Medicines: Marketing Authorisation Holders' submission of Nitrosamine risk evaluation, risk assessment and confirmatory testing

AI Summary

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has issued updated guidance for all Marketing Authorisation Holders (MAHs) regarding the mitigation of nitrosamine impurities in human medicines. This regulatory framework, based on Article 5(3) of Regulation (EC) No. 726/2004, applies to both chemically synthesised and biological products across the UK, including Great Britain and Northern Ireland. The primary issue addressed is the potential for nitrosamine contamination during manufacturing or storage, which poses safety risks to patients. Although initial deadlines for risk evaluations (Step 1) and confirmatory testing (Step 2) have passed, MAHs must immediately report any newly identified risks or impurities. Required actions for MAHs include a rigorous three-step process. Step 1 requires submitting risk evaluation outcomes using specific MHRA templates. If a risk is identified, Step 2 involves conducting confirmatory testing and reporting results. Step 3 necessitates submitting variations to the marketing authorization to implement permanent process changes or controls. Companies must also establish Corrective and Preventive Actions (CAPAs) within three years of an established Acceptable Intake limit. Furthermore, MAHs are responsible for ongoing lifecycle management, ensuring that changes in supply chains or manufacturing processes do not introduce new risks. Compliance will be monitored through market surveillance and regular Good Manufacturing Practice (GMP) inspections. Failure to adhere to these requirements or delays in CAPA implementation must be justified and reported to the MHRA as a priority.