Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Change of a starting material supplier Comparison of the global post authorization change requirements with focus on the API class of synthetic peptides

Christoph Hoerth (Abschlußjahr: 2018)

Summary
Language: English
From an API manufacturer´s point of view a change of a starting material supplier may be beneficial to reduce the purchase price or to increase the supply chain flexibility and often administrative changes for registered starting material suppliers occur. Starting material supplier changes have a special importance for synthetic peptides as they are more likely to arise for synthetic peptides and have a bigger impact than for small molecules.
The aim of this master thesis is to compare the post authorization requirements concerning synthetic peptides for a change of a starting material supplier in the regions of the three ICH founding members (European Union, Japan, and USA) and in the ICH associated countries Australia and Canada.
For this purpose, the specific requirements to provide details on starting material suppliers in a marketing authorization application for both human and veterinary drugs are analyzed and in a next step the framework for post authorization changes and the regulatory actions needed to change the details are discussed. Finally, possible approaches to minimize the necessity for regulatory actions are evaluated.
The analysis shows that the filing requirements for dossiers for marketing authorization are diverging within the observed regions and within drugs for human and veterinary use. Except for the EU, less information is required for drugs for veterinary use as for drugs for human use and in the majority of the observed regions also pre-starting material information and administrative details must be provided.
As for the filing requirements, also requirements for post-approval changes are diverging: In the USA and Japan, only changes that have an impact on the API quality need approval, whereas in the remaining regions the situation is more complex. For most supplier changes in Australia, in Canada and the EU batch data on API level are required, which is in view of the special aspects of synthetic peptides a substantial regulatory burden.
In order to minimize the need for regulatory actions a combination of several approaches seems to be beneficial: A working change control system for administrative changes and the non-GMP synthesis of starting materials together with adequate quality agreements reduces the number of unwanted changes. An initial marketing authorization dossier that still leaves room for changes can further diminish their number. Also, for compendial substances the use of the CEP procedure can significantly decrease the number of changes if multiple marketing authorizations in Australia, Canada and the EU are affected. However, the regulatory burden can still be so high that an in-house production of starting materials may be preferred, since it is the most efficient way to avoid starting material supplier changes.
Pages: 34
Annexes: 4, Pages: 10