Masterarbeit
Different Salts of a Drug Substance - Comparison of Regulatory Pathways in the EU and USA ***
Dr. Brita Schulze (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:
- 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
- the public assessment report should be available from the respective competent authority
- labelling and the outer packaging of products containing different salts should clearly point to differences in handling or storage
- competent authorities should consider to request a post-approval efficacy or safety study, respectively
- misleading branding (e.g., one brand is used by one company to cover products with significantly different properties) should be avoided
- multiple pre-clinical studies on the same pharmaceutical alternative should be avoided.
Pages: 52
Annexes: 0