PDA Technical Report Overview

Josh Eaton
Senior Project Manager
Scientific and Regulatory Affairs

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PDA Technical Report Overview

What is a technical report?

Guidance and Address a wide array of
opinions written challenging technical areas
by subject
matter experts Peer-reviewed global
consensus documents

Used as references by industry

and regulatory authorities

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PDA Technical Report Overview

Nearly 80 technical reports produced

Multiple disciplines addressed

Quality Risk Manufacturing

Sterilization
Management Science

Validation &
Microbiology Analytical Methods

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PDA Technical Report Overview

Increasing reliability through QRM

TR No. Title Publication
Parametric Release of Pharmaceuticals and Medical Device Products Terminally Sterilized by Moist Revised 2012
30
Heat (published 1999)

31 Validation and Qualification of Computerized Laboratory Data Acquisition Systems 1999

Quality Risk 44 Quality Risk Management for Aseptic Processes 2008
Management
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
Implementation of Quality Risk Management for Pharmaceutical and
54 2012
Biotechnology Manufacturing Operations
Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing
54-2 2013
Operation: Annex 1: Case Study Examples for Quality Risk Management in Packaging and Labeling
Implementation of Quality Risk Management for Pharmaceutical and
54-3 Biotechnology Manufacturing Operations Annex 2: Case Studies in the Manufacturing of 2013
Pharmaceutical Drug Products
Implementation of Quality Risk Management for Pharmaceutical and Biotechnology Manufacturing
54-4 2015
Operations Annex 3: Case Studies in the Manufacturing of Biotechnological Bulk Drug Substances
Application of Phase-Appropriate Quality Systems and CGMP to the Development of Therapeutic
56 2012
Protein Drug Substance
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

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 PDA Technical Report Overview

TR 54: Implementation of Quality Risk Management for Pharmaceutical

Quality Risk
Management
and Biotechnology Manufacturing Operations

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)

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 PDA Technical Report Digest

TR 54: Implementation of Quality Risk Management for Pharmaceutical

Quality Risk
Management
and Biotechnology Manufacturing Operations

QRM is integral to an effective

Pharmaceutical Quality System
Enabler for product quality
and patient safety
Facilitates continual
improvement

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 PDA Technical Report Digest

TR 54: Implementation of Quality Risk Management for Pharmaceutical

Quality Risk
Management
and Biotechnology Manufacturing Operations

Realization of QRM is an
evolutionary process Reactive Proactive

Requires a paradigm shift

in mindset and behavior
Retrospective Prospective
Corrective Preventative

Increased
compliance
Higher
efficiency
Knowledge
management
Fewer surprises

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 PDA Technical Report Overview

TR 54: Implementation of Quality Risk Management for Pharmaceutical

Quality Risk
Management
and Biotechnology Manufacturing Operations

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
TR No. Title Publication

12 Siliconization of Parenteral Drug Packaging Components 1988

Revised 2011
22 Process Simulation for Aseptically Filled Products (published 1996)

27 Pharmaceutical Package Integrity 1998

Manufacturing
Science 43
Identification and Classification of Nonconformities in Molded and Tubular Glass Containers Revised 2013
for Pharmaceutical Manufacturing (Published 2007)

45 Filtration of Liquids Using Cellulose-Based Depth Filters 2008

Detection and Mitigation of 2,4,6-Tribromoanisole and 2,4,6-Trichloroanisole Taints and Odors

55 2012
in the Pharmaceutical and Consumer Healthcare Industries

62 Recommended Practices for Manual Aseptic Processes 2013

66 Application of Single-Use Systems in Pharmaceutical Manufacturing 2014

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 PDA Technical Report Overview

TR 66: Application of Single-Use Systems in

Manufacturing
Pharmaceutical Manufacturing
Science

TR Purpose:
Holistic approach for
developing a science- and
risk-based manufacturing
strategy using SUS
Central focus is patient
safety

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 PDA Technical Report Overview

TR 66: Application of Single-Use Systems in

Manufacturing
Pharmaceutical Manufacturing
Science

Decision process for determining implementation of SUS is

appropriate for the particular product/process

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 PDA Technical Report Overview

TR 66: Application of Single-Use Systems in

Manufacturing
Pharmaceutical Manufacturing
Science

Holistic and comprehensive evaluation criteria for

SUS implementation

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PDA Technical Report Overview

Ensuring product safety

TR No. Title Publication
Validation of Moist Heat Sterilization Processes: Cycle Design, Development, Revised 2007
1
Qualification and Ongoing Control (published 1980)

Revised 2013
3 Validation of Dry Heat Processes Used for Depyrogenation and Sterilization (published 1981)

Revised 2008
26 Sterilizing Filtration of Liquids (published 1998)
Sterilization
40 Sterilization Filtration of Gases 2005

48 Moist Heat Sterilizer Systems: Design, Commissioning, Operation, Qualification and Maintenance 2010

Biological Indicators for Gas and Vapor-Phase Decontamination Processes: Specification,

51 2010
Manufacture, Control and Use

61 Steam In Place 2013

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 PDA Technical Report Overview

Sterilization
TR 61: Steam In Place

TR Purpose:
Comprehensive overview and practical recommendations for
design, qualification, and ongoing process control of SIP systems

Intended to
complement PDA
Technical Report No. 1 Focuses on applications of
Validation of Moist Heat steam for in situ sterilization
Sterilization Processes:
Cycle Design, Differentiated as steam in
Development, place versus sterilize in place
Qualification and
Ongoing Control

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 PDA Technical Report Overview

Sterilization
TR 61: Steam In Place

Validation

Process Development Process Qualification

Science and System Cycle Ongoing

Qualification
Technology Design Development Control

Mechanisms of User Cycle parameter Physical Routine operation

lethality requirements determination Biological Requalification
SIP applications Design Pre-exposure Change control
Sterilization Hardware phase
Sanitization Instrumentation Exposure phase
& controls Post-exposure
phase

Sterilization Science

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 PDA Technical Report Overview

Sterilization
TR 61: Steam In Place

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

TR No. Title Publication
Revised 2014
13 Fundamentals of an Environmental Monitoring Program (published 1990)

Revised 2013
33 Evaluation, Validation and Implementation of Alternative and Rapid Microbiological Methods (published 2000)

41 Virus Filtration 2008

Microbiology
50 Alternative Methods for Mycoplasma Testing 2010

Exclusion of Objectionable Microorganisms from Nonsterile Pharmaceuticals,

67 2014
Medical Devices, and Cosmetics

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 PDA Technical Report Overview

Recently updated technical reports

Microbiology

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

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 PDA Technical Report Overview

TR 67: Exclusion of Objectionable Microorganisms from Nonsterile

Pharmaceuticals, Medical Devices, and Cosmetics
Microbiology

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

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 PDA Technical Report Overview

TR 67: Exclusion of Objectionable Microorganisms from Nonsterile

Pharmaceuticals, Medical Devices, and Cosmetics
Microbiology

CHALLENGE How to define,

monitor, and manage
microbial risk?
Exclusion of objectionable
microorganisms can an
undefined critical quality
attribute

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 PDA Technical Report Overview

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

TR No. Title Publication
Revised 2008
14 Validation of Column-Based Chromatography Processes for the Purification of Proteins (published 1992)

Revised 2009
15 Validation of Tangential Flow Filtration in Biopharmaceutical Applications (published 1992)

Revised 2012
29 Points to Consider for Cleaning Validation
Validation & (published 1998)
Analytical Methods
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

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 PDA Technical Report Overview

TR 57: Analytical Method Validation and Transfer for

Validation & Analytical
Biotechnology Products
Methods

Analytical Method Development

Select and Design Establish Intended Use of Analytical Procedure

TR Purpose Identity
Impurity
Limit
Impurity
Quantity
Assay /
Potency

Provide practical and strategic Development and Optimization

guidance to efficiently use Performance Review, Qualification

historical data and knowledge Transfer of Methods

to design suitable risk-based Validation Prerequisites Assessment

AMV studies, and set

Analytical Method
Tech Resource Standards Verify Product

Validation
Stability
Transfer Assessment and Controls Specifications

appropriate protocol Validation Acceptance Criteria

acceptance criteria Validation

Built upon ICH Q2(R1)

(Post-Validation) Life
Post-Validation Life Cycle Steps

Cycle Steps
Maintenance Transfer Comparability OOS/Valiation
Study Failures

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 PDA Technical Report Overview

TR 57: Analytical Method Validation and Transfer for

Validation & Analytical
Biotechnology Products
Methods

Method Validation Readiness Flowpath

Practical Specification Regulatory

Requirements
Existing
Knowledge

methodology for
to meet (Product and
Process)

conducting Specificity Documented

validation
Precision Intended Use
Accuracy
QL/DL

process
Linearity
Range

AMV Acceptance

Risk-based
Criteria
Robustness
Data Documented

considerations
Summary of
Method
Performance Validation Risk
Characteristics Is Method AMV Protocol
Standards Assessment that Yes
(Handover ready for
Controls method meets
Package, Validation?
intended use
Development
Report)
Stability of
Reagents,
Samples No

Collect
more data
and/or
optimize
method

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 PDA Technical Report Overview

TR 57: Analytical Method Validation and Transfer for

Validation & Analytical
Biotechnology Products
Methods

Practical recommendations
for and explanation of
2 (t / 2,n1 + t ,n1 ) s IP2 2 (z / 2 + z ) s IP2
2 2
statistical methods n
2
2
Sample size
Acceptance criteria 120

%Recovery versus theoretical potency (in%)

Method transfer studies 110

100

90

80
Sending lab Receiving lab

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 PDA Technical Report Overview

Process Validation Tools

Validation & Analytical
Methods

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

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PDA Technical Report Overview

Science-
based,
Conclusion consensus,
peer
reviewed

Cover
Practical
significant
guidance
topics

Focus on
safety,
quality,
efficacy

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PDA Technical Report Overview

Technical Report Portal free to members and at PDA Bookstore

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PDA Technical Report Overview

Questions?
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: eaton@pda.org

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