On June 11, 2009, the Mexican Congress passed and published an amendment to the Mexican Health Law adding Article 222 Bis, which was enacted in the first weeks of September 2009. The new Article addresses the definition and regulation of biotechnology-related drugs, which is a longstanding and complex issue.

As long as they have existed, biologic drugs have been regulated in essentially the same manner as chemical synthesis drugs, raising the question of whether generic versions of biotechnology-derived molecules were entitled to seek regulatory health and marketing approval through the same channels and with the same requisites as chemical synthesis molecules. Article 222 Bis provides a clear distinction between chemical and biologic pharmaceutical products and also establishes the criteria with which non-innovative ("bio-comparable", as defined by the new Article) versions of these drugs must comply in order to obtain regulatory approval.

Bio-comparables defined

The newly added Article 222 Bis begins by defining a biotechnology drug as any substance that has been produced by molecular biotechnology procedures and has a therapeutic, preventive or rehabilitating effect, that is available in a pharmaceutical form and can be identified by its pharmacological activity and by its physical, chemical and biological properties. It further states that innovative biotechnology medicaments may be used as a reference for bio-comparables.

The Article continues by defining the criteria for obtaining regulatory approval for innovative biotechnology medicaments, wherein it provides that they must comply with all requisites and proof that show quality, safety and efficacy of the product in accordance with all regular dispositions of the Law, its regulations and other legal dispositions applicable to the matter. The Article further provides that, once the medicament is commercialised, a normal pharmacovigilance of the product will be required. In this sense, the requisites for approval of innovative biotech drugs seem to remain unaltered from that of other innovative drugs. The applicant for the approval of an innovative biotech drug must submit the results of all levels of preclinical and clinical studies and any further tests necessary for proving quality, safety and efficacy of the innovative medicament.

In the case of bio-comparable drugs, the applicant may base his application on the innovative version. However, he must additionally file the clinical and, if applicable, in vitro studies necessary to prove safety, efficacy and quality of the specific bio-comparable product subject to approval. In this instance, the new Article fails to further define the quality and quantity of the referenced studies and provides that such studies will be defined by further provisions in the Regulations of the Law. It is important to point out that, at this moment, the Regulations of the Law have not been equally amended and therefore such further provisions are still not available.

In spite of this, Article 222 Bis does provide that approval of applications will be handled on a case-by-case basis by the Committee of New Molecules, which will now have a Sub-committee for the Evaluation of Biotechnology Products, and will include specialists from the Health Authorities as well as from various recognised academic institutions. This sub-committee will be in charge of defining the type and number of studies that will be required for approval of each new bio-comparable drug application.

Finally, Article 222 Bis provides that all biotech drugs must include in their label: the manufacturer and origin, place of packaging and in such case the name of the importer as well as the Common International Denomination for the medicament.

A welcome clarification

In spite of certain shortcomings – such as uncertainty as to what degree the bio-comparable product will be permitted to base its application on the innovative version, as well as clear definitions of the actual studies that will be required for bio-comparables – this new Article now provides a considerable improvement in Mexican law regarding the regulatory approval of biotech drugs for both innovative and non-innovative products. Furthermore, it recognises that biotech drugs cannot be viewed and approved in the same manner as classic chemical drugs, and must therefore have specific requisites to prove their safety and efficacy, particularly with respect to bio-comparable drugs.

While chemical generic drugs need only to submit studies of bio-equivalence and bio-availability and use the so-called me too approach to prove safety and efficacy to obtain approval, in light of this new legal provision, bio-comparable drugs must now show specific clinical and/or in vitro studies carried out by the bio-comparable drug manufacturer showing their own safety and efficacy through specific required trials, which, for the time being and due to the absence of the corresponding Regulation provisions, will be defined in each case by a panel of experts. It is important to point out that we expect the clinical and/or in vitro studies required for bio-comparable products to be a less rigorous version of the actual safety and efficacy studies required for the innovator product.

The new amendment provides further advantages concerning protection for innovation to pharmaceutical companies even after patent expiry, since generic competitors will not be able to rely totally on the innovator party's safety and efficacy studies, as presently happens with chemical drugs, but will rather have to perform their own studies. This, of course, will make it more difficult for generic competitors to reach the market and compete with the innovator after a patent has expired.

Hope for brand drug makers

Although Mexico has been traditionally regarded as a country in which the regulatory and legal template for pharmaceutical products tend to benefit generic competition, this amendment, along with other legal changes that have preceded it, such as the Patent – Regulatory Approval Linkage issue that has been in force now for some years, provide some balance. Mexico is now on a path towards providing better protection of innovation in the pharmaceutical field, thereby establishing incentives for bringing new drugs into the Mexican market.

Further efforts are necessary, however, and some of them are ongoing. Work is now focused on developing the corresponding Health Law Regulation provisions that will seek to define, qualify and quantify the studies that are necessary for approving bio-comparable drugs provided in Article 222 Bis in order to complete the legal framework for biotechnology drugs.

Another amendment to the Health Law that is also pending and necessary looks to address the issue of pharmaceutical data package exclusivity rights which, even though provided in various International Treaties signed by Mexico, such as NAFTA and TRIPs, is not clearly provided and enforceable through National Law.

Rodrigo Calderón Ponce

Born in Mexico City on November 20 1974. He is an associate at Uhthoff Gomez Vega & Uhthoff SC. Biology degree, 1999, Mexico. Studies: Universidad Nacional Autonoma de Mexico (UNAM), School of Science, Campus Ciudad Universitaria, Mexico City (Degree in Biology, 1999). Universidad Nacional Autonoma de Mexico (UNAM) School of Medicine, Campus Ciudad Universitaria, (Diploma in Immunology, 2001). Author: "Chronic infection induces changes in B7 molecule expression and Th2 biased macrophage activation in a murine model of cysticercosis", Mexico, 1999. "Stat6 induces Th2 cytokine profiles", US, 2002. Member: Mexican Association for the Protection of Industrial Property (AMPPI); American Intellectual Property Law Association (AIPLA). Area: Chemical, pharmaceutical, biotechnological patents and plant varieties. Languages: Spanish, English and French.