Biological Reactiviy - USP Chapter is undergoing Revision

The USP has published a series of proposals for revision of existing chapters in the issue 49(2) of the Pharmacopoeial Forum. This concerns among others also chapter <87> "Biological Reactivity Tests, In Vitro". The proposal for revision is based on the version of this chapter published on 1 August 2016. It has to be taken into account that this means that the proposal published in PF 47(4) is now becoming obsolete. With the revision of this chapter and of its equivalent <88> "Biological Reactivity Tests, In Vivo" as well as of chapter <1031> "The Biocompatibility of Pharmaceutical Packaging Systems and their Materials of Construction" and with the omission of chapter <1184> "Sensitization Testing" the USP wants to accomplish several objectives. One of the objectives is to reduce the amount of redundant testing and another one is to refine the type of testing performed. This is to better align the tests with the potential risk, and replace in vivo testing with in vitro testing whenever this is possible. A further objective is to utilize other information using a risk-based approach focused on the knowledge of the material and pharmaceutical application.


The new draft is divided into six sections:

1. Scope
2. Preparation of Extracts
3. Cytotoxicity Tests
4. Skin Irritation Tests
5. Genotoxicity Tests
6. Appendices

The Agar Diffusion Test was removed from the list of cytotoxicity tests and the Neutral Red Uptake (NRU) Test was added to this section in the new document.

Newly added was also the Skin Irritation Test as well as the following genotoxicity tests:

  • Ames Bacterial Reverse Mutation Assay 
  • Mammalian Cell Genetic Toxicity Tests 
  • Chromosomal Aberration Test 
  • Gene Mutation Test 
  • Micronucleus (MNvit) Test


The objective of the chapter is to describe the in vitro tests which are designed to determine the biological response of cells to extracts of elastomers, plastics, and other polymeric materials used in packaging and delivery systems for medicinal products/drugs and packaging of combination products. This applies to the products regulated by the US FDA's Center for Drug Evaluation and Research (CDER). For combination products, where the packaging or delivery system is considered a device-constituent part, these are out of scope.

Further information is available on the website of the Pharmacopoeial Forum after registration.

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