oos guidance Essay

Submitted By jammer66
Words: 1922
Pages: 8

OOS
Guidance
September 6, 2013

Sept 6, 2013

1

Overview








cGMP’s 21 CFR 211.192
U.S.A. vs. Barr Laboratories, Inc.
Able Laboratories
Reportable Results
Specifications
OOS flowchart
Specific OOS topics
Sept 6, 2013

2

Specific Topics






OOS definition
Initial and full investigations
Testing and retesting
Sampling and resampling
Averaging and Outliers

Sept 6, 2013

3

cGMP’s 21 CFR 211.192
• “Any unexplained discrepancy of the failure of a batch or any of its contents to meet any of its specifications shall be thoroughly investigated, whether or not the batch has already been distributed.”

Sept 6, 2013

4

cGMP’s 21 CFR 211.192
• “The investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy.
• A written record of the investigation shall be made and shall include the conclusions and follow-up.” Sept 6, 2013

5

Barr Court Case
• Civil action by FDA, June 12, 1992.
• Judge Alfred M. Wolin
• Can the FDA expand the cGMP’s interpretation into the statistical areas of outliers, retesting, resampling, averaging and sample size and other areas of failure investigations, …”
Sept 6, 2013

6

Barr Background
• “The current conflict surrounding these rules is best characterized as a confrontation between a humorless warden and his uncooperative prisoner. … These witnesses revealed an industry mired in uncertainty and conflict, guided by vague regulations which produce tugs-of-war of varying intensity.” Sept 6, 2013

7

Able Laboratories
• On May 23, 2005, Able labs issued a Class
II recall of all of its 46 drug products
• The company immediately suspended operations and laid off 200 employees.
• The stock price in the last two weeks of
May dropped by more than 90%.
• The company went out of business.
Sept 6, 2013

8

OOS Philosophy
• “Testing lies at the heart of a drug manufacturer’s successful operation.
Through testing companies validate their processes and ensure the quality of batches for release.” Judge Wolin
• If we can’t trust our measurements, we don’t have anything.
Sept 6, 2013

9

Draft Version
• 30 September 1998
• “Guidance for Industry – Investigating Out of Specification (OOS) Test Results for
Pharmaceutical Production”
• Submitted comments by 30 November 1998
• These comments can be inspected by going to the FDA offices.
Sept 6, 2013

10

Final Guidance
• 12 October 2006 in the Federal Register
• FDA authors include:
– Richard Friedman – Director of the Division of
Manufacturing & Product Quality
– Paul Haynie is responsible for the Guidance
– (301) 827-9020
– Hayniep@cder.fda.gov
Sept 6, 2013

11

Controversial Topics








Definition of reportable values?
Use of averaging?
Number of retests?
Second analyst?
Use of outlier testing?
What specification limits?
Defining testing into compliance?
Sept 6, 2013

12

OOS Definition
• “… the term OOS results includes all test results that fall outside the specification or acceptance criteria established in drug applications, drug master files, official compendia, or by the manufacturer.
• Two Major Issues:
– What test results?
– What specifications?
Sept 6, 2013

13

Scope
• “These laboratory tests are performed on active pharmaceutical ingredients, excipients and other components, in-process materials and finished drug products.
• “Laboratory testing … is necessary to confirm that components, container and closures, in-process materials and finished products conform to specifications, including stability specifications.
Sept 6, 2013

14

Scope
• This guidance applies to chemistry-based laboratory testing of drugs regulated by
CDER.
• “The term also applies to all in-process laboratory tests ….”
• “… applies to in-house testing of drug product components that are purchased …”
Sept 6, 2013

15

Reportable Values for Out-of-Specification
Test results
Lynn Torbeck
Pharmaceutical Technology
Vol. 23, No. 2, February 1999
Special