USP <88> "Biological Reactivity Tests, In Vivo" is currently also undergoing Revision

Recommendation

7/8 May 2024

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Regulatory Requirements and Practical Implementation

Together with a series of further chapters in this subject area the USP has now published a revised version of the chapter "Biological Reactivity Tests, In Vivo" for commenting. The new version is based on the current official version published in 2013 and replaces the proposal published in PF 47(4).

As has already been described in the news on in vitro tests the revision's objectives are to evaluate strategies for performing biological reactivity testing, to achieve a harmonisation with the relevant chapters such as <87> "Biological Reactivity Tests, in Vitro", <1031> "The Biocompatibility of Pharmaceutical Packaging Systems and Their Materials of Construction" and to reduce the amount of redundancies. This also includes the omission of chapter <1184> "Sensitization Testing". Another objective is to achieve a reduction of in vivo tests.

Relevant changes

The key changes concerning the chapter are the following:

• Delete Classification of Plastics because the distinction of plastic materials into six classes (Class I to Class VI) no longer serves a current purpose because in practice only Class VI is now utilized by vendors and end users. 
• Delete Intracutaneous Test. 
• Delete Implantation Test. 
• Delete Safety Tests-Biologicals as the relevant FDA Code of Federal Regulations, 21 CFR §610.11, was revoked on 3 August 2015. 
• In 2.2 Apparatus, add the requirement that the autoclave has the ability to connect to a calibrated resistance thermometer or a calibrated thermocouple and that the autoclave must be calibrated before first use.

The USP stresses that it is also very interested in hearing stakeholder feedback since the changes and potentially their impacts are significant.

Scope

This chapter describes the Systemic Injection Test designed to determine the biological response of animals to elastomers, plastics, and other polymeric materials or their extracts used in packaging systems for medicinal products/drugs and packaging of combination products.

The Systemic Injection Test applies to elastomeric components only if components do not meet the requirements of Biological Reactivity Tests, In Vitro <87>. Elastomers and plastics used in packaging systems for oral or topical products are not covered. Guidance on these packaging materials can be found in "The Biocompatibility of Pharmaceutical Packaging Systems and Their Materials of Construction" <1031>.

Further information is available on the website of the USP after registration.