New Norm to Clear Pathway for Biopharmaceuticals

On December 11, 2014, Mexican Official Norm NOM-257-SSA1-2014 was published in the Official Journal of the Federation (DOF), setting out the requirements for the evaluation, registration, clinical trial authorization, and required specifications for biotechnology medicines. These medicines make up the most innovative drugs for cancer, rheumatoid arthritis, diabetes, and other chronic and degenerative diseases, and account for 35% of all new drug approvals. The complex manufacturing processes for biopharmaceuticals – comprising genetically engineered microorganisms and cells – make them expensive and challenging to replicate on a ‘generic’ level upon patent expiry. Nonetheless, with such high prices, alternatives are essential for public access and the growth of Mexico’s biocomparable market is seen as key. As Francisco Kuri, New Developments Manager of Landsteiner Scientific, warned at the Biopharma 2014 event in Mexico City, an unaffordable and inaccessible medicine is a medicine that essentially does not exist. In Mexico to date, the market entry of biocomparable products has already contributed to price reductions of up to 96% in the field. The approval of the Norm now goes some way to establishing an equal playing field for all biotechnology producers in the hope of allowing the industry to thrive.

Article 222 Bis of the General Health Law provided the definition and legal basis for biopharmaceuticals for the first time in Mexico in 2009. This established that the sale of only innovative and biocomparable biopharmaceuticals would be allowed in Mexico, and all biopharmaceuticals needed to comply with strict tests to demonstrate quality, safety, and efficacy. In October 2011, further requirements for products’ quality, safety, and efficacy validation were specified by virtue of the Regulations for Health Supplies (RIS). Subsequently, Mexican Official Norm NOM-177-SSA1-2013 was published in September 2013, setting out the tests and methods for drug interchangeability, including guidelines and requirements for third parties and research centers performing biocomparability studies. A period of uncertainty amongst the biotechnology community followed, in which companies feared the withdrawal of biogenerics from the market. The implementation of NOM 257 now clarifies the position further and should therefore provide some relief.

The norm sets out the role of COFEPRIS and its New Molecules Committee and Biotechnology Products Evaluation Subcommittee in determining the necessary tests for biocomparables on a case-by-case basis. The mandatory implementation of the quality assurance program, including process validations, product and process auditing, and preventative and corrective actions reporting is also established. Furthermore the norm dictates that authorization of clinical trials to use biotechnology drugs will follow the same process as any other pharmaceutical. Pharmacovigilance must be conducted according to NOM220-SSA1-2012 and biocomparability studies according to NOM-177-SSA1-2013. Reference drugs for biocomparability studies must be registered in Mexico and COFEPRIS will publish a list of authorized reference biopharmaceutical drugs online.

Prior to the development of the regulatory framework for biosimilars in Mexico, local companies registered biocomparables under the general generic category. Now that the regulation is approved and implemented, companies must comply with new, stricter requirements in demonstrating their biocomparability in order to renew current registrations. Such measures should reduce the likelihood of disputes similar to that between Roche and Probiomed, which culminated in the withdrawal of Probiomed’s Rituximab biocomparable from the market. To address such scenarios, NOM-257-SSA1-2014 includes a transitory article allowing companies an extended timeframe to meet new requirements and present the necessary tests required by COFEPRIS. This will also create both demand and opportunities for research centers and local laboratories in Mexico to provide services for the complete range of biocomparability studies.

Sandra Sanchez y Oldenhage, Director General of Probiomed, stresses the essentiality of biocomparables in meeting public health needs, with innovative biophamaceuticals representing a considerable strain on the public budget. Beyond even accessibility, on a broader level Sanchez believes that biocomparables will support further research and development by allowing greater reinvestment in future innovations. Mikel Arriola, head of COFEPRIS, has confirmed his commitment to establishing a complete, modern, and transparent rule system for both local and multinational manufacturers of biotechnology with the aim of placing Mexico at the forefront of the industry within Latin America. Former Comissioner of Sanitary Authorization of COFERPIS and industry expert, Augusto Bondani, believes that the new Norm is conducive to achieving a national policy for biotechnology. Looking ahead, Bondani emphasizes that further efforts by the government are essential and should include prioritization of new biopharmaceutical drug applications at COFEPRIS, the opening of the IMSS to clinical trials and biocomparability studies, increased investment of funds through CONACYT, and, following the precedent of Korea and India, provision of fiscal incentives for biotechnology companies.