Reinigungsvalidierung in der Wirkstoffherstellung
Prinzipien, Risikoanalyse/Risikobetrachtung, regulatorische Anforderungen und Akzeptanzkriterium PDE-Wert
Originale
Key WordsReinigungsanweisung/Reinigungscheckliste | Risikoanalyse/Risikobetrachtung „Reinigung“ | Bracketing (Apparategruppen, Produktgruppen) | Prüf- und Probenahmeplan | Akzeptanzkriterien (neuer PDE-Wert) | Beurteilung der Validität
Abstract
Cleaning Validation of multi-purpose equipment in API production / Principles, risk analysis/risk assessment, regulatory requirements and acceptance criterion PDE value
The regulatory requirements of authorities (FDA, local German authorities, …) on manufacturing of APIs have steadily increased in the recent years. This has also consequences with view to cleaning of equipment used for API production. This is also required within relevant guidelines to perform cleaning of equipment according to validated cleaning procedures especially when the manufacturing equipment is used to produce different products (multi-product equipment).
In the Cleaning Validation the documented evidence must be provided that a defined and described cleaning procedure meets the requirements reproducibly. As a result of a successful validation routine sampling and the analytical monitoring can be reduced to a necessary minimum.
With regard to the establishment of limits (acceptance criteria) a new approach is given by revision of the GMP- Guide (Chapter 3 + 5 and annex 15) and the PDE-Guideline of EMA which is briefly presented here.
Objective of the following article is to present the methodical execution of a cleaning validation project with regard to multi-product manufacturing equipment in the chemical industry and the special considerations that have to be made. Some new developments in the establishment of limits will be given as well.
Korrespondenz:
Jörg Koppenhöfer, gempex GmbH, Besselstr. 6, 68219 Mannheim, Germany; e-mail: public-relation@gempex.com
Zusammenfassung
Die Anforderungen seitens der Behörden (u. a. der EU, FDA) an die Herstellung pharmazeutischer Wirkstoffe sind in den letzten Jahren stetig gestiegen. In diesem Zusammenhang wird auch verstärkt die Notwendigkeit gesehen, die Reinigung von Anlagen zur Herstellung von Wirkstoffen in der chemischen Industrie nach validierten Verfahren durchzuführen. Dies wird in den entsprechenden Regularien auch gefordert, insbesondere wenn die Anlagen als Mehrprodukte-Anlagen betrieben werden.
Bei der
