good distribution practices latest guidance developments · united states pharmacopeia packaging,...

AAPS Mini Symposium

Frozen State Storage and Cold Chain Transportation

Storage & Shipping of Biopharmaceuticals

USP General Chapter <1083>

Good Distribution Practices

Latest Guidance Developments

Mary G. Foster, PharmD, USP Chair

Packaging, Storage & Distribution Expert Committee 2015-2020

June 9, 2015, San Francisco

United States Pharmacopeia Packaging, Storage and

Distribution Expert Committee & Process

Revision General Chapter <1079> Good Distribution

Practices (now <1083>)

Guidance latest developments

– Frozen, refrigerated & controlled room temperature bio/pharma

product

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Agenda

• GC = General Chapter

• EMS = Environmental Management System

• EP = Expert Panel

• GDP = Good Distribution Practices

• I/E = Import/Export

• PSD EC = Packaging Storage & Distribution Expert

Committee

• QMS = Quality Management System

• SC = Supply Chain

• SME = Subject Matter Expert

• USP = United States Pharmacopeia

Packaging, Storage and Distribution Expert Committee

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Developing & updating USP standards for packaging

systems & their materials of construction (e.g., Containers:

metal, glass, plastic, elastomeric closures for injections)

Revising packaging definitions (e.g., CRT); packaging &

storage requirements for compendial articles

Creating and revising guidance; examples:

– Good distribution practices

– Containers: Performance testing

– Sterile product packaging: Integrity & evaluation

– Good packaging & repackaging practices

– Extractables

– Leachables

Goals of PSD Expert Committee

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2010-2015 – ends May 2015

USP Liaison: Desmond Hunt

Government Agencies

– FDA: Don Klein, Vaikunth Prabu, and Brian Rogers

– Health Canada: Sarah Skuce

Academia: Marv Shepherd

Industry Manufacturing: Shirley Feld, Dennis Jenke, Dan Malinowski,

Dan Norwood, Kevin O’Donnell

Industry Consultants: Chris Chandler, Dana Guazzo, Devinder Pal,

Mike Ruberto

Industry Suppliers: Diane Paskiet

Chair: Mary Foster and Vice-Chair: Michael Eakins

2015-2020 – begins June 2015

PSD EC Members

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5- Year Work Plan

Working teams

– Subcommittees: Internal EC members

– Expert Panels: External SME working teams

Workshops

Education programs; webinars

Conclaves – SME from all facets

Meetings

– Bi-monthly telecoms

– Annual face-to-face/USP Bethesda office

– Telecoms

– Minutes & Action Items

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USP PSD EC Standard Way of Working

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

Chapter Structure

GDP Subjects Divided into Sub-Chapters

<1083>

• Sub-chapter process – 4 form foundation

• Leads to infinite number of subjects, as needed

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Supply Chain Management - Handling Biopharma

Scope: Applies to all organizations & individuals involved with packaging

materials & product, regardless of their category

Intended: Finished drug products (GC <1079>) & excipients (GC <1197>)

Also, Intended for,

• API’s & Excipients * Dietary supplements

• Medical devices; combination products * Radioactive products

• Biological /biotechnological products * Reagents & Solvents

• Cell & gene therapy products

• Clinical trial materials

• Not specifically called out: Medical gases

Covers: Diversion, cargo thefts, * SC integrity

• Counterfeiting; falsified medicine - Importation

• Traceability of products & shipments - Exportation

Working Internal Departments & Engaging External Partners

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Sub-Chapter <1083.1>

Quality Management System

(QMS)

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

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Responsibilities: Senior management & All Supply Chain 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

• Framework: Quality Manual & Policy, SOPs, Master Plans, risk management,

communication, procurement

• Adulterated product handling

• Counterfeit handling

• Product or Service Quality Reviews 12

Quality Management System (QMS)

Applies to All Temp Products

Working with Internal Departments

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Environmental Control Management

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

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Environmental Control Management

<1083.2>

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Environmental Control 2 Approaches:

1) Facilities, Equipment, Vehicles

2) Using packaging materials – thermal blankets,

temperature, stabilizers, light resistant materials, desiccants

Significant: Contingency plan for outages, breakdowns

• Prospective or concurrent PQ or monitor each shipment with

retrospective historical data & risk assessment to justify

shipping method

• Performance qualification

• Data monitoring: evaluation; communication

• Significant: Short term excursions: Combine stability data

from long-term & accelerated studies, Mean Kinetic Temp

(MKT), temp excursion studies & temp cycling studies

• CAPA 16

EMS – All Temp Conditions/All Products

Practically Speaking - EMS

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…, all necessary environmental conditions &

other vulnerability should be accounted for

during material and product importation and

exportation…, which includes storage in bonded

warehouses and during transportation (in-transit storage).

“Only referencing bonded warehouses can give the

impression that other storage scenarios do not have to be

maintained appropriately.”

Consider: “Appropriate storage conditions should be

maintained at all times.” (not listing any entity, covering all

aspects of distribution which includes in-transit storage)

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• Should we remove this statement?

• Replace it with a statement that covers the relative stability

and environmental sensitivity of the product, …?

• It is acknowledged that most companies ship outside el

labeled storage conditions but within allowable shipping

conditions.

• There may be excursions/events which occur and there

may be product quality impact which would be investigated

and still allow the product to be released based on stability

data, etc.…

The ability to maintain the product within specified labeled

environmental conditions, especially during transportation

1/2


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Current: The ability to maintain the product within specified

labeled environmental conditions, especially during

transportation.

• What about stating, “…follow shipping protocol…”

Is it necessary to maintain specific labeling temp controls

during transportation?

How about …? The ability to maintain the product within

acceptable specified labeled environmental conditions, during

storage and especially transportation.

• Regulatory input: …, maintain label controls and manage

excursions using stability – to cover the manufacture; what

about the wholesaler?

USP – Editing Process

2/2


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Importation & Exportation Management

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

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Intended to cover I/E processes

1. Business-to-business: All stakeholders (suppliers, brokers,

customers, …)

2. Business-to-government: Customs clearance,

documentation, port authorities

Knowledge of product & material

• International name(s), codes, hazards, classifications,

presentations

• Likelihood of theft; potential for abuse, counterfeiting,

diversion

• Contractual agreements to ensure security

Not intended to cover

• Importation & Exportation law

• Customs procedures (country specific) 19

20


2013 UPS Survey

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Supply Chain Integrity and Security

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

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1. General: QMS, RMS, SOPs & regulatory requirements

2. Product knowledge: ID, use, vulnerabilities, hazards,

processes

3. Global sourcing knowledge: Partners, suspicious orders,

information systems, qualifications

Supply Chain Integrity

• Economically motivated adulteration

• Counterfeit & falsified

• Diversion (expired; recalled donated)

• Inadequate transportation &/or storage

Supply Chain Security

• Theft; loss prevention; layered defenses

• Understanding threats; vulnerabilities; geography; routing

• Investigation process

Supply Chain Integrity & Security <1083.4>

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When creating the first final package design

consider GDP’s

Engage SC partners/organizations

All medicines, pharma/biotech, have same

requirements for temp control

Closing

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The Future

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>

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In-

Progress

Developing and updating USP standards for packaging

systems and their materials of construction (e.g.,

Containers: metal, glass, plastic, elastomeric closures for

injections)

Revising packaging definitions (e.g., CRT); packaging and

storage requirements for compendial articles

Creating and revising guidance; examples:

– Containers: Performance testing

– Sterile product packaging: Integrity & evaluation

– Good packaging & repackaging practices

– Extractables

– Leachables

– Good distribution practices

Goals of PSD Expert Committee

25

Submit an application to serve as an USP expert

volunteer: New, account-based online application

Promote the Call for Candidates to your

colleagues

Apply for current cycle’s Expert Panels

What other subjects would be of value as GDP

Sub-Chapters?

Questions? USP web site at www.usp.org

Contact USP at [email protected] or

301-816-8151

Join the Challenge! Focus On The Future

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http://www.usp.org/

mailto:[email protected]

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