Management circumvents Quality Department in Deviation Classification - FDA Warning Letter

From 6 February to 15 March 2024, the FDA inspected the pharmaceutical manufacturing facility of Wittman Pharma, Inc. in Brooksville and found violations of Current Good Manufacturing Practices (CGMP) for finished drug products, which led to a number of quality risks for the manufactured products. The subsequent 483 letter from the FDA was inadequately responded to, so that the FDA now published the following Warning Letter.

Number of deficiencies

In summary, the following deficiencies were listed in the FDA's Warning Letter :

1. Failures in quality control (in accordance with 21 CFR 211.22)
Quality assurance/quality control (QU) did not ensure that the products met the required identity, strength, quality and purity standards. Drug batches were released without proper product testing and, for example, in the case of colour-changed tablets, management bypassed QU responsibilities and downgraded deviation classifications to ‘minor’ without adequate investigation to eliminate the need for root cause analysis, resulting in non-compliance with CGMP regulations.

2. Inadequate written procedures for production (21 CFR 211.100(a))
The water system used for drug production was not properly qualified, resulting in the presence of harmful microorganisms (Objectionable Microorganisms) such as Burkholderia cepacia. Exceedances of the TAMC (Total Aerobic Microbial Counts) were also not tracked accordingly.  Despite these problems, medicines continued to be manufactured and distributed. Their justification that preservatives offset these risks is insufficient, as the use of preservatives does not render proper manufacturing practices obsolete. 

3. Lack of proper testing of components used (21 CFR 211.84(d)(1))
Your company failed to conduct identity testing for propylene glycol, a component at high risk for contamination with diethylene glycol (DEG) or ethylene glycol (EG), substances known to cause fatal poisoning incidents. Their response that comprehensive testing is not required is inadequate because proper identification testing is required under CGMP, e.g., FDA's Guidance on Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol.
The FDA also emphasises at this point that the argument that there is generally no mandatory requirement for routine testing of raw materials is incorrect, as this is required in 21 CFR 211.84. There it says under (d)(1) ‘At least one test shall be conducted to verify the identity of each component of a drug product. Specific identity tests, if they exist, shall be used.’

Further details can be found directly in the Warning Letter on the FDA website.