I like to keep an eye on FDA Warning letters, especially for anything related to sterilization process or equipment issues. This one has recently popped up, dated 5th June 2024.  

 

1. Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes [21 CFR 211.113(b)]. For example:

a. The aseptic processes used to manufacture your products have not been validated (e.g., by performing media fill simulations). These products purport to be sterile and are expected to be sterile.

b. The (b)(4) sterilization process used for equipment that comes into direct contact with your products has not been adequately validated. For example, you have not defined the optimal parameters and conditions, including the load configuration for sterilizing equipment such as the small instruments (e.g., forceps), glass beakers, and sometimes PPE, used in aseptic processing of your products.

 

This for me is really an own goal for this company, (based in the US).  GMP expectations in this matter are quite clear: -

In PDA Technical Report No.01, (section 4.4.1.3) it requires porous load patterns to be established after OQ prior to beginning PQ, ensuring items are loaded within the useable chamber space and orientated to aid air removal, steam penetration and condensate drainage, etc.  Loading instructions should be documented.

 

In the EU, Annex 1, validated loading patterns should be established for all sterilisation processes and load patterns should be subject to periodic revalidation. Maximum and minimum loads should also be considered as part of the overall load validation strategy, (clause 8.38).  Routine operating parameters should be established and adhered to for all sterilisation processes, e.g. physical parameters and loading patterns, (clause 8.40)

 

There should be mechanisms in place to detect a sterilisation cycle that does not conform to the validated parameters. Any failed sterilisation or sterilisation that deviated from the validated process (e.g. have longer or shorter phases such as heating cycles) should be investigated, (clause 8.41).

 

Need help in defining and qualifying your sterilization load configurations?  Worried you may not comply.  Reach out to me here and avoid an audit observation.