An annual FDA Warning Letter Report is published by the ECA in cooperation
with Concept Heidelberg – the 2005 report will be issued shortly. The
following concentrates on early trends.
As last year already, the paragraph 21 CFR 211.113 "Control of
microbiological contamination" is under the top Ten. While this
paragraph was listed as number 6 in 2004, it ranked third this time.
What does this paragraph mean? It requires written procedures to
prevent microbial contaminations in not sterile and sterile formulations.
It also requires the validation of the sterilisation processes.
The FDA warning letter report contains overall 8 citations relative to
21 CFR 211.113. However, a citation can comprise several deficiencies.
Therefore, the following detailed evaluation mentions more listed
deficiencies than the actual 8 citations:
- Insufficient media fills (4x), three of which are due to not being
representative
- Inadequate validation of the sterilisation processes (2x), one of
which directly mentions "heat penetration"
- Missing or insufficient monitoring (2x)
- No action limit established for the water system
- Insufficient filter validation
- Insufficient "smoke studies" in the clean room
- Missing protective clothing for personnel
- Returning samples into the process
- Design deficiencies for tanks
Deficiencies relative to qualification and validation aspects are
mentioned quite often, but most frequent are mentions with regards to media
fills deficiencies. They directly influence the validation of the
aseptic process. The agency directly referenced an incorrect PQ
when a sterilisation process was evaluated inadequate. The qualification
of clean rooms pertained to insufficient "smoke studies." Reason
for design deficiencies for tanks is insufficient DQ. Further
mentioned deficiencies related to unsatisfactory filter validation.
The following European Compliance Academy (ECA) education courses
relate to this area:
Environmental
Monitoring – Compliant and Reasonable,
18-19 May in Prague, Czech Republic,
The
Validation Manager, 3-Day GMP Education Course,
31 May to 2 June, Vienna, Austria,
Microbiology
for Non-Microbiologists,
19-20 October in Berlin, Germany
Author:
Sven Pommeranz
On behalf of the European Compliance Academy (ECA)
Source: FDA Warning Letter Report (will be published shortly)
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