Eaton Josh Technical Reports

Copyright © 2015 PDA

PDA Technical Report Overview Josh Eaton Senior Project Manager Scientific and Regulatory Affairs


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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Nearly 80 technical reports produced

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• Multiple disciplines addressed

Quality Risk Management

Manufacturing Science Sterilization

Microbiology Validation & Analytical Methods



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




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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


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



PDA Technical Report Digest

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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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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)



Improving efficiency

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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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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




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Decision process for determining implementation of SUS is appropriate for the particular product/process



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Holistic and comprehensive evaluation criteria for SUS implementation



Ensuring product safety

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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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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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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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TR 61: Steam In Place Sterilization

• System design and qualification – Piping/valve design – Thermocouple placement – BI placement and microbial

challenge evaluation



Ensuring microbial control

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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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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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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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How to define, monitor, and manage microbial risk?

Exclusion of objectionable microorganisms can an undefined critical quality attribute

CHALLENGE

Microbiology



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Microbiology



Assuring drug quality

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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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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)


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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• 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




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

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• 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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Science-based,

consensus, peer

reviewed

Cover significant

topics

Focus on safety, quality, efficacy

Practical guidance

Conclusion

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Technical Report Portal free to members and at PDA Bookstore

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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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mailto:[email protected]

Documents

Eaton Josh Technical Reports