Annex 15 - Qualification and Validation

In June 2020, the report "Lessons Learned from presence of N-nitrosamines impurities in sartan medicines" was published. This report provides a number of recommendations aimed at reducing unexpected impurities in human medicines.

One of the reason for the presence of N-nitrosamines was the lack of sufficient process and product knowledge during the development stage and GMP deficiences by active substance manufacturers and insufficient contamination control measures (amongst others).

Manufacturers, importers and distributors of medicinal products. Both for finished medicinal products and active substance manufacturers. The changes primarily affect active substance manufacturers.

Countries that do not have an active membership of the PIC/S and countries that are not part of the European Union.

• Annex 15 will be mandatory for active substance manufacturers,
• Enhanced focus on change control for active substance manufacturers and that quality system element's importance to knowledge management / retention in the organization,
• Extends expectations for validation by 3rd party contractors,
• Increase control over the process by extending the concepts of URS, FAT/SAT, OQ, DQ, PQ, IQ,
• Emphasis on robust process development,
• More guidance on verification of transportation of active substances.

Minor revisions include;

• The use of QRM in the design and validation/qualification of monitoring systems will be emphasised in the general section.