FDA Submission Requirements on Parametric Release for End-Sterilised Products

In the field of end-sterilised medicinal products, parametric release represents an alternative to sterility testing. With the Draft Guidance for Industry "Submission of Documentation in Applications for Parametric Release of Human and Veterinary Drug Products Terminally Sterilized by Moist Heat Processes", the FDA defines its requirements on parametric release within the framework of steam sterilisation that have to be fulfilled to obtain a marketing authorisation.

As a rule, batch release of end-sterilised products requires sterility testing. Due to several causes (small number of samples, low or no growth of microbes on standard nutrient media, etc.), the information value of sterility testing is limited.

Here, parametric release can be performed as an alternative. By means of observing critical sterilisation parameters, ultimately, the assurance that a batch meets the sterility requirement is greater than that achieved with a sterility test.

The use of parametric release must be approved by the FDA. Here, the basis is always the validated sterilisation process (see also Guidance for Industry on Submission of Documentation for Sterilization Process Validation in applications for Human and Veterinary Drug Product). Approval remains dependent on the assessment of the critical process parameters and the way in which they are controlled. It is the applicant's task to assess the risks with regard to product sterility. In the draft Guidance, the FDA defines which pieces of information it expects on the following areas:

  • Control strategies of the terminal sterilisation cycle
  • Risk analysis, process understanding, prior knowledge
  • Documentation on the parametric release process

The complete draft document can be found here.

It remains unclear if, as regards end-sterilised products, in the future the FDA intends to move away from the sterility test towards parametric release as a "standard procedure" - also in view of the PAT initiative. However, the now existing requirements will give rise to the question if the effort necessary for parametric release will be worthwhile.

Dr Andreas Mangel
On behalf of the European Compliance Academy (ECA)

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