In the article below, Andres Bayona, executive director in clinical monitoring and regional head of Latin America, and Mercedes Ponce de Leon, senior manager in regulatory affairs, discuss the regulatory landscape in Latin America.
In recent months, new winds have been blowing in the regulatory environment in Latin America (LA) with the promulgation or modification of regulations that encourage the development of research through clinical trials.
LA is not only becoming a region with robust clinical trial regulations, but also a world of opportunities due to its high-quality standards in trial management and improving economies. The recent changes demonstrate that regulatory entities from different countries are looking to each other to take ideas to improve processes. All these changes will help PPD clients develop and validate new medicinal products and efficiently bring them to market.
The proposed reforms are expected to have positive effects on regulatory cycle review timelines, while maintaining high standards of patient safety and data quality.
Strengthening Argentina’s clinical research regulations
The administration of the President Mauricio Macri of Argentina is collaboratively driving efforts to modernize and improve the efficiency of current regulatory processes and align them with those in the U.S. and the European Union.
In March 2016, the National Administration of Drugs, Food and Medical Technology (ANMAT) responsible for pharmaceutical regulation, voiced support for this collaborative activity, recognizing how important the timely generation of quality clinical trial data is to the approval of new medicines. As a result, new guidelines designed to streamline regulatory timelines in clinical research studies became effective June 5, 2017. The new regulatory guidelines were issued on April 26, 2017, and are aimed at allowing the decentralized government agency to manage its procedures with greater efficiency, economy, transparency and predictability, while adhering to strict international guidelines that preserve patient safety. In conjunction with the new regulation, ANMAT also is launching a new electronic submission platform for clinical trials. The principal objective of this new platform is to support the reduction in review process timelines.
Key improvements in Argentina
Some of the major changes being adapted to strengthen Argentina’s regulatory environment are:
- ANMAT has committed to performing an initial quality control data of regulatory packages within three days after being submitted.
- Full review timelines are to be completed within 70 working days.
- Implementation of a fast-track review process that allows 55 working days for studies approved and ongoing in at least one of the following countries: Austria, Belgium, Canada, Denmark, France, Germany, Israel, Italy, Japan, the Netherlands, Spain, Sweden, Switzerland, U.K. and U.S.
- ANMAT requires that responses to its questions/queries are answered within 15 working days.
- If ANMAT does not reply according to expected timelines, an administrative silent rule may be applied, although the sponsor needs to inform ANMAT about the initiation of a new trial before proceeding. ANMAT will then have five working days to issue a final decision. The new regulation also establishes requirements and expectations for Phase I trials that demand much faster regulatory timelines.
- Submissions processes and requirements for Phase I studies are set up within this new regulation. The study review process, after a mandatory pre-submission meeting, will take no more than 30 business days, while sites in the country must have the corresponding certification from ANMAT.
Solidifying Peru’s clinical trial regulations
The Peruvian president Pedro Pablo Kuczynski has proposed reforms expected to have positive effects on regulatory cycle review timelines, while maintaining high standards of patient safety and data quality.
On June 30, 2017, the Peruvian government published a new clinical trial regulation targeted to improve the protection, rights, safety and welfare of research subjects. The 2017 regulation removed hurdles the former clinical trial regulation, and the temporary preventive measures established in 2015 that prohibited clinical trials in pediatric populations. As a result, Peru returns to allowing clinical trials with children.
The Peruvian National Institute of Health and the General Office of Investigation and Technological Transfer (OGITT) designed a project for the new regulation. During the process, they requested the input of pharmaceutical companies, the CRO industry, scientific and professional associations, investigators and the public. In addition, forums and meetings were developed with the objective of listening to all the parties involved and obtaining a better scientific and ethical contribution to the new regulation. The experts in PPD’s regulatory affairs unit are closely tracking the implementation of these reforms, and provide strategic advice and practical operational support to help other PPD teams and clients.
Key improvements in Peru’s regulatory area
With the changes put in place in 2017, below are some of the key changes in Peru’s regulatory environment:
- Peru once again can conduct clinical trials in pediatric populations.
- An annual renewal authorization is no longer required. Instead, an authorization may be registered for a specific period when the request is initially filed.
- The import license (IL) application process has been simplified and shortened.
- No GMP certificate is required for comparator medications. Only a sponsor/manufacturer declaration with information about the manufacturer and manufacturer license.
- The regulations formalize that institutions without hospitalization beds are not forbidden, but they need to establish an agreement with a larger and nearby institution to provide such capability.
Peru and Argentina have continued to maintain their positions as important countries for conducting clinical trials because of the potential subjects in therapeutic areas such as oncology, cardiology and infectious diseases, in addition to a growing number of sites and investigators who have clinical trial experience. For these reasons, the new regulations not only allow the re-opening of clinical trials to minors in Peru and decrease regulatory timelines in Argentina, but also favor the development of medical research in the region, providing access to new information and technology, as well as generating new employment opportunities.
Decentralized regulations in Brazil’s governance of clinical trials
Since 2014, there has been significant pressure to improve regulatory timelines and make the country more competitive with new therapies and technologies.
The Brazilian Regulatory Agency (ANVISA) issued a regulation in March 2015 for drugs and another one for devices, which completely changed the regulatory process in that country. ANVISA adopted a review process that is like the U.S. FDA IND process by reviewing the experimental products, not per individual clinical trial. In addition, ANVISA was accepted as an ICH member in November 2016. It is expected that procedures and requirements in Brazil will more closely align with international standards.
In terms of CONEP (the Brazilian central ethics committee), timelines have improved considerably in recent months. Experience shows that the final opinion letter can be expected in turnaround times about 60 percent lower than when compared to two years ago.
Continuing with ethical aspects, there is a resolution published in March 2016 — but still in the implementation phase — for certification of local ethics committees (ECs) that establishes the criteria for EC accreditation. Local ECs will be able to review and approve all types of clinical trials, so CONEP will no longer centralize the review. This will permit the ethical review process in Brazil to “decentralize” with better cycle times.
Continued stability in Chile’s regulations
Chile is one of the most stable countries in the region in terms of regulations, requirements and timelines. This country is predictable and has fast regulatory approval timelines (1 to 1.5 months), while it is uncommon to receive queries from the Chilean Regulatory Agency, the Instituto de salud pública de Chile (ISP). In terms of ethical aspects, the local sanitary authority in charge of the accreditation process, named Secretaría Regional Ministerial (SEREMI), issued a voluntary process to register ECs. Only accredited ECs can review and approve clinical trials in Chile.
Colombia updated its clinical trial regulations
Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA), the Colombian regulatory agency, published updated guidelines in 2016 that brought changes to the agency’s structure. A group was created to focus on developing guidelines for clinical research. New timelines of 60 calendar days for clinical trial review were set up and the agency is also more willing to have meetings with open discussions to help facilitate the approval process.
Regulatory Guidelines in Mexico
In Mexico, a stable regulatory environment and clinical research development is part of the vision of the governmental regulatory agency Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS) that started back in 2015.
COFEPRIS proposes initiatives to enhance internal efficiency and during 2017 clear guidelines have been developed and published to improve the regulatory process.
One of the actions in 2014 was the creation of Unidades Habilitadas de Apoyo al Pre Dictamen-UHAP (Habilitated Units to Support the Pre-approval). These units are the authorized third parties for clinical trial pre-approval. Their creation provides an optional process that reduces COFEPRIS timelines from one to three months.
The changing regulatory climate will not only promote a better environment to implement clinical trials in the region, but also will provide tangible opportunities for scientific and health development in Latin America.
Andres Bayona is an executive director in clinical monitoring and regional head of Latin America. Mercedes Ponce de Leon is a senior manager in regulatory affairs.