August 2023 Pharma News Update

Nitrosamines continue to be a topic of discussion within the life sciences sector and this month we look at the EMA’s latest revision of their Q&A. The top story this month relates to the FDA and facility inspection priority ranking system, otherwise known as MAPP.

The US Food and Drug Administration Omnibus Reform Act (FDORA) 2022, required the FDA to adjust each facility’s inspection priority ranking based on the compliance history of other establishments in its country or region.

To implement this legal requirement, on 26 June 2023 CDER revised section 5014.1 of its Manual of Policies and Procedures (MAPP) to require a new risk factor in its site selection model that assesses “the compliance history of establishments in the country or region in which the establishment is located that are subject to regulation under the Food Drug & Cosmetic Act.” This MAPP outlines how the Office of Pharmaceutical Quality (OPQ) will manage the Site Selection Model (SSM) to prioritize manufacturing sites for routine quality-related (i.e., cGMP) surveillance inspections.

The revision also changes the name of the OPQ suboffice Office of Surveillance to Office of Quality Surveillance (OQS). OQS is responsible for producing CDER’s Site Surveillance Inspection List (SSIL) that prioritizes sites for routine surveillance inspections.

The revised MAPP also puts emphasis on sites’ needing to demonstrate that they have an effective quality system by showing “practices at a facility that not only support meeting cGMP compliance requirements to establish and maintain a robust state of control but also promote a quality culture that allows for exceeding this standard.”

On 7 July 2023 the EMA published revision 16 of their Q&A on nitrosamines. This revision amends Q&A 10 to include the Carcinogenic Potency Categorization Approach (CPCA) and the enhanced Ames test (EAT) for establishing AIs for N-nitrosamines.

This revision also adds three additional appendices:

• Q&A 10 Appendix 1, provides a listing the nitrosamines for which AI have been established by the Non-clinical Working Party (NcWP), including new AIs for N-nitrosamines determined using the CPCA
• Annex 2, describes the Carcinogenic Potency Categorization Approach for N-nitrosamines
• Annex 3, describes the Enhanced Ames Test Conditions for N-nitrosamines