 73 2.3.3.3 Duration of procedure/treatment……………………………………...23 74 2.3.3.4 Use of adjuvants……………………………………………………...23 75 2.3.4 Special processing procedures………………………………………………….23 76 2.3.4.1 Detoxification…………………….…………………………………...23 77 2.3.4.2 Enhancement or modification of therapeutic properties………………24 78 2.3.4.3 Use of adjuvants……………………………..………………………...24 79 2.3.5 Documentation……………………………………….………………………….24 80 81 3. GOOD HERBAL PROCESSING PRACTICES FOR THE PRODUCTION OF HERBAL 82

PREPARATIONS………………………………………………………………………………….25 83 3.1 General information…………………………………….………………………………..25 84 3.2 Extraction……………………………………………….…….………………………….25 85 3.2.1 Common methods of extraction………………………………………….……...26 86 3.2.2 Steps involved in the extraction of medicinal plants………………………….…28 87 3.2.3 Common herbal preparations prepared by extraction……………………….…..28 88 3.2.4 Controlling factors in extracting herbal materials…………………….…………29 89 3.3 Distillation………………………………………………………….…………………….29 90 3.4 Fractionation and purification…………………………….……………………………...30 91 3.4.1 Liquid-liquid partition………………………………………………….………..30 92 3.4.2 Chromatography…………………………………………………………….…...30 93 3.5 Concentration and drying…….…………………………………………………………..31 94 3.6 Fermentation……………………………………………………………….…………….31 95 3.7 Processing techniques and procedures……………………………………………….…..31 96 3.7.1 Preparation of herbal materials for processing………………………….……….31 97 3.7.2 Extraction………………………………………………….…………………….32 98 3.7.2.1 Selection of extraction methods…………………………………….....32 99 3.7.2.2 Extraction conditions and procedures…………………………...…….32 100



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3.7.3 Distillation……………………………………………………………….………33 101 3.7.4 Fractionation and purification……………………………………….…………..33 102 3.7.5 Concentration and drying…………………………………………………….….34 103 3.7.6 Fermentation…………………………………………………………….……….34 104 3.8 Documentation……………………………………………………………….…………..34 105 106 4. GOOD HERBAL PROCESSING PRACTICES FOR THE PRODUCTION OF HERBAL 107

DOSAGE FORMS…………………………………………...…………………………………….35 108 4.1 General information………………………………………………………….…………..35 109 4.2 Extract…………………………………………………………………….……………...35 110 4.3 Fluidextract………………………………………………………….…………………35 111 4.4 Infusion…………………………………………………………………………………..35 112 4.5 Decoction………………………………………………………………………………...36 113 4.6 Herbal tea bag…………………………………………………………………………….36 114 4.7 Tincture and spirit…………………………………………………………………….….36 115 4.8 Aromatic Water……………………………………………………………………….….36 116 4.9 Syrup………………………………………………………………………………….….36 117 4.10 Powder…………………………………….……………………………….……………..36 118 4.11 Granule…………………………………………………………………………….……..36 119 4.12 Pills……………………………………………………………………….………………37 120 4.13 Capsule…………………………………………………………………………….……..37 121 4.14 Tablet……………………………….………………………………………….…………37 122 4.15 Ointment/cream…………………………………………………………………….…….37 123 4.16 Inhalation………………………………………………………………………….…...…37 124 4.17 Plaster and patch…………………………………………………………………….……37 125 126 5. T E C H N I C A L I S S U E S S U P P O R T I N G G O O D H E R B A L P R O C E S S I N G 127

PRACTICES…………………………………………………….………………………………….38 128 5.1 Processing facilities………………………………………………………………….…...38 129 5.2 Packaging and labelling……………………………………………………………….…38 130 5.3 Storage and transportation……………………………………………………….…….…39 131 5.4 Equipment………………………………………………………………………….…….39 132 5.5 Quality assurance and quality control…………………………………………….……...40 133 5.6 Documentation……………………………………………………………….…………..40 134 5.7 Personnel……………………………………….…………………….…………………..40 135 5.7.1 General…………………………………….…………….……………………….40 136 5.7.2 Health, hygiene and sanitation…………………………………….……………..41 137 138 6. OTHER RELEVANT ISSUES………………………………………………………….………….41 139 6.1 Ethical and legal considerations……………………………………………….…………41 140 6.2 Research, research training and information sharing……………………………….……42 141 6.3 Adoption of good herbal processing practices………………….…………….………….42 142 6.4 Intellectual property rights and benefits-sharing……………………...………….………42 143 6.5 Threatened and endangered species……………………………………………………...42 144 145 7. REFERENCES…...…………………………………………………………………………….…..42 146 147 Annex 1: Example of a model format of good herbal processing practices monograph/SOP protocol to 148

produce a herbal material………………………………………..……… . .……44 149 Annex 2: Example of a model format of good herbal processing practices monograph/SOP protocol to 150

produce a herbal preparation…..……………………………………………………….…..47 151 Annex 3: Example of general rules for preparation of dosage forms related to herbal medicines……50 152 Annex 4: Processing facilities…………………….………………………………………….…..…….56 153



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1. INTRODUCTION 154

155

1.1 Background of guidelines development 156

157 Over the past three decades, there has been a constant, and at times, exponential growth in 158

global interest in the use of herbal medicines. This increase in popularity and usage of herbal 159

medicines is evidenced by the global market which also experienced similar growth. Herbal 160

medicines, including not only finished herbal products but also their starting materials for 161

production, such as medicinal plants, herbal materials, and herbal preparations, are moving 162

into international commerce and the global trade arena, which indicates increased economic 163

value and importance. When adverse events are reported to the regulatory authorities in 164

relation to the use of herbal products, a large portion of them are attributable to poor quality 165

of products, which may involve a variety of factors, including those due to natural (e.g. source 166

material) and human (e.g. manufacturing/processing) factors. Hence, the safety and quality of 167

herbal materials, herbal preparations and finished herbal products have become a major 168

concern to health authorities, healthcare providers, the pharmaceutical industry and the public. 169

170

The safety and efficacy of herbal medicines largely depend on their quality. Unlike 171

conventional pharmaceutical products, which are formulated from single molecule chemicals 172

produced synthetically or by isolation from natural source materials employing reproducible 173

methods, herbal medicines consist of simple processed herbs or finished products prepared 174

from source materials containing a multiplicity of chemical constituents, the quality and 175

quantity of which can vary from batch to batch due to intrinsic and extrinsic factors. 176

Consequently, the quality of finished herbal products is greatly influenced by the quality of 177

the raw materials and the intermediates; and the requirements and methods for quality control 178

of finished herbal products, particularly for mixture herbal preparations, are far more complex 179

than those employed for single molecule chemical drugs. 180

181

A number of World Health Assembly (WHA) resolutions relating to traditional medicine has 182

requested WHO to provide technical support to develop methodology to monitor or ensure the 183

quality, efficacy and safety of herbal medicines. The International Conferences of Drug 184

Regulatory Authorities (ICDRAs), and annual meetings of International Regulatory 185

Cooperation for Herbal Medicines (IRCH), as well as the Meetings of the National Centres 186

Participating in the WHO International Drug Monitoring Programme have also requested 187

WHO to develop and continuously update the technical guidelines on quality, safety, and 188

efficacy of herbal medicines. 189

190

Participants of the WHO Informal Meeting on Methodologies for Quality Control of Finished 191

Herbal Products (held in Ottawa, Canada, July 2001) looked at the overall picture of herbal 192

medicines: from raw materials to the distribution and supply of finished herbal products, 193

including key steps where quality control is required. 194

195

One of the main recommendations of the meeting was that WHO should prepare a series of 196

technical guidelines and documents covering quality control issues (from raw materials to 197

finished herbal medicinal products), as well as to update other existing documents. 198

199



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Following the meeting’s recommendations, and as a part of the implementation of relevant 200

WHO strategies (notably, WHO traditional medicine strategies and WHO medicines 201

strategies) and WHA resolutions, WHO undertook the development of four new guidelines 202

and to update other existing documents in order to provide technical guidance for quality 203

control required at key steps in the production of herbal medicines to support Member States 204

in their efforts to ensure the quality of herbal medicines. These cover: 205

206

WHO guidelines on good agricultural and collection practices (GACP) for medicinal 207

plants (published in 2003) [WHO, 2003a]; 208

WHO guidelines on assessing quality of herbal medicines with reference to contaminants 209

and residues (published in 2007) [WHO, 2007b]; 210

WHO guidelines for selecting marker substances of herbal origin for quality control of 211

herbal medicines (in preparation) [WHO, 2017]; and 212

WHO guidelines on good herbal processing practices (GHPP) for herbal medicines 213

(present document). 214

215

WHO has also updated two key technical guiding documents: 216

217

WHO guidelines on good manufacturing practices (GMP) for herbal medicines (published 218

in 2007) [WHO, 2007a]; and 219

Quality control methods for herbal materials (published in 2011) [WHO, 2011], which 220

includes the WHO good practices for pharmaceutical quality control laboratories as an 221

annex. 222

223

GACP for medicinal plants are only the first step in quality assurance. The next important 224

phase involves the GHPP of herbal materials. The processed materials are herbal materials or 225

herbal preparations, which may be used as a starting source material for the GMP production 226

of finished herbal products, or directly employed as herbal medicines in various herbal dosage 227

forms. For this reason, GHPP for herbal medicines is integrally linked to GACP for 228

medicinal plants and GMP for herbal medicines in the quality assurance and control of herbal 229

medicines. 230

231

The present guidelines are intended to complement, and should be read in conjunction with, 232

those guidelines provided in WHO guidelines on GACP for medicinal plants [WHO, 2003a] 233

and WHO guidelines on GMP for herbal medicines [WHO, 2007b]. Altogether, the present 234

guidelines plus the above-mentioned three new and two updated WHO guidelines form the 235

core technical guidance for the overall quality assurance and control of herbal medicines. 236

237

1.2 Scope 238 239

Processing refers to the unique procedures of preparing herbal materials and herbal 240

preparations for therapeutic applications. The process concerns not only ensuring the quality 241

of the herbal materials and preparations produced, but also their safety and efficacy in clinical 242

settings. 243

244

These guidelines will provide technical guidance on good processing practices in the: 245



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(1) processing of herbs into herbal materials; 246

(2) processing of herbal materials into herbal preparations; and 247

(3) processing of herbal materials or herbal preparations into herbal dosage forms. 248

249

In the case of processing herbs into herbal materials, three major categories of processing are 250

involved, namely, the “primary”, “secondary” and “special” processes. In the case of 251

processing of herbal materials into herbal preparations, as well as processing herbal materials 252

or herbal preparations into herbal dosage forms, the processing procedures involve the good 253

practice preparation or GMP production. 254

255

An outline of the major processes and examples of procedures are given below. 256

257

1.2.1 Processing of herbs into herbal materials 258

259 Primary processing encompasses the immediate post-harvest treatments accorded to herbs 260

obtained from cultivation or by wild crafting or field collection intended to free them from 261

foreign matters and other contaminants, and includes, for example, the procedures of garbling 262

(sorting), washing, and drying. For herbal materials that are used without further processing, 263

the primary processing may also include cutting, sectioning, and comminution. 264

265

Secondary processing is the next step concerned with converting the primary processed herbs 266

into herbal materials by various additional procedures, including, for example, 267

aging/sweating; baking/roasting; boiling/steaming; and stir-frying. 268

269

Special processing is an extension of the secondary process, which employs a specialized 270

method to treat selected herbs to reduce their toxicity or to alter and modify their therapeutic 271

activity. Examples of herbs so processed include Aconitum and Euphorbia species. 272

273

1.2.2 Processing of herbal materials into herbal preparations 274

275 The herbal materials described above may serve as crude materials for use as herbal 276

medicines. But in many cases, the herbal materials will undergo further treatment procedures 277

before being used to manufacture the finished herbal products. The active ingredients are 278

usually not purified but rather are obtained along with other components of the medicinal 279

plant part. Sometimes the active ingredients are further concentrated by the removal of 280

inactive and/or undesirable substances. The herbal preparations thus obtained include 281

extracts, decoctions, tinctures, essential oils, and others. The processes involved include 282

extraction, distillation, fractionation, purification, concentration, fermentation, or other 283

chemical/biological methods. 284

285

1.2.3 Processing of herbal materials or herbal preparations into herbal dosage forms 286

287 Depending on the intended use, herbal materials and herbal preparations could be regarded as 288

intermediates in the process of producing finished products or as final dosage forms for 289

clinical applications. In the latter case, it is not uncommon that simple dosage forms are 290

prepared from either herbal materials (such as ground powders of raw herbs) or herbal 291



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preparations (such as dried extracts) ready for administration to the patients. These herbal 292

dosage forms include fluidextract, decoction, tea bags, granules and syrups, among others. 293

294

1.3 Objectives of guidelines 295

296 These new guidelines will provide technical guidance on good herbal processing practices 297

(GHPP) for the production of herbal materials and herbal preparations. Under the overall 298

context of quality assurance and control of herbal medicines, the main objectives of this 299

guidelines are to: 300

301

provide general and specific technical guidance on GHPP for herbal medicines; 302

provide technical information on general as well as specific good herbal processing 303

techniques and procedures applied for the preparation of herbal materials from 304

herbs/medicinal plant; 305

provide technical information on good herbal processing techniques and procedures 306

applied for the production of herbal preparations from herbal materials; 307

provide technical information on good herbal processing techniques and procedures 308

applied for the production of dosage forms of herbal medicines; 309

provide a model for the formulation of national and/or regional good herbal processing 310

practice guidelines and monographs for herbal materials, as well as for herbal 311

preparations, and related standard operating procedures (SOP); and 312

contribute to the quality assurance and control of herbal materials, herbal preparations and 313

herbal dosage forms, and to promote safety, efficacy and sustainability of herbal 314

medicines. 315

316

This guidelines should be considered in conjunction with the existing documents and 317

publications relating to the quality assurance of herbal medicines and medicinal plants (for 318

details, see Bibliography), for example: 319

320

WHO guidelines on good agricultural and collection practices (GACP) for medicinal 321

plants [WHO, 2003a]; 322

WHO guidelines on assessing quality of herbal medicines with reference to contaminants 323

and residues [WHO, 2007b]; 324

WHO guidelines for selection of substances of herbal origin for quality control of herbal 325

medicines [in preparation, WHO, 2017]; 326

WHO guidelines on good manufacturing practices (GMP) for herbal medicines [WHO, 327

2007a]; 328

Quality control methods for herbal materials [WHO, 2011]; 329

WHO monographs on selected medicinal plants, Vol. 1-4 [WHOM-1999, WHOM-2002, 330

WHOM-2007, WHOM-2009]; 331

WHO monographs on selected medicinal plants commonly used in the Newly Independent 332

States (NIS) [WHOM-2010]; and 333

General guidelines for methodologies on research and evaluation of traditional medicine 334

[WHO, 2000]. 335

336

The WHO guidelines on good herbal processing practices (GHPP) for herbal medicines is 337



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one of a series of guidance documents concerned with control measures necessary to produce 338

quality herbal medicines for safe and efficacious use. The present document concerns the 339

assurance of the quality of the herbal materials being prepared through various “processing” 340

of the medicinal plant and its part materials obtained under GACP; and of the herbal 341

preparations being prepared through various “processing” of the herbal materials. Herbal 342

materials can be used directly as herbal medicines or to serve as source materials for the GMP 343

production of finished products. These guidelines are applicable to the processing operations 344

from post-harvest to finished medicinal forms. The processing of medicinal plants or plant 345

parts should meet all applicable national and/or regional quality standards. The guidelines 346

therefore may need to be adjusted according to each Member State’s situation. Each Member 347

State should develop its own national guidelines on good herbal processing practices for 348

herbal medicines that are appropriate to the country’s actual situation. 349

350

1.4 Glossary/definitions of terms 351

352 The terms used in these guidelines are defined below. The terms and their definitions have 353

been selected and adapted from other WHO documents and guidelines that are widely used by 354

WHO Member States, as well as from other reference sources (reference source is indicated 355

with [ ]). These definitions may differ from those included in national regulations, and are 356

therefore, for reference only. 357

358

1.4.1 Terms relating to herbal medicines 359 360

Herbal medicines include herbs and/or herbal materials and/or herbal preparations and/or 361

finished herbal products in a form suitable for administration for patients. [WHO, 2017, in 362

preparation] 363

Note: In some countries herbal medicines may contain, by tradition, natural organic or 364

inorganic active ingredients that are not of plant origin (e.g. animal and mineral 365

materials). [WHO, 2017, in preparation] 366

367

Herbs [WHO, 2017, in preparation] 368

Herbs are crude plant material which may be entire, fragmented or powdered. Herbs 369

include, e.g. the entire aerial part, leaves, flowers, fruits, seeds, roots, barks (stem or 370

root) of trees, tubers, rhizomes or other plant parts. 371

372

Herbal materials [WHO, 2017, in preparation] 373

Herbal materials include, in addition to herbs, other crude plant materials. These other 374

plant materials can be, e.g. gums, resins, balsams, exudates, and other such 375

matters. Herbal materials may also be referred to as “medicinal plant materials”. 376

377

Herbal preparations [WHO, 2017, in preparation] 378

Herbal preparations are produced from herbal materials by physical or biological 379

processes. These processes may be extraction (with water, alcohol, supercritical CO2), 380

fractionation, purification, concentration, fermentation, and other processes. They 381

also include preparations made by processing herbal materials with a natural vehicle 382

or steeping or heating them in alcoholic beverages and/or honey, or in other materials. 383



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Herbal preparations include simply comminuted (fragmented) or powdered herbal 384

materials as well as extracts, tinctures, fatty (fixed) or essential oils, expressed plant 385

juices, decocts, cold and hot infusions, among others. 386

387

Finished herbal products [WHO, 2017, in preparation] 388

Finished herbal products consist of one or more herbal preparations made from one or 389

more herbs (i.e. from different herbal preparations made of the same plant as well as 390

herbal preparations from different plants. Products contained different plant materials 391

are called “mixture herbal products”). 392

393

Finished herbal products and mixture herbal products may contain excipients in 394

addition to the active ingredients. However, finished products or mixture herbal 395

products to which chemically defined active substances have been added, including 396

synthetic compounds and/or isolated constituents from herbal materials, are not 397

considered to be “herbal”. 398

399

Herbal dosage forms 400 Herbal dosage forms are herbal products in the forms in which they are marketed for use or 401

taken by the patient, the production of which typically involve simple preparation procedures 402

using herbal materials (such as packing dried root or leaf powders into capsules or herbal tea 403

bags) or herbal preparations (such as grinding freeze-dried extracts into powders). The herbal 404

dosage forms may contain substances originated from a single herb or a combination of herbs. 405

406

Medicinal plants are plants (wild or cultivated) used for medicinal purposes [WHO, 2003a]; 407

[WHO, 2007a]. 408

409

Medicinal plant materials: see Herbal materials 410

411

1.4.2 Terms related to herbal processing practices 412 413

Processing 414 The processing of herbal materials refers to a series of post-harvest treatments applied to the 415

crude medicinal plant materials. For the purpose of the present guidelines, “processing” 416

includes primary processing, such as sorting, cleaning, and drying as described in the WHO 417

guidelines on GACP for medicinal plants [WHO, 2003a]; it also includes secondary, special, 418

and other processing as defined in the present guidelines. 419

420

Primary processing 421 Primary processing refers to a series of simple preparatory procedures that may be performed 422

at the harvest/collection site, including sorting, garbling, cleaning, and drying. For herbal 423

materials that do not require further processing prior to use as decoction materials or as 424

starting materials for manufacturing of finished products, the primary process may also 425

include cutting, sectioning, or comminution. 426

427

Secondary processing 428 Secondary processing refers to the preparative steps applied to herbs in addition to the 429



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primary processing before they can be used as direct decocting materials for immediate 430

therapeutic treatment or as starting materials for manufacturing of finished products. They 431

are considered important pharmaceutical techniques in the herbal industry, through which, 432

purity of raw herbs is assured (such as removal of foreign matters, prevention of microbial 433

and insect infection/infestation), the therapeutic properties of raw herbs are improved (such as 434

enhancement of efficacy or reduction of toxicity) for clinical applications. The secondary 435

processing procedures may vary from one herbal material to another, depending on the 436

characters of the active ingredients as well as the therapeutic target. These processes are 437

referred to as “specific processing” in the WHO guidelines on GACP for medicinal plants 438

[WHO, 2003a]. 439

440

Special processing 441 Special processing is an extension of the secondary processing in which a set of prescribed 442

procedures is employed to treat a particular herbal material for specific purposes such as 443

detoxification or ensuring clinical effects of that herbal material or resulting herbal 444

preparation. The special processing procedures vary from one herbal material to another, 445

depending on the characters of the active ingredients as well as the therapeutic target intended 446

to be treated. 447

448

Adjuvants 449 Adjuvants are adjunctive substances used during the herbal processing procedures alongside 450

the herbal materials, included for the purpose of altering the pharmacological/therapeutic 451

properties of the herbal preparations or neutralizing/reducing toxicity. Common adjuvants 452

include wine, vinegar, honey, milk and others. 453

454

1.4.3 Terms relating to herbal preparations 455

456

Extraction 457 Extraction is a separation process in which medicinally significant portions of plant chemical 458

constituents and tissues are removed from other plant metabolites and the insoluble cellular 459

marc by using selective solvent(s) (which is sometimes called the menstruum). Herbal 460

extracts include decoctions, infusions, fluidextracts, tinctures, and powdered extracts. The 461

herbal preparation so obtained may be ready for use as a medicinal agent, or it may be further 462

processed to afford finished products such as tablets and capsules. 463

464

Extract 465 Extract is a general description of the concentrated preparation of herbal materials obtained by 466

dissolving the active constituents in a suitable solvent and subsequent evaporation of all or 467

nearly all of the solvent. If the extract is completely freed from the solvent (dried) and 468

obtained either as fine or granular powder, it is called a Powdered Extract. 469

470

Decoction 471 Decoction is a liquid preparation made by boiling herbal materials with water. This is 472

probably the most common method of preparing herbal drugs in many traditional medicine 473

systems. 474

475



13

Infusion 476 Infusion is a liquid preparation made by extracting herbal materials with either cold or hot 477

water without boiling. Other solvents such as edible oil or vinegar may be used. 478

479

Fluidextract 480 Fluidextract is a liquid preparation from herbal materials made by maceration or percolation 481

in alcohol or wine. Typically, a fluidextract is made in such a ratio that one part (e.g. one 482

millilitre) of the liquid contains one part (e.g. one gram) of the original herbal materials. 483

484

Tincture 485 Tincture is a dilute alcoholic extract of herbal materials, typically made up of 1 part of herbal 486

material and 5-10 parts of solvent. 487

488

Powder 489 Powder is a form of herbal preparation processed as dry, granulated, or powdered materials. 490

Extracts, tinctures or other liquid preparations can be evaporated to dryness to obtain the 491

powders. 492

493

Essential (volatile) oil 494 Essential (volatile) oil constitutes the odorous principles of the plant from which it is 495

extracted. Each essential oil has its own characteristic colour, odour, and taste. 496

497

1.4.4 Terms relating to quality control 498

499 For a comprehensive list of terms on quality control of herbal medicines, please refer to the 500

Quality control methods for herbal materials [WHO, 2011], WHO guidelines for selection of 501

substances of herbal origin for quality control of herbal medicines [WHO, 2017], and WHO 502

guidelines on GMP for herbal medicines [WHO, 2007a]. The following terms are more 503

directly or indirectly applicable to the present guidelines than others. 504

505

Batch (or lot) [WHO, 2007a – WHO, 2003b]; [WHO, 2014] 506

A defined quantity of starting material, packaging material or product processed in a single 507

process or series of processes so that it is expected to be homogeneous. It may sometimes be 508

necessary to divide a batch into a number of sub-batches which are later brought together to 509

form a final homogeneous batch. In the case of terminal sterilization the batch size is 510

determined by the capacity of the autoclave. In continuous manufacture the batch must 511

correspond to a defined fraction of the production, characterized by its intended homogeneity. 512

The batch size can be defined either as a fixed quantity or as the amount produced in a fixed 513

time interval. 514

515

Batch number (or lot number) [WHO, 2007a – WHO, 2003b]; [WHO, 2014] 516

A distinctive combination of numbers and/or letters which uniquely identifies a batch on the 517

labels, its batch records and corresponding certificates of analysis, etc. 518

519

Contamination [WHO, 2007a – WHO, 2003b]; [WHO, 2014] 520

The undesired introduction of impurities of a chemical or microbiological nature, or of 521



14

foreign matter, into or on to a starting material or intermediate during production, sampling, 522

packaging or repackaging, storage or transport. 523

524

Cross-contamination [WHO, 2007a- WHO, 2003b]; [WHO, 2014] 525

Contamination of a starting material, intermediate product or finished product with another 526

starting material or product during production. 527

528

Good manufacturing practice (GMP) [WHO, 2014] 529

GMP is that part of quality management which ensures that products are consistently 530

produced and controlled according to the quality standards appropriate to their intended use 531

and as required by the marketing authorization, clinical trial authorization or product 532

specification. GMP is concerned with both production and quality control. GMP is aimed 533

primarily at managing and minimizing the risks inherent in pharmaceutical manufacture to 534

ensure the quality, safety and efficacy of products. 535

536

In-process control [WHO, 2007a – WHO, 2003b]; [WHO, 2014] 537

Checks performed during production in order to monitor and, if necessary, to adjust the 538

process to ensure that the product conforms to its specifications. The control of the 539

environment or equipment may also be regarded as a part of in-process control. 540

541

Master formula [WHO, 2007a – WHO, 2003b];[WHO, 2014] 542

A document or set of documents specifying the starting materials with their quantities and the 543

packaging materials, together with a description of the procedures and precautions required to 544

produce a specified quantity of a finished product as well as the processing instructions, 545

including the in-process controls. 546

547

Chemical reference substance (or standard) [WHO, 2007c] 548

An authenticated, uniform material that is intended for use in specified chemical and physical 549

tests, in which its properties are compared with those of the product under examination, and 550

which possesses a degree of purity adequate for its intended use. 551

552

Specification [WHO, 2007a – WHO, 2003b]; [WHO, 2014] 553

A list of defined requirements with which the products or materials used or obtained during 554

manufacture have to conform. They serve as a basis for quality evaluation. 555

556

Standard operating procedure (SOP) [WHO, 2007a – WHO, 2003b]; [WHO, 2014] 557

An authorized written procedure giving instructions for performing operations not necessarily 558

specific to a given product or material (e.g. equipment operation, maintenance and cleaning; 559

validation; cleaning of premises and environmental control; sampling and inspection). 560

Certain SOPs may be used to supplement product-specific master and batch production 561

documentation. 562

563

2. GOOD HERBAL PROCESSING PRACTICES FOR THE PRODUCTION OF 564

HERBAL MATERIALS 565

566

2.1 General information 567



15

568 “Processing” is a unique process in the preparation of herbal materials from medicinal plant 569

and plant parts and has been practiced as a material specific procedure. Historically, this 570

process is as old as that of the use of medicinal plants for the alleviation of human ailments. 571

572

When the medicinal plant and its parts are obtained through wild collection or cultivation 573

under GACP for medicinal plants [WHO, 2003a], they must be subjected to a series of good 574

practice of post-harvest processing procedures in order to ensure the maximum safety, 575

efficacy and desired therapeutic outcome. The exact processing procedures may vary from 576

one herbal material to another. Some consist of only a few simple steps such as sorting, 577

cleaning and drying, and they are generally referred to as the “primary processing”. For 578

herbal materials that are used without further processing, the primary processing may include 579

cutting, sectioning, and comminution, etc. Others may require some more complicated steps 580

such as aging/sweating, baking/roasting, boiling/steaming, and stir-frying, for the purpose of 581

improving the purity, preventing damage from mould and other microorganisms, detoxifying 582

indigenous toxic ingredients, or enhancing therapeutic efficacy. Such processing procedures 583

are referred to as the “secondary process” in these guidelines. They may have a significant 584

impact on the quality of the resulting herbal materials. 585

586

Special processing is an extension of the secondary process, in which a series of special 587

treatment procedures are applied to the herbs for specific purposes such as reduction of 588

toxicity or alteration/modification of therapeutic properties. Examples of herbs (medicinal 589

plants) so processed include Aconitum and Euphorbia species. 590

591 The safety and efficacy of herbal medicines are intricately dependent on the quality of the 592

starting and processed source materials. To assure their quality, the good practices for 593

processing herbal materials may be considered. In general, good practices for processing 594

herbal materials mirror the good manufacturing practices for herbal medicine as delineated in 595

the WHO guidelines on GMP for herbal medicines [WHO, 2007a], with the first step being 596

the post-harvest handling and preparation of the starting medicinal plant materials under 597

sanitary conditions. All critical equipment for processing must be qualified; all processing 598

methods and procedures are standardized (SOP); master formulae, master and batch records 599

documented; and quality control parameters established and adhered to. GHPP 600

monograph/SOP protocol on specific herbal material should be developed and implemented. 601

602

2.2 Purposes and functions of processing 603

604 Through experiences gained over the centuries, knowledge has been acquired for the 605

development of processing procedures for maximizing the quality and therapeutic value of 606

herbal materials. The final form a herbal medicines takes depends upon the nature of the herb 607

and the nature of the disease to be treated. In general, the processing of herbal materials 608

serves several purposes, such as to improve bioavailability of active components, reducing 609

toxicity and/or side effects, enhancing potency and effectiveness, modifying the therapeutic 610

properties, facilitating storage, and eliminating other undesirable properties. Thus, the major 611

purposes of the processing for herbal materials are: 612

613



16

Neutralization of toxicity and diminishing side effects 614 Herbal materials that possess significant levels of toxicity, highly potent pharmacological 615

actions, or severe side effects must be pre-treated in certain specific manners in order to 616

neutralize the toxicity or to reduce the side effects prior to use. Such a detoxifying process is 617

particularly important for those medicinal plants that are known to contain toxic or 618

undesirable chemical components; they must be properly “cured” to remove those unwanted 619

substances. Through the pre-treatment processes such as “steaming” and “frying”, the heat-620

sensitive toxic components will be degraded. In other cases, processes such as “sweating” 621

and “aging” would result in enzymatic degradation of the toxic ingredients. For example, raw 622

aconite (Aconitum species) tuber, containing significant amounts of toxic alkaloids such as 623

aconitine, must be boiled or steamed for hours to hydrolyse aconitine into less toxic 624

derivatives. In the case of cascara (Rhamnus purshiana) bark, they have to be aged for at 625

least one year before use, to allow oxidation reaction to occur, by which the strongly laxative 626

hydroxyanthracene glycosides are converted to oxidized compounds of lower laxative 627

potencies. 628

629

Modification of therapeutic properties 630 Some herbal materials require specific processing to alter their therapeutic properties. For 631

example, rhubarb (Rheum rhabarbarum) in its raw form possesses purgative action and is 632

useful as a cathartic. After processing, however, the purgative action is attenuated and the 633

processed rhubarb can be used for other purposes such as anti-inflammation. 634

635

The specific action of some herbal materials may be reinforced through processing. For 636

example, the unprocessed raw rehmannia (Rehmannia glutinosa) root is used to treat fever, 637

hypertension and skin eruptions; whereas after being cooked in wine, the processed 638

rehmannia is often used for tonic, emmenagogue and anti-aging purposes. 639

640

In the case of ginseng (Panax ginseng) roots, different post-harvest processing procedures 641

give rise to several processed products, such as "white ginseng" and "red ginseng". "White 642

ginseng" is the material dried by the sun or heat, whereas “red ginseng” is made through a 643

series of steaming and cooking steps. These two types of ginseng products have been shown 644

to exert opposite pharmacological actions on human blood pressure, among other differing 645

therapeutic effects. 646

647

Enhancing efficacy and reinforcing therapeutic effects 648 The therapeutic efficacy of certain herbal materials can be augmented through specific 649

methods of preparation. For instance, the pain-relieving property of corydalis (Corydalis 650

yanhusuo) rhizomes is increased when they are stir-fried with rice vinegar. Similarly the 651

honey-treated ephedra (Ephedra species) would possess stronger antitussive and anti-asthma 652

properties than the unprocessed ephedra, which is mostly used as a diaphoretic. 653

654

2.3 Processing techniques and procedures 655

656 Appropriate measures of general processing are dependent on the individual materials. These 657

processes should be carried out in conformity with national and/or regional quality standards, 658

regulations and norms. These protocols should also comply with the regulatory requirements 659



17

that apply in the producer and the purchaser countries. The SOP of processing should 660

describe in detail the various operations to be performed on the medicinal plant material, such 661

as sorting, washing, drying, crushing, milling, pulverization and sifting. They should also 662

include the length of time and temperature, among others. As much as possible, the SOP 663

should be adhered to. If modifications are made, they should be justified by adequate test data 664

demonstrating that the quality of the herbal materials is enhanced and/or not compromised. 665

666

2.3.1 Preparation of harvested/collected medicinal plant part for processing 667

668 Prior to general or special processing, the starting raw medicinal plant materials should be 669

inspected and sorted in order to ensure there is no contamination or cross-contamination by 670

untargeted plants, unwanted plant parts, foreign matters, and obvious damages. 671

672

Harvested or collected raw medicinal plant materials should be promptly unpacked upon 673

arrival at the processing facility. Prior to processing, they should be protected from rain, 674

excessive sunlight, moisture and any other conditions that might cause microbial fermentation 675

and thermal degradation. The unprocessed raw medicinal plant materials should be stored in 676

appropriate containers at ambient or lower temperature under well ventilated conditions; as 677

well as protected from insects, rodents, birds, livestock, domestic animals, and other pests. 678

679

Consistent quality for the finished herbal products can only be assured if the starting raw 680

medicinal plant materials are defined in a rigorous and detailed manner. For this reason, the 681

crude/raw medicinal plant materials must be adequately documented prior to the processing 682

procedures to include, as far as possible and at a minimum, the following information; 683

684

Botanical name of the medicinal plant; local name; plant part(s); 685

Source (cultivation/wild growing region); 686

Batch (or lot) number; 687

Collection (harvest) conditions (e.g. season/month and date; plant part; wet/dry 688

environment); 689

Botanical authentication of the source medicinal plant materials; 690

Physical appearance such as colour, odour, form, sharp, size and texture; 691

Suitable identification tests such as TLC or other chromatographic fingerprints; 692

Assay results, where appropriate, of active ingredient(s) or Chemical reference 693

standard(s); 694

Limit tests such as ash value, water content, and extractives; and 695

Determination of possible contaminants such as pesticides and heavy metals, mycotoxins 696

and where and when appropriate, radioactivity. 697

698

2.3.2 Primary processing procedures 699

700 Harvested/collected medicinal plants and/or their parts undergo a series of good practice post-701

harvest (and post-collection) processing procedures, which in the broadest sense include all 702

steps from the immediate on-site primary clean-up of the desired medicinal plant part to its 703

being processed into a form (herbal materials) ready for therapeutic use or as a starting source 704

material for the production of a finished herbal products. While the exact processing methods 705



18

may differ from one herbal material to another, the procedures shall be adopted from those 706

good practice protocols specified in the national pharmacopoeia or recommended by other 707

authoritative documents of the end-user’s country. In the event that no acceptable good 708

processing procedures are available, or that modification of existing or reference cited 709

protocols are required, they should be justified by adequate quality control test data that the 710

efficacy of the herbal material is not diminished. In the absence of national/regional 711

procedures or protocols, international guidelines, such as WHO guidelines on GACP for 712

medicinal plants [WHO, 2003a], and the present guidelines, may be consulted. 713

714

Garbling (Sorting) 715

The garbling process serves as the first step to ensure the purity and cleanness of the 716

medicinal plant materials. After the bulk amount of the desired plant part is harvested or 717

collected, all extraneous and unwanted matters including dirt (e.g. soil, dust, mud, rubbles), 718

impurities (e.g. insects, rotten tissues), and residual non-medicinal parts must be separated 719

from the medicinal part(s). The process may involve, depending on the plant material, 720

procedures such as removing dirt and foreign substances, discarding damaged parts, peeling 721

(to separate unwanted plant parts from the medicinal plant parts such as removing unwanted 722

root bark from the roots or collecting stem bark from the stem), sieving, trimming, singeing 723

(to remove hairs or rootlets), removal of residuals of unwanted plant parts (e.g. removing 724

unwanted seeds from fruits and stripping leaves from stems). Although sorting may be done 725

by mechanical means in some cases, it is usually performed by hand operation. Only suitably 726

trained staff should carry out this work. 727

728

Washing 729

After sorting, the medicinal plant materials should be cleaned well to remove remaining soil, 730

dirt, dust, and other unwanted matters from the surface. They, especially roots, rhizomes and 731

tubers, are commonly washed with clean water, dried soon after harvest/collection. During 732

the washing process, scraping and brushing may be necessary. It is generally recommended 733

not to soak the medicinal plant materials in water for an unnecessarily long period of time. 734

Change water frequently as required. 735

736

Parboiling (Blanching) 737

After washing, certain raw medicinal plant materials may undergo a parboiling or blanching 738

process in which they are put into boiling water for a brief period of time without being fully 739

cooked. Such a heating procedure may serve several purposes, such as improving storage life 740

of the processed materials by gelatinizing the starch and preventing mould/insect 741

contamination, and facilitating further processing such as removal of the seed coat of 742

almonds. 743

744

Leaching 745

Some impurities can be removed by the action of running water over the raw medicinal plant 746

materials. The length of leaching has to be controlled in order to prevent excessive loss of 747

other ingredients. 748

749

Drying 750



19

Unless used in the fresh state, the raw medicinal plant materials are to be dried after being 751

sorted and washed. In general, they must be dried as soon as possible to remove as much 752

moisture as possible in order to ensure good keeping qualities and to reduce damage from 753

mould and other microbial infestation. Drying will also avoid tissue deterioration and 754

phytochemical alteration caused by the actions of enzymes and microbial organisms; and will 755

also facilitate grinding and milling, and convert the herbal materials into a convenient form 756

for further processing. 757

758

The final moisture content for dried herbal materials varies depending on the tissue structure, 759

but should generally be below 12%. Information on the appropriate moisture content for 760

particular herbal material may be available from pharmacopoeias or other authoritative 761

monographs. 762

763

Proper drying involves three major aspects: control of temperature, humidity and air flow. 764

The drying conditions are determined by the nature of the raw medicinal plant material to be 765

dried (tissue structure and chemical composition) and by the desired appearance of the final 766

form. The drying method used may have considerable impact on the quality of the resulting 767

herbal materials. Hence, the choice of proper operational procedure is crucial. Information 768

on the appropriate drying methods and procedures for particular herbal materials may be 769

available from pharmacopoeias or other authoritative monographs. In general, raw medicinal 770

plant materials are most often dried by sun-drying, shade-drying, or by artificial heat. 771

772

The drying conditions chosen should be appropriate to the type of the medicinal plant 773

material. They are dependent on the character (e.g. volatility, stability) of the active 774

ingredients and the texture of the plant part collected (e.g. root, leaf or flower). In general, the 775

following drying processes can be adapted.; 776

777

Sun-drying 778

Most medicinal plant materials can be dried in open-air under direct sunshine, provided the 779

climate is suitable for such a practice. The duration of the drying process depends largely on 780

the physical structure of the medicinal plant material and the weather condition. 781

782

In the case of natural drying in the open air, medicinal plant materials should be spread out in 783

thin layers on drying frames and kept away from possible contaminations such as vehicle 784

exhaust, heavy dusts, and rain, as well as protected from insects, rodents, birds and other 785

pests, livestock and domestic animals. The drying frames should be located at a sufficient 786

height above the ground. Efforts should be made to achieve uniform drying within the 787

shortest period of time to avoid mould formation. 788

789

Shade-drying 790

Some medicinal plant materials can be dried in the shade with or without artificial air flow to 791

avoid direct exposure to strong sunlight. The drying process is slow, but it is preferred to 792

maintain (or minimize loss of) colour of leaves and flowers. Low temperatures (relative to 793

heat-drying) will also preserve most of the volatile and aromatic components from being 794

evaporated. 795

796



20

Drying by artificial heat 797

Drying by artificial heat is more rapid than open-air drying and is often necessary on rainy 798

days or in regions where the humidity is high. Medicinal plant materials may be dried by 799

means of ovens, stoves, belt driers, other heating devices or with open fires. 800

801

For artificial-heat drying, the temperature, humidity and other conditions should be governed 802

by the physical nature of the drug and the physical/chemical properties of its active 803

ingredients. Over-heating may lead to an excessive loss of the volatile components and/or 804

decomposition of chemical ingredients. As much as possible, the temperature should be kept 805

below 60 °C. 806

807

2.3.3 Secondary processing procedures 808

809 In addition to the primary processing, the WHO guidelines on GACP for medicinal plants 810

[WHO, 2003a] also addressed, albeit very briefly, the fact that some herbal materials require 811

“specific” processing to improve their purity and quality. This section highlights the 812

principles and practice of the commonly used secondary processing techniques. In all cases, 813

good in-process control measures must be employed to assure the quality of the end product. 814

Nationally established botanical and chemical quality standards for each processed herbal 815

material must be met. In absence of national standards, regional or international 816

pharmacopoeial standards may be adopted. Guidance for compliance measures can be found 817

in the annex to the Quality control methods for herbal materials [WHO, 2011], WHO 818

guidelines for selection of substances of herbal origin for quality control of herbal medicines 819

[WHO, 2017], WHO guidelines on GMP for herbal medicines [WHO, 2007a], and the present 820

guidelines. An example of a model format of good herbal processing practices 821

monograph/SPO protocol on secondary processing is given as Annex 1. 822

823

The applicable procedures of the secondary processing nature are as follows: 824

825

Cutting, sectioning, and comminution 826

When thoroughly dried, the herbal materials are processed by cutting and sectioning into 827

convenient sizes and shapes for storage, direct use as decoction pieces, and/or further 828

processed for the manufacture of finished herbal products. Where applicable, the herbal 829

materials should be cut or sectioned into specific shapes or forms, or comminuted/pulverized 830

into powder form according to common practice found in herbal medicines. 831

832

Decoction slices or pieces available in many Member States for use as herbal medicines are 833

herbal materials processed only by cutting, sectioning, slicing or comminution/pulverization. 834

White ginseng products presented as root pieces or in powder form prepared from naturally 835

dried roots of Panax ginseng, marketed as herbal medicines, are good examples of herbal 836

materials derived from a simple processing procedure. 837

838

Aging/Sweating 839

The aging process refers to storing the herbal materials for a period of time after being 840

harvested or collected from the field prior to use. It is generally done under the sun or in the 841

shade for up to a year, depending on the specific herbal material. During the process of aging, 842



21

excessive water is evaporated and enzymatic reactions (such as hydrolysis of the glycone 843

portion from glycosides) may occur to alter the chemical composition of the herbal material. 844

For example, cascara sagrada (Rhamnus purshiana) bark should be aged for at least one year 845

(or artificially heated to speed up the process) prior to use in medicinal preparations, for the 846

purpose of curtailing the strong irritating effects that may cause vomiting and upset stomach. 847

848

A similar process known as sweating involves keeping the herbal materials at a temperature 849

of 45-65 °C with high humidity for an extended period of time, from one week to a couple of 850

months, depending on the plant species. The herbal materials are usually densely stacked 851

between woollen blankets or other kinds of cloth. The sweating process is considered a 852

hydrolytic and oxidative process in which some of the chemical ingredients within the herbal 853

materials are hydrolysed and/or oxidized. 854

855

For example, vanilla beans (Vanilla planifolia) are well known to undergo repeated sweating 856

between woollen blankets in the sun during the day and packing in wool-covered boxes at 857

night for about two months, during which the vanilla pods lose up to 80% of weight and take 858

on the characteristic colour and odour of the commercial drug. 859

860

Baking/Roasting 861

The baking/roasting process is a dry-heating procedure using indirect, diffused heat, where 862

the herbal materials are put in a heating device, often embedded in bran or magnesium silicate 863

(talc) powder to ensure even heating on the entire surface at an elevated temperature for a 864

period of time. Some herbal materials are wrapped in moistened papers during the roasting 865

process. The exact temperature used and duration of baking/roasting vary from one herbal 866

material to another. Some are baked or roasted until the surface colour turns yellowish 867

brown; some may be further heated until charred. 868

869

For example, the processing procedure of nutmeg (Myristica fragrans) and kudzu (Pueraria 870

lobata) root requires being roasted together with bran. 871

872

Boiling/Steaming 873

The boiling process involves cooking the plant materials in water or another liquid solvent 874

such as vinegar, wine, milk or animal urine. 875

876

In the steaming process, herbal materials are kept separate from the boiling water but have 877

direct contact with the steam, resulting in a moist texture to the herbal materials. Such 878

treatment is often done by placing the herbal materials in a steamer or in a special utensil 879

equipped with a flat frame hanging over boiling water. In some cases, the herbal materials are 880

pre-mixed with excipient substances such as wine, brine, or vinegar before being steamed. 881

The boiling/steaming process serves to soften plant tissues, to denature enzymes present in the 882

herbal materials, and/or to thermally degrade selected chemical constituents. At the same 883

time, the excipient, if used, is absorbed into the plant tissues to become an integral part of the 884

processed herbal materials. 885

886

For example, Polygonum multiforum root is often steamed in the presence of a black-bean 887

decoction in order to enhance its tonic effects. Boiling the rhizome of Acorus calamus in 888



22

cow’s urine can enhance its anti-convulsant activity. On the other hand, boiling the raw 889

materials such as Croton tiglium, Abrus precatorius, Nerium indicum, Gloriosa superba, and 890

Semecarpus anacardium in cow’s milk would reduce the levels of their toxic ingredients and 891

thus diminish the toxicity of the herbal materials. 892

893

Stir-frying 894

Stir-frying is a process in which the herbal materials are put in a pot or frying pan, 895

continuously stirred or tossed for a period of time under heating, until the external colour 896

changes, charred, or even carbonized. Depending on the medicinal plant species, the stir-897

drying process may require the addition of adjuvants such as wine, vinegar, honey, saline, and 898

ginger juice, which would be infused into the herbal matrix to become an integral part of the 899

processed herbal material. 900

901

To ensure even heating on the surface of the herbal materials, sand, rice, bran, talc or clay can 902

be admixed with the herbal material during stir-frying. 903

904

For example, liquorice (Glycyrrhiza glabra) root and rhizome and Astragalus 905

membranaceous roots are often stir-fried with honey for the preparation of decoction slides, 906

whereas the Salvia miltiorrhiza root is stir-fried with wine. In the case of ginger, fresh ginger 907

is often stir-fried together with sand until the surface colour turns brown. In other instances, 908

ginger can be further stir-fried over intense fire to a carbonized state. 909

910

Fumigation 911

Fumigation by sulphur dioxide has been employed in post-harvest handling of some 912

medicinal herbs for the purpose of preserving colour, improving fresh-looking appearance, 913

bleaching, preventing the growth of insect and overcoming decays caused by moulds. Thus 914

the process has been frequently applied to herbal materials of light and bright colours to avoid 915

“browning”. Due to concerns about the undesirable residues, such process should be avoided 916

as much as possible. If the process is required, all relevant regulations (e.g. limits on sulphur 917

residue) should be compiled. 918

919

2.3.3.1 Selection of processing method 920

Herbal materials derived from the same species but processed by different methods may show 921

significant differences in quality and therapeutic property, owing to the influence of the 922

treatment process on the chemical composition. 923

924

It is not uncommon to find different processing methods for the same medicinal plant/plant 925

part, depending on intended use. For example, raw (unprocessed) liquorice is used as an 926

antitussive and expectorant; but after being stir-fried with honey and ghee, the processed 927

liquorice becomes a tonic drug to be used for replenishing body strength. 928

929

Prior to processing, consult the national or regional regulatory standards and other literature 930

sources to decide on the most appropriate method to use. Once a method is adopted, adhere to 931

the SOP to ensure batch-to-batch consistency. For industrial production, method validation 932

should be adopted as part of the SOP. 933

934



23

Only suitably trained staff should carry out the work, which should be conducted in 935

accordance with the SOP and national and/or regional regulations in both the grower/collector 936

and the end-user countries. 937

938

2.3.3.2 Temperature 939

In processing procedures that involve heating, the temperature used is critical. Make sure the 940

required temperature is achieved during the process. In some cases, pre-heating the 941

equipment (e.g. oven, frying pan and steamer) and/or the additives (such as sand, bran and 942

rice) is required before putting in the herbal materials. When heating equipment (e.g. electric 943

oven) is used, the heating device should be regularly calibrated. 944

945

2.3.3.3 Duration of procedure/treatment 946

It is also critical to control the time of procedure/treatment of the herbal materials. Both over- 947

and under- treatment will affect the quality of the resulting materials. The traditional 948

approach would specify the duration of treatment on the basis of organoleptic alterations such 949

as changes in colour, odour, and texture. If a modern method or instrument is used, the timing 950

should also be accurately controlled. 951

952

2.3.3.4 Use of adjuvants 953

Any adjuvant (e.g. wine, vinegar) used in the processing procedures should be of the 954

required/appropriate quality. The exact amounts and quality of these adjuvants used (the ratio 955

of herbal material and the adjuvant) should also be consistent from batch to batch. 956

957

2.3.4 Special processing procedures 958

959 For herbal materials derived from toxic medicinal plants, general primary and/or secondary 960

processing is insufficient to reduce or attenuate their adverse effects. Such herbal materials 961

require further specific (special) processing procedures before they can be used for 962

therapeutic purpose. These special processing procedures serve as a means to detoxify or 963

neutralize the toxicity, or to reduce the side effects. Such processes are particularly important 964

for those medicinal plant parts that are known to contain toxic or undesirable chemical 965

components; they must undergo proper processes in order to have the unwanted substances 966

degraded. On the other hand, a number of herbal materials require special methods of 967

processing in order to enhance their therapeutic efficacy or to modify their therapeutic 968

properties for the treatment of other disease conditions. The following are examples of 969

special herbal material processing. 970

971

2.3.4.1 Detoxification 972

Aconite (Aconitum species) root, even after having undergone general processing, is an 973

extremely lethal substance and should not be taken in the crude form. Only after proper 974

processing procedure can the toxicity of aconite root be reduced and becomes suitable for 975

use in herbal medicine. The specific process generally involves boiling in water or 976

steaming, or both, to significantly reduce the content of aconitine and related alkaloids. 977

Nux-vomica (Strychnos nux-vomica) seeds are specifically processed by frying or boiling 978

in water or other media such as cow’s milk and ghee to reduce the contents of its toxic 979

ingredients, strychnine and brucine. 980



24

Pinellia ternata tuber: To reduce the gastrointestinal irritant property, the raw herb is 981

soaked in a solution containing glycyrrhiza and calcium oxide at a pH ≥ 12. Alternatively, 982

the raw herb is soaked in water together with potassium aluminum sulphate, or boiled in 983

water together with ginger and potassium aluminum sulphate. 984

Arisaema erubescens rhizome: The raw herbal material is first soaked in water together 985

with potassium aluminum sulphate for several days, followed by cooking with ginger and 986

potassium aluminum sulphate to reduce the strong irritant effect on the respiratory and 987

gastrointestinal tracts. An alternate method for processing Arisaema rhizome is by 988

steaming with animal bile. 989

Euphorbia kansui and E. pekinensis herb: Processing by frying with vinegar to degrade 990

the toxic components that cause severe vomiting and diarrhoea, and central nervous 991

system poisoning. 992

Seeds of Xanthium sibircum, Ricinus communis and Croton tiglium are often processed by 993

stir-frying for the purpose of degrading their contained toxic proteins. 994

Cascara sagrada (Rhamnus purshiana) bark: Following primary post-harvest processing, 995

the bark is aged (stored) for at least one year prior to use as a laxative. During the aging 996

period, natural enzymatic action reduces the drastic cathartic potency of its active 997

glycoside constituents to a non-toxic level. 998

999

2.3.4.2 Enhancement or modification of therapeutic properties 1000

Ginseng (Panax ginseng and Panax quinquefolius): Fresh ginseng is converted to red 1001

ginseng through a series of repeated steaming procedures to afford a product with altered 1002

pharmacological actions or differing therapeutic effects. 1003

Corydalis yanhusuo rhizome is stir-fried or cooked with rice vinegar to enhance its pain-1004

relieving property for use as an analgesic agent. 1005

Rehmannia glutinosa root: The unprocessed herbal material is used to treat fever, 1006

hypertension and skin eruptions; whereas after being cooked in wine, the processed 1007

rehmannia is used as a tonic, emmenagogue and anti-aging drug. 1008

1009

2.3.4.3 Use of adjuvants 1010

Common adjuvants used during the special processing procedures include wine (e.g. rice 1011

wine, wheat wine, and sorghum wine), vinegar, honey, ginger juice, liquorice extract, and 1012

brine, etc. Under special circumstances, other auxiliaries such as human/cow urine, cow/goat 1013

milk, animal bile, butter, cow’s ghee, goat fat, black bean extract, and coconut water, etc. 1014

have been used. 1015

1016

The use of animal parts/products in any processing procedures should be evaluated for safety 1017

and contamination prior to use. 1018

1019

2.3.5 Documentation 1020

1021 Good documentation is an essential part of the processing procedures as set out in the Good 1022

Manufacturing Practices for Pharmaceutical Products: main principles [WHO, 2007a – 1023

WHO, 2003b]; [WHO, 2014]. Thus it is important to prepare and keep in record the details 1024

of the entire processing procedures for each batch of herbal materials. 1025

1026



25

Written processing record should include, but not limited to, the following information; 1027

1028

Botanical (scientific) and the local/common names of the source medicinal plant material; 1029

and plant part(s) being processed; 1030

Site and time of harvesting/collection; 1031

Batch number and any other identification code; 1032

Dates of receipt of the material, processing of the material, and completion of the process; 1033

Name of person in charge of the processing; 1034

General processes that the plant material has already undergone (drying, washing, cutting, 1035

for example., including drying time and temperatures, and size of herbal material); 1036

Gross weight of the plant material before and after processing; 1037

Method used for special processing; 1038

Details of the procedures (master formula), including descriptions of the utensil and 1039

equipment used, steps of operation, amount and quality grade of the auxiliary (e.g. wine, 1040

vinegar) and/or other substances (e.g. sand, bran) used, temperature control, length of 1041

processing time, after-process steps (e.g. cooling, drying, cutting), and other relevant 1042

information; 1043

Batch production detail deviations/modifications of the master formula; 1044

In process control, e.g. organoleptic changes of the plant material after processing (such as 1045

change in colour, shape, texture, odour); and 1046

Quality control parameters and assay results, where appropriate, of active ingredient(s) or 1047

Chemical reference standard(s). 1048

1049


HERBAL PREPARATION 1051

1052


1054 The herbal materials described in Section 2 of these guideline may be ready to serve as the 1055

starting materials for use as herbal medicines. In some cases, they are ground into powder 1056

and used directly as the final dosage form. But in many other cases, the herbal materials will 1057

undergo further treatment processes before being used to manufacture the finished herbal 1058

products. The active ingredients are usually not purified but rather are obtained along with 1059

other components of the medicinal plant part. Sometimes the active ingredients are further 1060

concentrated by the removal of inactive and/or undesirable substances. 1061

1062 Herbal preparations are thus obtained by subjecting the herbal materials to treatments such as 1063

extraction, distillation, fractionation, purification, concentration, fermentation, or other 1064

chemical/biological methods. These include extracts, decoctions, tinctures, essential oils, and 1065

others. 1066

1067

3.2 Extraction 1068 1069

The purpose of extraction of medicinal plant matrix is to eliminate unwanted materials and to 1070

concentrate the active constituents in a soluble form. In some cases, extraction also increases 1071

the shelf life of the product; for example, an alcoholic extract may have a longer shelf life 1072



26

compared to raw herbal materials. The resulting extracts are complex mixtures of chemical 1073

substances, which may be ready for use as a medicinal agent, or they may undergo further 1074

purification to obtain the active constituent(s). The extract may also be processed into 1075

finished products such as tablets and capsules. Herbal extracts include decoctions, infusions, 1076

fluidextracts, tinctures, and powdered extracts. 1077

1078

Various techniques are used for medicinal herb extraction, including maceration, infusion, 1079

digestion, percolation, and decoction. Modern separation techniques can also be applied, e.g. 1080

counter-current extraction, microwave-assisted extraction, ultrasonic extraction (sonication), 1081

and supercritical fluid extraction. For the extraction of volatile components of the herbal 1082

materials (such as essential oils), techniques such as hydrodistillation, expression and 1083

enfleurage may be employed. 1084

1085

3.2.1 Common methods of extraction 1086

1087 In order to produce herbal preparations of defined quality, the use of appropriate extraction 1088

technology, extraction solvents, and type of equipment are crucial. Some common methods 1089

of extraction are illustrated below. 1090

1091

Maceration involves the procedures of mixing the properly comminuted herbal materials 1092

with the solvent and allowing the mixture to stand at room temperature for a defined period of 1093

time with frequent agitation. During the maceration process, chemical constituents are 1094

separated from the plant tissues through a dissolution process into the liquid solvent. A 1095

common practice is to put the herbal material in a container and add solvent until the herbal 1096

powder is thoroughly moistened. An additional amount of solvent is then introduced. The 1097

mixture is agitated occasionally for a period of one day, strained, and the marc (the solid 1098

materials) is pressed. All liquids are collected, combined, and filtered. The maceration 1099

process may be repeated if desirable. In the process of maceration, the herbal materials are 1100

macerated in definite quantities of a solvent (at an optimal ratio of the amounts of dried herbal 1101

material and solvent), and a definite period of time should be specified. Exhaustive bulk 1102

extractions can be quite time-consuming and require large volumes of solvent. 1103

1104

In a special case, a modified maceration procedure involves pre-soaking the herbal material in 1105

water for a period to time to induce fermentation. In other cases, maceration can be 1106

performed by gentle heating in order to enhance the extraction efficiency in a process known 1107

as digestion. 1108

1109

Sonication-assisted extraction and microwave-assisted extraction are modified methods of 1110

maceration, in which ultrasound or microwave is utilized to enhance the extraction efficiency, 1111

to reduce the amount of solvent used, and to shorten the extraction time. For sonication, the 1112

herbal material is placed in a container together with a solvent, which is in turn put in an 1113

ultrasonic bath. The ultrasound provides sufficient power to breakdown the cell walls of the 1114

herbal material and facilitates the solubilization of metabolites into the solvent. The 1115

frequency of ultrasound, length of treatment, and temperature of sonication are important 1116

factors affecting the extraction yield. For microwave-assisted extraction, the herbal material is 1117

placed in a container together with water and subjected to microwave treatment. Heat 1118



27

generated by the microwave energy facilitates the dissolution of compounds from the herbal 1119

matrix into the solvent. Sonication-assisted and microwave-assisted extraction is rarely 1120

applied to large-scaled extraction; they are used mostly for the initial extraction of a small 1121

amount of material. 1122

1123

Infusion refers to an extraction procedure in which the herbal material is immersed in cold 1124

or hot water for a brief period of time to produce a dilute liquid preparation. Typically, the 1125

herbal material is moistened with water and allowed to stand for 15 minutes. A Sufficient 1126

quantity of cold or hot water is then added and allowed to stand for another 30 minutes or 1127

longer. The mixture is strained and ready for use. In the case of hot infusion, the herbal 1128

material is not subjected to the boiling process, although it is common to pour boiling water 1129

over it. Infusion is commonly employed to make herbal teas. 1130

1131

Percolation is the procedure in which the solvent is allowed to continuously flow through 1132

the powdered herbal material in a percolator (a cone-shaped vessel open at both ends). 1133

Typically, the properly comminuted herbal material is moistened with an appropriate amount 1134

of solvent and allowed to stand (macerate) for a few hours before being packed into the 1135

percolator. Additional solvent is added to totally wet the plant powder for a day or two. The 1136

bottom end of the percolator is then opened, with fresh solvent being replenished from the top 1137

of the percolator to maintain a steady flow of solvent through the bed of herbal materials. The 1138

flowrate of the liquid is controlled by adjusting the valve of the outlet. The extraction liquid 1139

is collected from the bottom outlet of the percolator. When the process is completed, the 1140

marc is pressed and all liquids are pooled to obtain the percolate. In addition to the solvent 1141

used for the extraction, the flow rate and the temperature would influence the extraction yields 1142

and they have to be carefully controlled. Percolation is applicable to both initial and large-1143

scale extraction. 1144

1145

Decoction is the most common method to make herbal preparations in many traditional 1146

medicine systems. It involves boiling the herbal material in water, during which time the 1147

chemical ingredients are dissolved into the hot liquid. This procedure is suitable for 1148

extracting water-soluble and heat-stable ingredients of the medicinal plant. 1149

1150

A special technique of decoction is the hot continuous (Soxhlet) extraction using the Soxhlet 1151

apparatus. Typically, the Soxhlet instrument includes an extraction chamber with reflux 1152

condenser and a collection flask. The chamber is placed between the collection flaks and the 1153

condenser. The herbal powder or pieces are kept inside the extraction chamber. A suitable 1154

solvent is added to the flask and heated under refluxing. The solvent will first be evaporated 1155

up into the condenser, then liquefied and drops into the chamber and covers up the herbal 1156

powder. When the condensed solvent in the chamber reaches a certain height, it is siphoned 1157

back into the flask, and the next cycle of extraction starts. Usually, 50-60 times of recycling 1158

are necessary for an extraction to complete. Due to continuous extraction, this method is 1159

more efficient than simple decoction with less consumption of solvent. However, due to 1160

continuous heating at the boiling point of the solvent used, thermos-labile compounds may be 1161

damaged and/or artefacts may be formed. Besides the laboratory scale setup for continuous 1162

extraction, industrial scale stainless steel extractors and high pressure extraction are 1163

commonly used in many manufacturing facilities. 1164



28

1165

Supercritical fluid extraction makes use of the solvating property of a supercritical fluid 1166

(carbon dioxide is the most common supercritical solvent) to dissolve the chemical 1167

constituents in herbal materials. The density of the supercritical fluid (thus its solvating 1168

property) can be adjusted by altering the temperature and pressure, or by the addition of 1169

modifiers (e.g. methanol) to change the polarity of the supercritical fluid. 1170

1171

3.2.2 Steps involved in the extraction of medicinal plants 1172

1173 The following steps are generally involved in the extraction procedures. 1174

1175

Grinding or milling 1176

Prior to extraction, the medicinal plant part is generally dried and reduced to a size between 1177

30-40 mesh (the actual size can be adjusted as the need arises). If fresh material is used for 1178

extraction, it is necessary to perform extraction as soon as possible after the material is 1179

collected to avoid deterioration (microbial fermentation). The purpose of powdering the plant 1180

material is to rupture its tissues and cell structures so that the chemical ingredients are more 1181

readily exposed to the extraction solvent. Moreover, size reduction increases the surface area, 1182

which in turn enhances the mass transfer of chemical ingredients from plant tissue to the 1183

solvent. 1184

1185

Extraction 1186

The extraction process is carried out in the selected solvent at a desirable temperature for an 1187

optimal period of time. Depending on the polarity of the desirable chemical components, 1188

water or other solvents can be used, either at room temperature (“cold” extraction) or at an 1189

elevated temperature (“hot” extraction). 1190

1191

Filtration 1192

After the completion of extraction, the liquid so obtained is separated from the marc by 1193

filtration through a filter cloth or filter paper to remove any particulate insoluble residues. 1194

Other filtering devices may also be used. 1195

1196

Concentration 1197

The enriched extract is often concentrated by the removal of excessive solvent to a thick 1198

concentrated extract or to a solid mass. The concentration procedures may involve 1199

evaporation under reduced pressure (temperature is recommended to below 40 °C) or freeze-1200

drying. 1201

1202

3.2.3 Common herbal preparations prepared by extraction 1203 1204

Decoction is a water-based herbal preparation most commonly utilized in many traditional 1205

medicine systems. It is recommended that only freshly prepared decoctions should be used, 1206

and the amounts of herbal materials and water used, as well as the length of the decocting 1207

process, should be specified. 1208

1209



29

Infusion is a dilute solution prepared by steeping the herbal materials in hot water over a short 1210

period of time. Typically, water is boiled and then poured over the herb. The resulting 1211

solution (the infused tea) should be consumed freshly made or stored at low temperature for 1212

future use. Infusions prepared in edible oil or vinegar are also available. 1213

1214

Fluidextract is an aqueous alcoholic preparation typically made in a ratio of one part (e.g. one 1215

millilitre) of liquid to one part (one gram) of herbal materials. When the liquid preparation is 1216

dilute, e.g. 1:5 or 1:10 liquid-to-herb ratio, it is called a Tincture. Tincture can be prepared by 1217

extracting herbal materials with ethanol or a spirit (an alcoholic beverage). 1218

1219

Extract is a preparation of herbal materials made by an extraction process. In some cases, the 1220

extract is completely freed from the solvent (dried) to become fine or granular powder; it is 1221

called Powdered Extract. 1222

1223

Powder is a form of herbal preparation existing as dry, granulated, or ground materials. 1224

Extracts, tinctures or other liquid preparations can be evaporated to dryness to obtain the 1225

powders. 1226

1227

3.2.4 Controlling factors in extracting herbal materials 1228 1229

There are a number of factors that would influence the efficiency and reproducibility of the 1230

extraction process. A few issues to consider include the solvent used to make an extract, 1231

particle size of the herbal material, the herb-to-solvent ratio, extraction time and temperature. 1232

All these factors should be optimized and incorporated into the SOP, and be strictly adhered 1233

to. 1234

1235

3.3 Distillation 1236 1237

Essential (volatile) oil, the odourous principles of certain medicinal plant materials, is usually 1238

obtained by hydrodistillation from the plant matrix. 1239

1240

Water or steam distillation is a method of choice for extracting volatile ingredients from 1241

medicinal plants. In brief, the herbal material is packed in a still, a sufficient amount of water 1242

is added and brought to a boil (water distillation). Alternatively a stream of steam is 1243

introduced to the herbal material pre-soaked in water (water-steam distillation), or a stream of 1244

steam is introduced to fresh medicinal plant materials without water being added (direct steam 1245

distillation). The method of distillation depends on the condition of the herbal materials. 1246

Water distillation is applied to dried medicinal plant material that is heat stable. Water-steam 1247

distillation is best used for either dried or fresh medicinal plant materials that may be 1248

damaged by boiling, while direct steam distillation is often used for fresh medicinal plant 1249

materials. Freed from the plant tissue, the essential oil is carried away with the steam. Upon 1250

condensation, both water and oil are collected in the liquid form, and the latter separates from 1251

the former into two immiscible layers. 1252

1253

The yield and quality of essential oil obtained by distillation is affected by the process 1254

parameters. It is advisable to design the most optimal conditions in order to obtain the best 1255



30

results. Among the contributing factors are: mode of distillation, condition of raw medicinal 1256

plant materials, loading of raw medicinal plant materials, steam pressure and temperature, and 1257

length of time for distillation. 1258

1259

For volatile oils that may be decomposed during distillation, they can be obtained by 1260

expression (mechanical pressing) or by the enfleurage process. 1261

1262

3.4 Fractionation and Purification 1263

1264 Fractionation is a separation process in which a mixture is divided into a number of smaller 1265

quantities (fractions) with higher purity. The crude extracts of herbal materials contain 1266

complex mixtures of secondary metabolites with diversified chemical and physical 1267

characteristics. It is often desirable to divide the chemical constituents into different groups 1268

based on their similarities in chemical and physical properties, such as a flavonoid-rich 1269

preparation, total glycosides, or an alkaloid fraction. Fractional separation of an herbal 1270

extract can be achieved by subjecting the extract to a variety of fractionation techniques such 1271

as liquid-liquid partition and various forms of chromatography. The method can be applied to 1272

produce semi-purified preparations in order to enrich pharmacologically active constituents, 1273

to remove inactive constituents, and to deplete toxic components. 1274

1275

3.4.1 Liquid-liquid partition 1276

1277 The liquid-liquid partition (or solvent partition) method involves the use of a series of liquid 1278

solvents. The herbal extract is usually dissolved or suspended in water and partitioned with 1279

organic solvents successively in a sequence of increasing polarities, e.g. n-hexane, 1280

dichloromethane, ethyl acetate, and water-saturated n-butanol. As a result, chemical 1281

compounds possessing different polarities are transferred from the water portion to different 1282

solvent fractions according to the principle of “like dissolves like”. For example, the initial 1283

step of partition using non-polar solvents (such as n-hexane or petroleum ethers) removes 1284

lipophilic substances (such as alkanes, fatty acids, sterols) from the herbal mixture, and such a 1285

process is sometimes referred to as “defatting”. The compounds with intermediate polarity 1286

(such as flavonoids and quinones) will dissolve in the medium-polarity solvents (such as 1287

dichloromethane and ethyl acetate), whereas more polar compounds (such as glycosides, 1288

polyphenols) will be concentrated in the more polar solvents (such as butanol) or retained in 1289

the water phase. The organic portion after each step of partition is then evaporated to dryness. 1290

1291

3.4.2 Chromatography 1292

1293 Further purification of the extract fractions can be achieved by various chromatographic 1294

techniques, of which column chromatography is commonly employed, particularly in the 1295

preparative scale. Column chromatography can be carried out using materials based on 1296

different mechanisms. Common modes are adsorption, partition, size exclusion, and ion-1297

exchange. The most frequently used stationary phases (sorbents) are silica gel and alumina in 1298

adsorption chromatography; in size exclusion and ion-exchange chromatography, polymeric 1299

gels and ion-exchange resins, respectively, are used. A proper column packed with the 1300



31

appropriate stationary phase and eluted by a mobile phase with suitable elution power is 1301

crucial to obtain optimized separation of the herbal extract. 1302

1303

3.5 Concentration and drying 1304

1305 The herbal extracts or semi-purified extracts are often concentrated to produce a concentrated 1306

liquid preparation by the removal of excessive solvent. This can be achieved through 1307

evaporation or vaporization. Solvent (single) is generally recovered and may be reused. 1308

Mixed or mixture of solvents cannot be so conserved. The degree of concentration depends 1309

on the desired end product. 1310

1311

Equipment for concentration may include descending film, thin layer or plate concentrators. 1312

Any method used to concentrate the extracts must avoid excessive heat because the active 1313

compounds may be subject to degradation. The liquid preparation so obtained may be used as 1314

is or further processed into a dry powder. 1315

1316

When complete drying is required, the drying process can make use of vacuum freeze dryers, 1317

cabinet vacuum dryers, continuously operating drum or belt dryers, microwave ovens, or 1318

atomizers. The technique for drying depends on the stability of the product and the amount of 1319

moisture that must be removed. The resulting powdered extract is less subject to microbial 1320

contamination than are liquid extracts. 1321

1322

3.6 Fermentation 1323 1324

In some cases, herbal preparation is obtained after undergoing through a fermentation process 1325

of the plant powder or decoction. Fermentation can be either natural (“self-fermentation”) or 1326

by introducing an appropriate microbial organism (e.g. Lactobacillus bacteria). 1327

1328

For natural fermentation, the dry plant powder, a decoction, or infusion of herbal material is 1329

often mixed with the juice of sugarcane, brown sugar or honey, and the mixture is kept in an 1330

airtight utensil for several weeks for anaerobic fermentation to occur. 1331

1332

In some cases, herbal materials are mixed with a small amount of water and shaped to bricks, 1333

followed by microbial cultivation in an incubation room for a week or so, letting the mould 1334

grow on the surface of the herbal materials. 1335

1336

3.7 Processing techniques and procedures 1337

1338 In general, for processes such as extraction, fractionation, purification and fermentation, the 1339

rationale for the guidelines should be established on a case-by-case basis. An example of a 1340

model format of good herbal processing practice monograph/SOP protocol to produce a 1341

herbal preparation is given as Annex 2. The general guidance is provided below. 1342

1343

3.7.1 Preparation of herbal materials for processing 1344

1345 Authentication of herbal materials should be performed prior to extraction. Purity should 1346



32

also be ensured. 1347

Proper documentation on the herbal material should be available as recommended in 1348

Section 2.3.5. 1349

The herbal material should be cleaned, dried, and comminuted into an optimal size for 1350

extraction. 1351

The herbal materials should be processed as soon as possible after arrival at the processing 1352

facility. Otherwise they must be properly stored to avoid contamination, damage, and 1353

deterioration. 1354

All operational steps should be reproducible and performed hygienically, forming parts of 1355

the processing SOP. 1356

1357

3.7.2 Extraction 1358

1359 3.7.2.1 Selection of extraction method 1360

The selection of an extraction method is governed by the nature (stability, solubility, etc.) 1361

and amount of material to be extracted. For large amounts, the feasibility of extracting in 1362

bulk scale should be considered. 1363

The extraction method should be as exhaustive as possible, i.e. removing as much of the 1364

desired ingredients as possible from the plant matrix. 1365

It should be fast, simple, economical, environment-friendly, and reproducible. 1366

1367

3.7.2.2 Extraction conditions and procedures 1368

Solvent 1369

Depending on the nature of the active constituents, an appropriate solvent (or solvent 1370

mixture) should be selected for use. Although water is used as a solvent for many 1371

traditional medicines, organic solvents of varying polarities are generally selected in 1372

modern methods of extraction to exploit the various solubilities of plant constituents. 1373

Typically, an aqueous solution of alcohol (e.g. 60-80% aqueous ethanol) can extract the 1374

majority of organic secondary metabolites from herbal materials. Other solvents may 1375

apply for the extraction of specific types of ingredients (such as proteins and 1376

polysaccharides). 1377

When selecting a solvent or solvent mixture, the following factors should be considered: 1378

solubility of the target compounds, stability and reactivity of the solvent, safety (low 1379

toxicity, low flammability, non-corrosiveness), cost, ease of subsequent solvent removal 1380

and solvent recovery (low boiling point), and environmental friendliness. 1381

Before using a solvent, the material safety data sheet (MSDS) should be reviewed and 1382

appropriate protective measures should be used. Precautions must be taken to minimize 1383

the risk of fire and explosion. Care should be taken to reduce environmental 1384

contamination and to protect the workers and other people in the vicinity from exposure to 1385

chemical hazards. 1386

Toxic solvents and those detrimental to the environment, e.g. benzene, toluene, and carbon 1387

tetrachloride, must not be used. Diethyl ether should be avoided as it is highly flammable 1388

and can lead to the formation of explosive peroxides. The use of chlorinated solvents is 1389

discouraged; if used, dichloromethane is preferred to chloroform, the latter being more 1390

toxic. 1391

Solvents of general-purpose grade available in plastic containers are often contaminated by 1392



33

plasticizers, and minimizing contamination is especially important when bulk extraction is 1393

carried out requiring large volumes of solvent. It is advisable to distill solvents prior to use. 1394

The ratio of herbal material to the extraction solvent is a decisive factor for the 1395

effectiveness of extraction. Thus, the amounts of solvent used must be optimized to ensure 1396

batch-to-batch conformity. 1397

The quality and specification of solvent used should be specified and controlled. 1398

Solvents should be properly stored in non-plastic containers in a well ventilated, fire and 1399

explosion containable area; and away from direct exposure to sun light. 1400

When solvents are recycled, the purity must be confirmed prior to re-use. 1401

Waste solvents must be disposed safely and properly. Guidelines from national, local, or 1402

institutional regulations of waste solvent disposal must be strictly observed and followed. 1403

1404

Temperature 1405

To avoid thermal degradation of the chemical constituents, extractions are preferably 1406

performed under 40 °C, unless evidence is available for the use of higher temperatures. 1407

For heat stable constituent, Soxhlet extraction or decocting in boiling water can be used. 1408

In any case, higher than required temperature should be avoided. 1409

Temperature during the entire extraction process should be controlled and recorded. 1410

1411

Length of treatment 1412

The length of extraction time depends on the purpose for which the extraction is performed 1413

and the nature of the active constituents. Insufficient time will result in incomplete 1414

extraction, but prolonged extraction will lead to excessive extraction of the unwanted 1415

constituents (e.g. tannins), and/or degradation of active chemical ingredients. 1416

The number of repeated extraction cycles required for the complete removal of the 1417

desirable constituents is as important as the length of time per each extraction. 1418

The length of extraction time and the number of cycles should be controlled and recorded. 1419

1420

3.7.3 Distillation 1421 1422

The distillation apparatus must be set up properly and safely according to the 1423

manufacturer’s instructions. 1424

Distillation should be carried out in a well ventilated room. 1425

Optimum extraction conditions, e.g. heating rate and distilling rate, have to be specified 1426

and controlled. 1427

When distillation is performed on an industrial scale, the equipment employed should be in 1428

conformance with the official safety standards and all procedures must conform to the 1429

operational instructions and safety requirements. 1430

1431

3.7.4 Fractionation and purification 1432

1433 Liquid-liquid partition 1434

The storage, use, and disposal of solvents must be handled with care and in conformance 1435

with the national/local/institutional regulations. 1436

The experimental procedures should be carried out in certified facilities with sufficient 1437

ventilation and safety measures. They are preferably preformed inside exhaustive fume 1438



34

hoods. 1439

1440

Chromatography 1441

The choice of stationary phase depends on the polarity, molecular size, or the charge of the 1442

desired ingredients. It should be supported by good rationale. 1443

The choice of mobile phase (solvent system) must be optimized. 1444

Column operation and development procedures (e.g. column size, amount of stationary 1445

phase used, column packing, sample application, elution gradient formation, flow rate, 1446

temperature, fraction collection, and detection method), should be specified and 1447

standardized. 1448

1449

3.7.5 Concentration and drying 1450

1451 The minimization of loss and/or damage to the chemical constituents of interest is critical 1452

to the efficacy of the preparation. Therefore, the preservation of the active ingredients is 1453

of paramount importance during the concentration stage when heat is often applied to 1454

evaporate the solvent. Any concentration process should ensure minimal thermal 1455

decomposition and chemical reactions (such as oxidation) to occur. For organic solvents, 1456

evaporation under reduced pressure at a temperature below 40 °C is preferred. 1457

Solvent removal should be done as soon as possible after extraction. Prolonged exposure 1458

to sunlight should also be avoided. 1459

While evaporation is the most common and the most applied technique for concentration, 1460

other approaches such as membrane technology and freeze concentration are available. 1461

1462

3.7.6 Fermentation 1463

1464 When fermentation is required to produce a herbal preparation, all utensils should be 1465

completely cleaned. A non-corrosive fermentor is required. 1466

The water to be used should not be alkaline and should be free of inorganic matters 1467

(deionized water). 1468

The temperature and length of fermentation should be optimized and controlled. 1469

When fermentation is complete, the solution is filtered and stored in bottles. 1470

1471

3.8 Documentation 1472 1473

The general principles for documentation are set out in the GMP for pharmaceutical 1474

products: main principles [WHO, 2007a – WHO, 2003b]; [WHO, 2014]. 1475

1476

In addition to the data called for in the above guidelines, the specifications for herbal 1477

preparations should as far as possible include, as a minimum, the following information; 1478

1479

Botanical (scientific) and the local/common names of the source medicinal plant material; 1480

and plant part(s) being processed; 1481

Site and time of harvest/collection of the plant; 1482

Batch number and any other identification code; 1483



35

Dates of receipt of the herbal material, processing of the material, and completion of the 1484

process; 1485

Name of person in charge of the processing; 1486

Previous processes that the herbal material has already undergone; 1487

Methods used for processing to produce herbal preparation; 1488

Details of the procedures (master formula), including descriptions of the steps of 1489

operation, operational conditions used during the process, and other relevant information; 1490

Batch production detail deviations/modifications of the master formula; and 1491

Quality control parameters and assay results, where appropriate, of active ingredient(s) or 1492

Chemical reference standard(s). 1493

1494

The SOP including all processing steps should be adopted and documented in the Master 1495

Record. Batch records should be kept, particularly in cases of deviation from the SOP. 1496

Name(s) of all operators and the dates on which each step/stage are carried out should be 1497

documented. 1498

1499


HERBAL DOSAGE FORMS 1501

1502


1504 In contrast to pharmaceutical drugs, many herbal materials and herbal preparations may 1505

undergo only simple processes to become suitable dosage forms for administration. 1506

Generally, these dosage forms are produced under good practice procedures, such as those 1507

given in the Japanese Pharmacopoeia (16th Edition) (see Annex 3). This section describes 1508

some common dosage forms of herbal medicines. 1509

1510

4.2 Extracts 1511 1512

Extracts are prepared by concentrating the extractives of herbal materials. There are two 1513

kinds of extracts: concentrated extract and dried extract. 1514

1515

In general, after being pulverized to a suitable size, the herbal material is extracted for a 1516

certain period of time with suitable solvents by means of cold or warm extraction as described 1517

in Section 3.7.2. The solid and liquid are separated by filtration or centrifugation, followed by 1518

concentration by a suitable method to obtain a concentrated extract, or by bringing to 1519

complete dryness to obtain solid extract in the form of solid masses, granules or powder. 1520

1521

4.3 Fluidextracts 1522 1523

Fluidextracts are liquid percolates of herbal materials, usually prepared by maceration or 1524

percolation of coarse powder or cut pieces of herbal materials as described in Section 3.2.1, to 1525

such a concentration that each milliliter contains soluble substances from one gram of the 1526

herbal material. 1527

1528

4.4 Infusions 1529



36

1530

Infusions are fluid preparations obtained by macerating herbal materials in water. Herbal 1531

materials are cut into a suitable size and wetted with water (usually using 1 milliliter of water 1532

for each gram of herbal material) for 15 minutes. A larger amount of hot water is then added 1533

and heat for a period of time (usually 5-10 minutes), followed by filtration and cooling to 1534

obtain a clear liquid. 1535

1536

4.5 Decoctions 1537 1538

Decoctions are fluid preparations obtained by macerating herbal materials in water. Herbal 1539

materials are cut into a suitable size and cooked with a sufficient quantity of boiling water in a 1540

decoction apparatus for a period of time, usually until about half of the water is dried. 1541

Additional water can be added to repeat the process if desirable. The decoction is obtained by 1542

decanting or filtration. 1543

1544

4.6 Herbal tea bags 1545 1546

Herbal tea bags are prepared by packing finely ground herbal materials (such as dried roots, 1547

leaves or flowers) into paper or cloth bags. When used, boiling water is poured onto the bag 1548

in order to make an infusion. 1549

1550

4.7 Tinctures and spirits 1551

1552 Tinctures and spirit are liquid preparations, usually prepared by extracting herbal materials 1553

with ethanol or with a mixture of ethanol and water by means of either maceration or 1554

percolation. They should be kept away from open fire or directly under the sun. 1555

1556

4.8 Aromatic Waters 1557 1558

Aromatic waters are water preparations containing saturated essential oils or other volatile 1559

substances. Usually, an essential oil is shaken in water and set aside for 12 hours or longer. 1560

The solution is filtered and made up to a certain volume with water. Aromatic waters have a 1561

characteristic odour of the essential oil or volatile substances used. 1562

1563

4.9 Syrups 1564

1565 Syrups are viscous liquid containing sugars or other sweetening agents. They are prepared by 1566

dissolving, mixing, suspending or emulsifying herbal extracts or decoctions in a solution of 1567

honey, sucrose or other sweetening agents. When necessary, the mixture is boiled and 1568

filtered. 1569

1570

4.10 Powders 1571

1572 Powders are prepared by grinding herbal materials or dried extracts to a suitable particle size. 1573

1574

4.11 Granules 1575



37

1576 Granules are dried extracts or decoctions in the form of spherical particles. They are prepared 1577

by adding diluents, binders or other suitable excipients to extract powders, mixed to 1578

homogenize and granulated by a suitable method. Typically, granules are dissolved in hot 1579

water to make a “herbal tea” for administration. 1580

1581

4.12 Pills 1582

1583 Pills are dried extracts or decoctions in the form of small, spherical solids, similar to granules. 1584

They may be prepared by adding suitable excipients to extract powders, mixed to homogenize 1585

and granulated by a suitable method. Typically, pills are swallowed with warm water. 1586

1587

4.13 Capsules 1588

1589 Capsules are prepared by enclosing herbal powder or dried extract in capsule shells or in a 1590

suitable capsule base such as gelatin in a particular shape and size. 1591

1592

4.14 Tablets 1593

1594 Tablets are solid preparations having a defined shape and size. They are usually prepared by 1595

mixing the homogenous herbal powder or dried extract with excipients such as diluents and 1596

binders, followed by compression into a defined shape and size. 1597

1598

4.15 Ointments/creams 1599

1600 Ointments/creams are topical preparations for application to the skin. They are usually semi-1601

solid emulsions dissolved or dispersed in a suitable base. Alongside with the herbal 1602

ingredients, they may contain emulsifiers or thickening agents. 1603

1604

4.16 Inhalations 1605

1606 Inhalations are preparations intended for administration as aerosols to the bronchial tubes or 1607

lungs. They are usually either dry powder inhalers or inhalation liquid preparations. For 1608

administration of inhalations, suitable devices or apparatus are required. 1609

1610

Dry powder inhalers are prepared by pulverizing dried extracts into fine particles. When 1611

necessary, lactose or other suitable excipients are added to make a homogenous mixture. 1612

Inhalation liquid preparations are usually prepared by mixing dried herbal extracts with a 1613

vehicle and suitable pH adjusting agents to make a solution or suspension. Suitable 1614

preservatives may be added to prevent the growth of microorganisms. 1615

1616

4.17 Plasters and Patches 1617

1618 Plasters and patches contain herbal preparations such as dried extracts or decoctions on pieces 1619

of fabric or plastic sheets. When applied topically to the skin, they deliver the herbal 1620

ingredients through the skin to underlying tissues, usually for the relief of pain, backache, or 1621



38

sore muscles. 1622

1623

An example of general good practice for the preparation of herbal dosage forms is given in 1624

Annex 3. 1625

1626

5. TECHNICAL ISSUES SUPPORTING GOOD HERBAL PROCESSING 1627

PRACTICES 1628

1629 In the formulation of a good practice protocol for processing herbal materials, a number of 1630

supporting technical issues must be considered and adopted. Since the primary objective is to 1631

produce quality processed herbal materials and preparations, many of the same technical 1632

issues associated with the GACP, GMP and quality control (QC) methods are applicable to 1633

GHPP. 1634

1635

Therefore, these guidelines have been consulted for applicable good practice items for 1636

adoption. Moreover, the same technical issues on the post-harvest processing of cultivated 1637

and collected medicinal plant materials were addressed in section 4 of the WHO guidelines on 1638

GACP for medicinal plants [WHO, 2003a]. Therefore, the applicable good practice 1639

guidelines have been adopted in whole or modified as appropriate for the present guidelines. 1640

1641

5.1 Processing facilities 1642

1643 The ideal design and construction of a herbal material processing facility incorporating the 1644

most appropriate location, buildings, medicinal plant material handling and processing areas, 1645

water supply, effluent and waste disposal, changing facilities and toilets, hand-washing 1646

facilities in processing areas, disinfection facilities, lighting, ventilation, dust and storage of 1647

waste and unusable materials, have already been fully described in Sections 4.1.5 (pages 19-1648

23) of the WHO guidelines on GACP for medicinal plants [WHO, 2003a]. Therefore, they 1649

are adopted for the present guidelines and the descriptions are excerpted and presented in 1650

Annex 4 for easy reference. 1651

1652

5.2 Packaging and labelling 1653

1654 Processed herbal materials or herbal preparations should be packaged as quickly as possible to 1655

preserve their quality by preventing deterioration of the herbal medicines and to protect 1656

against unnecessary exposure to pest infestations and other sources of contamination. 1657

1658

Continuous in-process quality control measures should be implemented to eliminate sub-1659

standard materials, contaminants and foreign matter prior to and during the final stages of 1660

packaging. Processed medicinal plant materials should be packaged in clean, dry boxes, 1661

sacks, breathable bags or other containers in accordance with standard operating procedures 1662

and meeting national and/or regional regulations of the producer and the end-user countries. 1663

Materials used for packaging should be non-polluting, clean, dry and in undamaged condition 1664

and should conform to the quality requirements for the processed herbal materials or herbal 1665

preparations concerned. Fragile medicinal plant materials should be packaged in rigid 1666

containers. Wherever possible, the packaging used should be agreed upon between the 1667



39

supplier and buyer. 1668

1669

A label affixed to the packaging should clearly indicate the scientific name, the processed 1670

plant part with date, the processing techniques used, the name and address of the processor, as 1671

well as quantitative information. The label should also contain information indicating quality 1672

approval and compliance with other national and/or regional labelling requirements. The 1673

label should bear a number that clearly identifies the production batch. Additional 1674

information about the production and quality parameters of the medicinal plant materials may 1675

be added in a separate certificate, which is clearly linked to the package carrying the same 1676

batch number. 1677

1678

Records should be kept of batch packaging, and should include the product name, place of 1679

origin, batch number, weight, assignment number and date. The records should be retained 1680

for a period of three years or as required by national and/or regional authorities. 1681

1682

5.3 Storage and transportation 1683

1684 All processed herbal materials or herbal preparations should be properly stored and preserved 1685

before use. They must be protected from microbial and insect contaminations, and rodents 1686

and other pests. Every effort should be tried to use the type of packaging that provides ample 1687

protection against physical damages to the materials and to keep away, as much as possible, 1688

from exposure to moisture, light, heat, and insect attack. 1689

1690

Storage areas should be of sufficient capacity to allow orderly storage of the various types of 1691

processed herbal materials and herbal preparations with proper separation and segregation. In 1692

particular, they should be clean, dry, sufficiently lit and maintained within acceptable 1693

temperature and humidity limits, and controlled, monitored and recorded where appropriate to 1694

ensure good storage conditions. 1695

1696

Conveyances used for transporting processed herbal materials and herbal preparations from 1697

the place of processing to storage should be clean and, where appropriate, well ventilated to 1698

keep an appropriate level of and to prevent condensation. 1699

1700

Fumigation against pest infestation in conveyances and in storage areas should be carried out 1701

only when necessary, and should be carried out by licensed or trained personnel. Only 1702

registered chemical agents authorized by the regulatory authorities of the source country and 1703

the countries of intended end-use should be used. All fumigation, fumigation agents, and 1704

dates of application should be documented. When freezing or saturated steam is used for pest 1705

control, the humidity of the materials should be checked after treatment. 1706

1707

5.4 Equipment 1708

1709 All equipment, including tools and utensils used in the processing of herbal materials and 1710

herbal preparations should be made of materials that do not transmit toxic substances, odour 1711

or taste; are non-absorbent; are resistant to corrosion and are capable of withstanding repeated 1712

cleaning and disinfection. The use of wood and other materials that cannot be adequately 1713



40

cleaned and disinfected should be avoided, except when their use would clearly not be a 1714

source of contamination. The use of metals where contact corrosion may occur should be 1715

avoided. 1716

1717

All equipment and utensils should be designed and constructed so as to prevent hygienic 1718

hazards and permit easy and thorough cleaning and disinfection. Where practicable, they 1719

should be accessible for visual inspection. Stationary equipment should be installed in such a 1720

manner as to permit easy access and thorough cleaning. 1721

1722

Containers for unusable materials or waste should be leak-proof, constructed of metal or other 1723

suitable impervious materials, should be easy to clean or be disposable, and should close 1724

securely. 1725

1726

All refrigerated spaces should be equipped with temperature measurement or recording 1727

devices. 1728

1729

5.5 Quality assurance and quality control 1730

1731 Compliance with quality assurance measures should be verified through regular internal 1732

oversight personnel (QC manager) and external auditing visits to processing facilities by 1733

expert representatives of buyers and other stake holders and through inspection by national 1734

and/or local regulatory authorities. 1735

1736

5.6 Documentation 1737

1738 The SOP should be adopted and documented. All methods and procedures involved in the 1739

processing of herbal materials and herbal preparations and the dates on which they are carried 1740

out should be documented. 1741

1742

The types of information that should be collected include the items described in Sections 2.3.5 1743

and 3.8 above. Additionally, documentation on post-processing transportation and storage of 1744

processed products should be prepared. 1745

1746

Where applicable, the results of inspection should be documented in an inspection report 1747

which contains copies of all documents, (QC) analysis reports, and local, national and/or 1748

regional regulations, and which are stored according to their requirements. 1749

1750

5.7 Personnel 1751

1752

5.7.1 General 1753

1754 All personnel should receive proper post-harvest handling and herbal processing training. 1755

1756

All personnel required to handle chemical solvents and adjuvants should receive adequate 1757

training and possess sufficient knowledge and appropriate techniques employed for their safe 1758

handling and proper use. 1759



41

1760

Local, national and/or regional regulations governing labour should be respected in the 1761

employment of staff for all phases of herbal processing. 1762

1763

5.7.2 Health, hygiene and sanitation 1764

1765 All personnel involved in the pre-processing and during processing handling of herbal 1766

materials should be trained and perform tasks in compliance with local, national and/or 1767

regional regulations on safety, materials handling, sanitation and hygiene. 1768

1769

All personnel should be protected from contact with toxic or potentially allergenic herbs by 1770

means of adequate protective clothing, including gloves and masks. 1771

1772

Health status 1773

All personnel known, or suspected to be suffering from or to be a carrier of a disease or illness 1774

likely to be transmitted, should not be allowed to enter any processing area, and should 1775

immediately be reported to the management, and suspended from work as deemed medically 1776

appropriate. 1777

1778

Health conditions that should be reported to the management for consideration regarding 1779

medical examination and/or possible exclusion from handling of medicinal plant and 1780

processing/processed herbal materials and associated equipment including but not limited to: 1781

such as jaundice, diarrhoea, vomiting, fever, sore throat with fever, visibly infected lesions 1782

(boils, cuts, among other conditions) and discharges from the ear, nose or eye. Any personnel 1783

who have cuts or wounds and are permitted to continue working should cover their injuries 1784

with suitable waterproof dressings. 1785

1786

Personal hygiene and behaviours 1787

Personnel who handle processing/processed herbal materials should be trained to maintain a 1788

high degree of personal cleanliness, and, where appropriate, wear suitable protective clothing 1789

and gloves, including head/hair covering and footwear. 1790

1791

Personnel should always wash their hands at the start of handling activities, after using the 1792

toilet, and after handling medicinal plant materials or any contaminated material. 1793

1794

Smoking, drinking, and eating should not be permitted in medicinal plant processing areas. 1795

1796

Visitors 1797

Visitors to processing and handling areas should wear appropriate protective clothing and 1798

adhere to all of the personal hygiene provisions mentioned above [WHO, 2003a]. 1799

1800

6. OTHER RELEVANT ISSUES 1801

1802

6.1 Ethical and legal considerations 1803 1804

All herbal processing must be carried out in accordance with applicable legal and 1805



42

environmental requirements and with the ethical codes or norms of the community and 1806

country in which the activities take place. 1807

1808

6.2 Research, research training and information sharing 1809

1810 Research to find alternate processing procedures to achieve the same therapeutic efficacy as 1811

traditional or historical methods is needed. Additionally, research to determine the chemical 1812

conversion process and mechanism involved in the qualitative and quantitative alteration of 1813

the biologically active or adjuvant chemical constituents following processing is also needed 1814

and encouraged. 1815

1816

Technical information resulting from processing method research is useful instrument for 1817

promoting technical advancement, and should be shared through publication, conferences or 1818

otherwise conveyed to interested stakeholders. 1819

1820

As in all technical endeavours, education and research training are essential to preserve 1821

technical expertise and to promote innovation in development of new and better techniques 1822

and procedures in herbal processing. 1823

1824

Research to develop good herbal processing practices of each medicinal plant – such as 1825

monographs. 1826

1827

6.3 Adoption of good herbal processing practices 1828 1829

Member States or nations that have not adopted good herbal processing practices for herbal 1830

medicines are encouraged to establish or adopt such practices as part of quality assurance and 1831

control measures, as well as a part of their regulatory requirements for herbal medicines. 1832

1833

6.4 Intellectual property rights and benefits-sharing 1834 1835

Agreements on intellectual property rights and the return of benefits and compensation for the 1836

use of source herbal materials or herbal preparations concluded in writing by the sourcing 1837

contractor, shall be acknowledged and followed by the processor as appropriate. 1838

1839

6.5 Threatened and endangered species 1840 1841

When obtaining medicinal plants that are protected by national and international laws, such as 1842

those listed in national “red” lists, for processing, the processor shall ascertain and obtain 1843

appropriate documentation from the sourcing contractor that said materials were acquired 1844

only by relevant permission according to national and/or international laws, and that the 1845

provisions of the Convention on International Trade in Endangered Species of Wild Fauna 1846

and Flora (CITES) have been complied with. 1847

1848

7. REFERENCES 1849 1850 WHO, 2000:General guidelines for methodologies on research and evaluation of traditional medicine 1851 WHO/EDM/TRM/2000.1, Geneva, World Health Organization, 2000. 1852



43

1853 WHO, 2003a:WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants. 1854 Geneva, World Health Organization, 2003. 1855 1856 WHO, 2003b: Good Manufacturing Practices for pharmaceutical products: main principles In: WHO 1857 Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-seventh report. Geneva, 1858 World Health Organization, 2003 (WHO Technical Report Series, N0. 908), Annex 4. 1859 1860 WHO, 2007a: WHO guidelines on good manufacturing practices (GMP) for herbal medicines. Geneva, 1861 World Health Organization, 2007. 1862 1863 WHO, 2007b:WHO guidelines on assessing quality of herbal medicines with reference to contaminants 1864 and residues, Geneva, World Health Organization, 2007. 1865 1866 WHO, 2007c:General guidelines for the establishment, maintenance and distribution of chemical reference 1867 substances. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-first 1868 report. Geneva, World Health Organization, 2007 (WHO Technical Report Series, No. 943), Annex 3. 1869 1870 WHO, 2011:Quality control methods for herbal materials. Geneva, World Health Organization, 2011. 1871 1872 WHO, 2014:Good Manufacturing Practices for pharmaceutical products: main principles In: WHO Expert 1873 Committee on Specifications for Pharmaceutical Preparations. Forty-eighth report. Geneva, World Health 1874 Organization, 2014 (WHO Technical Report Series, N0. 986), Annex 2. 1875 1876 WHO, 2017:WHO guideline for selecting marker substances of herbal origin for quality control of herbal 1877 medicines. Geneva, World Health Organization, 2017 (in preparation). 1878 1879 WHOM-1999:WHO monographs on selected medicinal plants, Volume 1, Geneva, World Health 1880 Organization, 1999. 1881 1882 WHOM-2002:WHO monographs on selected medicinal plants, Volume 2, Geneva, World Health 1883 Organization, 2002. 1884 1885 WHOM-2007:WHO monographs on selected medicinal plants, Volume 3, Geneva, World Health 1886 Organization, 2007. 1887 1888 WHOM-2009:WHO monographs on selected medicinal plants, Volume 4, Geneva, World Health 1889 Organization, 2009. 1890 1891 WHOM-2010:WHO monographs on selected medicinal plants commonly used in the Newly Independent 1892 States (NIS), Geneva, World Health Organization, 2010. 1893

1894



44

Annex 1: Example of a model format of good herbal processing practices 1895

monograph/SOP protocol to produce a herbal material 1896 1897

TITLE of the monograph/protocol: 1898 1899 Processing of [name of the plant] (Scientific name of the medicinal plant; medicinal plant part) 1900 1901 1. Objective of the SOP Protocol 1902 1903 2. Scope 1904 1905 3. Procedures 1906 1907 3.1 Sampling 1908 1909 Sampling of herbal materials should follow applicable national or regional specifications. In absence 1910 of appropriate specifications, the following method may be considered: When a batch consists of five 1911 containers or packaging units, take a sample from each one. From a batch of 6-50 units, take a sample 1912 from five. In the case of batches of over 50 units, sample 10%, rounding up the number of units to the 1913 nearest multiple of ten (WHO, 2011). 1914 1915 Quality testing of the raw material 1916 Perform morphological identification/validation by macroscopic and microscopic examinations and 1917 physicochemical tests by following the procedures set out in the national pharmacopoeia or other 1918 authoritative documents. 1919 1920 The following requirements must be fulfilled. 1921 Morphology: Conform with the national pharmacopoeial standards 1922 Identification (including microscopic examination, colorimetric and/or chromatographic tests): 1923

Conform with the pharmacopoeial standards 1924 Water content: ≤ xxx % 1925 Total ash: ≤ xxx % 1926 Extractive: ≥ xxx % 1927 1928 3.2 Quality control assay 1929 1930 3.2.1 Marker compound 1931 Compound “Z” is used as the marker compound for plant X..y.. for quality control purpose. Obtain 1932 analytical grade Compound Z (≥ 98% purity) from a reliable source to serve as Chemical reference 1933 substance. 1934 1935 3.2.2 High-performance liquid chromatographic (HPLC) analysis 1936 Set up the HPLC system. Perform system suitability test to ensure suitability of the instrument and 1937 method. 1938 Under the recommended HPLC conditions, establish calibration curves by injecting an appropriate 1939 amount of the chemical reference (marker) standard solution in a series of concentrations. 1940 Obtain HPLC chromatogram of the herbal material. Identify the analyte signal in the chromatogram 1941 by comparing the retention time with that of the peak of the chemical reference substance obtained 1942 under same HPLC conditions. 1943 Calculate the percentage content of the analyte in the sample using the calibration curve. 1944



45

Determine the percentage content of the marker compound again after final drying of the processed 1945 herbal material (section 3.10 below). 1946 1947 The following requirement must be fulfilled. 1948 Content of Compound Z before processing: ≥ xxx % calculated with reference to the dry weight of 1949

the starting material 1950 Content of Compound Z after processing: ≥ xxx % calculated with reference to the dry weight of 1951

the processed material 1952 1953 3.3 Testing of the excipient* 1954 1955 Perform tests by following the procedures set out in the SOP document. The following requirements 1956 must be fulfilled. 1957 Appearance: Conform with internal standards 1958 Total excipient content: ≥ xxx % 1959 1960 3.4 Initial sorting of the plant material for processing 1961 1962 The source herbal materials are manually sorted by trained personnel according to the requirements 1963 specified in the SOP. Impurities (e.g. dirt and non-medicinal plant parts) should be removed, and any 1964 materials of non-uniformed sizes should be excluded. 1965 1966 The following requirements must be fulfilled. 1967 Impurity: ≤ xxx % 1968 Size uniformity: ≥ xxx % 1969 Total recovery: ≥ xxx % (Recovery = Weight after sorting / Weight before sorting X 100%) 1970 1971 3.5 Washing 1972 1973 Washing should be performed by following the procedures set out in the SOP document. Pay attention 1974 to the quality of water used, the length of washing time, and any precautions applicable to the specific 1975 herb. 1976 1977 The following requirements must be fulfilled. 1978 Appearance after washing: in conformance with the SOP standard 1979 Recovery: xxx-xxx % (Recovery = Weight after washing/Weight before washing X 100%) 1980 1981 3.6 Steaming (or other treatment) 1982 1983 The procedures set out in the SOP document should be strictly followed. All equipment should be 1984 properly maintained, clean, and performing at optimal and safe conditions. 1985 1986 The following requirements must be fulfilled. 1987 Appearance after steaming/treatment: in conformance with the SOP standard 1988 Recovery: ≥ xxx % (Recovery = Weight after steaming/Weight before steaming X 100%) 1989 1990 3.7 Semi-drying 1991 1992 If required, dry the samples according to SOP guideline, either by sunlight or by artificial heating. 1993 1994 The following requirements must be fulfilled. 1995



46

Appearance after semi-drying : in conformance with the SOP standard 1996 Recovery: xxx-xxx% (Recovery = Weight after drying/Weight before drying X 100%) 1997 1998 3.8 Cutting/sectioning/comminuting 1999 2000 The processed material should be comminuted into the required size and shape in conformance with 2001 the SOP standard. 2002 2003 The following requirements must be fulfilled. 2004 Non-conformed pieces: ≤ xxx % 2005 Recovery: ≥ xxx % (Recovery = Weight after cutting/Weight before cutting X 100%) 2006 2007 3.9 Final drying of processed herbal material 2008 2009 The cut materials should be thoroughly dried according to the SOP requirement. 2010 2011 The following requirements must be fulfilled. 2012 Water content of the final product: xxx-xxx % 2013 Recovery: ≥ xxx % (Recovery = Weight after drying/Weight before drying X 100%) 2014 2015 3.10 Final sorting 2016 2017 The dried material should be carefully inspected by trained personnel, with impurities removed, and 2018 sorted into specific grades in accordance with the pharmacopoeial or trading standard. 2019 2020 The following requirements must be fulfilled. 2021 Impurity: ≤ xxx % 2022 Grade-1 pieces: ≥ xxx% 2023 Grade-2 pieces: xxx –xxx% 2024 Recovery: ≥ xxx % (Recovery = Weight after sorting/Weight before sorting X 100%) 2025 2026 3.11 Packaging, labelling, and storage 2027 2028 3.11.1 Packaging 2029 Processed materials should be packaged quickly and appropriately in air-tight, non-corrosive 2030 containers, and protected from light to preserve quality, prevent deterioration and to protect against 2031 contamination. 2032 2033 3.11.2 Labelling 2034 Labels affixed to each package should clearly indicate the scientific name of the medicinal plant, the 2035 plant part, the processing method, the date of processing, the batch number, quality specification and 2036 compliance, quantitative and other relevant information. 2037 2038 3.11.3 Storage 2039 The packaged products must be stored in a clean, dry and well-ventilated area, at a constant 2040 temperature appropriate for the proper maintenance of the final product, and protected against 2041 microbial and other sources of contaminations and free from insects and animal pest attacks. 2042 2043

*This step is not required if excipient(s) are not employed in the processing protocol 2044 2045



47

Annex 2: Example of a model format of good herbal processing practices 2046

monograph/SOP protocol to produce a herbal preparation 2047 2048

TITLE of the monograph/protocol 2049 2050

Processing of [name of the plant] (Scientific name of the medicinal plant; medicinal plant part) 2051 2052 1. Objective of the SOP Protocol 2053 The objective of this protocol is to establish a procedure for preparation of the finished product. 2054 2055 2. Scope 2056 This procedure applies to processes required in the preparation of the juice of the herb of X..y... 2057 2058 3. Procedures 2059 This protocol should be carried out in accordance with the standard operating procedures (SOP) for 2060 the processing of material X.. y... as described in this document, the SOP for equipment operation and 2061 maintenance, as well as those for facility management and cleaning. Any other relevant requirements 2062 may also apply. 2063 2064 The protocol should be adhered to in conjunction with relevant internal standards of the processing 2065 facility. 2066 2067 After the completion of each processing step, the products should be inspected by qualified personnel. 2068 All inspection records should be properly filed and retained for a period of three years or as required 2069 by national and/or regional authorities. 2070 2071 4. Plant substance 2072 The identity of the raw plant material should be confirmed using morphological 2073 identification/validation by macroscopic and microscopic examinations and physicochemical tests by 2074 following the procedures set out in the pharmacopoeia or other authoritative documents. 2075 2076 Specifications such as those below should be in place. 2077 2078 Origins of the plant material (natural state/cultivation): Describe appropriate origins of the 2079

plant material 2080 Part plant: Describe the desired plant part/parts (i.e. flowers) 2081 Growing conditions: 2082

o fertilizers: Specify allowable fertilizers in compliance with applicable regulations 2083 o pest controls: Specify allowable pesticides and/or biological pest controls, in compliance 2084

with applicable regulations 2085 o fungicides: Specify allowable fungicides (if any) in compliance with applicable regulations 2086 o fumigants: Specify allowable fumigants (if any) in compliance with applicable regulations 2087

Harvest time: Describe the appropriate months for harvest (i.e. during flowering (June-July) 2088 Harvesting: Describe the process for harvesting (i.e. mechanical process) 2089 Drying conditions: Describe the process for drying, if applicable 2090 Purification: Describe the process for inspection and removal of impurities 2091 Storage conditions: Specify the storage conditions. In general, the plant material should be 2092

stored in a clean, dry and well-ventilated area, at an appropriate constant temperature, protected 2093 against microbial and other sources of contaminations, free from attack by insects and animal 2094 pests 2095



48

Transportation conditions: Commercial vehicles should be clean, dry, deprived of any foreign 2096 matter. Conditions should ensure protection against moisture and contamination. Baskets, chests 2097 and jute bags can be used as containers. Each container will be labelled with the name of the 2098 material, date of harvest, harvesting site, net and gross weight and the name of the supplier 2099

2100 5. Processing 2101 Descriptions of the processing facility requirements are included in this section, i.e. certification of the 2102 site as a good practice facility. Details are given for the raw components to be used in the production 2103 of the final herbal preparation. 2104 2105 As an example, raw X...y... material to be processed into X...y... juice are detailed in the table below. 2106 In this example, the plant material is extracted using ethanol 95% (V/V) and water as needed. The 2107 drug extract ratio (DER) is 1:1. 2108 2109

Raw Material Components in the Production of X...y...juice 2110 Raw Materials Function Amount per 100 kg Standard

Fresh X...y... herb Plant material 100.0 kg Standard specification

Ethanol 95% Extraction solvent Xx litres Pharmacopoeia .XYZ

Extraction water Extraction solvent q.s. Pharmacopoeia .XYZ

2111 Raw materials accepted for processing must meet specifications for identity and quality. 2112 Specifications include appearance/description of the plant material(s), the particle size, water content, 2113 total ash, as well as appropriate chemical assays. These criteria may follow criteria detailed in 2114 pharmacopoeial monograph(s). 2115 2116 The steps below describe the preparation of the juice of the herb of X..y.. 2117 Step 1. The fresh fragmented plant material is stabilized with the vapours of boiling 95% ethanol 2118

in an autoclave. The duration, temperature and vapour pressure are specified in the SOP. When 2119 the process is completed, the fluid separates from the plant material. 2120

Step 2. The stabilized plant material is placed in a macerator with post-stabilization fluid and 2121 water. The maceration process lasts for a period of time (n days) specified. At the end of the 2122 extraction process, the extract is separated from the plant matter in a manner specified by the SOP. 2123 The ethanol content of the extract and density of the extract are specified. 2124

Step 3. The resulting extract is stored in a stainless steel container for a minimum time 2125 (days/weeks) specified. The process ensures sedimentation of inorganic residual waste. 2126

Step 4. The extract is filtered using a pressurized process. Both the input pressure and filter size 2127 are specified by the manufacturer. 2128

2129 6. Process controls 2130 Controls for tests conducted during the process should be described. A description of the tests, their 2131 methods and the acceptance criteria should be given. These include appearance (i.e. colour), particle 2132 size (amount expected to pass through a specified sieve size), water or alcohol content, and/or relative 2133 density. 2134 2135 7. Release specifications of final product 2136 Identify criteria that must be met for release of the final product. These criteria generally include 2137 appearance, relative density, and specified quantities for chemical constituent(s), as well as limits for 2138 heavy metals, microbial content and residual matter. 2139 2140 Chemical profile: i.e. TLC/HPLC fingerprint of chemical constituents 2141



49

Pharmacopoeial/standard quantitation of chemical markers, where applicable 2142 Heavy metals: limits defined 2143 Microbial: limits defined 2144 Residuals: limits for pesticides, fertilizers, foreign matter, etc. 2145 2146 8. Certificate of analysis 2147 A certificate of analysis will be generated following completion of quality control testing. This 2148 document should include the assay methods as well as the results obtained using those methods. 2149 2150 9. Packaging 2151 The appropriate packaging the containers should be described. Processed materials should be 2152 packaged quickly and appropriately in air-tight, non-corrosive containers, and protected from light to 2153 preserve quality, prevent deterioration and to protect against contamination. 2154 2155 10. Labelling 2156 Labels affixed to each package should clearly indicate the scientific name of the medicinal plant, the 2157 plant part, the processing method, the date of processing, the batch number, quality specification and 2158 compliance, quantitative and other relevant information. 2159 2160 11. Storage conditions 2161 The packaged products must be stored in a clean, dry and well-ventilated area, at a constant 2162 temperature appropriate for the proper maintenance of the final product, and protected against 2163 microbial and other sources of contaminations and free from insects and animal pest attacks 2164 2165 12. Stability 2166 Stability testing should be conducted to determine an appropriate shelf-life. 2167 2168 13. Retained samples 2169 Sufficient materials (raw material and finished goods) must be retained in proper storage conditions to 2170 allow for future verification of identity and quality. 2171 2172



50

Annex 3: Example of general rules for preparation of dosage forms related to herbal 2173

medicines 2174 2175 [Reference Source: Japanese Pharmacopoeia 16th edition, Ministry of Health, Labour and Welfare, Mach 2011] 2176

2177

Japanese Pharmacopoeia, 16th Edition (2011): 2178

General Rules for Preparations/Monographs for Preparations Related to Crude Drugs 2179

2180 Monographs for Preparations Related to Crude Drugs 2181

2182 Preparations Related to Crude Drugs 2183 2184 (1) Preparations related to crude drugs are preparations mainly derived from crude drugs. Extracts, 2185 Pills, Spirits, Infusions and Decoctions, Teabags, Tinctures, Aromatic Waters, and Fluidextracts are 2186 included in this category. 2187 2188 Definitions, methods of preparations, test methods, containers and packaging, and storage of these 2189 preparations are described in this chapter. 2190 2191 (2) The descriptions of the test methods and the containers and packaging in this chapter are 2192 fundamental requirements, and the preparation methods represent commonly used methods. 2193 2194 1. Extracts 2195 (1) Extracts are preparations, prepared by concentrating extractives of crude drugs. There are 2196 following two kinds of extracts. 2197

(i) Viscous extracts 2198 (ii) Dry extracts 2199

2200 (2) Unless otherwise specified, Extracts are usually prepared as follows. 2201

(i) Crude drugs, pulverized to suitable sizes, are extracted for a certain period of time with 2202 suitable solvents by means of cold extraction or warm extraction, or by percolation as directed in (ii) 2203 of (2) under 6. Tinctures. The extractive is filtered, and the filtrate is concentrated or dried by a 2204 suitable method to make a millet jelly-like consistency for the viscous extracts, orto make crushable 2205 solid masses, granules or powder for the dry extracts. Extracts, which are specified the content of 2206 active substance(s), are prepared by assaying active substance(s) in a portion of sample and adjusting, 2207 if necessary, to specified strength with suitable diluents. 2208

(ii) Weigh crude drugs, pulverized to suitable sizes, according to the prescription and heat for a 2209 certain period of time after adding 10 ñ 20 times amount of water. After separating the solid and liquid 2210 by centrifugation, the extractive is concentrated or dried by a suitable method to make a millet jelly-2211 like consistency for the viscous extracts, or to make crushable solid masses, granules or powder for the 2212 dry extracts. 2213

2214 (3) Extracts have odour and taste derived from the crude drugs used. 2215 2216 (4) Unless otherwise specified, Extracts meet the requirements of Heavy Metals Limit Test <1.07>

1 2217 (for detail of test methods, procedure, and regents and solutions, see end note of this annex), when 2218 the test solution and the control solution are prepared as follows. 2219 2220 Test solution: Ignite 0.30 g of Extracts to ash, add 3mL of dilute hydrochloric acid, warm, and filter. 2221 Wash the residue with two 5-mL portions of water. Neutralize the combined filtrate and washings 2222



51

(indicator: a drop of phenolphthalein TS) by adding ammonia TS until the color of the solution 2223 changes to pale red, filter where necessary, and add 2mL of dilute acetic acid and water to make 2224 50mL. 2225 2226 Control solution: Proceed with 3mL of dilute hydrochloric acid in the same manner as directed in the 2227 preparation of the test solution, and add 3.0mL of Standard Lead Solution and water to make 50mL. 2228 2229 (5) Tight containers are used for these preparations. 2230 2231 2. Pills 2232 (1) Pills are spherical preparations, intended for oral administration. 2233 2234 (2) Pills are usually prepared by mixing drug substance(s) uniformly with diluents, binders, 2235 disintegrators or other suitable excipient(s) and rolling into spherical form by a suitable method. They 2236 may be coated with a coating agent by a suitable method. 2237 2238 (3) Unless otherwise specified, Pills comply with Disintegration Test. 2239 2240 (4) Well-closed or tight containers are usually used for these preparations. 2241 2242 3. Spirits 2243 (1) Spirits are fluid preparations, usually prepared by dissolving volatile drug substance(s) in ethanol 2244 or in a mixture of ethanol and water. 2245 2246 (2) Spirits should be stored remote from fire. 2247 2248 (3) Tight containers are used for these preparations. 2249 2250 4. Infusions and Decoctions 2251 (1) Infusions and Decoctions are fluid preparations, usually obtained by macerating crude drugs in 2252 water. 2253 2254 (2) Infusions and Decoctions are usually prepared by the following method. 2255

Cut crude drugs into a size as directed below, and transfer suitable amounts to an infusion or 2256 decoction apparatus. 2257

Leaves, flowers and whole plants: Coarse cutting 2258 Woods, stems, barks, roots and rhizomes: Medium cutting 2259 Seeds and fruits: Fine cutting 2260

2261 (i) Infusions: Usually, damp 50 g of crude drugs with 50mL of water for about 15 minutes, pour 2262

900 mL of hot water to them, and heat for 5 minutes with several stirrings. Filter through a cloth after 2263 cooling. 2264

(ii) Decoctions: Usually, heat one-day dose of crude drugs with 400 ñ 600mL of water until to 2265 lose about a half amount of added water spending more than 30 minutes, and filter through a cloth 2266 while warm. Prepare Infusions or Decoctions when used. 2267 2268 (3) These preparations have odour and taste derived from the crude drugs used. 2269 2270 (4) Tight containers are usually used for these preparations. 2271 2272



52

5. Tea bags 2273 (1) Tea bags are preparations, usually packed one day dose or one dose of crude drugs cut into a size 2274 between coarse powder and coarse cutting in paper or cloth bags. 2275 2276 (2) Teabags are usually used according to the preparation method as directed under 4. Infusions and 2277 Decoctions. 2278 2279 (3) Well-closed or tight containers are usually used for these preparations. 2280 2281 6. Tinctures 2282 (1) Tinctures are liquid preparations, usually prepared by extracting crude drugs with ethanol or with a 2283 mixture of ethanol and purified water. 2284 2285 (2) Unless otherwise specified, Tinctures are usually prepared from coarse powder or fine cuttings of 2286 crude drugs by means of either maceration or percolation as described below. 2287 2288

(i) Maceration: Place crude drugs in a suitable container, and add an amount of a solvent, 2289 equivalent to the same volume or about three-fourths of the volume of the crude drugs. Stopper 2290 container, and allow the container to stand for about 5 days or until the soluble constituents have 2291 satisfactorily dissolved at room temperature with occasional stirring. Separate the solid and liquid by 2292 centrifugation or other suitable methods. In the case where about three-fourths volume of the solvent is 2293 added, wash the residue with a suitable amount of the solvent, and squeeze the residue, if necessary. 2294 Combine the extract and washings, and add sufficient solvent to make up the volume. In the case 2295 where the total volume of the solvent is added, sufficient amounts of the solvent maybe added to make 2296 up for reduced amount, if necessary. Allow the mixture to stand for about 2 days, and obtain a clear 2297 liquid by decantation or filtration. 2298 2299

(ii) Percolation: Pour solvent in small portions to crude drugs placed in a container, and mix well 2300 to moisten the crude drugs. Stopper container, and allow it to stand for about 2 hours at room 2301 temperature. Pack the contents as tightly as possible in an appropriate percolator, open the lower 2302 opening, and slowly pour sufficient solvent to cover the crude drugs. When the percolate begins to 2303 drip, close the opening, and allow the mixture to stand for 2 to 3 days at room temperature. Then, open 2304 the opening, and allow the percolate to drip at a rate of 1 to 3mL per minute. Add an appropriate 2305 quantity of the solvent to the percolator, and continue to percolate until the desired volume has passed. 2306 Mix thoroughly, allow standing for 2 days, and obtain a clear liquid by decantation or filtration. The 2307 time of standing and the flow rate may be varied depending on the kind and amount of crude drugs to 2308 be percolated. 2309 2310 Tinctures, prepared by either of the above methods and specified the content of marker constituent or 2311 ethanol, are prepared by assaying the content using a portion of the sample and adjusting the content 2312 with a sufficient amount of the percolate or solvent as required on the basis of the result of the assay. 2313 2314 (3) Tinctures should be stored remote from fire. 2315 2316 (4) Tight containers are used for these preparations. 2317 2318 7. Aromatic Waters 2319 (1) Aromatic Waters are clear liquid preparations, saturated essential oils or other volatile substances 2320 in water. 2321 2322 (2) Unless otherwise specified, Aromatic Waters are usually prepared by the following process. Shake 2323



53

thoroughly for 15 minutes 2mL of an essential oil or 2 g of a volatile substance with 1000 mL of 2324 lukewarm purified water, set the mixture aside for 12 hours or longer, filter through moistened filter 2325 paper, and add purified water to make 1000 mL. Alternatively, incorporate thoroughly 2 mL of an 2326 essential oil or 2 g of a volatile substance with sufficient talc, refined siliceous earth or pulped filter-2327 paper, add 1000 mL of purified water, agitate thoroughly for 10 minutes, and then filter the mixture. 2328 To obtain a clear filtrate repeat the filtration if necessary, and add sufficient purified water passed 2329 through the filter paper to make 1000mL. 2330 2331 (3) Aromatic Waters have odour and taste derived from the essential oils or volatile substances used. 2332 2333 (4) Tight containers are used for these preparations. 2334 2335 8. Fluidextracts 2336 (1) Fluidextracts are liquid percolates of crude drugs, usually prepared so that each mL contains 2337 soluble constituents from 1 g of the crude drugs. Where the content is specified, it takes precedence. 2338 2339 (2) Unless otherwise specified, Fluidextracts are usually prepared from coarse powder or fine cutting 2340 of crude drugs by either of following maceration or percolation. 2341 2342

(i) Maceration: Place a certain amounts of crude drugs in a suitable vessel, add a solvent to cover 2343 the crude drugs, close the vessel, and allow the vessel to stand at room temperature with occasional 2344 stirring for about 5 days or until the soluble constituents have satisfactorily dissolved. Separate the 2345 solid and liquid by centrifugation or other suitable method. Usually, reserve a volume of the liquid 2346 equivalent to about three-fourths of the total volume, and use it as the first liquid. Wash the residue 2347 with appropriate amount of the solvent, combine the washings and the remaining of the first liquid, 2348 concentrate if necessary, mix with the first liquid, and use it as solution (A). To the solution (A) add 2349 the solvent, if necessary, to make equal amount of the mass of the crude drugs. Allow the mixture to 2350 stand for about 2 days, and collect a clear liquid by decantation or filtration. 2351 2352

(ii) Percolation: Mix well 1000 g of the crude drugs with the first solvent to moisten them, close 2353 the container, and allow it to stand for about 2 hours at room temperature. Transfer the content to a 2354 suitable percolator, stuff it as tightly as possible, open the lower opening of the percolator, and slowly 2355 pour the second solvent to cover the crude drugs. Close the lower opening when the solvent begins to 2356 drop, and allow the mixture to stand for 2 to 3 days at room temperature. Open the lower opening, and 2357 allow the percolate to run out at the rate of 0.5 to 1.0mL per minute. Set aside the first 850 mL of the 2358 percolate as the first percolate. Add the second solvent to the percolator, then drip the percolate, and 2359 use it as the second percolate. 2360 2361 The period of standing and the flow rate during percolation may be varied depending on the kind and 2362 the amount of crude drugs used. The flow rate is usually regulated as follows, depending on the using 2363 amount of crude drugs. 2364 2365

Mass of crude drug

Volume of solution running per

minute

Not more than 1000 g

Not more than 3000 g

Not more than 10000g

0.5 - 1.0mL

1.0 - 2.0mL

2.0 - 4.0mL

2366 Concentrate the second percolate, taking care not to lose the volatile substances of the crude drug, mix 2367 with the first percolate, and use it as solution (A). To the solution (A) add the second solvent to make 2368



54

1000 mL, and allow the mixture to stand for about 2 days. Decant the supernatant liquid or filter the 2369 liquid to obtain a clear solution. 2370 2371 Fluidextracts for which the content of marker constituent or ethanol is specified are obtained by 2372 adjusting the content with a sufficient amount of the second solvent as required on the basis of the 2373 result of the assay made with a portion of the solution (A). 2374 2375 (3) Fluidextracts have odour and taste derived from the crude drugs used. 2376 2377 (4) Unless otherwise specified, Fluidextracts meet the requirements of Heavy Metals Limit Test 2378 <1.07>

1 when the test solution and the control solution are prepared as follows. 2379

2380 Test solution: Ignite 1.0 g of Fluidextracts to ash, add 3 mL of dilute hydrochloric acid, warm, and 2381 filter. Wash the residue with two 5-mL portions of water. Neutralize the combined filtrate and 2382 washings (indicator: a drop of phenolphthalein TS) by adding ammonia TS until the colour of the 2383 solution changes to pale red, filter if necessary, and add 2 mL of the dilute acetic acid and water to 2384 make 50 mL. 2385 2386 Control solution: Proceed with 3 mL of dilute hydrochloric acid in the same manner as directed in the 2387 preparation of the test solution, and add 3.0 mL of Standard Lead Solution and water to make 50 mL. 2388 2389 (5) Tight containers are used for these preparations. 2390 2391 1Test <1.07> 1.07 Heavy Metal Limit test (JP 16, pp21-23) 2392

Heavy Metals Limit Test is a limit test of the quantity of heavy metals contained as impurities in drugs. The heavy metals 2393 are the metallic inclusions that are darkened with sodium sulfide TS in acidic media, as their quantity is expressed in terms of 2394 the quantity of lead (Pb). In each monograph, the permissible limit for heavy metals (as Pb) is described in terms of ppm in 2395 parentheses. 2396 2397 Procedure: 2398 Add 1 drop of sodium sulfide TS to each of the test solution and the control solution, mix thoroughly, and allow to stand for 5 2399 minutes. Then compare the colors of both solutions by viewing the tubes downward or transversely against a white 2400 background. The test solution has no more color than the control solution. 2401 2402 Solutions and Reagents: 2403 Standard Lead Solution 2404 Measure exactly 10 mL of Standard Lead Stock Solution, and add water to make exactly 100 mL. Each mL of this solution 2405 contains 0.01 mg of lead (Pb). Prepare before use. 2406 2407 Standard Lead Stock Solution 2408 Weigh exactly 159.8 mg of lead (II) nitrate, dissolve in 10 mL of dilute nitric acid, and add water to make exactly 1000 mL. 2409 Prepare and store this solution using glass containers, free from soluble lead salts. 2410 2411 Ammonia solution (28) 2412 NH4OH [K 8085, Ammonia Water, Special class, Density: 0.90 g/mL, Content: 28- 30%] 2413 2414 Ammonia TS 2415 To 400 mL of ammonia solution (28) add water to make 1000 mL (10%). 2416 2417 Acetic acid, dilute 2418 Dilute 6 g of acetic acid (100) with water to make 100 mL (1 mol/L). 2419 2420 Acetic acid (100) 2421 CH3COOH [K 8355, Acetic Acid, Special class] 2422 2423 Dilute acetic acid 2424 See acetic acid, dilute. 2425



55

2426 Dilute hydrochloric acid 2427 See hydrochloric acid, dilute. 2428 2429 Hydrochloric acid, dilute 2430 Dilute 23.6 mL of hydrochloric acid with water to make 100mL (10%). 2431 2432 Hydrochloric acid 2433 HCl [K 8180, Special class] 2434 2435 Phenolphthalein TS 2436 Dissolve 1 g of phenolphthalein in 100 mL of ethanol (95). 2437 2438 Phenolphthalein 2439 C20H14O4 [K 8799, Special class] 2440 2441 Ethanol (95) 2442 C2H5OH [K 8102, Special class] 2443 2444 Sodium sulfide enneahydrate 2445 Na2S.9H2O [K 8949,Special class] 2446 2447 Sodium sulfide TS 2448 Dissolve 5 g of sodium sulfide enneahydrate in a mixture of 10 mL of water and 30 mL of glycerin. Or dissolve 5 g of 2449 sodium hydroxide in a mixture of 30 mL of water and 90 mL of glycerin, saturate a half volume of this solution with 2450 hydrogen sulfide, while cooling, and mix with the remaining half. Preserve in well-filled, light-resistant bottles. Use within 3 2451 months. 2452 2453 Sodium hydroxide 2454 NaOH [K 8576, Special class] 2455 2456 Glycerin 2457 C3H8O3 [K 8295, Glycerol, Special class. Same as the monograph Concentrated Glycerin] 2458 2459 Hydrogen sulfide 2460 H2S Colorless, poisonous gas, heavier than air. It dissolves in water. Prepare by treating iron (II) sulfide heptahydrate with 2461 dilute sulfuric acid or dilute hydro chloric acid. Other sulfides yielding hydrogen sulfide with 2462 dilute acids may be used. 2463 2464 Sulfuric acid 2465 H2SO4 [K 8951, Special class] 2466 2467 Sulfuric acid, dilute 2468 Cautiously add 5.7 mL of sulphuric acid to 10 mL of water, cool, and dilute with water to make 100 mL (10%). 2469 2470 Iron (II) sulfate heptahydrate 2471 FeSO4.7H2O [K 8978, Special class] 2472 2473



56

Annex 4: Processing facilities 2474

2475 The following is extracted from Section 4.1.5 of the WHO guidelines on good agricultural and collection 2476 practices (GACP) for medicinal plants (WHO, 2003) (pages 19-23). 2477 2478 4.1 Processing facilities 2479 2480 In constructing or designing a processing facility, the following elements should be considered that 2481 will allow the establishment of a quality assurance system adaptable to the different types and steps of 2482 processing to yield the desired end products. 2483 2484 Location 2485 Facilities should preferably be located in areas that are free from objectionable odours, smoke, dust or 2486 other contaminants, and are not subject to flooding or other natural adverse conditions. 2487 2488 Buildings 2489 Buildings should be of sound construction and maintained in good repair. Filthy areas must be isolated 2490 from clean processing areas. All construction materials should be such that they do not transmit any 2491 undesirable substance including toxic vapours to medicinal plant materials. Electrical supply, lighting, 2492 and ventilation should be appropriately installed. 2493 2494 Buildings should be designed to: 2495 provide adequate working space and storage room to allow for satisfactory performance of all 2496

operations; 2497 to ensure the logical flow of materials and personnel; 2498 facilitate efficient and hygienic operations by allowing a regulated flow in processing from the 2499

arrival of the raw medicinal plant materials at the premises to the dispatch of the processed 2500 medicinal plant materials; 2501

permit appropriate control of temperature and humidity; 2502 permit control of access to different sections, where appropriate; 2503 permit easy and adequate cleaning and facilitate proper supervision of hygiene; 2504 prevent the entry of environmental contaminants such as smoke, dust, the entrance and harbouring 2505

of pests, livestock and domesticated animals. 2506 2507 Medicinal plant material handling and processing areas 2508 The layout and design of the work area should be such as to minimize the risk of errors and permit 2509 effective cleaning and maintenance in order to avoid cross contamination, and otherwise avoid any 2510 adverse effect on the quality of the processed product. 2511 2512 Windows and other openings should be constructed so as to avoid accumulation of dirt, and those 2513

that open should be fitted with insect-proof screens. Screens should be easily removable for 2514 cleaning and kept in good repair. Internal window sills, if present, should be sloped to prevent use 2515 as shelves. 2516

Doors should have smooth, non-absorbent surfaces and, where appropriate, be self-closing and 2517 close-fitting. 2518

Overhead structures and fittings should be installed in such a manner as to avoid contamination of 2519 medicinal plant materials (both raw and processed) by condensation and drippings, and should be 2520 protected to prevent contamination in case of breakage. They should be insulated, where 2521 appropriate, and be designed and finished so as to prevent the accumulation of dirt and to 2522 minimize condensation, mould development and flaking. They should be easy to clean. 2523



57

Food preparation and eating areas, changing facilities, toilets should be completely separated from 2524 and not open directly onto medicinal plant material processing areas. 2525

2526 Water supply 2527 An ample supply of potable water, under adequate pressure and at suitable temperature, used for 2528

processing medicinal plant materials, should be available with appropriate facilities for its storage, 2529 where necessary, and distribution, and with proper protection against contamination. 2530

Ice should be made from potable water; it should be manufactured, handled and stored so as to 2531 protect it against contamination. 2532

Non-potable water used for steam production, refrigeration, fire control and other similar purposes 2533 not connected with processing should be carried in completely separate pipes, identifiable 2534 preferably by colour, and with no cross-connection with or back siphonage into the system 2535 carrying potable water. 2536

2537 Effluent and waste disposal 2538 Facilities should have an effective effluent and waste disposal system, which should at all times be 2539 maintained in good order and repair; and should be constructed so as to avoid contamination of 2540 potable water supplies. 2541 2542 Changing facilities and toilets 2543 Adequate, suitable and conveniently located changing facilities and toilets should be provided. Hand-2544 washing facilities with warm or hot and cold water, a suitable hand-cleaning preparation and hygienic 2545 means of drying should be provided adjacent to toilets and located so that employees have to pass 2546 them when returning to the processing area. Notices should be posted directing personnel to wash 2547 their hands after using the toilet. 2548 2549 Hand-washing facilities in processing areas 2550 Adequate and conveniently located facilities for hand-washing and a hygienic means of drying should 2551 be provided whenever the process demands. Where appropriate, facilities for hand disinfection should 2552 also be provided. 2553 2554 Disinfection facilities 2555 Where appropriate, adequate facilities for cleaning and disinfection of working implements and 2556 equipment should be provided. These facilities should be constructed of corrosion-resistant materials, 2557 should be easy to clean, and should be fitted with hot and cold water supplies. 2558 2559 Lighting 2560 Adequate natural or artificial lighting should be fitted throughout the facility. Where appropriate, the 2561 lighting should not alter colours of the medicinal plants undergoing processing. 2562 2563 Ventilation 2564 Adequate ventilation should be provided to prevent excessive heat, steam condensation and dust and 2565 to remove contaminated air from both the processing and storage areas/facilities. 2566 2567 Storage of waste and unusable materials 2568 Facilities should be provided for the storage of waste and unusable materials prior to removal from the 2569 premises. 2570

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