Keeping up with current regulatory trends

Keeping Up with Current Regulatory Trends

Carole Crowe Agilent Technologies Validation Week IVT18 October 23, 2012

October 23, 2012 Crowe - 18th Annual Validation Week

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Quality Systems

Guidance for Industry: Quality System Approach to Pharmaceutical cGMP Regulations


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ICH Q10 Pharmaceutical Quality System

ICH Q10 ( Management responsibility) … :

‘Leadership is essential to establish and maintain a

companywide commitment to quality and for the

performance of the pharmaceutical quality

system’


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Major Reasons for Recalls (OTC and Rx) – FY 2010 – 2012* Year Top Reasons

2010 GMP Deviations Temperature Abuse Marketed without an Approved NDA/ANDA

2011 Penicillin Cross Contamination

GMP Deviations Marketed without an Approved NDA/ANDA

2012 Penicillin Cross Contamination Microbial Contamination of Non-Sterile Products GMP Deviations

2012* - as of 3/7/2012


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European 2012 PDA/EMA Joint Conference

Compliance: A prerequisite for

Availability of Medicinal Products


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What is Compliance? And

How Do We Enforce it?


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FDA Compliance

The Food and Drug Administration (FDA) is an agency of the U.S. federal government. The FDA is responsible for regulating the safety of food, drugs, cosmetics, biological products, medical devices, and consumer products that emit radiation. It has the power to establish federal rules and regulations about these products. FDA compliance is the act of following these regulations


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www.fda.gov/downloads/ICECI/EnforcementActions

October 23, 2012

725 535 538 471 445 474

673

1720

0 200 400 600 800

1000 1200 1400 1600 1800 2000 2200 2400 2600 2800 3000

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

FDA Warning Letter Trends Fiscal Years 2004 - 2012

2767 ?

Crowe - 18th Annual Validation Week


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Do You Feel Lucky ?

Approximately 1 in 6 FDA 483 Inspectional Observations Results in a Warning Letter…

How Do We Enforce It?


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Quality Systems


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Regulatory Landscape

• USP <1058> - New Stimuli Paper for updates

• GAMP 5 rev. 2– Computer Systems Validation •  FDA Compliance Program Guide - Data

Integrity •  21 CFR Part 11/Annex 11

PQ DQ OQ IQ

Does it Meet your USER REQUIREMENTS

Design Qualification

Installation Qualification

Has it been INSTALLED

CORRECTLY Operational Qualification

Performance Qualification

Does it WORK as YOU

EXPECTED

Will it CONTINUE to

work CORRECTLY

But, no “Set Rules”, Regulators / Consultants / Scientists / Customers don’t Agree on the detail:

•  WHAT - Some of The Stages Contain •  HOW - Often an OQ should be Done / RQ Vs OQ •  WHO - Performs Some of The Stages (OQ / PQ)

4Q Stages of Instrument Qualification…

October 23, 2012 14 Crowe - 18th Annual Validation Week

Instrument Life Cycle – From a Regulators Perspective

DQ

Use OQ

IQ Maintenance

Re-Qualification (Justification)

Breakdown

Repair Re-Qualification (Justification)

Co Policy

1 Is the Instrument Suitable for use

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3

5

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2 Is it installed Correctly

3 Is there an SOP Are people Trained Is it Calibrated Method Validation

5 Maintenance Routine ?

4 Failure Mgt. Impact of Failure CAPA ?

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6 Re-Qualification / Calibration



Frequent Customer Questions

Justification:

OQ - How Often RQ – What to include



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3 Categories on Instruments – USP <1058>

“ Group A includes standard equipment with no measurement capability or usual requirement for calibration, where the manufacturer's specification of basic functionality is accepted as user requirements”

“Group B includes standard equipment and instruments providing measured values as well as equipment controlling physical parameters (such as temperature, pressure, or flow) that need calibration, where the user requirements are typically the same as the manufacturer's specification of functionality and operational limits”

“Group C includes instruments and computerized analytical systems, where user requirements for functionality, operational, and performance limits are specific for the analytical application”

GAMP 5 rev 2 (Amazon Bestsellers Rank: 1,031,332)

More Flexible: – Risk Based

– Not Prescriptive

– Will include examples

– Better GAMP - <1058> Alignment

– Flow chart to support use

GAMP Good Practice Guide

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GAMP - Validation of Computerized Laboratory Systems, moving away from 7 instrument categories to a fully RISK BASED approach.

GAMP Changes

Crowe - 18th Annual Validation Week


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Data Integrity


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Requirements Validation of computerized systems,

Limited and authorized access to computer systems

E-records and signatures

Electronic audit trail

Accurate and complete copies of records,

Instant Availability of e-records

FDA Regulation 21Part CFR 11


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FDA Regulation 21Part CFR 11

The Paperless Advantage

The benefits of a paperless lab •  Improves efficiency, reduces risk

• Positions you better for the future with Regulatory Agencies going paperless

• Streamlines the review process for faster turnaround times

• Maintains a complete audit trail

• Reduces the cost of archiving paper and the risk of lost or damaged documents


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Keeping Up With Regulatory Trends

Best in class companies – keep current with the latest FDA and USP directions and

regulations on analytical instrument qualification

– continually review and adapt their corporate master validation plan to evolve with advancing technology

– take a “risk-based” and “science-based” approach to define the exact tests necessary for qualification

– document and demonstrate a state of control across their manufacturing organization

Questions ?


Keeping up with current regulatory trends

Documents

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