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FDA issues guidance on co-crystals and impurities Posted 23/03/2018

The US Food and Drug Administration has finalized new guidance establishing co-crystals as a drug product intermediate. The agency has also released new information on when to submit elemental impurity data, acknowledging that new guidelines on reporting elemental impurities had slowed approvals in January 2018.

The guidance on co-crystals provides applicants planning to submit new drug applications (NDAs) and abbreviated new drug applications (ANDAs) with information on the appropriate regulatory classification of pharmaceutical co-crystal solid-state forms.

Regulatory classification of pharmaceutical co-crystals
Date: February 2018
www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm281764.pdf

Co-crystals are crystalline materials composed of two or more different molecules, typically active pharmaceutical ingredient (API) and co-crystal formers (coformers), in the same crystal lattice. Co-crystals can be tailored to enhance drug product bioavailability and stability and to enhance the processability of APIs during drug product manufacture. 

For NDAs and ANDAs for products containing a co-crystal form evidence must be submitted to prove that both the API and coformers are present in the unit cell, where both the API and coformer have ionizable functional groups it must be shown that the component API and coformer co-exist in the co-crystal which interact non-ionically and that the API dissociates from the co-crystals before reaching the site of pharmacological activity.

With respect to elemental impurity data, the agency released new information on the guiding principles and approaches for establishing drug substance and drug product impurity acceptance criteria for non-mutagenic impurities in NDAs, ANDAs and biologics license applications (BLAs), based on the consideration of clinical relevance.

Establishing impurity acceptance criteria as part of specifications for NDAs, ANDAs, and BLAs based on clinical relevance MAPP 5017.2
Date: 18 January 2018
https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProcedures/UCM590073.pdf

Low approvals for generics in January 2018 (just 25, down from 78 in December and 84 in November) had been linked to a new USP requirement on documentation of elemental impurities, as outlined in a draft guidance document from June 2016: ‘Control of Elemental Impurities in Drug Products’.

This new information hopes to help sponsors more easily determine impurity acceptance criteria and reduce the number of rejections due to inadequate information on impurities.

Related article
FDA evaluation of impurities in generics

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Source: US FDA

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