Christian López-Silva
Partner- Healthcare and Life Sciences
Baker McKenzie
/
Expert Contributor

Mexico in Urgent Need of Emergency Use Regulation

By Christian López-Silva | Mon, 01/24/2022 - 10:52

We are facing an extreme situation in Mexico, where there is not a single provision that regulates emergency use authorizations (EUAs).

Let there be no doubt, the focus of this piece is not to call for the invalidation of emergency authorizations granted so far or to call for the imposition of further restrictions to any existing EUAs. It is rather an urgent call for the development of a regulatory framework for emergency uses. We need to define where the limits are.

The situation is now becoming critical because the federal government has erratically but persistently argued that it is inherent to the emergency nature of such authorizations that a crucial restriction should exist. That is, that the products authorized this way can only be made available to the public sector. This has created a profound restriction or exclusion that did not exist before, arbitrarily excluding access to critical treatments in the private health sector.

Undoubtedly, the pandemic, and the way it has been managed by this federal administration, has put a great deal of visibility on a discrete area of law: health law and health regulation. Unfortunately, this has occurred for the wrong reasons. Nevertheless, it is an opportunity to consolidate this area of law for the benefit of the country and its patients, which includes all of us.

Is dedicated regulation really necessary?

Yes, it is. We can take one example from another jurisdiction that is very close to us geographically, historically and commercially. EUAs are regulated in the US through five different pieces of legislation: (i) the Federal Food Drug and Cosmetic Act (FDCA) of 1938, (ii) the Project BioShield Act of 2004, (iii) the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013, (iv) the 21st Century Cures Act of 2016, and (v) the amendment of FDCA of 2017.

Those legislative instruments address different aspects, including: (i) the type and extent of scientific evidence required for approval; (ii) the potential immunity for product liability claims filed by injured patients; (iii) the nature, scope and limits of the power to grant them, and (iv) its connection with or its transition toward full approval. In addition, the FDA issued further regulatory guidance for EUAs relating to COVID-19 vaccines[1].

Even with dedicated regulation, it has been pointed out[2] that the US system requires careful implementation to: (i) avoid undue political influence, (ii) strike the right balance between putting some people at greater risk in the hope of preventing a greater amount of suffering, and (iii) maintaining the trust of the general public in the health regulator.

Thus, yes, we do need dedicated regulation. There are multiple issues to address and define.

At the same time, while looking at that system, we could also ask the following: Is the aforementioned restriction an essential part of the US system? No, it is not.

Also, if we think a bit more about this, the reality in which federal governments around the world have secured purchase agreements for COVID-19 vaccines much faster and more effectively than any other private entity is rather just a reflection of how governments can sometimes mobilize and leverage larger volumes and resources to achieve a result. However, that recent experience, relating only to vaccines, does not mean that by their very nature EUAs should contain a strong restriction to exclude products from the private health sector.

How do EUAs fit into the regulation of medical products in Mexico?

They do not fit very well. In Mexico, the framework law that controls the regulatory system, which is the General Health Law (GHL), has only one standard and main approval route for medical products, a concept that includes medicines and medical devices.

Certainly, there have been attempts at modernizing the regulatory framework and introducing faster approval routes. This is the case with the "equivalence routes," where a dossier will be more quickly evaluated if the product has been already approved by a recognized foreign regulatory agency. However, we do not have regulatory pathways for either an accelerated review (for neglected or priority diseases, for example) or for emergency approvals.

From an administrative law perspective, it is critical to recall or understand that our civil law system in Mexico follows closely the principle of legality, which operates differently for private individuals than for public authorities. Whereas private individuals can do anything that it is not (validly) prohibited explicitly, public authorities can only do something that was granted explicitly within its powers. This would be relevant for asserting the existence of the power to issue EUAs in the first place, let alone for imposing restrictions through it.

From a constitutional and human rights perspective, a heavy limitation to a human right, such as the aforementioned restriction, according to the Mexican Supreme Court of Justice[3], would have to: (i) be contained in a law and (ii) the restriction must be proportional to the intended goal, in comparison to other available alternatives that could achieve the same goal. This would be crucial for the legal standing of the restriction.

Human rights, of course, sit at the top of the normative hierarchy and can be used as a measure and a reason to invalidate other legal provisions or administrative acts of lesser hierarchy. Here we have a collection of relevant human rights, such as the right to the protection of human health, the right not to be discriminated against, the freedom of trade, the principle of legal security and the principle of legality.

Has any existing provision been claimed as a potential legal basis?  

Not quite. The current federal administration has not found it necessary to elaborate on this. The closest argument over the legislative basis for emergency authorizations can be found in a partially related document: a ministerial decree stating that the National Policy of Vaccination for COVID-19 (NPV) shall be publicized on the webpage of the Ministry of Health[4].

In the relevant portion, the decree has a recital that recalls that GHL indicates the possibility of authorizing products in relation to which there is still no sufficient scientific evidence over its efficacy. It does not identify the provision but that would be Article 102 of GHL.

However, Article 102 of GHL is the legal basis for clinical trials, which as the reader may know, precede the approval of medical products and therefore precedes the possibility to use them widely. Well, clearly, the NPV is by no means a research protocol and Mexicans are not human subjects to a huge clinical trial. It is an entirely different system, which is why other countries developed a full legal regime for EUAs.

In which cases have EUAs been used in Mexico?

In a large variety of cases. This federal administration has issued emergency authorizations for different COVID-19-related services and products[5], including: (i) authorization of disinfection services[6], (ii) authorization for lab testing services[7], (iii) authorization of serological tests[8], (iv) authorization of ventilators[9], (v) authorization for vaccines and (vi) authorization for medicines[10]. Thus, it has intervened in both products and (health) services and both medicines and medical devices.

Was the same restriction incorporated into all other approved cases?

No. The restriction has only been consistently and clearly articulated in relation to all COVID-19 vaccines. There, the federal government asserted the legal position that the nature of the emergency authorizations required that all authorized vaccines should be restricted to the public sector and not be available in the private sector.

Now, to recall, with COVID-19 vaccines, restrictions were introduced on both ends; that is, on the supply side and on the demand side.

On the demand side, the early position of the federal government was that neither local governments nor private employers were allowed to acquire COVID-19 vaccines. On the supply side, the health regulator added to the emergency authorization a condition for the holder to comply with the NPV, which in turn did not open at all any role for the private sector.

In relation to the demand limitation, it is useful to recap the background. When the prospect of having vaccines available for COVID-19 finally became a near reality, the alternatives for its acquisition were heavily discussed. Both the local governments and the private sector wanted to acquire them and provide them to their population and employees, as a means to reactivate the economic activity and support and accelerate the biggest vaccination effort in the history of humankind. A huge political and power struggle ensued, resulting in the federal administration being forced to issue a decree containing guidelines for the acquisition of vaccines by local governments and private individuals[11]. Nevertheless, the guidelines made compliance virtually impossible and has, therefore, not been implemented.

In relation to the supply limitation, the health regulator also introduced language to the product authorizations themselves, which resulted in an availability only in the public health sector. The way in which the restrictive effect was achieved was apparently the following. The authorization did not restrict directly the availability to the private sector. Instead, it made a reference to the National Policy of Vaccination for COVID-19 ("NPV"), which only made reference to the public health sector.

In contrast, the federal administration did not assert the restriction when authorizing health services or when authorizing other medical products such as the diagnostic tests or the ventilators, both medical devices, which were undoubtedly available in the private sector.

Also in contrast, in relation to COVID-19 medicines[12], the restriction had been asserted (publicly) in relation to the first of them (remdesivir), but not with the second (bamlanivimab/etesevimab). In the first case where it was asserted, however, it added even further restrictions.

The further restrictions included apparently a control scheme where only a few private hospitals (specialized hospitals) could request and had to secure an agreement with public health institutions, through which the authorized medicine could be provided. These additional restrictions were criticized by physicians in the private sector as cumbersome and unnecessarily creating incentives for the black market[13].

Against that mixed background, more recently, in relation to the two oral COVID-19 medicines that were approved in recent weeks (molnupiravir and nirmatrelvir/ritonavir), the federal government has insisted and argued intensely in favor of introducing the same availability restriction, as well as additional control restrictions.

Now, it is worth noting as well that the "controlled nature" of the referred scheme does not correspond to the existing regulation for "controlled medicines," which has a different set of regulatory mechanisms, including a license to operate for the warehouse, authorizations of the prescription books for physicians, and authorizations of the recording books for the warehousing site and at the retailing site. The power to implement that different kind of control is not foreseen in the regulatory framework either. However, even if that was the intention, again, it is very doubtful why patients in the private health sector should be discriminated against in relation to the patients in the public health sector.

At the same time, further controls that require implementation by multiple parties, which adds institutional complexity (which is not precisely the forte of our authorities), would make it unnecessarily harder for patients to have quick access to critical treatments during a life-threatening pandemic. 

Without any doubt, EUAs for different services and products have been treated differently. The reasons for that differentiated treatment are not clear, which is creating arbitrary distinctions of questionable legal validity.

This all demonstrates why multiple implications should be regulated, first at the law level (issued by the Congress), and then at the secondary regulation level (prepared by the health authorities of the Executive Branch).

What exactly has been said in relation to the most recent approvals of oral medicines?

It was first announced in the daily presidential press conference (DPPC) of Jan. 11, 2022,[14] that the two medicines would only be available in the public sector due to its emergency authorization. Then, in subsequent DPPCs this was raised again. On Jan. 17, the president declared[15] that "he wanted the medicines to be available only in the public health sector, like with vaccines, but that the matter would be addressed and defined by the health authorities the day after." On Jan. 18, the Vice Minister of Health declared[16] that "it would be the same as with vaccination: a program of the government of Mexico." He further stated that: "At the moment they have (an) emergency use authorization and that is a limited authorization that does not allow commercial purposes and only operates in the context of the emergency. … The way we do it, and we already did it very successfully with remdesivir at the time (and) we are doing it with all the vaccines … is that the Mexican State protects the correct use of this medicine … we were able to make use of it under the tutelage of the government," and for that "we established a formal relationship with certain care units in the private sector."

Final remarks

We should take away a simple question: Why should COVID-19 patients in private hospitals be excluded completely from having access to life-saving medicines, or even struggle with additional access restrictions? It would seem that there are no sufficiently robust reasons to legally justify such restrictions, which makes them arbitrary and challengeable.

In fact, the aforementioned restriction for COVID-19 vaccines has not withstood judicial review. It has been successfully litigated in courts by many specific groups of individuals, including private physicians, indigenous communities, adults with comorbidities, teenagers and children, who won against the restriction that excluded them from having access to the COVID-19 vaccine, all asserting their human right to the protection of human health.

For some, it may be rather surprising to find out that our legal regulatory framework simply does not have a type of approval that limits the commercialization exclusively to the public sector. However, as put forward here, what should really be the main surprise for all of us is that we are not yet urgently developing the required regulation.

 

 

[1] For an overview see: Aiken, K., Peeples-Dyer, V. (2021), "FDA's new guidance on emergency use authorizations for COVID-19 vaccines". InsightPlus by Baker McKenzie. Available here: https://insightplus.bakermckenzie.com/bm/resilience-recovery-renewal/international-fdas-new-guidance-on-emergency-use-authorizations-for-covid-19-vaccines

[2] Iwry, J. (2021) "FDA Emergency Use Authorization: A Brief History From 9/11 to COVID-19", Newsletter, Food and Drug Law Institute. Available at: https://www.fdli.org/2021/09/fda-emergency-use-authorization-a-brief-history-from-9-11-to-covid-19/

[3] Jurisprudence Case No. 2003975: "Human rights. Requirements to restrict or suspend them in accordance with articles 1 of the Constitution and article 30 of the American Convention on Human Rights." Available here: https://sjf2.scjn.gob.mx/detalle/tesis/2003975

[4] This decree is available here: https://www.dof.gob.mx/nota_detalle.php?codigo=5609647&fecha=08/01/2021

[5] This is a very short article, but you can contact the author for further elaboration over the different cases, as well as for advice.

[6] This refers to the authorization that was originally created for companies offering sanitizing services. The authorization was later replaced by a registry operating through notifications, which can still be subject to observations. The authorization was removed when they realized they did not have the installed capacity (nor the legal powers) to handle such a pre-approval or pre-market system. Current scheme available here: https://www.gob.mx/cofepris/acciones-y-programas/servicio-para-sanear-o-desinfectar-sanitizar-excepto-fumigacion-o-aplicacion-de-plaguicidas?state=published

[7] This refers to the authorization for individual diagnostic tests that was originally created for testing labs, under an authorization system implemented with the National Institute of Epidemiological Reference (IndRE). However, testing labs are rather regulated as health services and its regulatory framework does not foresee an authorization for the individual tests they perform. This was also eliminated once they realized they did not even have the institutional capacity to meet the huge demand (or the legal powers). See further information here: https://www.gob.mx/salud/documentos/coronavirus-covid-19-240014

[8] This refers to the provisional authorization created for serological tests (rapid tests), under an evaluation system implemented with the National Institute of Nutrition and Medical Sciences (INCMN), a governmental body of the Ministry of Health, and TecSalud, the health  program of the National Technological Institute of Monterrey (ITESM), a major private university. Furthermore, it also created the obligation to obtain an Import Permit. More information here: https://www.gob.mx/cofepris/acciones-y-programas/permisos-sanitarios-de-importacion-psi-de-pruebas-serologicas-para-determinar-igg-e-igm-para-covid-19-con-oficio-de-autorizacion-temporal?state=published and here: https://www.gob.mx/cofepris/acciones-y-programas/pruebas-autorizadas-para-covid-19?state=published

[9] This refers to the provisional authorization system created for ventilators, comprised both of a product approval and a manufacturing site approval, implemented with the National Council of Science and Technology (CONACYT), the National Institute of Respiratory Diseases (INER), the National Institute of Nutrition and Medical Sciences (INCMN) and COFEPRIS. Further information here: https://www.gob.mx/cofepris/articulos/informacion-sobre-los-lineamientos-de-ventiladores-actualizacion-9-de-mayo?idiom=es

[10] This refers to the emergency authorizations for: (i) remdesvir (https://www.gob.mx/cofepris/articulos/cofepris-emite-autorizacion-para-uso-de-emergencia-de-remdesivir?state=published); (ii) bamlanivimab / etesevimab (https://www.gob.mx/cofepris/articulos/cofepris-emite-autorizacion-para-uso-de-emergencia-de-combinacion-inyectable-para-tratar-covid-19?idiom=es); (iii) molnupiravir (https://www.gob.mx/cofepris/es/articulos/cofepris-autoriza-tratamiento-oral-para-covid-19-en-uso-de-emergencia-controlada?idiom=es) and (iv) nirmatrelvir / ritonavir (https://www.gob.mx/cofepris/articulos/segundo-tratamiento-oral-para-covid-19-autorizado-para-uso-de-emergencia-controlada?idiom=es). In the two last cases the authorization was issued for controlled use and under prescription.

[11] See Lopez-Silva, C. (2021)," Mexico's COVID-19 Vaccination Program: The Federal government establishes the conditions for the participation of local governments and private sector"", InsightPlus by Baker McKenzie. Available here: https://insightplus.bakermckenzie.com/bm/healthcare-life-sciences/mexico-mexicos-covid-19-vaccination-program-the-federal-government-establishes-the-conditions-for-the-participation-of-local-governments-and-private-sector

[12] To recall, vaccines represent mainly a preventive approach and medicines mainly a curative one, each embodying two different models of medicine, each corresponding to different legal models. See more on Cossio, J.R. and Perez Tamayo, R. "Medicine Models and Law Models", Ed. Tirant Lo Blanch, Mexico, 2015

[13] An example of news report available here: https://www.animalpolitico.com/2021/03/por-que-cofepris-restringe-comercializacion-remdesivir-covid-19/

[14] The stenographic version of the DPPC is available at: https://www.gob.mx/presidencia/es/articulos/version-estenografica-conferencia-de-prensa-del-presidente-andres-manuel-lopez-obrador-del-11-de-enero-de-2022?idiom=es

[15] The stenographic version of the DPPC is available at: https://www.gob.mx/presidencia/articulos/version-estenografica-conferencia-de-prensa-del-presidente-andres-manuel-lopez-obrador-del-17-de-enero-de-2022?idiom=es 

[16] The stenographic version of the DPPC is available at: https://www.gob.mx/presidencia/articulos/version-estenografica-conferencia-de-prensa-del-presidente-andres-manuel-lopez-obrador-del-18-de-enero-de-2022?idiom=es