What we talk when we talk about orphan drugs in Chile: access, research and sanitary registrations
Andrea Abascal Marín
Bofill Mir, Santiago
Andrés Sepúlveda Matteo
Bofill Mir, Santiago
Introduction
One of the pending regulatory challenges in small economies, particularly in smaller countries, is precisely the provision of favourable conditions for the introduction of orphan drugs. This is because, in the context of smaller nations, the incidence of certain diseases is often minimal. Consequently, from a somewhat rudimentary perspective, there are often insufficient incentives for both the pharmaceutical industry and the state to promote the development of measures to ensure access, encourage research and facilitate regulatory approvals.
Access to orphan drugs in Chile: when universality benefits everyone
Chile faces significant challenges due to the lack of clear regulations regarding orphan drugs, which is particularly evident in the absence of a comprehensive framework for accessing these drugs when needed. While existing legislation does provide mechanisms for accessing orphan drugs, such as:
- Law No. 19,966, which establishes a regime of explicit health guarantees;
- Law No. 20,850, known as the ‘Ricarte Soto Law’, which provides financial protection for high-cost treatment diagnoses; and
- Law No. 21,258, the Cancer Law.
None of these frameworks guarantees universal access or ensures coverage for orphan drugs. For instance, the Ricarte Soto Law specifies a catalogue of diseases eligible for state financial mechanisms, but does not ensure the registration of pharmaceutical products or provide a broad catalogue of covered diseases.
This situation has led to an unintended and undesirable consequence that ultimately generates greater expenses for the state than could have been avoided: patients requiring access to orphan and high-cost drugs have increasingly resorted to filing amparo actions, alleging that the lack of treatment jeopardises a fundamental right – the right to life. Chile's higher courts have granted these urgent requests for access due to the imminent danger to the patients’ lives.
In such cases, the state is obligated to procure these medications, even if they involve unregistered pharmaceutical products in Chile. This is achieved through mechanisms established in the Regulation on the Control of Pharmaceutical Products for Human Use, specifically Article 21(a), which permits the importation of unregistered pharmaceutical products in cases of shortage or inaccessibility, justified on public health grounds.
This scenario not only entails the financial burden of purchasing the medication but also involves the state engaging in litigation to contest these actions. Ultimately, due to the lack of guaranteed universal access, the state forfeits an opportunity typically offered by pharmaceutical companies: better pricing when universal access is ensured.
In essence, this approach superficially attempts to address a systemic issue, despite clear evidence that access mechanisms not only improve health outcomes for individuals but also secure more favourable pricing for essential medications.
Research and clinical trials in Chile: progress has been made, but more can be done
It is undeniable that Chile has made significant progress in increasing the number of clinical trials conducted within the country, providing greater clarity to pharmaceutical industry stakeholders regarding the procedures for conducting pharmaceutical research. However, it remains challenging to directly link this growth in research to efforts aimed at developing new orphan drugs.
Measures to address this gap are still pending, particularly those that could provide clearer information to research companies about the prevalence, potential and scope of testing an orphan drug in Chile. Mechanisms that could enhance these conditions include those outlined in the National Health Strategy for the 2021–2030 Period of the Ministry of Health, which proposed the creation of a national registry of rare diseases. Such a registry would undoubtedly improve the recruitment phases for clinical trials, offering a more robust framework for advancing orphan drug research in the country.
Additionally, Chile does not mandate either compulsory or optional genetic testing for newborns, which hinders early diagnosis of rare diseases often treated with orphan drugs. This lack of early diagnostic measures also complicates the ability to estimate the population affected by specific diseases that might be of interest for research. This contrasts with countries like Uruguay, where such data is available from birth, providing a clearer epidemiological picture and facilitating targeted research initiatives.
It must be acknowledged that, in Chile, Phase III clinical trials for orphan drugs are allowed with a reduced number of patients. However, the validity of these studies will depend on the evaluation of their design and the risk-benefit profile of the participants and patients.
Sanitary registrations of orphan drugs: tools are not enough, clear messages are needed
In Chile, the regulatory authority (the Institute of Public Health) established the first guidelines on orphan drugs through Exempt Resolution No. 411 of 28 February 2015. These guidelines define orphan drugs as ‘medications intended for the diagnosis, prevention, or treatment of a rare disease or a condition whose etiology presents an equivalent frequency’.
Although the aforementioned resolution offers a simplified system for registering orphan drugs, it is true that accessing this registration system requires the fulfilment of certain requirements, such as:
- the most recent safety update that the applicant maintains in their international records or authorisations;
- provision of data protection for trial data, provided it is feasible under local regulations;
- concrete justifications that the drug is orphan, through certificates from the United States Food and Drug Administration (FDA) or European Medicines Agency (EMA);
- indication of whether the product is distributed by the administration through ministerial programmes; and
- designs for accelerated stability studies, among others.
This means that, although the registration process is faster, regulatory documentation remains crucial and must be completed to achieve product registration. Therefore, when it comes to completely new and experimental drugs, the challenge persists in demonstrating that the Phase III clinical studies conducted are sufficient.
Notwithstanding the above, we believe that the main obstacle to the lack of orphan drug registration in Chile stems precisely from the difficulties related to universal access. Since the administration consistently requires the acquisition of orphan drugs and is obligated to purchase them under the previously mentioned regulations, the companies supplying these drugs often have little incentive to register them. This is especially true considering that registration entails the implementation of quality control mechanisms that often increase product costs.
These companies can avoid such mechanisms, particularly in cases like those under Article 21(a) of the Regulation on the Control of Pharmaceutical Products for Human Use. As a result, many companies choose to sell directly to the state without registering the drugs, since the incentive for registration is often non-existent in these cases.
Conclusion
Notwithstanding the existence of mechanisms to allow access to orphan drugs in Chile, the lack of regulatory coherence has transformed historically significant initiatives, such as the Ricarte Soto Law, into mere ‘sirens’ calls’, leaving the challenges unresolved. The lack of universal access, combined with individual regulations that do not necessarily complement or align with each other, is undoubtedly one of the major obstacles to creating a conducive environment that would make orphan drug registration attractive in Chile.
Thus, while the state is often obligated to acquire orphan drugs for rare diseases, the lack of clarity for the pharmaceutical industry in these matters has ultimately harmed the public treasury, leaving the state with limited tools to negotiate prices or incentivise the execution of clinical trials in Chile.
Therefore, the development of a rare disease policy in Chile, involving clear access mechanisms to orphan drugs, is imperative to ensure access to medications and encourage the industry to register such products, thus complying with the necessary safety measures for human consumption of products in Chile.