Masterstudiengang "Drug Regulatory Affairs"
Master-Thesis
Changes in an excipient manufacturing location and process - an analysis of regulatory implications ***
Agnès Raust-Sutils (Abschlußjahr: 2015)
Summary
Language: English
Pharmaceutical excipients are intentionally combined with one or more active ingredient in a drug product to contribute to the delivery of the active ingredient. The functionality of an excipient is an important characteristic that should remain constant over the time. A change in the manufacturing of the excipient may modify its functionality and may thus have an impact on the final dosage form.
When a significant change involving the manufacture of excipients is carried out, all customers purchasing the excipient have to be informed, so that they can evaluate the impact of the change on the final dosage form. The regulatory authorities also need to be informed about the nature of the change and its impact on excipient quality, if information about the excipient is filed in a Drug Master File (DMF) in the U.S. or Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP).
In this context the IPEC-Americas® published a Significant Change Guide for bulk pharmaceutical excipients in 2006, a voluntary guidance for the pharmaceutical excipient industry. It was developed to give recommendations and a process to evaluate the significance of a change in the manufacture of an excipient and to determine the need for informing customers or/and authorities about the change.
The IPEC Significant Change Guide achieves its goals: it provides a practical assistance for the excipient manufacturer and a well-defined framework to assure an efficient change management. The notification of the users of the excipients and the regulatory authorities is a guarantee for the patient safety. Indeed the users of the excipient need an accurate evaluation of the risk related to the change to assess the resulting impact on the final dosage form. The risk will be also taken into account by the regulatory authorities when reviewing applications for the final dosage form.
The third revision of the guide is a harmonized version between IPEC-Americas® and IPEC Europe and represents a real improvement compared to the limits of the previous versions. The decision process is clarified by limiting the classification of the changes into 2 levels and by installing the concept of risk management for the evaluation of the impact.
Pages: 62