In 2014, after several years of discussion and heated debate, Colombia issued a regulation for sanitary registration of biotechnological medicines, including biogenerics. The regulation explicitly included an abbreviated pathway for the registration of biogenerics, which allows for reduction or, in some cases, even waivers of comparative efficacy clinical trials. PK/PD and inumunogenicity studies are required.
This regulation favors public health, access and market competition. It actually does exactly what was requested by World Health Organization (WHO) Member States in Resolution WHA67.21[1] about Access to biotherapeutic products including similar biotherapeutic products and ensuring their quality, safety and efficacy:
“(1) to develop or strengthen, as appropriate, national regulatory assessment and authorization frameworks, with a view to meeting the public health needs for biotherapeutic products, including similar biotherapeutic products;
(2) to develop the necessary scientific expertise to facilitate development of solid, scientifically-based regulatory frameworks that promote access to products that are affordable, safe, efficacious and of quality, taking note of the relevant WHO guidelines that may be adapted to the national context and capacity;
(3) to work to ensure that the introduction of new national regulations, where appropriate, does not constitute a barrier to access to quality, safe, efficacious and affordable biotherapeutic products, including similar biotherapeutic products;”
The big pharmaceutical industry has always opposed the referred to regulation using all sorts of methods: from diplomatic pressure (e.g. letter by US Vice President Joe Biden to President Santos asking him not to issue the regulation), to economic pressure (request of inclusion of the subject in the Office of the United States Trade Representative (USTR) Special Section 301 Report,[2] raising the issue in the context of Colombia´s accession process to the Organisation for Economic Co-operation and Development (OECD)), to denigrating practices (paid leaflet in a highly prestigious magazine[3] calling the biocompetitors subject to the regulatory waiver “biolimbos”, not to mention the numerous presentations at medical conferences and messages delivered to doctors through direct marketing).
The latest move in this long-term match was a law suit. AFIDRO, Colombia´s Big Pharma guild, decided to contest the regulation in court. Colombia allows for abstract judicial review of laws and general administrative acts.[4] AFIDRO argued that the abbreviated pathway for marketing authorization of biogenerics (as contained in article 9 of Presidential Decree 1782 of 2014[5]) contravened a superior law and also the right to life and to health; consequently, AFIDRO argued, it should be removed from Colombia´s legal regime.
AFIDRO moved for a preliminary injunction, asking the Council of State to “provisionally suspend” article 9 while litigation happened and until a final decision was made. “Provisional suspension” means that the provision cannot take effect or cannot be applied or used during the trial. In a court case about abstract judicial review of a general administrative act, a “provisional suspension” has the same effect as if the plaintiff would have prevailed in the case, even if temporarily. A preliminary injunction of “ provisional suspension” in Colombia is rare and if granted, it generally means that the final decision by the Court will find the regulation illegal or unconstitutional. So the stakes in this particular move for preliminary injunction were really high.
The merits for a “provisional suspension” should be different than the merits of the case. In other words, such preliminary injunction cannot be argued on the basis that the regulation in question contradicts a superior law or the constitution. But AFIDRO did just that. Its memorandum requesting the injunction was just a summary of the law suit. It actually demanded the Council of State to give an opinion on the substance of the case, and not, as it should have been, about the merits of the “provisional suspension”.
That is exactly what happened. The Council of State denied the preliminary injunction and in its decision, it took some views on the arguments of AFIDRO regarding the illegality of the regulation, that will be very difficult to take back in its final ruling. So even if technically this decision is not the ultimate victory for the Ministry of Health, it very much feels like it.
Let us examine the decision[6].
Decree 1782 of 2014 is a Presidential Decree, signed by the President and the Minister of Health. Therefore, the Presidency and the Ministry of Health (MOH) were in charge of defending the regulation in court. Given the importance of the issue, the National Agency for the Legal Defense of the State (a public entity in charge of just that - defending the State in courts) decided to join the law suit on the side of the MOH. 6 amicus briefs were filed: 5 in favor of the defendant[7], and one in favor of the plaintiff[8].
The main argument by AFIDRO is that the abbreviated pathway for marketing authorization of biogenerics contradicts a law (superior in the legal hierarchy) that mandated that the regulation for marketing authorization of medicines produced through biotechnology should be done by the government taking into account “international quality standards”[9]. AFIDRO claimed that the fact that the government did not copy the regulations of the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the WHO meant a violation of the superior law.
The Council of State, very wisely, protected the regulatory sovereignty of Colombia clarifying that regulations of the FDA or EMA are not “international”. They are just regulations of other countries and Colombia remains free to make its own regulations. For those of us working in pharmaceutical regulation in middle income countries, this is music to our ears. We constantly have to fight sophisticated forms of neo-colonialism, disguised as technical or scientific standards, preached by industry, technocrats from regulatory agencies of developed countries or from international organizations (or, sometimes, even officers from the ministries of trade or the ministries of foreign affairs of our own countries), who are very far away from the local realities and who underestimate the technical capacity of our scientists and regulators. Those standards that multinational pharmaceutical companies advocated for so strongly are usually shaped to their interest and made in a way that is only possible for them to meet.
Regarding WHO guidelines[10], the Council of State reminded us that even if the WHO is indeed an international organization, the guidelines it produces are not mandatory. It quoted the guidelines on Evaluation of Similar Therapeutic Products where it is written that national regulatory agencies are responsible “for determining a suitable regulatory framework for licensing similar biotherapeutic products, [they] may choose to use or amend existing pathways or to develop a new pathway for this purpose”, and noted that the fact that such guidelines do not expressly contemplate an abbreviated pathway for marketing authorization of biogenerics does not necessarily mean that our national regulation contradicts it.
AFIDRO also argued that the abbreviated pathway for marketing authorization of biogenerics violated the right to life and to health of Colombians because it allowed for the registration of medicines of poor quality, safety and efficacy. The Council of State ruled that this was an unproven charge for which the plaintiff did not produce evidence or justification, but was merely based on an unsubstantiated argument about a presumed harmful effect of the regulation.
For the people in Colombia (including the former Minister of Health, Alejandro Gaviria, his senior advisor Claudia Vaca, myself and many others), who have worked on this regulation from the beginning and who have taken part in this long match on the side of public health, access and sustainability of healthcare systems, it feels good to read a judicial tribunal, an impartial referee, rule just that. We have always maintained that this fuss around the regulation of biogenerics is more about market, money and greed, than it is about regulatory science or technical issues. There is no doubt that this lawsuit is yet another publicity stunt to undermine market competition and prolong monopolies, and this concept of “presumption of harm by the plaintiff” seems to reinforce that idea.
In Colombia, false information has been intentionally disseminated suggesting that biogenerics submitted for marketing authorization through the abbreviated pathway will be approved without any “evidence or test” of their quality, safety and efficacy. The Council of State said otherwise in its ruling, explaining in detail the requirements of such pathway. Nonetheless a lot of harm has been done. Many doctors, patients and other members of the healthcare community have believed that lie and fear biogenerics. We call it the “biopanic strategy”, spread around by sales representatives and paid physician speakers of big Pharma companies and the patient organizations they support. A court ruling is not enough to overcome the fear that has possessed many, but it certainly is a valuable step towards acceptance and uptake of biogenerics.
[1] Available here: https://apps.who.int/medicinedocs/documents/s21459en/s21459en.pdf
[2] The issue was systematically included in the USTR Reports since 2013:
http://phrma-docs.phrma.org/sites/default/files/pdf/PhRMA%20Special%20301%20Submission%202013.pdf
http://phrma-docs.phrma.org/sites/default/files/pdf/2014-special-301-submission.pdf
https://www.keionline.org/wp-content/uploads/PhRMA_2015_Special_301_Review_Comment.pdf
http://phrma-docs.phrma.org/sites/default/files/pdf/PhRMA_2016_Special_301_Submission.pdf
http://phrma-docs.phrma.org/files/dmfile/PhRMA-2017-Special-301-Submission.pdf
https://www.phrma.org/policy-paper/phrma-special-301-submission-2018
http://phrma-docs.phrma.org/files/dmfile/PhRMA-2019-Special-301-Submission.pdf
[3]https://www.semana.com/hablan-las-marcas/multimedia/colombianos-en-alto-riesgo/558067
[4] This usually happens in one of Colombia´s highest courts. Colombia has three: 1) The Constitutional Court, which, amongst other issues, decides on the constitutionality of laws without previous intervention of lower courts; 2) The Council of State, highest court in litigations about administrative law and sole instance to decide on the legality and constitutionality of abstract administrative acts; 3) the Supreme Court, the highest court in all other litigations (criminal, labor, civil, commercial etc.).
[5] https://www.minsalud.gov.co/Normatividad_Nuevo/Decreto%201782%20de%202014.pdf
[6] Full decision can be seen here: http://anterior.consejodeestado.gov.co/SENTPROC/F11001032400020170002500ADJUNTARAUTOS20190426162015.doc
[7] Misión Salud, a civil society organization working on various access issues; ASINFAR, a Colombian guild of generic producers; Federación Médica Colombiana, one guild of doctors very active in various discussions regarding healthcare, including medicines’ prices; The Law Clinic of Environment and Public Health at Los Andes University; and the Research Group on Law and Development from the National University School of Law.
[8] FUNDARE: Foundation for the Support of Rheumatic Patients
[9] Article 89 of Law 1438 of 2011, available here: https://www.minsalud.gov.co/Normatividad_Nuevo/LEY%201438%20DE%202011.pdf
[10] WHO Expert Committee on Biological Standarization, Guidelines on Evaluation of Similar Biotherapeutic Products, available here: https://www.who.int/biologicals/publications/trs/areas/biological_therapeutics/TRS_977_Annex_2.pdf
