The transition between tests that measure the same entity (e.g., LAL cascade) can be made by comparing the two tests to verify the equivalence of the new method. The comparison of the limit of detection and inhibition/enhancement is fundamental. The sensitivity of the new method can be evaluated on spiked product samples. In addition to using spiked samples, a battery of field samples of product found to be positive may be a good source for comparing results from the methods. The method validation should also attempt to address the variability found in the normal use of the method and the manufacturing environment (e.g., source materials or seasonal changes).
For drug, animal drug, and biological products, the transition to a new method should be submitted in a prior approval supplement (PAS). Alternatively, once a firm has established a general method for making the transition between tests, it may submit the method for review in a PAS—comparability protocol (CP). The CP should describe, in detail, the methods used to transition between assays and the acceptance criteria used to establish the equivalence of the new method. After approval of the CP, results of implementation of the CP may be directed to be reported in a reduced reporting category (Supplement—Changes Being Effected or Annual Report or Special Report (21 CFR 314.80)). The firm should maintain the study protocol, final report, and all data at the facility for FDA review. The firm should confirm the filing process with the appropriate review division before submitting a CP. For Class III devices, the transition to a new assay requires a 30-day notice filed under 21 CFR 814.39(e). Manufacturing changes for Class I and II devices should be in accordance with the quality system regulation, 21 CFR part 820. Design control, production and process control requirements can be found at 21 CFR 820.30, 21 CFR 820.70, 21 CFR 820.72, and 21 CFR 820.75.
For devices, a 30-day notice may be appropriate for changes to quality control testing used on incoming components, raw materials, the in-process device, or the finished device, including performing end-product pyrogen testing on nonsterile samples prior to sterilization. [25] Manufactures of medical devices should demonstrate a sensitivity that is consistent with the route of administration for the device and the type of body contact. Manufacturers may use another endotoxin test after demonstrating a reproducible correlation between methods and the USP reference standard.
