Differing Assessments within a Company are a poor Basis for an FDA Inspection

In a recent Warning Letter, the FDA criticises the lack of airflow visualisation and smoke studies, as well as poor maintenance of facilities - why?

Citing 21 CFR 211.113 (control of microbiological contamination) and 21 CFR 211.58 (maintenance), the FDA criticises the lack of airflow visualisation and the absence of smoke studies. The RABS (Restricted Access Barrier System) was modified, but according to the validation department, smoke studies would not have been necessary. The in-house engineers disagreed, however, and recommended smoke studies. Interventions were also not covered by smoke studies to demonstrate that unidirectional airflow was still assured. Deficiencies in the maintenance of the cleanrooms were also addressed. During the inspection, peeling paint was found on the walls and plastic parts on the floor.

The response letter

In its response letter, the company concerned committed to carrying out airflow visualisation studies in accordance with a plan (form). The change control procedure is also to be revised.

The FDA's requirements

The FDA would like to know how smoke studies should be carried out in future so that interventions in the aseptic area and design modifications can be evaluated. It then describes in some detail, in the Warning Letter, the criticality of Zone A and the risks to be expected from interventions in the aseptic area. It also explicitly refers in this context to its guidance on aseptic processing. In this case, the FDA even recommends that the company arrange a teleconference with the FDA to discuss the CAPA measures in detail.

Conclusion

In aseptic manufacturing, airflow visualisation and smoke studies are essential for the FDA - and departments within a company should agree on GMP measures.

You can find the full Warning Letter on the FDA website.