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 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.*
• 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.*
• Chapter 5.1.10 officially became effective on July 1st, 2016. 510(K) submissions have been approved by the FDA using PyroGene^TM rFC assay as a final release test. Lonza has also submitted a comprehensive FDA Master File.

*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.)