In this warning letter breakdown, we are going to focus on a recent citation from the FDA in relation to laboratory records and complete data.
Reference From Actual Warning Letter
1. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).
“Your firm did not maintain complete and accurate data from all laboratory testing. Without reliable laboratory data, you cannot assure appropriate decisions regarding batch release, product stability, and other drug aspects of quality. For example:
a. On May 19, 2018, the peak detection function was disabled multiple times during the gas chromatography (GC) residual solvent testing of your incoming active pharmaceutical ingredient (API), (b)(4) batch (b)(4). After reviewing the chromatograms, our investigators noted unknown peaks that were not reported or integrated as required per your procedure.
Our investigators requested your firm to reprocess the sample set sequence, which subsequently showed > (b)(4)% total unknown impurity peaks. You used this batch of API to manufacture multiple batches of (b)(4) tablets which were released to the U.S. market.
This was not an isolated incident. Our investigators also noted unknown peaks which were not reported or integrated during the method transfer of related compounds testing for (b)(4) USP API batch (b)(4). Your firm did this study to support the (b)(4) for (b)(4) tablets.”
Response from the Firm
“In your response, you attributed the root cause to “inadequate knowledge and awareness” by your laboratory personnel. You also stated that a contributing root cause was “the unavailability of a proper SOP on identification of extraneous peaks.” Your response was inadequate. You did not discuss why your analysts did not follow your procedure to integrate known and unknown peaks. Your response also failed to identify the cause of the unknown peaks.”
Learn More About 21 CFR 211.194(a)
Watch the video at the top of this post to learn more about 21 CFR 211.194(a) and how you can prevent getting a warning letter like this, or click on the course below this post to get an overview of our 21 CFR Part 211 Subpart J – Records and Reports online course.