Prepared by: Diwakar Chudal

Institute of medicine, IOM

Pharmaceutical certification:

Pharmaceutical Certification refers to the confirmation of certain essential characteristics of pharmaceutical industry which is required to produce safe, efficacious and standard quality pharmaceutical products.

This confirmation is always provided by some form of external review, assessment, or audit.

Most widely adopted certification system for pharmaceutical sectors are:

WHO-GMP certification

ISO 9000 series

ISO 14000 series

WHO certification scheme

What is GMP ?

Good manufacturing practice (GMP) is a system for ensuring that products are consistently produced and controlled according to quality standards and as required by the marketing authorization.

GMP covers all aspects of production; from the starting materials, premises and equipment to the training and personal hygiene of staff.

GMP requires detailed written procedures for each process that could affect the quality of the finished product. Hence there must be a system to provide documented proof that correct procedures are consistently followed at each step in the manufacturing process - every time a product is made.

Sanitation and Hygiene

Qualification and Validation

Complaints

Product recalls

Self inspection and Quality audits

Qualified personnel and Training

Premises

Equipments

Materials

Documentation

The guiding principle of GMP is that quality is built into a product, and not just tested into a finished product.

Therefore, the assurance is that the product not only meets the final specifications, but that it has been made by the same procedures under the same conditions each and every time it is made.

GMP is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.

Many countries have legislated that pharmaceutical companies must follow GMP procedures, and have created their own GMP guidelines based on WHO-GMP that correspond with their legislation. Therefore, complying with GMP is a mandatory aspect in pharmaceutical manufacturing.

GMP guidelines are not prescriptive instructions on how to manufacture products. They are a series of general principles that must be observed during manufacturing. When a company is setting up its quality program and manufacturing process, there may be many ways it can fulfill GMP requirements. It is the company's responsibility to determine the most effective and efficient quality process.

The national regulatory authority of Nepal i.eDepartment of drug administration (DDA) is responsible for issuing and renewing the WHO-GMP certificate to domestic pharmaceutical industries.

DDA has it’s own GMP guidelines based on WHO-GMP principles which is used as reference standard for checking compliance with GMP system.

Inspection department of DDA assigns auditors and sends them to respective pharmaceutical industry for GMP audit.

Upon completion of the audit, the auditors generates an audit report identifying any non-conformances (NC’s) to the GMP guidelines. At the same time auditors gives CAPA to the QA manager.

After receiving CAPA, QA manager works along with other managers and HOD’s to resolve the NC’s in a given frame of time.

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The auditors submits the audit report and NCs to the Administrator/Director of DDA.

The audit documentation is then reviewed by Director of DDA for approval of GMP audit.

Once the Director of DDA approves the closure of the NCs, the WHO-GMP certificate is issued and sent to respective pharmaceutical industry.

GMP certification must be renewed by pharmaceuticals at a regular interval of 2 years and same audit procedures will be carried out by DDA.

What is ISO? The International Organization for standardization (ISO) is an

international standard-setting body composed of representatives from various nation.

Founded on 1947, ISO is an independent non-governmental organization, the members of which are the standards organizations of the 164 member countries with its headquarter located in Switzerland. It is the world's largest developer of voluntary international standards and facilitates world trade by providing common standards between nations.

Nearly twenty thousand standards have been set by ISO covering everything from manufactured products, technology, food safety, agriculture, healthcare, etc

Most commonly issued ISO certifications for pharmaceutical industries are:

ISO 9000 series

ISO 14000 series

• The ISO 9000 Series is a set of international standards for quality management and quality assurance by an industry/company.

• They are not specific to any one type of industry or company.

How ISO 9000 series was developed?

• ISO based the foundation of ISO 9001 in the content of a British set of standards, BS5750, an older document for military applications. BS5750 aimed at tightly controlling the quality of products in factory that built bombs in United Kingdom during World War II.

• With this encouragement from the British government, ISO drafted the first version of these standards in 1987

• As opposed to ISO 9000 which was introduced in 1987, ISO 9001,ISO 9002,ISO 9003 and ISO 9004 were gradually developed.

ISO 9001 – Standard for quality assurance in design and development

ISO 9002 – Standard for quality assurance in production & installation

ISO 9003 – Standard for quality assurance in final inspection and tests

ISO 9004 – Standard for Quality management.

• Later in the year 2000 AD, ISO 9001,9002,9003 and 9004 were combined together and was called ISO 9001:2000.

• ISO 9001:2000 was again updated in year 2008 AD and was called as ISO 9001:2008. However the changes were considered minor.

• Recently in the year 2015 AD, ISO 9001:2008 was further updated and now called as ISO 9001:2015.

• ISO 9000, represents a standards for quality management methodology which must be adopted by pharmaceutical industries to deliver products and services that meet customer expectations.

• ISO helps to facilitate international trade of drug products by providing a internationally-accepted standards for everybody's reference.

• ISO can be used to enhance a GMP based Quality System.

ISO 9000 certification gives world-class specifications for products, services and systems. Hence it helps to develop reputation of pharmaceutical industries.

ISO standards acts as strategic tools that reduce costs by minimizing waste and errors and increasing productivity.

ISO certification helps companies to access new markets and level the playing field for developing countries like Nepal.

ISO 14000 series is the world’s most recognized framework for environmental management systems.

ISO 1400O series gives standard for organizations to manage the impact of their activities on the environment and to demonstrate sound environmental management system.

The ISO 14000 family of environmental management standards can be implemented in any type of organization in either public or private sectors.

ISO 14000 has developed standards that helps pharmaceutical industries to take a proactive approach to manage environmental issues.

ISO 14000 helps to overcome the challenge of climatic changes.

ISO 14000 further increases the degree of product’s quality by encouraging the inclusion of environmental aspects in product design.

ISO offers a wide-ranging portfolio of standards for sampling and test methods to deal with specific environmental challenges. It has developed some 570 International Standards for the monitoring of such aspects as the quality of air, water, soil, as well as noise, radiation, etc

ISO does not itself certify organization. Many countries have formed accreditation bodies to authorize

certification bodies, which audit organization applying for ISOcompliance certification.

Both the accreditation bodies and certification bodies chargefees for their services.

The various accreditation bodies have mutual agreementswith each other to ensure that certificates issued by one of theaccreditation certification bodies are accepted worldwide

The applying organization is assessed based on its sites,functions, products, services and processes.

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A list of problems/NC will be made

If there are no major problems/NC, Certification bodywill issue ISO certification to organization.

An ISO certificate must be renewed at regularintervals.

One of the main problems of comparing GMP and ISO is that the two standards are not the same and are not really trying to do the same thing.

GMP is a product quality standard, with a focus on consistently getting the right quality product to the only customer of GMP –the patient. ISO 9001 on the other hand is more about running a whole business, a goal of which will be getting product of the international standard quality globally.

GMP mainly focuses on Production and Quality Control but ISO focuses on the all departments and processes of an organisation. Hence ISO is more encompassing than GMP.

List of the clauses of ISO 9001 are below. Those in GREEN text are requirements of ISO that are not specifially mentioned in GMP. From this list we can see that there are a number of areas that ISO covers that are not covered by GMP.

Section 1 – Scope Section 2 – Normative Reference Section 3 – Terms and Definitions

Section 4 – Quality Management System 4.1 – General Requirements (Process Approach) 4.2 – Documentation Requirements 4.2.1 General 4.2.2 Quality Manual 4.2.3 Control of Documents 4.2.4 Control of Records

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Section 5 – Management Responsibility

5.1 – Management Commitment 5.2 – Customer Focus 5.3 – Quality Policy 5.4 – Planning 5.4.1 Quality Objectives 5.4.2 Quality Management System planning 5.5 – Responsibility, authority and communication 5.5.1 Responsibility and authority 5.5.2 Management Representative 5.5.3 Internal Communication 5.6 – Management Review 5.6.1 General 5.6.2 Review Input 5.6.3 Review Output

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Section 6 – Resource Management 6.1 – Provision of Resources 6.2 – Human Resources 6.2.1 General 6.2.2 Competence, awareness and training 6.3 – Infrastructure 6.4 – Work Environment

Section 7 – Product Realization 7.1 – Planning of Product Realisation 7.2 – Customer-related processes 7.2.1 Determination of requirements related to the product 7.2.2 Review of requirements related to the product 7.2.3 Customer Communication 7.3 – Design and Development 7.3.1 Design and Development Planning 7.3.2 Design and Development Inputs 7.3.3 Design and Development Outputs 7.3.4 Design and Developm ent Review 7.3.5 Design and Development Verification

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7.3.6 Design and Development Validation 7.3.7 Control of Design and Development changes 7.4 – Purchasing 7.4.1 Purchasing Process 7.4.2 Purchasing Information 7.4.3 Verification of Purchased Product 7.5 – Production and Service provision 7.5.1 Control of production and service provision 7.5.2 Validation of processes for production and service provision 7.5.3 Identification and Traceability 7.5.4 Customer Property 7.5.5 Preservation of Product 7.6 – Control of Monitoring and Measuring Equipment

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Section 8 – Measurement, Analysis and Improvement 8.1 – General 8.2 – Monitoring and Measurement 8.2.1 Customer Satisfaction 8.2.2 Internal Audit 8.2.3 Monitoring and Measurement of processes 8.2.4 Monitoring and Measurement of product 8.3 – Control of nonconforming product 8.4 – Analysis of Data 8.5 – Improvement 8.5.1 Continual Improvement 8.5.2 Corrective Action 8.5.3 Preventive Action

From the above list, we will see that there are certainly some areas where ISO can be used to enhance a GMP based Quality System.

What is WHO Certification scheme?

It is a Scheme developed by the World Health Organization (WHO) in response to the request of WHO Member States to facilitate international trade in pharmaceutical products between Member States.

was first developed in 1975. Since then it has been revised in 1988, 1992 and in 1997.

Any member state, which intends to participate in the scheme, shouldwrite to the Director general of WHO

of its willingness to participate in the scheme, name and address of national drug regulatory authority of thecountry.

A Member State intending to use the Scheme should first satisfy itself that it possesses:

an effective national licensing system, for pharmaceutical products, manufacturers and distributors;

Implementation of GMP requirements, recommended by WHO.

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Effective control measures to control the quality of

pharmaceutical products registered or manufactured within its

country.

Highly qualified staffs, who can investigate to ensure that

manufacturers conforms to these requirements.

Administrative capacity to issue the required certificates and do

inquiries in case of complaint.

Three types of certificates can be requestedunder this scheme:

A certificate of a pharmaceutical product.

A statement of licensing status ofpharmaceutical products.

A batch certificate of a pharmaceuticalproduct.

CPP should Incude the following informations for eachproduct:

Brand name

Generic name (International Non-proprietary Name)

Name and address of manufacturing facility,

Formulation

Product information for medical professionals andfor patients as approved in the exporting country,

Labeling on retail and wholesale containers, and

Packaging details.

This attests only that a license has been issued for a specified

product, or products, for use in the exporting country.

Example- No. of statement: Exporting (certifying) country: Importing (requesting) country: This statement indicates only whether or not the following

products are licensed to be put on the market in the exporting country.

Applicant (name/address):

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This certificate is issued by the manufacturer of the exporting country.

This certificate is used to provide an attention concerning the quality and expiry date of a specific batch of product which is to be exported.

Example:1. No. of Certificate:2. Importing (requesting) authority:3. Name of product:

Dosage form: Active ingredient and amount per unit dose: Is the composition of the product identical to that registered in thecountry of export?

(yes/no/not applicable)If no: please attach formula (including excipients) of both products.

4. Product-licence holder(name and address): Product-licence number: Date of issue: Product licence issued by: Product certificate number:

5.1 Batch number:5.2 Date of manufacture: CONT…

5.3 Shelf life (years):5.4 Contents of container:5.5 Nature of primary container:5.6 Nature of secondary container/wrapping:5.7 Specific storage conditions:5.8 Temperature range:6 Remark:7 Quality analysis:7.1 What specifications apply to this dosage form. Either specify the

pharmacopoeia or append company specifications.In the case of a product registered in the exporting country, have thesecompany specifications been accepted by the competent authority?(yes/no)

7.2 Does the batch comply with all parts of the above specifications? (yes/no)

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