Accepted by several global regulatory authorities including the FDA and the European Pharmacopeia, the recombinant Factor C method is a recognized, comparable endotoxin detection method to LAL-based assays. USP 28-NF 33 General Notices states that alternative testing methods, such as recombinant Factor C (rFC) can be used if the alternative method provides advantages in accuracy, sensitivity, precision, selectivity, or adaptation to automation.
- In Jan 2019, recombinant Factor C (rFC) has been listed and described as a new compendia method for bacterial endotoxin testing in the Chinese Pharmacopeia, following the EP, JP, and USP. The 4th version of the Chinese Pharmacopeia will be effective in 2020
- In December Dec 2018, The European Pharmacopeia released a draft of their new compendial Chapter 2.6.32 that is dedicated to the recombinant Factor C method
- In September 2018,the U.S. Food and Drug Administration approved the first drug released using a recombinant method for endotoxin testing instead of traditional LAL-based methods for a monoclonal antibody drug treatment for the prevention of migraines in adults. Read Press Release
- Chapter 5.1.10 officially became effective on July 1st, 2016. 510(K) submissions have been approved by the FDA using PyroGeneTM rFC assay as a final release test. Lonza has also submitted a comprehensive FDA Master File
- In July 2015, rFC became officially recognized by the European Pharmacopoeia (Ph. Eur.) as an alternative endotoxin detection methodology to the LAL and Rabbit Pyrogen Tests in the new draft of Chapter 5.1.10*
- In June 2012 the FDA issued the document “Guidance for Industry Pyrogen and Endotoxins Testing: Questions and Answers” which allows for the use of a recombinant Factor C based assay as an alternative to LAL-based assays*
*The rFC assay will still be considered an “Alternative Test”, subject to the validation requirements of USP <1225> or ICH Q2B. Regulatory authorities will accept the test results of the recombinant Factor C assay, but a validation study must be performed for each product that will be tested using this method. (Validation studies are used to compare the alternative and compendial method, and verify the equivalence between the two methods of the assay. Post-validation, it is necessary to follow up with the appropriate regulatory filing for the drug product or device.)