Q: I'm designing a sterilization validation and, in general, a sterilization assurance system. All the products that will be sterilized were reviewed by a qualified team and only few products were shortlisted, being the most difficult to be sterilized products. Is it mandatory to select only one "Worst-case product" before entering the sterilization validation (ISO 11135:2014 annex B) or can I start the validation with more than one candidates "worst-case products"? Working with an Overkill approach, I can for example demonstrate the appropriateness of the internal PCD, comparing it with all candidate products in sublethal cycles! Is it mandatory to identify the most difficult to sterilize location within the product? How can I use this information in following validation steps? According to ISO 11135:2014 (8.6) "The PCD shall present a challenge to the sterilization process that is equivalent or greater than the challenge presented by the natural bioburden at the most difficult to sterilize location within the product". In my case I have more than one products / locations but it is possible to analyze whole product (for all candidate products) so I suppose there is no need to identify the most difficult to sterilize location.

A: As a point of information, a “validation” is comprised of an Installation Qualification (IQ), Operational Qualification (OQ), and a Performance Qualification (PQ) (both a Microbiological Performance Qualification (MPQ) and a Physical Performance Qualification (PPQ). If you are specifically talking here about qualifying the delivered lethality to the product, you are technically designing the MPQ. To be acceptable, the review by “a qualified team,” must be performed by an individual(s) that is (are) considered to be a “sterilization specialist(s).” It is not mandatory to select the worst case product before entering the MPQ, but it is mandatory that it is identified and properly qualified before the start of routine sterilization processing. In my opinion, it would be acceptable to identify this in the sublethal run(s) by comparing various products and eliciting data that demonstrates which is the worst case product. If you are then using an external process challenge device (EPCD), then you have to also demonstrate that the EPCD has equal to, or (I prefer) greater resistance than the internal process challenge device (IPCD) and the bioburden. Yes, it is mandatory to identify the most difficult to sterilize location within the product. This is typically done in one of two ways. One is to have this declared by a qualified individual who is a “sterilization specialist.” The other way is through physically demonstrating this with experimentation and data. For the latter method, one of the ways to do this is to seed some devices with biological indicators (BIs) at multiple locations within the device, run the devices through a sublethal cycle(s), and the determine through survivor curve or fraction negative results where is the most difficult location to sterilize.