The translational gap for gene therapies in low- and middle-income countries.

Gene therapies are designed to address the root cause of disease. As scientific understanding of disease prevention, diagnosis, and treatment improves in tandem with technological innovation, gene therapies have the potential to become safe and effective treatment options for a wide range of genetic and nongenetic diseases. However, as the medical scope of gene therapies expands, consideration must be given to those who will benefit and what proactive steps must be taken to widen development and access potential, particularly in regions carrying a high disease burden.

Redefining informed consent form in cell and gene therapy trials.

Informed consent is a foundation of the ethical conduct of research involving human participants. Based on the ethical principle of respect for persons, the goal of informed consent is to ensure that participants are aware of the risks and potential benefits and make a voluntary decision about participating in clinical trial research. The extraordinary scientific advances happening globally, have demonstrated the potential of regenerative therapies in transforming the health of the nation by providing a therapeutic option for diseases that were previously considered incurable. These therapies, which include cells and gene therapy (GT) labeled as Advanced Therapeutic Medicinal Products globally, have complex mechanisms of action. Owing to their highly personalized and intricate nature of these therapies, developing the latter often presents unique challenges above and beyond those encountered for small molecule drugs. We recently looked through some cell and GT clinical trials and realized the lacunae in the informed consent form (ICF) provided by the investigators. Especially in a country like India, where the general understanding and perception of patients is limited regarding clinical trials, it is felt that any lapses in the consent process may jeopardize the informed decision-making and safety of the participants and tarnish the reputation of India globally. The present article highlights the need for appropriate patient and public education on the various aspects of cell and gene therapies and aims to address all the elements of ICF in light of the challenges associated with these innovative therapies.

Regulation of Clinical Research for Cellular and Gene Therapy Products in India.

The understanding of disease biology and advances in cellular and molecular biology platforms have ushered in a new era of cell and gene based therapeutic products. The US-FDA refers to this category of products as Cellular and Gene Therapy Products (CGTPs), while the European Medicines Agency, Europe, refers to them as Advanced Therapy Medicinal Products (ATMPs). The research and development (R&D) and final commercialization of these products have thus picked up pace, especially in the last decade. This emerging scenario necessitates framing regulations and guidelines that take into consideration the unique biological nature of these products. Regulators and government agencies of different countries across the globe have come up with regulations and guidance documents to guide, monitor, and regulate the research and development in this field. India, given its powerful resources of skilled scientific manpower and infrastructure, is also contributing to development of these innovative therapeutic products. Keeping in line with the international counterparts, the Indian regulators and government agencies have developed regulations and guidelines for stakeholders. This chapter summarizes the regulatory landscape for research and development of CGTP in India. It provides an overview of the government agencies and committees overseeing this field and their roles that a stakeholder working in this field needs to have knowledge of. Furthermore, the chapter outlines the salient features of rules, regulations, and guidelines relevant to CGTP, the approval process, the current approved products in Indian market, and finally, the challenges and way forward for CGTP in India.

Stem cell/cellular interventions in human spinal cord injury: Is it time to move from guidelines to regulations and legislations? Literature review and Spinal Cord Society position statement.

PURPOSE: In preclinical studies, many stem cell/cellular interventions demonstrated robust regeneration and/or repair in case of SCI and were considered a promising therapeutic candidate. However, data from clinical studies are not robust. Despite lack of substantial evidence for the efficacy of these interventions in spinal cord injury (SCI), many clinics around the world offer them as "therapy." These "clinics" claim efficacy through patient testimonials and self-advertisement without any scientific evidence to validate their claims. Thus, SCS established a panel of experts to review published preclinical studies, clinical studies and current global guidelines/regulations on usage of cellular transplants and make recommendations for their clinical use. METHODS: The literature review and draft position statement was compiled and circulated among the panel and relevant suggestions incorporated to reach consensus. This was discussed and finalized in an open forum during the SCS Annual Meeting, ISSICON. RESULTS: Preclinical evidence suggests safety and clinical potency of cellular interventions after SCI. However, evidence from clinical studies consisted of mostly case reports or uncontrolled case series/studies. Data from animal studies cannot be generalized to human SCI with regard to toxicity prediction after auto/allograft transplantation. CONCLUSIONS: Currently, cellular/stem cell transplantation for human SCI is experimental and needs to be tested through a valid clinical trial program. It is not ethical to provide unproven transplantation as therapy with commercial implications. To stop the malpractice of marketing such "unproven therapies" to a vulnerable population, it is crucial that all countries unite to form common, well-defined regulations/legislation on their use in SCI. These slides can be retrieved from Electronic Supplementary Material.