Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Differences between EU and US registration requirements for sterile human and veterinary products (quality part) for: a) First filing b) CMC changes

Anja Karstens (Abschlußjahr: 2007)

Language: English

For granting of a marketing authorisation of a medicinal product, it is required to present data to the competent authorities that demonstrate safety, efficacy and quality of the product. With this work any differences in requirements regarding the quality aspects of the drug product between the two markets Europe and USA and also between veterinary and human medicinal products have been identified. This includes original marketing applications as well as subsequent changes to the quality part with focus on chemically defined, sterile drug products.

Procedural differences in marketing authorisation applications include different competent authorities for evaluation of the application, different types of marketing authorisations (national/ decentralised or community authorisations, limited versus indefinitely validity), different review processes (phased review versus traditional review process) as well as varying formats of the application (CTD, NADA, NtA). The options for referencing information submitted in separate files vary between the markets (MF type II to type V, ASMF, CEP). In addition, the change submission processes differ significantly between US and EU regarding procedures, change categories and time frames.

Differences in quality aspects between US and EU include non-harmonised pharmacopoeial requirements (USP/NF versus Ph.Eur.), non-substantial differences in GMP standards, and different requirements for the active content acceptance range at release (± 10% versus ± 5%). For veterinary products the limits on impurities are less stringent than on the human side. Furthermore, the stability data to be provided in the veterinary application need only to cover 6 months (12 months for human applications) and extrapolation may be up to three years (for human products limited to 12 months).

General differences in the application content of US products compared to EU products include provision of raw data, batch records, and non-product specific GMP information like description of the sterile facilities. EU applications on the other hand require the submission of a process validation scheme, summary reports, information on any medical devices, and a GMP declaration on the active material manufacture. For veterinary application the differences in submission requirements are wider due to the fact that the application structure is not harmonised.

Pages: 49