the usp s approach to good distribution practices … practices clinical trial supply east coast...
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The USP’s Approach to Good
Distribution Practices
Clinical Trial Supply East Coast 2014
October 28 – 29, 2014
Michael N. Eakins, Ph.D., Vice - Chair,
USP Packaging, Storage and Distribution
Expert Committee
• USP - NF
• <1083> Good Distribution Practices
– How did we get there?
– Current <1083> Chapters
– Clinical Trial Materials
Agenda
2
• 15 Active General Chapters
– Packaging Materials and Components
– Storage and Distribution
– Packaging Practices
Packaging, Storage
& Distribution
Expert Committee
USP-NF
• Scientific, independent, volunteer-driven, nonprofit organization
– Established in 1820; Headquartered in Rockville, MD
– Facilities in Brazil, China, India, Switzerland
• Sets public quality standards for prescription and over-the-counter medicines, excipients (inactive ingredients), dietary supplements, and food ingredients
• Worked closely with FDA and predecessors for >100 years, developing and revising drug quality standards
• Standards recognized and used in over 130 countries
• Translated into Chinese and Spanish
U.S. Pharmacopeial Convention
USP General Chapters
• Chapters <1> to <999> are enforceable in
the USA
USP General Information Chapters
• Chapters <1000> to <1999>
• Chapters provide information – they
contain no standards, tests, assays, nor
other mandatory specifications, with
respect to any Pharmacopeial articles
USP General Chapters
New or Revised General Chapters
New or Revised
Chapter published in
Pharmacopeial Forum
(PF)
Expert Committee
(EC) Generates
Chapter
Approved; New Text
Becomes Effective in
Next USP Publication
EC Reviews
Comments; Accepts
or Rejects Comments
and Alters Text as
Appropriate
USP General Chapters
Public Comment
Period 90 Days
Not Approved: EC
Determines that the
Revised Chapter be
Republished in PF
due to Nature or
Significance of
Changes
• Official forum for new or revised Monographs,
General Chapters and Stimuli Articles
• Six publications/year
• Free access after registration on USP website
• Log into USP website:
www.usp/org/usp-nf/pharmacopeial-forum
• Comment period is 90 days after publication
• Anyone may comment
Pharmacopeial Forum (PF)
• General Chapter <1079> Good Storage and Distribution Practices for Drug Products
– Provides recommendations for those activities and
practices that ensure Good Distribution Practices for
finished drug products
– Became official in 2005 and recently was revised
• General Chapter <1197> Good Distribution Practices for Bulk Pharmaceutical Excipients
– Provides recommendations for activities and
practices that ensure Good Distribution Practices for
pharmaceutical excipients
GDP Chapters in USP 37 – NF 32
8
Chapter <1079> Outline
Good Storage & Distribution Practices for Drug Products
• Introduction, Definitions, Scope
• Background Information
• Responsibilities
• Labeling Information
• Quality Management System
– Good Documentation Practices
– Storage Management System
– Distribution Management System
– Environmental Management System
– Risk Management System
Chapter <1197> Outline
Good Distribution Practices for Bulk Pharmaceutical Excipients
• Key Strategies:
– Qualification of good quality starting materials
– Maintenance of quality throughout the distribution chain
– Confirmation of the quality by the end users
– Avoid potential issues and misunderstandings as to whether the sourced material can qualify as suitable for its intended use
– Prevent substandard or adulterated material from entering the pharmaceutical supply or being detected when present
Chapter <1083> Outline
Good Distribution Practices – Supply Chain Integrity
• Covered 4 main areas
• Importation – Supply Chain Risk Management, Effective Supplier Partnerships, Supply Chain Quality System
• Counterfeit Drugs & Medical Devices – medical consequences
• Best Practices to Combat Counterfeit Drugs:
– Packaging Technologies
– Establishment of Drug Pedigrees
– Application of Machine-Readable Data Carriers
– Repackaging Guidance, Information Retention & Security
– International Standards
– Combating Illegal Internet Pharmacies
– Best Anti-Counterfeiting Practices
• Diversion & Theft
• USP <1083> Good Distribution Practices –
Supply Chain Integrity
– Published in Pharmacopeial Forum (PF) 38(2) March – April 2012
– USP held a Supply Chain Workshop in May 2012 to obtain direct feedback and comment
– Written comments received by May 30
– Draft chapter was withdrawn
Draft GDP Chapter in PF
12
USP Supply Chain Workshop
What did we learn?
• USP’s current approach to GDP has been piecemeal:
– Individual components, e.g. Excipients; Drug Products
– Individual topics, e.g. Storage, Distribution, Integrity
• A holistic approach to GDP is preferred:
– Acquisition of ingredients (drug substances, excipients)
– Authentication and drug pedigree steps
– Delivery of medicines to the end-users
– Adherence to labeled storage conditions (“cold chain”)
• Integrate individual components and topics under a single overarching GDP (umbrella) chapter with sub-headings for the major sections
Good Distribution Practices (GDP)
Good
Importation
Practices
Label
Storage
Requirements
Distribution
Control
Systems
General
GDP
Provisions
GDP
New USP <1083> Chapters
• New series of GDP chapters are proposed
• The introduction and 4 sub-chapters have been
written
– <1083> Good Distribution Practices
– <1083.1> Quality Management System
– <1083.2> Environmental Conditions Management
– <1083.3> Good Importation and Exportation Practices
– <1083.4> Supply Chain Integrity and Security
• The four sub-chapters, provide the overarching best
practices and principles that may be applied
• Subsequent sub-chapters will address these
practices and principle in depth to individual topics
New USP <1083> Chapters
<1083.1> <1083.2> <1083.3> <1083.4>
GDP Subjects Divided into Sub-Chapters
<1083>
• Published Pharmacopeia Forum 40 (2) Mar-Apr 2014
• Comments due May 31, 2014
• Chapters under revision
8
GOOD IMPORTATION AND
EXPORTATION
PRACTICES
17
USP General Chapter <1083>
Good Distribution Practices
15
Sub-Chapter <1083.1>
Quality Management System
QUALITY MANAGEMENT SYSTEMS
MANAGEMENT
RESPONSIBILITY,
DOCUMENTATION,
RESOURCES
MANAGEMENT,
OPERATIONS
COMPLAINTS,
DEVIATIONS,
RECALLS
COUNTERFEIT,
REPROCESS
MONITORING &
IMPROVEMENT,
VALIDATION
REGULATORY
AFFAIRS
18
USP General Chapter <1083>
Good Distribution Practices
15
Sub-Chapter <1083.2>
Environmental Conditions Management
ENVIRONMENTAL CONDITIONS
MANAGEMENT
ENVIRONMENTAL
CONTROLLED
FACILITIES,
EQP & STORAGE
PACKAGING FOR
SHIPPING
PERFORMANCE
QUALIFICATION
DATA
MONITORING
SHORT-TERM
EXCURSIONS
19
USP General Chapter <1083>
Good Distribution Practices
15
Sub-Chapter <1083.3>
Good Importation and Exportation Practices
IMPORTATION AND EXPORTATION
PRACTICES
GENERAL
REQUIREMENTS
MATERIAL OR
PRODUCT
KNOWLEDGE
GLOBAL
SOURCING
KNOWLEDGE
20
USP General Chapter <1083>
Good Distribution Practices
15
Sub-Chapter <1083.4>
Supply Chain Integrity & Security
SUPPLY CHAIN INTEGRITY
& SECURITY
PRODUCT THEFT PRODUCT
DIVERSION
<1083> Current Status GOOD DISTRIBUTION PRACTICES
<1083> Introduction
QUALITY MANAGEMENT
SYSTEM
<1083.1>
ENVIRONMENTAL CONDITIONS
MANAGEMENT
<1083.2>
GOOD IMPORTATION & EXPORTATION
PRACTICES
<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>
Started
• General Chapter <1079> Good Storage and Distribution Practices for Drug Products
– Incorporate into <1083.5> Finished Drug Products
• General Chapter <1197> Good Distribution Practices for Bulk Pharmaceutical Excipients
– Incorporate into <1083.6> Excipients
Incorporation of <1079> and <1197> into <1083>
• CTM top 3 risks = product integrity, supply chain disruptions, meeting timelines*
• Differences between CTMs & approved Drug Products
– Raw material in short supply
– Small batches
– Knowledge of product stability may be at early stages
– Minimize product loss due to container-closure defects
– Invest in glass containers with increased level of inspection
– Placebos and blinding may be required
• Similarities between CTMs & approved Drug Products
– Both require Good Distribution Practices
* PAREXEL Survey at ISR fall 2013
Clinical Trial Materials (CTM)
• USP <1660> Evaluation of the Inner Surface Durability of Glass Containers provides guidance on glass container quality and approaches to be able to screen vials on a lot-to-lot basis or between different manufacturers
• Glass vial vendors are offering vials will reduced inhomegeneities in the inner surface – lower tendency to delaminate
– e.g. Schott Vials DC
• Glass vial vendors are offering vials that are ready to fill in a tub format – e.g. Schott, Nuova Ompi
Clinical Trial Glass Containers
European Regulations
• European Commission. Guidelines of November 5,
2013 on Good Distribution Practice of Medicinal
Products for Human Use
• EudraLex: The Rules Governing Medicinal Products
in the EU, Vol 4 – EU Guidelines for Good
Manufacturing Practice for Medicinal Products for
Human and Veterinary Use. Jan 2013
• Product Recalls: 8.24 Investigational Medicinal
Products
– Identify trial sites and countries
– Implement a procedure for rapid unblinding of
blinded products where a recall in needed
Guidance for Industry: CGMP for Phase I Investigational New Drugs. July 2008
G. Packaging, Labeling and Distribution
• Establish written procedures for controlling packaging, labeling and storage operations
• Appropriate measures should be in place for control of batches, especially where there is potential for mix-ups, e.g., placebos, blinded products, multiple strengths
• Handle Phase I drugs in accordance with labeled conditions
• Ensure traceability to facilitate a recall if needed
FDA Guidance
• Expert Panel: GDP & CTM – Rafik Bashara, Technical Advisor & PDA Chair, PCCIG
– Glaucia Karime Braga, Brazil Government Agency
– Steve Jacobs, Industry Consultant
– Marty Jeiven, Industry Consultant
– Claude Jolicoeur, Wholesaler, McKesson Canada
– Desiree Valentine, Industry Consultant
– USP PSD Expert Committee, Mary Foster
– USP Senior Scientific Liaison, Desmond Hunt
Clinical Trial Materials
• Should Clinical Trial Materials have
their own <1083> sub-chapter?
28
a. Sub-chapter needed?
b. Sub-chapter not needed – incorporate
under Drug Products sub-chapter.
Close with Audience Poll Question
Contact Information:
Michael N. Eakins PH.D.
Principal Consultant, Eakins & Associates
609 448 3411