Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Different Salts of a Drug Substance - Comparison of Regulatory Pathways in the EU and USA ***

Dr. Brita Schulze (Abschlußjahr: 2016)

Summary
Language: English
The development of a different salt (pharmaceutical alternative) pertaining to an already approved drug substance can have various reasons such as a line extension or freedom to operate.
Medicinal products containing a pharmaceutical alternative will undergo different regulatory pathways in the EU and US. In the EU an application is possible as pure generic product, as a hybrid application or based on a full dossier. In the USA such medicinal products are typically approved as 505(b)(2) NDA. As a consequence, the information to be provided by the applicant on the new medicinal products can vary significantly.
The thesis analyses the following cases where medicinal products with different salts of a drug substance have been approved: amlodipine, clopidogrel, pemetrexed, diclofenac and perindopril. Based on the information which was publicly available for these examples, the following recommendations are made:

1. in the EU, for BCS II and IV compounds bioequivalence between the original product and the generic product containing a different salt should be demonstrated with at least two studies, one in the fasted and on in the fed state
2. the public assessment report should be available from the respective competent authority
3. labelling and the outer packaging of products containing different salts should clearly point to differences in handling or storage
4. competent authorities should consider to request a post-approval efficacy or safety study, respectively
5. misleading branding (e.g., one brand is used by one company to cover products with significantly different properties) should be avoided
6. multiple pre-clinical studies on the same pharmaceutical alternative should be avoided.

Pages: 52
Annexes: 0