Fundamental GMP Deficiencies at US-American Pharmaceutical Manufacturer

Recommendation

17-19 September 2024

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GMP Compliance and Technology for the Manufacture of Oral Solid Dosage Forms

During the inspection of a pharmaceutical manufacturer in the USA, the FDA discovered fundamental GMP deficiencies which concern - among other things - cleaning of equipment, cleaning validation, the water system and the stability programme.

Deficiencies in equipment cleaning / cleaning validation

The US-American manufacturer produces both medicinal and non-medicinal products (such as hair removal creams or insect repellents) on the same equipment. The FDA sees a great risk of cross-contamination and the associated damage to patients. In response, the manufacturer stated that cleaning validation was under development.
However, the FDA has demanded an immediate stop of the production of pharmaceuticals and non-pharmaceuticals on the same equipment. If the manufacturer intends to continue manufacturing both product types in his facility, he should submit a plan to the FDA on how to separate the areas and dedicate his manufacturing equipment. In addition, the FDA expects a risk assessment for all medicinal products manufactured on the shared equipment. The assessment shall include how the risk of cross-contamination will be assessed, what risks could arise for patients and whether batch recalls are required.

Missing microbiological tests

According to the FDA, the US-American manufacturer has released medicinal products for the American market without testing for the aerobic total bacterial count and objectionable microorganisms. The company then stated that the microbiological specifications will be updated. This is not sufficient for the FDA who expects to receive detailed specifications for each of the company's medicinal products as well the microbiological testing of the retain samples of all batches that are on the market within expiry.

Deficiencies in the pharmaceutical water system

The FDA also criticises the pharmaceutical water system. The manufacturer uses water from a non-validated system to manufacture its OTC products and for cleaning the equipment. According to the FDA, the design, control, maintenance and monitoring of the system are inadequate.

In its response, the manufacturer stated that he was improving the procedures. For the FDA, this is totally inadequate and an assessment of the risk of using water from a non-validated system is expected, as well as validation of the whole system and improvements in control and maintenance.

Deficiencies in the stability programme

According to the FDA, the company's stability programme is not adequate to demonstrate the shelf-life of its products. The method validation of numerous products lacks specific considerations of known APIs' degradation products. Moreover, the time intervals for conducting stability testing haven't been complied with several times.

Conclusion

Similar GMP deficiencies had already been noticed by the FDA during an inspection in 2016. The FDA regards repeated GMP deficiencies as a lack of management oversight.  In addition, the company, which operates as a CMO, had failed to register with the FDA for many of the manufactured products. The FDA recommends that the US manufacturer engage a GMP consultant to remedy the GMP deficiencies.

To find out more please also see the FDA's Warning Letter to Ecometics.