"Production Record Review" - The most frequently cited Paragraph in FDA Warning Letters

In the past Fiscal Year (FY 2011, from October 2010 through September 2011) the US Food & Drug Administration (FDA) issued a total of 39 Warning Letters to domestic and foreign drug manufacturing companies. That is nearly as many as in the Fiscal Year 2010 in which the authority forwarded 41 Warning Letters.

After analysing the Warning Letters the amazing fact is that the same GMP deficiency has been observed for the 4th time already - and that is the violation against the requirements defined in 21 CFR 211.192 "Production Record Review". The according wording in the Warning Letters with regard to this CFR paragraph can be summarised as follows:

"Your firm has not thoroughly investigated the failure of a batch or any of its components to meet its specifications"

Another interesting detail can be noticed after a more detailed analysis: about a Third of the companies violating the requirements laid down in 211.192 are companies located outside the US (at least for the last three Fiscal Years).

The following table illustrates these findings in further details:

Violation against 21 CFR 211.192

Warning Letters in Fiscal Year

Companies in the US

Companies in Europe

Companies in other Countries



3 (UK, Sweden, Poland)

4 (Australia, Canada, India, Israel)



2 (Belgium, France)

4 (Canada, India, Singapore, Venezuela)



1 (UK)

4 (Brazil, Canada 2x, India)




2 (India)

Quite interesting is the fact that the share of foreign, not US-based companies (drug product manufacturers) receiving a Warning Letter is even higher than in the year before. From the 39 letters issued in the Fiscal Year 2011, 12 were sent to companies outside the US:

Europe: Germany, UK, Poland, Sweden

Other countries: Australia, Canada, China (2x), India (3x), Israel

In the Warning Letters issued to the two Chinese drug manufacturers no CFR paragraphs were cited. These companies are also neither registered nor do they have medicinal products listed at the FDA - as required in 21 C.F.R. 207.40 and in the Federal Food, Drug, and Cosmetic Act ("The Act") § 21 U.S.C. § 360(i), Part 501(i)

By the way - most of these 12 not US-based companies are manufacturing sterile medicinal products.

For the past 10 years, Concept Heidelberg has been collecting and systematically analysing the FDA Warning Letters issued to manufacturers of medicinal products, blood and blood processing products as well to API manufacturers.

Centrepieces of the annual analysis are the excerpts from the respective original Warning Letters - that are reduced so they are easily readable without neglecting the context in which the GMP deficiency was observed. 

The entire Warning Letters Report for the Fiscal Years 2011 will be issued on 16 January 2012. It is part of a complete analysis of the past 10 years which can be purchased in form of the "FDA Navigator CD" for 399,- Euros.

Reservations can already be submitted now. Please send an eMail to info@gmp-compliance.org

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

Go back


Stay informed with the GMP Newsletters from ECA

GMP Newsletter

The ECA offers various free of charge GMP newsletters for which you can subscribe to according to your needs.

To subscribe, please click here.