Selection of comparator

1. Selection of comparator Drs. Jan Welink Training workshop: Assessment of Interchangeable Multisource Medicines, Kenya, August 2009

2. Introduction Quality of generics:

3. Introduction Multi-source (generic) drug products must satisfy the same standards as those applicable to the originator’s product. In addition, reasonable assurance must be provided that they are, as intended, clinically interchangeable with nominally equivalent market products.

4. Comparator Introducing the comparator: * a pharmaceutical product with which the multi-source product is intended to be interchangeable in clinical practice. * the selection of the comparator product is usually made at the national level by the drug regulatory authority.

5. Comparator Quality Clinical Pre-clinical Introducing the comparator: innovator product, approved on full documentation: - established safety and efficacy

6. WHAT IS THE DIFFERENCE BETWEEN INNOVATOR AND GENERIC? Physically:

7. BE WHAT IS THE RELATION BETWEEN INNOVATOR AND GENERIC? Scientifically: INNOVATOR GENERIC

8. Choice of the comparator:

9. Comparator Selection by the DRA: • choose national granted innovator for which quality, safety and efficacy has been established (nationally authorised innovator) • choose WHO comparator product from the comparator list (WHO comparator product) • choose innovator product from well-regulated country (ICH et al. innovator) • if no innovator can be identified, choice must be justified

10. Comparator Justification if no innovator can be identified: • approval in ICH- and associated countries • pre-qualified by WHO • extensive documented use in clinical trials (reports) • long and unproblematic post-market surveillance

11. List A and B WHO provides a list with comparator products - information DRA/pharmaceutical companies List A: WHO model list of Essential Drugs - ‘best’ innovator products on national markets List B: Products for which no innovator product could be identified - no equivalence test can be performed - quality, safety and efficacy based upon local, national, or regional pharmacopoeia - innovator products with insufficient information No innovator, but market leader available! ……………………………… ………………………………

12. Decision tree Choosing comparator complex WHO provides criteria decision tree NO YES ? ? YES NO NO ?

13. Decision tree Innovator product known? Consider innovator product as comparator Consider obtaining innovator: List A Innovator product available? Available on local market? Consider innovator product as comparator Consider market leader product Comparator pharmaceutical product of known quality, safety and efficacy + + - + -

14. Decision tree Comparator pharmaceutical product of known quality, safety and efficacy Innovator product known? Present on List B? Follow compendial standard approach Acceptable results? Quality market leader known? Consider market leader product as comparator Consider market leader product Conduct comparative compendial tests on multisource and market leader products Consider second market leader product Consider market leader product as comparator - - + - + + -

15. Bio-creep Annex 11 also written for a single market WHO: cannot be translated in case other countries are at stake national comparator may be the national market leader no problem in that market but others!?

16. Bio-creep Interchangeable Not interchangeable

17. EMEA (Europe) Differentiate between use for single market or many countries! EMEA: For an abridged application claiming essential similarity to a reference product, application to numerous Member States based on bioequivalence with a reference product from one Member State can be made.

18. Prequalification project List of acceptable reference products for the prequalification project for reproductive health List of acceptable reference products for the prequalification project for reproductive health

19. Conclusion - Let quality rules - Comparators helps you into quality - Do not fall in the bio-creep

20. End Thank you for your attention