An interesting FDA Warning Letter concerning the inspection and acceptance procedures for Biological Indicators, used in the site sterilization process.

11th October 2024

New Zealand

 

1. Failure to establish and maintain procedures for acceptance activities, which include inspections, tests, or other verification activities, as required by 21 CFR 820.80(a).

 

For example:

1) Your firm's current incoming inspection and acceptance procedure for Biological Indicator (b)(4) (BI) is not adequately established. This inadequacy could compromise the sterilization process, potentially affecting the safety and effectiveness of the NeoZoline Ventilation Tubes. Your firm discards the Certificate of Conformance provided by (b)(4) with each BI batch, which was requested by the FDA investigator during the inspection. It appears that your firm failed to retain critical documents such as the reconciliation sheet, production batch record, or (b)(4) Certification of Conformance, which are required under your own WI22 "Production QC and Release Product Register," specifically section 2.3, to demonstrate that the product was successfully sterilized. The inspection revealed that your firm does not perform BI Population verification tests on the received BI batches to ensure that the population has not changed during shipping or storage. This is a critical step is necessary to provide a high degree of assurance that the BIs are viable to support verification that finished product is successfully sterilized through the (b)(4) Sterilization process. Additionally, the inspection revealed that critical information such as the batch number and expiration date of the BI used in the sterile load is not documented on the post-sterilization B1 Test Reports, which are used as part of the finished device acceptance and release process.

 

We reviewed your firm's response dated June 13, 2024, and conclude that it is not adequate. Your firm's response indicates that its Initial Action was completed on June 1, 2024. Your firm concluded that a risk analysis of the specific observation indicates no risk to end users for products currently in distribution and manufacturing. That conclusion is based on the following factors:

 

• The (b)(4) Biological Indicator is an off the shelf product from supplier where (b)(4) has claimed compliance with ISO 11138-1:2017 and ISO 11138-2:2017.
• The BI is packaged in a foil pouch designed to protect the product from humidity excursions.
• The pottles are used to store non-sterile Ventilation Tubes hence the sterility of the pottle is not a requirement.

 

Additionally, your firm has outlined a plan with the following actions to be completed by December 1, 2024, which includes the following actions:

 

(b)(4)

Based on your firm's response there is an ambiguity in the definition of the term `pottle' and whether it is required to be sterile or not. (b)(4) your firm's response states that there is no risk for the sterile products manufactured at your facility because the BIs that they use conform to ISO 11138-1:2017 and ISO 11138-2:2017, and that they are in their sterile packaging until they are needed. However, the inspection demonstrated that your firm does not do any testing to verify that the BIs purchased for the purpose of demonstrating that terminal sterilization is achieved, are actually viable when they are used. Additionally, the inspection revealed that they do not capture key data such as BI batch number and expiration date, and thus if a BI falsely indicated that a sterilization was successful, there is no mechanism by which your firm can trace the lots of sterile products back to a failed BI.

 

Additionally, your firm did not include documentation or evidence of the corrections or corrective actions because they are in progress and have not been completed. Additionally, given the observations described above, your firm has not provided a commitment to conduct a retrospective assessment of all finished devices whose sterilization was verified using Biological Indicator (b)(4) to determine whether sterility was compromised.