1. Keeping Up with Current
Regulatory Trends
Carole Crowe
Agilent Technologies
Validation Week IVT18
October 23, 2012
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2. Quality Systems
Guidance for Industry: Quality System Approach to Pharmaceutical cGMP Regulations
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3. 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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4. 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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5. European 2012 PDA/EMA Joint Conference
Compliance:
A prerequisite for
Availability of Medicinal
Products
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6. What is Compliance?
And
How Do We Enforce it?
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7. 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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11. How Do We Enforce It?
Approximately 1 in 6 FDA
483 Inspectional
Observations Results in a
Warning Letter…
Do You Feel Lucky ?
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12. Quality Systems
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13. 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
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14. 4Q Stages of Instrument Qualification…
Does it Does it
Meet your USER Installation WORK as YOU
EXPECTED
Performance
REQUIREMENTS
Qualification Qualification
DQ IQ OQ PQ
Has it been Will it
Design INSTALLED Operational CONTINUE to
CORRECTLY work
Qualification Qualification 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)
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15. Instrument Life Cycle – From a Regulators
6
Perspective 1 Is the Instrument
Re-Qualification Suitable for use
(Justification)
2
Co Policy 5 2 Is it installed
Maintenance Correctly
1 3
IQ
DQ Use 3 Is there an SOP
Are people Trained
OQ 4 Is it Calibrated
Breakdown Method Validation
6
Re-Qualification Repair 4 Failure Mgt.
(Justification)
Impact of Failure
CAPA ?
Justification:
5 Maintenance
Routine ?
OQ - How Often
Frequent Customer Questions RQ – What to include
6 Re-Qualification
/ Calibration
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16. 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”
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17. GAMP Changes
GAMP Good Practice Guide
GAMP - Validation of Computerized
Laboratory Systems, moving away from
7 instrument categories to a fully RISK
BASED approach.
More Flexible:
– Risk Based
– Not Prescriptive
– Will include examples
– Better GAMP - <1058> Alignment
GAMP 5 rev 2 – Flow chart to support use
(Amazon Bestsellers Rank: 1,031,332)
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October 23, 2012
18. Data Integrity
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19. FDA Regulation 21Part CFR 11
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
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20. FDA Regulation 21Part CFR 11
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21. 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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22. 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
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