Copyright © 2015 PDA
PDA Technical Report Overview Josh Eaton Senior Project Manager Scientific and Regulatory Affairs
Copyright © 2015 PDA
PDA Technical Report Overview
Guidance and opinions written by subject matter experts
Address a wide array of challenging technical areas
Peer-reviewed global consensus documents
Used as references by industry and regulatory authorities
What is a technical report?
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Copyright © 2015 PDA
PDA Technical Report Overview
Nearly 80 technical reports produced
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• Multiple disciplines addressed
Quality Risk Management
Manufacturing Science Sterilization
Microbiology Validation & Analytical Methods
Copyright © 2015 PDA
PDA Technical Report Overview
Increasing reliability through QRM
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TR No. Title Publication
30 Parametric Release of Pharmaceuticals and Medical Device Products Terminally Sterilized by Moist Heat
Revised 2012 (published 1999)
31 Validation and Qualification of Computerized Laboratory Data Acquisition Systems 1999
44 Quality Risk Management for Aseptic Processes 2008
46 Last Mile: Guidance for Good Distribution Practices for Pharmaceutical Products to the End User 2009
52 Guidance for Good Distribution Practices for the Pharmaceutical Supply Chain 2011
53 Guidance for Industry: Stability Testing to Support Distribution of New Drug Products 2011
54 Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing Operations 2012
54-2 Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing Operation: Annex 1: Case Study Examples for Quality Risk Management in Packaging and Labeling 2013
54-3 Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing Operations Annex 2: Case Studies in the Manufacturing of Pharmaceutical Drug Products
2013
54-4 Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing Operations Annex 3: Case Studies in the Manufacturing of Biotechnological Bulk Drug Substances 2015
56 Application of Phase-Appropriate Quality Systems and CGMP to the Development of Therapeutic Protein Drug Substance 2012
58 Risk Management for Temperature-Controlled Distribution 2012
63 Quality Requirements for the Extemporaneous Preparation of Clinical Trial 2013
65 Technology Transfer 2014
68 Risk-Based Approach for Prevention and Management of Drug Shortages 2014
Quality Risk Management
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PDA Technical Report Overview
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TR Purpose: Provide detailed guidance for the application and implementation of Quality Risk Management (QRM) principles throughout the product lifecycle • Aligned with ICH Q9 • Emphasis on:
– Application during manufacturing – Integrating QRM into Pharmaceutical Quality System (PQS)
TR 54: Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing Operations Quality Risk
Management
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PDA Technical Report Digest
TR 54: Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing Operations
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QRM is integral to an effective Pharmaceutical Quality System • “Enabler” for product quality
and patient safety • Facilitates continual
improvement
Quality Risk Management
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PDA Technical Report Digest
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TR 54: Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing Operations Quality Risk
Management
Realization of QRM is an evolutionary process • Requires a paradigm shift
in mindset and behavior
• Increased compliance
• Higher efficiency
• Knowledge management
• Fewer surprises
Reactive
• Retrospective • Corrective
Proactive
• Prospective • Preventative
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PDA Technical Report Overview
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TR 54: Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing Operations Quality Risk
Management
Three annexes with case studies:
QRM in Packaging and Labeling (TR 54-2)
QRM in Manufacturing of Pharmaceutical Drug Products (TR 54-3)
QRM in Manufacturing of Biotechnological Bulk Drug Substances
(TR 54-4)
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PDA Technical Report Overview
Improving efficiency
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TR No. Title Publication
12 Siliconization of Parenteral Drug Packaging Components 1988
22 Process Simulation for Aseptically Filled Products Revised 2011 (published 1996)
27 Pharmaceutical Package Integrity 1998
43 Identification and Classification of Nonconformities in Molded and Tubular Glass Containers for Pharmaceutical Manufacturing
Revised 2013 (Published 2007)
45 Filtration of Liquids Using Cellulose-Based Depth Filters 2008
55 Detection and Mitigation of 2,4,6-Tribromoanisole and 2,4,6-Trichloroanisole Taints and Odors in the Pharmaceutical and Consumer Healthcare Industries 2012
62 Recommended Practices for Manual Aseptic Processes 2013
66 Application of Single-Use Systems in Pharmaceutical Manufacturing 2014
Manufacturing Science
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PDA Technical Report Overview
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TR 66: Application of Single-Use Systems in Pharmaceutical Manufacturing
TR Purpose: Holistic approach for developing a science- and risk-based manufacturing strategy using SUS • Central focus is patient
safety
Manufacturing Science
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PDA Technical Report Overview
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TR 66: Application of Single-Use Systems in Pharmaceutical Manufacturing
Manufacturing Science
Decision process for determining implementation of SUS is appropriate for the particular product/process
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PDA Technical Report Overview
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TR 66: Application of Single-Use Systems in Pharmaceutical Manufacturing
Manufacturing Science
Holistic and comprehensive evaluation criteria for SUS implementation
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PDA Technical Report Overview
Ensuring product safety
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TR No. Title Publication
1 Validation of Moist Heat Sterilization Processes: Cycle Design, Development, Qualification and Ongoing Control
Revised 2007 (published 1980)
3 Validation of Dry Heat Processes Used for Depyrogenation and Sterilization Revised 2013 (published 1981)
26 Sterilizing Filtration of Liquids Revised 2008 (published 1998)
40 Sterilization Filtration of Gases 2005
48 Moist Heat Sterilizer Systems: Design, Commissioning, Operation, Qualification and Maintenance 2010
51 Biological Indicators for Gas and Vapor-Phase Decontamination Processes: Specification, Manufacture, Control and Use 2010
61 Steam In Place 2013
Sterilization
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PDA Technical Report Overview
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TR 61: Steam In Place
• Focuses on applications of steam for in situ sterilization
• Differentiated as “steam in place” versus “sterilize in place”
Intended to complement PDA
Technical Report No. 1 Validation of Moist Heat Sterilization Processes:
Cycle Design, Development,
Qualification and Ongoing Control
Sterilization
TR Purpose: Comprehensive overview and practical recommendations for design, qualification, and ongoing process control of SIP systems
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PDA Technical Report Overview
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TR 61: Steam In Place Sterilization
Validation
Cycle Development
System Design Qualification Ongoing
Control Science and Technology
• User requirements
• Design • Hardware • Instrumentation
& controls
• Physical • Biological
• Routine operation • Requalification • Change control
• Mechanisms of lethality
• SIP applications • Sterilization • Sanitization
• Cycle parameter determination
• Pre-exposure phase
• Exposure phase • Post-exposure
phase
Process Development Process Qualification
Sterilization Science
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PDA Technical Report Overview
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TR 61: Steam In Place Sterilization
• System design and qualification – Piping/valve design – Thermocouple placement – BI placement and microbial
challenge evaluation
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PDA Technical Report Overview
Ensuring microbial control
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TR No. Title Publication
13 Fundamentals of an Environmental Monitoring Program Revised 2014 (published 1990)
33 Evaluation, Validation and Implementation of Alternative and Rapid Microbiological Methods Revised 2013 (published 2000)
41 Virus Filtration 2008
50 Alternative Methods for Mycoplasma Testing 2010
67 Exclusion of Objectionable Microorganisms from Nonsterile Pharmaceuticals, Medical Devices, and Cosmetics 2014
Microbiology
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PDA Technical Report Overview
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Recently updated technical reports
TR 13: Fundamentals of an Environmental Monitoring Program • Conforms with revised air quality classification conventions and
sampling methodologies
TR 33: Evaluation, Validation, and Implementation of Alternative and Rapid Microbiological Methods • Outlines new methods and regulatory expectations for method
qualification
Microbiology
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PDA Technical Report Overview
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TR 67: Exclusion of Objectionable Microorganisms from Nonsterile Pharmaceuticals, Medical Devices, and Cosmetics
TR Purpose • Present strategies for managing microbial risks associated
with the presence of objectionable microorganisms in nonsterile products – Covers nonsterile pharmaceutical drug products, over-the-counter
(OTC) drug products, medical devices, cosmetics, and personal care products
Microbiology
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PDA Technical Report Overview
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TR 67: Exclusion of Objectionable Microorganisms from Nonsterile Pharmaceuticals, Medical Devices, and Cosmetics
How to define, monitor, and manage microbial risk?
Exclusion of objectionable microorganisms can an undefined critical quality attribute
CHALLENGE
Microbiology
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PDA Technical Report Overview
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TR 67: Exclusion of Objectionable Microorganisms from Nonsterile Pharmaceuticals, Medical Devices, and Cosmetics
Microbiology
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PDA Technical Report Overview
Assuring drug quality
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TR No. Title Publication
14 Validation of Column-Based Chromatography Processes for the Purification of Proteins Revised 2008 (published 1992)
15 Validation of Tangential Flow Filtration in Biopharmaceutical Applications Revised 2009 (published 1992)
29 Points to Consider for Cleaning Validation Revised 2012 (published 1998)
31 Validation and Qualification of Computerized Laboratory Data Acquisition Systems 1999
42 Process Validation of Protein Manufacturing 2005
49 Points to Consider for Biotechnology Cleaning Validation 2010
57 Analytical Method Validation and Transfer for Biotechnology Products 2012
57-2 Analytical Method Development and Qualification for Biotechnology Products 2015
59 Utilization of Statistical Methods for Production Monitoring 2012
60 Process Validation: A Lifecycle Approach 2013
Validation & Analytical Methods
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PDA Technical Report Overview
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TR 57: Analytical Method Validation and Transfer for Biotechnology Products
TR Purpose • Provide practical and strategic
guidance to efficiently use historical data and knowledge to design suitable risk-based AMV studies, and set appropriate protocol acceptance criteria – Built upon ICH Q2(R1)
Validation & Analytical Methods
Analytical M
ethod Developm
ent
A
nalytical Method
Validation
(Post-Validation) Life C
ycle Steps
Select and Design – Establish Intended Use of Analytical Procedure
Development and Optimization
Performance Review, Qualification
Validation Acceptance Criteria
Validation
Post-Validation Life Cycle Steps
Transfer of Methods
Validation Prerequisites Assessment
Identity ImpurityLimit
Impurity Quantity
Assay / Potency
Tech Transfer
Resource Assessment
Standards and Controls Stability Verify Product
Specifications
Maintenance Transfer Comparability Study
OOS/Valiation Failures
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PDA Technical Report Overview
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TR 57: Analytical Method Validation and Transfer for Biotechnology Products
• Practical methodology for conducting validation process
• Risk-based considerations
Method Validation Readiness Flowpath
SpecificityPrecisionAccuracy
QL/DLLinearityRange
Robustness Data
Regulatory Requirements
Validation Risk Assessment that method meets intended use
StandardsControls
Stability of Reagents, Samples
Existing Knowledge
(Product and Process)
AMV Protocol
No
Is Method ready for
Validation?
Collect more data
and/or optimize method
AMV Acceptance Criteria
Specification to meet
Documented Summary of
Method Performance
Characteristics (Handover Package,
Development Report)
Yes
Documented Intended Use
Validation & Analytical Methods
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PDA Technical Report Overview
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TR 57: Analytical Method Validation and Transfer for Biotechnology Products
Practical recommendations for and explanation of statistical methods • Sample size • Acceptance criteria • Method transfer studies
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Validation & Analytical Methods
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PDA Technical Report Overview
• TR 42: Process Validation of Protein Manufacturing – Covers process and product characterization in support of drug
substance production – Offers examples outlining cell culture and downstream purification
processes
• TR 60: Process Validation: A Lifecycle Approach – Conforms to 3-stage process validation model outlined in FDA PV
Guidance – Offers practical examples of process validation lifecycle
Process Validation Tools
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Validation & Analytical Methods
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PDA Technical Report Overview
Science-based,
consensus, peer
reviewed
Cover significant
topics
Focus on safety, quality, efficacy
Practical guidance
Conclusion
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Copyright © 2015 PDA
PDA Technical Report Overview
Technical Report Portal free to members and at PDA Bookstore
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Copyright © 2015 PDA
PDA Technical Report Overview
Contact:
Josh Eaton Sr. Project Manager, Scientific and Regulatory Affairs Parenteral Drug Association® (PDA) Bethesda Towers, Suite 150 4350 East-West Highway Bethesda , MD 20814 USA Tel: +1 (301) 656-5900, ext. 112 E-mail: [email protected]
Questions?
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