Biopharmaceutical Regulatory R equirements

1. Biopharmaceutical Regulatory Requirements

2. Marketing Authorization for Chemical Entities • MoH Federal Commission for the Protection against Health Risks (COFEPRIS) responsible for drug testing and approval • New drug submissions required to undergo safety, efficacy and quality testing • All generics now required to submit bioequivalence tests • Re-registration required every 5 years (elimination of similares) • COFEPRIS actively monitors availability of unapproved/sub-standard drugs • Recent delays in approvals; 2011-12 new target maximum approval time 180 days • COFEPRIS observes and has adopted guidelines of International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)

3. Removal of Similares from the Mexican Market • Similaresformalized in 1998 reform to General Law on Health • Reform identified three classes of drugs approved by MoH (innovative, interchangeable generics and similar generics) • Similaresdid not undergo bioequivalence tests; not sanctioned as interchangeable with the original drug • Accounted for 36% of medicines sold in private sector in 2002 • Quality and safety debate over non-bioequivalence tested products in both public and private sectors 2002-2005 • Effort to phase out similares from the market, 2005-2010 • 2005 amendment to General Law on Health, Art.376 required all generics to undergo bioequivalence tests • All generics registered prior to 2005 had to be re-registered using bioequivalence tests by 2010 • Not yet fully implemented; severe delays in re-registration (1,000 applications remaining in Oct 2012)

4. Marketing Authorization for Biologics and Biosimilars • Biological drugs undergo the same procedure and testing requirements as new chemical entities • “Biocomparables” (biosimilars) pathway came into force in 2012 (Mexican Health Law, Art 222bis and COFEPRIS guidelines) • Mexican biosimilar pathway de facto resembles that used by the European Medicines Agency • Biologic similares(bio-similares) being phased out along with other similares • RDP protection/periods do not exist for biologics and biosimilars