COFEPRIS, IMPI Patent Clearance Collaboration: Time for Change

Both the United States and Canada have systems in force to ensure that patent holders have an opportunity to initiate actions to prevent an infringing product from being approved/entering the market.

These models, which are materialized in the Orange Book (US) and Patent Register (Canada) are in compliance with USMCA article 20.50, and contain key elements allowing proper functioning of the system, which include. 

(i) transparency by providing information regarding applicable patents and relevant periods of exclusivity for pharmaceutical products that have been approved in the relevant Country; (1).

(ii) a system to provide notice to a patent holder when a generic product is being applied for, and adequate time (by way of time barred stay of final approval of the regulatory examination) for such patent holder to seek patent-based injunctions; (2) and 

(iii) incentives for generic companies for assertions of invalidity or non-infringement, intended to bring products into the market sooner (3).

In contrast to this, the system in force in Mexico, regulated by article 167 Bis of the Regulations for Health Supplies and article 47 Bis of the Industrial Property Law Regulations, and intended to comply with USMCA Annex 20-A – allowed as an alternative to article 20.50 – has several flaws.

Under this system, IMPI manages a patent list (Linkage Gazette) in which any patent holder can list various patents, regardless of whether they have claims covering an approved pharmaceutical product or not. Most types of patents may be listed, with some restrictions regarding process patent and secondary use patents

Once an application for a generic/biosimilar product is received, the Federal Agency for Protection against Sanitary Risks  (COFEPRIS) publishes it on its website, allowing patent holders to file opposition formats.  The relevant information is then provided to IMPI for a patent analysis, without allowing for additional arguments from the interested parties. This analysis will include any granted patent, regardless of whether it is published in the Linkage Gazette or if it covers the innovator product or not. 

If IMPI considers that a patent is relevant, the applicant must then demonstrate, to the satisfaction of IMPI, that said patent is not infringed to secure a marketing authorization.  Invalidity arguments are not relevant to the process. 

The Mexican system fails in all three relevant elements to be considered as functional since:

1. It lacks transparency, by allowing patents that are not associated with an innovator product to be listed, and a review by IMPI of unlisted patents. On the innovator side, the opposition format is done with very limited information on the nature of the generic product.

2. It does not allow for a patent holder to initiate infringement and seek injunctions for a set period.  It also does not establish a set time for the parties to engage in litigation before the generic product application is granted.

3. It does not provide any incentive for a generic product applicant that is successful in launching, which would in turn improve access and lower drug costs. 

A better alternative for compliance with USMCA is for Mexico to switch systems by modifying existing regulations. The switch would also have the benefit of diminishing the work burden of both authorities, and allowing parties to bring their cases to the judiciary as is done in other jurisdictions. 

In Mexico, enforcement of regulations surrounding biologic and biosimilar products is entrusted to COFEPRIS. This agency has identified that biosimilar products have very low penetration in the Mexican Market — below 30% when compared to the United States and Europe – and thus published, in February 2024 Guidelines on “Regulatory certainty for biosimilars.”  

This document is looking to establish public policies for the following key factors: 

• To provide incentives for the development of biocomparable products in the country. 

• Establish a regulatory framework providing certainty to manufacturers in Mexico, ensuring quality, safety and efficacy 

• To eliminate the requisite for studies in the Mexican population. 

To accomplish these policy goals, COFEPRIS will:

1. Establish a committee for good regulatory practices, with a specific working group to implement the strategy as a whole.

2. Create a specialized unit for biosimilars, focused on regulatory evaluations

3. Create a Pharmaceutical Development Committee, focused on providing early stage guidance to industry participants. 

The guidelines also refer to improvement of the ecosystem to conduct biocomparability studies, by adopting WHO guidelines, allowing comparability studies with products not available in Mexico and eliminating the requirement for specific studies in the Mexican population. 

In this regard, a reform is shortly expected to the Regulations for Health Supplies (RIS), Official Norm 177, which establishes tests to prove interchangeability/biosimilarity, and the guides for biocomparability studies.

On the legal/intellectual property front, the guidelines refer to two main topics:

1. Clarification on applicability and reaches of the Bolar type exemption.

This exemption, as currently applied in Mexico has two main problems:

1. Even though the Mexican IP Law established since 2020 that pharmaceutical patents are not enforceable against parties seeking to obtain regulatory approval, the RIS contains a three-year period for small molecules and an eight-year period for biologics, and 

2. There are no clear pathways to ensure that the regulatory analysis will be concluded prior to patent expiry, guaranteeing that a marketing authorization will be granted the day after.  This has caused several cases where even after patent expiry, the regulatory process is delayed.

2. Modifications to the linkage mechanism.

The policy document, proposes to create a working group with three objectives:

1. Specify the limits and applications of the legal provisions regulating linkage between patents and marketing authorizations, including cooperation with the Patent Office, while guaranteeing compliance with Mexico’s treaty obligations.

2. Implement more effective mechanisms for appeals and requests for clarifications by innovation-based companies, and 

3. Simplify the hurdles faced by biosimilar manufacturers to carry out clinical phases of product development.

For these purposes, COFEPRIS has created a working group, including representatives of the main pharmaceutical industry associations acting in the country, that is expected to create regulatory proposals in the near term.

Overall, the policy document represents a concerted effort to modernize and enhance the regulatory landscape of Mexico's healthcare sector. By prioritizing transparency, efficiency, innovation, and compliance, the strategy aims to foster a conducive environment for the development, approval, and access of safe and effective health products. 

Moving forward, effective implementation and continuous evaluation will be crucial to realizing the full potential of this regulatory initiative and maximizing its benefits for public health and industry innovation alike. A balanced approach will be crucial to ensure that the objective of increasing biosimilar penetration in the market is reached. 

Sources:

1 - USMCA, section 20.50, 2 (b).

2 -  USMCA, section 20.50, 1 (a) 

3 - USMCA, section 20.50, 2 (a)