Warning Letters Report 2010: Laboratory Controls and Analytical Methods again among Top Five GMP Deviations

Since 2002, CONCEPT HEIDELBERG has been analysing the Warning Letters annually, which the FDA issued to drug and API manufacturers after an unsatisfactory GMP inspection. Meanwhile, we have collected a large Warning Letters database covering the last 9 fiscal years (a fiscal year begins in October of the previous calendar year and ends in September of the current year). Over this 9-year period, interesting trends have been noticed.

During the fiscal year 2010 (FY 10= Oct. 2009 until Sept. 2010), 41 Warning Letters were issued, which is 60% more than during FY 09 (only 27 issued Warning Letters).

The Top 5 deviation ranking shows almost the same results as the years before. Following paragraphs have not been complied with:

  •  211.192 Production record review
  •  211.100 Written procedures; deviations
  •  211.22 Responsibilities of quality control unit
  •  211.160 General requirements (Subpart I - Laboratory Controls)
  •  211.84 Testing and approval or rejection of components, drug product containers, and closures

The Warning Letters from last fiscal year also give a large variety of case studies. The description of observed deviations in the original Warning Letters is very detailed. The FDA Navigator's data library contains, among other things, citations from the Warning Letters, which are sorted by CFR paragraphs. This "Original Wording" depicts the quintessence of the deficits. The citations have been shortened for a better readability and understanding of the context. They can be useful to prepare for a FDA inspection.

The "General requirements on Laboratory Controls" topic has always been prevalent over the last 9 years. Still, it belongs to the Top Five topics, the most frequently occurred deviations. "Laboratory Controls" is also a focus of a FDA inspection and as a consequence, investigators find more and more deficits in that field. Following examples are taken from paragraph 211.160. 

"Your firm has not established scientifically sound and appropriate specifications, standards, sampling plans, and test procedures.... For example your firm changed the upper specification range of the final pH for ... drops... without written justification in response to Non-conformance/Discrepancy Investigation Report..."

"Your firm has not recorded and justified any deviation from the written specifications, standards, sampling plans, test procedures or other laboratory control mechanisms.... For example your firm failed to follow your SOP...for expiration dating of "in-house" reference standards."

"Performance of test methods such as loss on drying, residue on ignition and sulphated ash is not adequately documented."

"Method verifications for compendial tests are not performed."

CONCEPT HEIDELBERG offers a complete data analysis of the Warning Letters issued over the last 9 fiscal years (2002 - 2010). You can purchase this analysis as a CD called FDA Navigator - which includes a handbook - for 399, - €. Find more information here.

Dr Gerhard Becker
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

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