Vaccination is now a common and successful method of disease prevention and mitigation around the world. As an injectable product, there is a danger of endotoxin contamination, which could have serious health risks to the person receiving the vaccine. In the United States, such products are regulated under the authority of the Food, Drug, and Cosmetic Act by the U.S. Food and Drug Administration. The regulations may be found in Title 21 of the U.S. Code of Federal Regulations. Under 21 CFR 211.167 it states:
Sec. 211.167 Special testing requirements.
(a) For each batch of drug product purporting to be sterile and/or pyrogen-free, there shall be appropriate laboratory testing to determine conformance to such requirements. The test procedures shall be in writing and shall be followed.
Vaccines are regulated as a biological by FDA’s Center for Biologics Evaluation and Research (CBER). All biological products are required to be tested for pyrogenicity, unless the product is specifically exempted by regulation. Under Part 610 General Biological Products Standards, it states:
Sec. 610.13 Purity.
(b) Test for pyrogenic substances. Each lot of final containers of any product intended for use by injection shall be tested for pyrogenic substances by intravenous injection into rabbits as provided in paragraphs (b) (1) and (2) of this section: Provided, That notwithstanding any other provision of Subchapter F of this chapter, the test for pyrogenic substances is not required for the following products: Products containing formed blood elements; Cryoprecipitate; Plasma; Source Plasma; Normal Horse Serum; bacterial, viral, and rickettsial vaccines and antigens; toxoids; toxins; allergenic extracts; venoms; diagnostic substances and trivalent organic arsenicals.
As an exempted biological, viral vaccines need not be tested in rabbits for pyrogenicity for several reasons. First, there is a possibility that the vaccine itself is incompatible with rabbits, causing the rabbit to die. Secondly, vaccines are meant to stimulate the immune system, and cause a fever in the animal unrelated to endotoxin contamination. Therefore, a different analysis method for pyrogenicity must be used, such as the Limulus Amebocyte Lysate (LAL) Assay, and performed as per the United States Pharmacopeia (USP) General Chapter <85> Bacterial Endotoxins Test.