Advanced and Innovative Therapies – Regulatory Challenges

The use of human body parts as therapeutic products is an ancient and highly regulated clinical practice.

Over the last 50 years, the transplantation of cells, tissues, or human organs has become a successful practice worldwide, saving many lives and restoring essential functions where no comparable alternatives existed. (World Health Organization - WHO - Transplantation)

In this context, with scientific progress and advancements in the biotechnology sector, a new class of products derived from human cells, called Advanced Therapy Products, has emerged.

These products are being applied in various pathological or clinical conditions previously without alternatives. Currently, these therapies represent a highly diverse range of medicinal products that continue to expand as technology develops and matures.

Advanced therapy products include three categories: advanced cell therapy products, gene therapy products, and tissue engineering products, which may or may not be combined with medical devices. (Cell, Tissue, and Gene Therapy Products)

However, with the growing diversity of types and indications for the use of these products, their regulatory oversight has become increasingly crucial to ensure access to products with proven quality, safety, and efficacy, obtained under ethically acceptable principles.

Thus, it is important to understand the products, their origins, manufacturing processes, and mechanisms of action, and have appropriate classification schemes for their effective regulation. At the same time, it is important that regulatory environments do not hinder their development or accessibility, and therefore, both regulatory harmonization and the use of regulatory trust are strongly encouraged by the WHO.

On the global stage, Brazil falls behind other countries in the number of clinical studies being conducted with CAR-T cells. As of May 2024, China had 619 ongoing studies, the United States had 365, Europe had 97, and Brazil only had 5. Despite these few studies, the country was a pioneer in Latin America and has served as a showcase in the region.

Regarding national challenges for the regulation of Advanced Therapies, according to a lecture by Dr. João Batista da Silva Junior, manager of the Blood, Tissues, Cells, Organs, and Advanced Therapy Products Department at Anvisa, during the Clinical Research Meeting event held by Inovatie in August 2024, the Agency's experience with the clinical development and regulation of innovative therapies has been positive, although there is still room for improvement in both the agency's processes and the entire production chain of these therapies.

According to Dr. Silva Jr., Brazil has a complex regulatory mechanism in the field of clinical research: agencies that work with ethical regulation, agencies that regulate genetically modified organisms (GMO), such as CTNBio, and Anvisa itself, which also plays an important role in clinical research.

Anvisa is responsible for regulating a wide variety of products and services, each embedded in a vast, innovative landscape. Therefore, in the field of innovation, Anvisa must closely monitor the development, approval, and monitoring processes of everything it regulates.

Technological advances have created numerous opportunities for innovation in healthcare, becoming the focus of various research efforts, including clinical research. According to the World Health Organization (WHO), innovations such as organ and tissue production in laboratories, the use of nucleic acid-based platforms as drug mechanisms, and gene therapy products are among the most promising discoveries.

These advances present significant challenges for regulatory bodies. The Organization for Economic Co-operation and Development (OECD) warns of the need to balance the growing complexity of biotechnology products with the demand for more advanced treatment technologies. To achieve this, dynamic regulatory strategies are needed to manage the risks and uncertainties associated with these innovative products.

In the case of medicines, the evolution has been remarkable. Medicines have moved from simple chemical molecules or plant-based compounds to large biological molecules, monoclonal antibodies, and more recently, living cells formulated as drugs. These advances, while revolutionizing the treatment of various diseases, present new challenges for regulators.

Brazil's legislation on clinical research defines advanced therapy products as special and complex medicines, encompassing cell therapies, gene therapy (with in vivo and ex vivo genetic modifications), and tissue engineering. The country has made progress in regulating these treatments, with specific norms for registration, clinical trials, and good manufacturing practices.

Anvisa closely monitors global developments and seeks greater interaction with researchers to drive the development of these therapies in Brazil. Currently, seven gene therapy products are approved in Brazil, with two more in the final stages of registration. However, clinical trials, particularly those for diseases with no therapeutic alternatives, face challenges such as small sample sizes, the need for adaptive approaches, and difficulty in obtaining robust evidence.

For Brazilian researchers with projects in advanced therapies, Dr. Silva Jr. advises: "Persistence and resilience are key, keep researching and seek regulatory knowledge. Brazil has the capacity to produce cutting-edge science, but it is essential that regulation be considered from the start of projects, as is already done in the United States and Europe. Universities could offer courses on regulation to help researchers better structure their studies."

Regulation should not be seen merely as a bureaucratic obstacle but as an essential part of scientific development. Just as new molecules are developed, strategies must also be created to make their regulations feasible. Society must engage with regulatory agencies, presenting scientific evidence and proposing more effective regulatory approaches. Well-founded projects aligned with regulation tend to advance more easily, strengthening research in the country.

National development still faces challenges, such as the lack of entrepreneurial training in healthcare and inadequate infrastructure to transform academic research into viable products. To boost the sector, it is essential to invest in strengthening research centers, professional qualifications, and cooperation between national and international regulators.

Above all, the focus should remain on benefiting the patient.