How to deal with Indefinite Legal Terms in GMP Regulations?

Recommendation

23/24 March 2021

Live Online Training: GMP and Quality Requirements for Radiopharmaceuticals

The GMP regulations contain many indefinite legal terms. Procedures and processes should be appropriate, regularly repeated, or sufficient. To be precise, this can also be found as a requirement in the EU GMP Guidelines Part I, Chapter 2 (Personnel). For example, the general requirements state: "The manufacturer should have an adequate number of personnel with  the necessary qualifications and practical experience." The US American regulations in 21 CFR 211.25 (c) specify similar requirements: "There shall be an adequate number of qualified personnel to perform and supervise the manufacture, processing, packing, or holding of each drug product."

Example of an FDA Warning Letter

A current Warning Letter shows that those general legal terms should be taken seriously.

The FDA criticised the company Centurion Laboratories for performing insufficient cleaning (product residues on cleaned apparatus) and maintenance (holes in an air filter) as required in 21 CFR 211.67. According to the company's explanation, this was due to a shortage in manpower. So they stated that they did not fulfill 21 CFR 211.25 (c).

Concretisation of indefinite legal terms

Why are there so many indefinite legal terms in the GMP regulations? The idea behind GMP is to set a goal, but to leave the flexibility for companies to adapt it as individually as possible to their products and processes. One way to find such an individual product- and process-specific solution would be to carry out a risk analysis in order to define the undefined legal terms with concrete measures on the basis of a rationale. The implementation (e.g. specifications in SOPs) and control (e.g. via self-inspections) are then carried out within the framework of the quality management system.

You can find the complete Warning Letter on the FDA Website.