Cobwebs On Oxygen Analyzer Foil Trans Ox During FDA Inspection

Trans Ox Citations Result in Warning Letter (June 8, 2015)

During a November 13, 2014, through November 20, 2014, inspection of Trans Ox pharmaceutical manufacturing facility at 2543 Morningside Drive, Suite A, West Columbia, South Carolina, an investigator from the U.S. Food and Drug Administration (FDA) identified significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211.

The investigator observed specific violations during the inspection, including, but not limited to, the following:

1. For each batch of drug product, your firm must have appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, before release (21 CFR 211.165(a)). Your firm does not have appropriate documentation.

During our inspection of your facility, we documented multiple incidents of inaccurate batch production records containing erroneous statements, including results that were not derived from analytical testing or from your supplier’s Certificates of Analysis (CoAs).

According to your batch production records, your results were obtained from a “Post Fill Purity Test.” The records are labeled “ANALYTICAL RESULTS OBTAINED BY USING THE (b)(4) OXYGEN ANALYZER.” However, on November 13, 2014, the FDA investigator observed cobwebs between the portable (b)(4) Oxygen Analyzer and the adjacent wall. The general manager stated that your firm does not use the (b)(4) Oxygen Analyzer, which directly contradicts your batch production records.

Further, on November 13, 2014, our investigator reviewed a number of batch records and asked you why all the analytical results reported on these batch production records were identical. Although your batch production records indicate that analytical results were obtained from the (b)(4) Oxygen Analyzer, you responded to the investigator’s question by stating that the values were actually obtained from your supplier’s CoAs. However, the values reported on multiple batch production records disagree with the CoAs for those lots.

a)    For instance, the batch production record for your lot 011514 (supplier lot 515244) states your purity test result on the (b)(4) Oxygen Analyzer was 99.9%. In contrast, the CoA for supplier lot 515244, dated December 23, 2013, states 99.74% purity.

b)    Similarly, the batch production record for your lot 032614 (supplier lot 515240) states your purity test result on the (b)(4) Oxygen Analyzer was 99.9%. In contrast, the CoA for supplier lot 515240, dated March 20, 2014, states 99.84% purity.

In your response, you stated that you have created a Policy and Procedure Manual, which includes Batch Production and Control Records and an Equipment Calibration Schedule. However, your response does not include any retrospective reconciliation of batch production records and CoAs, or testing of lots currently in stock or in distribution. Retrospective assessment is essential to determining if batches released prior to your implementation of new procedures met purity specifications.

COMMENT

Data obtained from testing should reflect the actual testing. The presence of cobwebs was a “give away” as to the non-use of the Oxygen Analyzer. Using data from supplier’s information may be used once one’s own data has demonstrated consistent results with the supplier’s Certificate of Analysis (COA). Then, on a periodic basis (as determined by the firm), additional tests must be performed. 

However, as noted in the above Observation, the purity test result did not meet the result from the vendor’s COA – even though all that was required was a transcription of the data.  

Creating Policy and Procedure Manuals as well as Batch production and Control Records, by themselves, are not sufficient to determine if batches released prior to implementation of new procedures met purity specifications.