USP <151> - Pyrogen Test

What it says

Certain pharmaceutical products must be tested for pyrogenic contamination using a rabbit-based biological response test, measuring temperature rise following injection, for product categories where the bacterial endotoxin test described in USP <85> is not considered an adequate or appropriate substitute.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• This test exists specifically for the narrower set of situations where the endotoxin-specific test in USP <85> does not adequately cover all pyrogenic risk, such as certain non-endotoxin pyrogenic contaminants, meaning the two tests are not simply interchangeable options.
• Because this test relies on a live biological response rather than a chemical or enzymatic reaction, its result variability and animal welfare considerations are part of why many products have shifted to endotoxin testing wherever scientifically justified.
• Using this test in place of endotoxin testing, or vice versa, requires a documented scientific justification specific to the product, not simply a preference for one method over the other.

What inspectors look for

• Whether the choice between pyrogen testing and bacterial endotoxin testing for a given product is scientifically justified and documented, rather than selected without rationale.
• Whether test animals and test conditions used meet the chapter's defined requirements for a valid result.
• Whether a product historically tested by this method has been reassessed for whether a validated endotoxin test could now appropriately replace it.

Related regulations