TERMINALLY STERILIZED PHARMACEUTICAL PRODUCTS—PARAMETRIC RELEASE (NEW USP<1222>) AND ITS RELATIONSHIP TO THE NEW BRITISH TERMINAL STERILIZATION

Parametric release is defined as the release of terminally sterilized batches or lots of sterile products based upon compliance with the defined critical parameters of sterilization without having to perform the requirements under USP<71> Sterility Tests.

Parametric release becomes possible when the mode of sterilization is 1) very well understood, 2) the physical parameters of processing are well defined, predictable, and measurable, 3) and the lethality of the cycle has been microbiologically validated through the use of appropriate biological indicators or, in the case of ionizing radiation, the appropriate microbiological and dosimetric tests.

The use of parametric release for sterilization processes requires prior FDA approval. It should be expected that the regulatory agencies evaluating submissions including the use of parametric product release would insist upon a well supported scientific rationale for the sterilization process and well documented validation data.

The agencies would need assurance that any marketed sample of product will be sterile and if tested after release would pass the requirements for sterility as found in the General Chapter USP<71>.

It is important to consider the limitations of the USP<71> in the evaluation of terminally sterilized products. The sterility test described in General Chapter USP<71> is limited in its sensitivity and is statistically ill-suited to the evaluation of terminally sterilized products given the exceedingly low probability of finding contaminated units.

Therefore, once a sterilization process is fully validated and operates consistently, a combination of physical sterilization data such as accumulated lethality or dosimetry in combination with other methods, such as load monitors (e.g., biological indicators, thermochemical indicators, or physicochemical integrators), can provide more accurate information than the sterility test regarding the release of terminally sterilized product to the marketplace.

There are four modes of sterilization that theoretically and practically could qualify for parametric release: moist heat, dry heat, ethylene oxide, and ionizing radiation sterilization.

This General Information Chapter (USP<1222>) will first cover the general issues related to parametric release, regardless of the modes of sterilization, and then discuss some specific modes of sterilization. It will also include information on USP<55> Biological Indicators as well as EU “Guideline on the Sterilization of Medicinal Products…” (March 2019). The webinar will discuss why it provides more accurate information than the sterility test regarding the release of terminally sterilized product to the marketplace.

Please plan to bring a team to this Webinar to examine how these issues and their solutions may assist you in more rapidly releasing sterile products from 1 your facilities. Please learn more about this webinar which will be offered through barryafriedmanphdllc.com on Wednesday, April 22 at 12 Noon NY time.