The registration dossier (RD) of a hybrid medicinal product may contain additional preclinical and clinical study data.

Rationale: Chapter 7 Section II Appendix N 1 to Marketing Authorization and Expert Assessment of Medicinal Products for Human Use.

What Information Should the RD of Hybrid MP Contain

Module 1

1) In Section 1.8.2 of the RD for generic product, the applicant must provide a summary (maximum 5 pages) of justifications and facts showing the medicinal product is a hybrid product relative to the corresponding original product.

The summary must contain the information about:

• The product,
• The active pharmaceutical substance,
• The dosage form,
• Dosages,
• Therapeutic indications,
• Method of administration versus the original product
• If required, information on bioavailability and bioequivalence of the product

2) Risk management plan in certain cases

3) Justification of why any elements missing in the corresponding sections of the registration dossier for the MP.

Module 2

A special focus of the preclinical and clinical data summary must be placed on the following elements:

1) Summary of the active substance impurity profile and, if applicable, of potential degradation products in commercial batches of the medicinal product.

2) Update of publications about the active substance of the medicinal product. To comply with this requirement, references to publications in peer reviewed journals may be provided.

3)  Previously unknown or the following characteristics of the product or its therapeutic group: general characteristics of the medicinal product to be analyzed in preclinical and clinical reviews (summaries) and supplemented with scientific publications or evidence from additional trials.

4) Additional information demonstrating that the safety and efficacy profiles of the product submitted for marketing authorization are similar to those of the reference product, if there are any differences in the chemical forms of the active substance: salts, ethers, isomers, isomer mixture, compounds or derivatives of the active substance of the reference product.

Module 3

Module 3 of the registration dossier for the medicinal product should be provided in full.

Module 4 and Module 5

Preclinical and clinical study data for the hybrid medicinal drug should be included into the corresponding sections of Module 4 and Module 5.

Expert Evaluation of a Hybrid MP

It is specified in Paragraph 2, Article 59 of the Marketing Authorization and Expert Assessment of Medicinal Products for human use that based on the results of expert evaluation of the registration dossier for a generic or hybrid medicinal product, the expert authority of the member-state must prepare expert evaluation reports following specific templates, according to  Appendices N 8, 10, 12 and 22 to these Rules.

According to paragraph 3 art. 94 of the Marketing Authorization and Expert Assessment of Medicinal Products for Human Use, the evaluation of a registration dossier for a generic or hybrid medicinal product, the authorized body (expert panel) of the reference state should provide the following documents to the authorized bodies (expert panels) of the member states within 60 business days:

• Copies of reports with comments and inquiries to the applicant according to a template as specified in Appendices N 8 and 22 to these Rules,
• Or an interim evaluation report according to the template as specified in Appendix N 11 to these Rules,
• Or copies of inquiries to the applicant.

In conclusion, additional safety and efficacy information is required for the marketing authorization of a hybrid MP for successful benefit-risk assessment.

See more detailed information on the procedure for supplementary studies, required for generic and hybrid medicinal products in our next article.

January 20, 2023