USP <88> - Biological Reactivity Tests, In Vivo

What it says

General Chapter <88> describes in vivo biological reactivity testing using animal models to assess material biocompatibility, establishing a classification system, Class I through VI, for plastics based on the extent and type of testing performed, with higher classes reflecting more extensive testing appropriate to more direct or prolonged patient contact.

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

What it means in practice

• The Class I through VI system provides a structured way to match testing rigor to actual use risk, with materials intended for more direct or prolonged contact with the drug product or patient generally requiring the more extensive testing associated with higher classification levels.
• This testing typically follows, and is informed by, in vitro results under Chapter <87>, with in vivo testing reserved for materials and applications where the lower-cost in vitro screening is insufficient to fully characterise biocompatibility risk.
• Container-closure and other manufacturing component qualification decisions should reference the appropriate plastic class for the material's actual intended use, connecting this classification system directly to broader container-closure qualification expectations.

What inspectors look for

• Whether the plastic class testing performed for a given material is appropriate to its actual intended use and degree of patient or product contact.
• Whether classification testing results are documented and support the specific material's qualification for its intended pharmaceutical application.
• Whether a material substitution is assessed against the same classification requirements as the original qualified material, rather than assumed equivalent without testing.

Related regulations