Hi,

Find the FDA answer below:

" Yes, firms may use alternative methods and/or procedures if they provide advantages in terms of accuracy, sensitivity, precision, selectivity, or adaptability to automation or computerized data reduction, and in other special circumstances. Such alternative procedures and methods should be validated as described in the USP General Chapter , Validation of Compendial Procedures,[17],[18] and should be shown to achieve equivalent or better results.[19] When a difference appears or in the event of a dispute, the final decision is made based upon the USP compendial gel clot method unless otherwise indicated in the monograph for the product being tested.[20]1225>

            Below are two examples of alternative assays.

 (1) Recombinant Horseshoe Crab Factor C Assay    

If a manufacturer chooses to use a recombinant factor C-based assay, then method validation should be in accordance with the requirements of USP Chapter , Bacterial Endotoxins Test, as described in the section for Photometric Quantitative Techniques, and USP Chapter , Validation of Compendial Procedures. [21]1225>85>

(2) Monocyte Activation Type Pyrogen Test

Product-specific validation is necessary to establish whether a particular test substance or material is appropriate for evaluation of the monocyte activation method. The validation should include, but is not limited to, interference testing, accurate detection of pyrogen in individual test samples, and, for devices, ability of test system to provide direct contact to the monocytes. (...)

For human and animal drugs, some USP monographs still require a rabbit pyrogen test. Even with such monographs, a firm may substitute an endotoxins test or alternative cell-based test if the firm can demonstrate equivalent pyrogen detection. The appropriate FDA review division will consider alternative methods, such as monocyte activation, on a case-by-case basis. "

Ref:

GUIDANCE DOCUMENT Guidance for Industry: Pyrogen and Endotoxins Testing: Questions and Answers JUNE 2012

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-pyrogen-and-endotoxins-testing-questions-and-answers

Best regards

Tomasz

Kindly check https://www.researchgate.net/publication/330338244_Intricacies_in_the_approval_of_radiopharmaceuticals-regulatory_perspectives_and_the_way_forward

Also check https://www.intechopen.com/books/nuclear-medicine-physics/an-overview-of-pet-radiopharmaceuticals-in-clinical-use-regulatory-quality-and-pharmacopeia-monograp