13/14 April 2021
GMP News No. 864
Warning Letters Report 2006
After the warning letters addressed to manufacturers of medicinal products had decreased in number over the previous five fiscal years, this trend seems to have come to a halt. In the last fiscal year (October 2005 to September 2006), 20 warning letters were issued compared to 17 in the (fiscal) year before. The number of warning letters to manufacturers of blood and blood products has practically remained the same. The greatest part of the warning letters is still directed at manufacturers of medical devices; however, their number has slightly gone down.
As to their subjects and frequency, the deficiencies are about the same as in 2005. Again, the most frequently referenced paragraphs of the Code of Federal Regulations (CFR) are:
However, one citation that was last mentioned in a warning letter of August 2004 and not heard of after that has reappeared surprisingly among the most frequent deviations: Laboratory Records! As many as 6 warning letters feature this deviation with reference to the corresponding CFR paragraph 211.194. The following original quotations explain in detail which facts were considered to be non-compliant with current GMP.
"Laboratory records did not always include a description and identification of the sample received for testing, the date the sample was taken; the date the sample was received for testing and the data derived from the testing."
"There were not always the initials or signature of a second person showing that the original records have been adequately reviewed for accuracy, completeness, and compliance with established standards."
"Laboratory records do not include a complete record of all data secured in the course of each test, including all graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific drug product and lot tested. Review of stability data by our investigative team disclosed that your firm did not maintain documentation of conditions and settings used for analysis nor the complete raw data."
Evidently, inappropriate raw data handling is a reality faced by FDA inspectors more frequently again.
The following table places the 5 most frequent deficiencies of the fiscal years 2005 and 2006 next to each other.
The five most frequent GMP deviations in the warning letters issued during fiscal year 2005 and 2006 respectively.
It is striking that the laboratory control system is mentioned so
often, namely with such pivotal functions as "testing and release for
distribution", "laboratory records" (especially raw data
handling) and, of course, like in the previous year, "stability
Do you want to learn more about FDA Compliance? Then we recommend the following new Training Course:
With regard to the most frequent deviation (21 CFR 211.22 - Responsibilities of Quality Control Unit) we are currently preparing the Training Course "FDA Compliance in Analytical Labs". Please send an e-mail to info (at) gmp-compliance (dot) org if you are interested in this course.
The most frequent statement regarding 21 CFR 211.22 was: "Failure to
thoroughly investigate the failure
21 CFR 211.42 (Design and Construction Features) was among the Top Five Deviations in 2005. A 4-day intensive GMP Education Course will inform you about the current GMP requirements:
As Quality Risk Management is one of the key elements of the new FDA cGMP approach, we recommend the following courses: