PDA Technical Report Overview

Josh Eaton
Senior Project Manager
Scientific and Regulatory Affairs

Copyright 2015 PDA

PDA Technical Report Overview

What is a technical report?

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

Used as references by industry

and regulatory authorities
Copyright 2015 PDA

PDA Technical Report Overview

Nearly 80 technical reports produced

Multiple disciplines addressed

Quality Risk
Management

Manufacturing
Science

Microbiology

Sterilization

Validation &
Analytical Methods
Copyright 2015 PDA

PDA Technical Report Overview

Increasing reliability through QRM

TR No.
30

Quality Risk
Management

Title
Parametric Release of Pharmaceuticals and Medical Device Products Terminally Sterilized by Moist
Heat

Publication
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

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

54-2

Implementation of Quality Risk Management for Pharmaceutical and

54-3 Biotechnology Manufacturing Operations Annex 2: Case Studies in the Manufacturing of
Pharmaceutical Drug Products

2013

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

54-4

Copyright 2015 PDA

PDA Technical Report Overview

Quality Risk
Management

TR 54: Implementation of Quality Risk Management for Pharmaceutical

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)

Copyright 2015 PDA

PDA Technical Report Digest

Quality Risk
Management

TR 54: Implementation of Quality Risk Management for Pharmaceutical

and Biotechnology Manufacturing Operations

QRM is integral to an effective

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

Copyright 2015 PDA

PDA Technical Report Digest

Quality Risk
Management

TR 54: Implementation of Quality Risk Management for Pharmaceutical

and Biotechnology Manufacturing Operations

Realization of QRM is an
evolutionary process
Requires a paradigm shift
in mindset and behavior

Reactive

Retrospective
Corrective

Proactive

Prospective
Preventative

Increased
compliance
Higher
efficiency
Knowledge
management
Fewer surprises

Copyright 2015 PDA

PDA Technical Report Overview

Quality Risk
Management

TR 54: Implementation of Quality Risk Management for Pharmaceutical

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)

Copyright 2015 PDA

PDA Technical Report Overview

Improving efficiency
TR No.

Manufacturing
Science

Title

Publication

12

Siliconization of Parenteral Drug Packaging Components

22

Process Simulation for Aseptically Filled Products

27

Pharmaceutical Package Integrity

43

Identification and Classification of Nonconformities in Molded and Tubular Glass Containers

for Pharmaceutical Manufacturing

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

1988
Revised 2011

(published 1996)

1998
Revised 2013

(Published 2007)

Copyright 2015 PDA

PDA Technical Report Overview

Manufacturing
Science

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

Copyright 2015 PDA

10

PDA Technical Report Overview

Manufacturing
Science

TR 66: Application of Single-Use Systems in

Pharmaceutical Manufacturing

Decision process for determining implementation of SUS is

appropriate for the particular product/process

Copyright 2015 PDA

11

PDA Technical Report Overview

Manufacturing
Science

TR 66: Application of Single-Use Systems in

Pharmaceutical Manufacturing

Holistic and comprehensive evaluation criteria for

SUS implementation

Copyright 2015 PDA

12

PDA Technical Report Overview

Ensuring product safety

TR No.

Sterilization

Title

Publication

Validation of Moist Heat Sterilization Processes: Cycle Design, Development,

Qualification and Ongoing Control

Validation of Dry Heat Processes Used for Depyrogenation and Sterilization

26

Sterilizing Filtration of Liquids

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

Revised 2007

(published 1980)

Revised 2013

(published 1981)

Revised 2008

(published 1998)

Copyright 2015 PDA

13

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
Validation of Moist Heat
Sterilization Processes:
Cycle Design,
Development,
Qualification and
Ongoing Control

Focuses on applications of
steam for in situ sterilization
Differentiated as steam in
place versus sterilize in place

Copyright 2015 PDA

14

PDA Technical Report Overview

Sterilization

TR 61: Steam In Place

Validation
Process Qualification

Process Development

Science and
Technology

Mechanisms of
lethality
SIP applications
Sterilization
Sanitization

System
Design

User
requirements
Design
Hardware
Instrumentation
& controls

Cycle
Development

Cycle parameter
determination
Pre-exposure
phase
Exposure phase
Post-exposure
phase

Qualification

Physical
Biological

Ongoing
Control

Routine operation
Requalification
Change control

Sterilization Science

Copyright 2015 PDA

15

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

Copyright 2015 PDA

16

PDA Technical Report Overview

Ensuring microbial control

TR No.

Microbiology

Title

Publication
Revised 2014

13

Fundamentals of an Environmental Monitoring Program

33

Evaluation, Validation and Implementation of Alternative and Rapid Microbiological Methods

41

Virus Filtration

2008

50

Alternative Methods for Mycoplasma Testing

2010

67

Exclusion of Objectionable Microorganisms from Nonsterile Pharmaceuticals,

Medical Devices, and Cosmetics

2014

(published 1990)

Revised 2013

(published 2000)

Copyright 2015 PDA

17

PDA Technical Report Overview

Microbiology

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
Copyright 2015 PDA

18

PDA Technical Report Overview

Microbiology

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

Copyright 2015 PDA

19

PDA Technical Report Overview

Microbiology

TR 67: Exclusion of Objectionable Microorganisms from Nonsterile

Pharmaceuticals, Medical Devices, and Cosmetics

CHALLENGE

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

Copyright 2015 PDA

20

PDA Technical Report Overview

Microbiology

TR 67: Exclusion of Objectionable Microorganisms from Nonsterile

Pharmaceuticals, Medical Devices, and Cosmetics

Copyright 2015 PDA

21

PDA Technical Report Overview

Assuring drug quality

TR No.

Validation &
Analytical Methods

Title

Publication
Revised 2008

14

Validation of Column-Based Chromatography Processes for the Purification of Proteins

15

Validation of Tangential Flow Filtration in Biopharmaceutical Applications

29

Points to Consider for Cleaning Validation

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

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

57-2

(published 1992)

Revised 2009

(published 1992)

Revised 2012

(published 1998)

Copyright 2015 PDA

22

PDA Technical Report Overview

Validation & Analytical

Methods

TR 57: Analytical Method Validation and Transfer for

Biotechnology Products

Identity

Impurity
Limit

Impurity
Quantity

Assay /
Potency

Development and Optimization

Performance Review, Qualification

Transfer of Methods

Validation Prerequisites Assessment

Tech
Transfer

Resource
Assessment

Standards
and Controls

Stability

Verify Product
Specifications

Validation Acceptance Criteria

Analytical Method
Validation

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

Analytical Method Development

Select and Design Establish Intended Use of Analytical Procedure

Validation

Post-Validation Life Cycle Steps

Maintenance

Transfer

Comparability
Study

OOS/Valiation
Failures

Copyright 2015 PDA

(Post-Validation) Life
Cycle Steps

Built upon ICH Q2(R1)

23

PDA Technical Report Overview

Validation & Analytical

Methods

TR 57: Analytical Method Validation and Transfer for

Biotechnology Products
Method Validation Readiness Flowpath

Practical
methodology for
conducting
validation
process
Risk-based
considerations

Specification
to meet

Regulatory
Requirements

Existing
Knowledge
(Product and
Process)

Documented
Intended Use

Specificity
Precision
Accuracy
QL/DL
Linearity
Range

AMV Acceptance
Criteria
Robustness
Data

Standards
Controls

Stability of
Reagents,
Samples

Documented
Summary of
Method
Performance
Characteristics
(Handover
Package,
Development
Report)

Validation Risk
Assessment that
method meets
intended use

Is Method
ready for
Validation?

Yes

AMV Protocol

No

Collect
more data
and/or
optimize
method

Copyright 2015 PDA

24

PDA Technical Report Overview

Practical recommendations
for and explanation of
statistical methods
Sample size
Acceptance criteria
Method transfer studies

2 (t / 2,n1 + t ,n1 ) s IP2 2 (z / 2 + z ) s IP2

n

2
2

120

%Recovery versus theoretical potency (in%)

Validation & Analytical

Methods

TR 57: Analytical Method Validation and Transfer for

Biotechnology Products

110

100

90

80
Sending lab

Receiving lab

Copyright 2015 PDA

25

PDA Technical Report Overview

Validation & Analytical

Methods

Process Validation Tools

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

Copyright 2015 PDA

26

PDA Technical Report Overview

Conclusion

Sciencebased,
consensus,
peer
reviewed

Cover
significant
topics

Practical
guidance

Focus on
safety,
quality,
efficacy

Copyright 2015 PDA

27

PDA Technical Report Overview

Technical Report Portal free to members and at PDA Bookstore

Copyright 2015 PDA

28

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

Copyright 2015 PDA

29