Biopharmaceutical Regulatory Requirements 1

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; 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) 2

Removal of Similares from the Mexican Market Similares formalized in 1998 reform to General Law on Health Reform identified three classes of drugs approved by MoH (innovative, interchangeable generics and similar generics) Similares did 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 Effort to phase out similares from the market, 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) 3

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 4