United States PharmacopeiaGood Distribution Practices Update

Marv Shepherd, Ph.D.President

Partnership for Safe MedicinesMember

USP Package Storage and Distribution Expert CommitteeProfessor, University of Texas at Austin

Email: marvshepherd@austin.utexas.edu

} “To improve the health of people around the world through public standards and related programs that help ensure the quality, safety and benefits of medicines and foods.”

Mission of United States Pharmacopeia

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Purpose of USP} 130 countries use USP standards

} USP-NF (National Formulary) contains the specifications, storage, packaging and other requirements. “Specifications” are lists of series of specific tests and acceptance criteria of drug substances or excipients.

} USP-NF is the “official U.S. Drug Compendium.”

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} Introduction

} Overview of Packaging Storage and Distribution Committee (PSD) Expert Committee (EC)

} Goals of the PSD Expert Committee

} Processes of the Committee

} Reorganization of Good Distribution Practices Chapter (1083)

Agenda

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Packaging, Storage & Distribution Expert Committee

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– USP Liaison: Desmond Hunt (USP)– Govt Agencies: Sarah Skuce (Health Canada), FDA Liaisons: Don

Klein, – Academia: Marv Shepherd (University of Texas)– Industry Mfging: Shirley Feld (Sanofi), Dennis Jenke (Baxter), Dan

Malinowski (Pfizer), Dan Norwood (Boehringer Ingelheim), Kola Stucker (BMS)

– Industry Consultants: Dana Guazzo (Rx Pax), Kevin O’Donnell (Exelsus Cold Chain Management), Devinder Pal (Catalyst Pharma), Mike Ruberto Material Needs Consulting), Chris Chandler (GS1 US);

– Industry Suppliers: Diane Paskiet (West)– Chair: Mary Foster (Foster Group)– Vice-Chair: Michael Eakins (Eakins and Associates)

Package, Storage and Distribution Expert Committee Members

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1. Developing and updating USP standards for packaging systems and their materials of construction (metal, glass, plastic, elastomeric).

2. Revising packaging definitions including storage requirements for compendial articles.

3. Creating and revising guidance for the good distribution of compendial articles; good packaging & repackaging practices; extractable and leachable.

Goals of the Packaging Storage and Distribution Expert Committee

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– Subcommittees – within the Expert Committee(s)– Expert Panels – external partner working teams– Workshops– Education programs; webinars– Conclaves – experts from all facets discussion– Bi-monthly telecoms; annual meetings– Charter– Minutes– Action Items

Working Process

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} UPS conducts an global annual survey of healthcare suppliers to get their perceptions on the concerns/issues in distributing health care products, including pharmaceuticals. In 2013, they surveyed 440 health care companies. The results corresponds closely with the initiatives of the USP.

} http://www.ups.com/content/us/en/bussol/browse/industries/pain-in-the-chain.html

UPS 2013 “Pain in the Chain” Healthcare Survey

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2013 UPS Survey

Please note:Product security ranked higher than managing supply chain cost in 2013

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US/W EU - regulatory compliance• Asia Pacific - product security

2013 UPS Survey Found

} Process: General Chapters (GC), Review/Revise every 3 years

} Actions, this cycle:– The two General Chapters on Good Distribution Practices

are being reviewed by two Expert Committees (EC)• Package Storage Distribution EC review <1079> Good Distribution

Practices for Drug Products; Revision official Dec 1, 2012, [USP 35 (2)]

• Excipients EC: <1197> Good Distribution Practices For Bulk Pharmaceutical Excipients; New chapter, official May 1, 2013

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Current Process, Actions & Outcomes

– Significant: Collaboration with 4 Expert Committees: 1) Packaging, Storage and Distribution EC2) Excipients EC3) Dietary Supplements EC4) Compounding EC

– Significant– Proposed change is to have one overarching Good

Distribution Practices General Chapter <1083> – With ‘sub-chapter’ structure: Good Distribution for Drugs

<1079> & Good Distribution for Excipients <1197> become sub-chapters of chapter <1083>

1) 4 sub-chapters completed and 5 sub-chapters in writing

Outcomes of this cycle:

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Current Process, Actions & Highlights

<1083.1> <1083.2> <1083.3> <1083.4>

Chapter StructureGDP Subjects Divided into Sub-Chapters

<1083>

Significant:• Pharmacopeia Forum 40 (2) Mar-Apr 2014; comments in from May 31, 2014

being edited now by Expert Committee• Sub-chapter process – 4 form foundation; 5 started; next subjects up for

consideration8

Significant Scope Changes

Scope: Applies to all organizations & individuals involved in any aspect ...

Intended: drugs & excipients… NOT Intended for •API’s, Medical devices; gases•Radioactive products, reagents & Solvents•CTM- no storage requirement

GC’s<1079><1197>

… NOT Intended To Cover, •Counterfeiting; falsified medicine, pedigrees, supply chain security, chain of custody

Scope: Applies to all organizations & individuals involved with packaging materials & product regardless of their category…Intended: drug products & excipients Also, Intended for,•API’s, Medical devices; combination products, Radioactive products, reagents & SolventsAdded: Dietary supplements; biological & biotechnological; cell & gene therapy

… Intended To Cover,•Counterfeiting; falsified medicine•Traceability SC integrity, Cargo thefts, Diversion

GC<1083>

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PLEASE NOTE: Applies to all organizations not just traditional manufacturers, wholesalers, exporters importers, etc.It covers: Hospital to hospital, wholesaler or supplier to pharmacy, mail order pharmacy to patient, pharmacy to pharmacy, pharmacy to health care facilities (i.e. long-term-care facility).

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USP General Chapter <1083> Good Distribution Practices

Sub-Chapter <1083.1> Quality Management System

(QMS)

<1083> Good Distribution Practices

<1083.1> <1083.2> <1083.3> <1083.4>11

Significant: Quality Management System (QMS)

Responsibilities * Applicant holder, OTC (no application) & repackager

• QMS – 4 Management Systems (MS)

1.Storage MS2.Distribution MS3.Environmental MS4.Risk MS• Refrigerators & freezers (not covered

yet in new work)• Labeling (depth not covered yet in new

work)

GC’s<1079><1197>

Responsibilities• * Senior management (all SC partners)

• QMS – 8 Standard practices, more depth

• Management responsibility• Documentation• Resources management• Operations• Complaints, deviations, returns,

recalls, counterfeits, reprocessing, rework

• Monitoring & improvements• Validation• Regulatory affairs

GC<1083>

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Significant: Why not just use cGMPs & GDPs from regulators or other sources?

} USP must cover all stakeholders•May seem redundant to a few, but needed by smaller companies, virtual firms or new business entities•Compendial Standard – as such is translated into multiple languages; not every country has a standard QMS expectation•Does not supersede or supplant national requirements

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Quality Management System

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USP General Chapter <1083> Good Distribution Practices

Sub-Chapter <1083.2> Environmental Control Management

<1083.1> <1083.2> <1083.3> <1083.4>

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Environmental Conditions Management

Temperature * Monitoring * Mapping * MKT during storage

Disribution

Temp data loggers•Significant: not covered yet in new chapter

GC’s<1079><1197>

Mail delivery distribution not covered yet in new chapter

Environmental Control 2 Approaches: 1) Facilities, Equipment, Vehicles2) Using packaging materials – thermal

blankets, temp stabilizers, light resistant materials, desiccantsSignificant: Contingency plan for outages,

breakdowns •Monitor each shipment with retrospective historical data & risk assessment to justify shipping method•Data monitoring: evaluation; communication

• Significant: Short term excursions: Combine stability data from long-term & accelerated studies, temp studies

GC<1083>

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USP General Chapter <1083> Good Distribution Practices

Sub-Chapter <1083.3> Importation & Exportation Management

<1083.1> <1083.2> <1083.3> <1083.4>

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Importation & Exportation Management

<1079> No discussion <1197> Covers Audits, container seals,

cargo inspection, customs, brokers, trade rules, product verification

• <1197> knowing product & applicable regulatory requirements

• Supply agreements

GC’s<1079><1197>

Intended to cover I/E process: 1. Business-to-business – all stakeholders (suppliers, brokers,

customers, …) 2. Business-to-government – customs

clearance, documentation, port authorities

Knowledge of product & material•Likelihood of theft, abuse, counterfeiting, diversion.•Contractual agreements to ensure security

Not intended to cover:•Importation & Exportation law•Customs procedures (country specific)

GC<1083>

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Importation & Exportation Management

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USP General Chapter <1083> Good Distribution Practices

Sub-Chapter <1083.4> Supply Chain Integrity and Security

<1083.1> <1083.2> <1083.3> <1083.4>

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<1079> Covers SMS 1 line: Theft, diversion & counterfeit <1197> Covers1. Legal & illegal outlets2. Packaging technologies

GC’s<1079><1197>

1. General: QMS, RMS, SOPs & regulatory requirements 2. Product knowledge: ID, use, vulnerabilities, hazards, processes3. Global sourcing knowledge: Partners,

suspicious orders, information systems Supply Chain Integrity

•Economically motivated adulteration•Counterfeit & falsified •Diversion (expired; recalled donated)•Inadequate transportation, storage

Supply Chain Security •Theft; loss prevention; layered defenses, understanding vulnerabilities, geography, routing

GC<1083>

<1083.4> Supply Chain Integrity & Security

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GOOD DISTRIBUTION PRACTICES <1083>

Introduction

QUALITY MANAGEMENT

SYSTEM

<1083.1>

ENVIRONMENTAL CONDITIONS

MANAGEMENT<1083.2>

IMPORTATION & EXPORTATION

MANAGEMENT

<1083.3>

SUPPLY CHAIN INTEGRITY &

SECURITY

<1083.4>

Finished Drug Products

<1083.5>

Excipients <1083.6>

Clinical Trial Materials

<1083.9>

Active Pharmaceutical

Ingredients <1083.7>

Packaging Components &

Materials <1083.8>

• Bringing in new support, experts in each field for panels, suppliers • Forming Expert Panels now!

NEW NEW NEW

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Regulatory Compliance: No one regulatory authority/ organization can secure the supply chain–Prevention through strengthened regulatory capacity and

tight supply chains (partnerships)–Entity-to-Entity visibility & collaboration–A collective response when substandard & counterfeit

products are found

– Product Security: Protection & Damage Early and rapid detection of suspicious productsSolutions for security and damage

Closing

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} Submit an application to serve as an USP expert volunteer} Apply for current cycle’s Expert Panels

} What other subjects would be of value as GDP Sub-Chapters?

} Questions?} Visit the USP web site at www.usp.org} Contact USP at USPVolunteers@usp.org or

301-816-8151

Join the Challenge !

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A special thanks goes to Dr. Mary Foster,

Chair USP Packaging Storage and

Distribution Expert Committee. She was

extremely helpful to me in putting this

presentation together.

Thanks

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