Policy Considerations for Stem Cell Therapy in India

1. Policy Considerations for Stem Cell Therapy in India Dr. B. M. Gandhi CEO, NeoBioMed Services Formerly Adviser , Government of India, Ministry of Science and Technology, Department of Biotechnology dr.bmgandhi@yahoo.co.in, gandhidbt@hotmail.com www.neobiomed.com Presented at STEM 2014 at Bangalore on 31th January, 2014

2. Challenges • Length of time; long gestation period from research to market; • Patient’s acceptance / awareness / medical insurance and coverage; • Cost effectiveness, exorbitant cost of therapy ; • Regenerative medical technology difficult to evaluate; • Capital resources; difficult to arrange sustained funding from govt.; • Many companies not interested in financing cell therapies; • There is limited interest in early-stage start-up companies; • Small cell therapy developers unable to fund clinical trials; • Limited nos. of RM companies have commercial status; • Regulatory uncertainties; no universal agreement on regulations; • Multiple regulations for product registration; • Restrictive government’s policies limit international collaborations.

3. Funding Different funding possibilities and modules need to be explored: • Consider RM high priority for funding by government and private agencies; • Public funding routed through Translational Stem Cell Research facilities; • Therapy developers supported with public and private sources for early stage research; • Evolve Public–Private Partnerships and similar models; • Funding should come from foundations likely to be the ultimate beneficiaries; • Foundations generate fund through public appeals to improve specific disease Rx. • Big pharma / health sector should support and nurture small cell therapy developers; • RM companies collaborating for co-development of therapy/product must be encouraged and given incentives. • Stem cell centres of excellence should be supported in the states.

4. Limitations in Translational Research • Commercially viable therapies complex, lack innovation, regulatory flexibility; • Clear flexible industry oriented policy on therapeutic applications to curtail unapproved therapies; • R&D limited; institutes lack resources to fund further development, upscale; • Limited funds available for most institutions for clean room facility; • Ethical conduct of study; limitations of research, large animals and clinical trials • Joint development of products by research institutions and industry; • Industry ill-equipped for adaptive research for absorbing new technology; • Lack of sufficient strong patent protection discourages investment by industry • Collective representations of industry for SC therapy; Consortium suggested protecting interest of the industry.

5. Role of Funding Agencies Increasing role of stem cells in healthcare requires funding agencies to be innovative in identifying priorities / funding patterns to support SCR, upscale and therapy. • Awareness creation of stem cell based products and therapies among stake holders; • Encourage industry academic interaction; • Skill generation through cooperation and consultation with industry; • Consultancy/ guidance for starting new ventures in stem cells, like banking facilities; • Facilitation of technology scouting; • Establish centralized GMP facilities for testing, standards and characterization of stem cells; • Creation of centralized low-temperature banks of stem cells and tissues; • Support centralized facilities for development of animal models based on the requirements of researchers and clinicians; • Easing procedure for licensing, trade and regulation; • Industrial R&D supported by public funds without strings of collaboration with public research organisations.

6. Role of Local Bodies • Institute regulations and safeguard measures for research and therapeutic use of stem cells that harmonize the imbalance between the research and application that: • Differentiate between approved/standard therapies and other cellular therapies for marketing; • Allow limited controlled clinical trials; • Allow treatments subject to independent scientific and ethical review; • Enact pro-industry legal measures for safe therapeutic use of stem cells ; • Compassionate use of unapproved therapies; • Ensure common understanding of trial registration, data reporting and safety standards; • IECs given significant role where regulations protecting patient’s rights are weak; • Ensure sufficient information to patients on approved technologies and therapies ; • Ensure patients are aware of their rights and able to differentiate between the validated and fraudulence therapies.

7. Role of the Investigators • Ensure activities comply with requirements of regulators and IECs; • Compliance with GCP standards and regulations to ensure patient safety; • Publish trial results including negative results to benefit of healthcare professionals and patients • Ensure fair advertising on safety and efficacy of trials/experimental therapies • Must report any adverse event or side effects to respective regulatory bodies • Follow ethics of cellular therapy including disclosing any financial interest

8. Guiding Indian Policies • Policy Statement on Ethical Guidelines- ICMR 1980 • Ethical Guidelines for Biomedical Research in Human Subjects- ICMR 2000 • GOI Guidelines for Exchange of Human Biological Material for Biomedical Research Purpose – ICMR 1997 • Guidelines for Accreditation, Supervision and Registration of Infertility Clinics – ICMR 2004 • DBT Guidelines for Genetics and Stem Cell Research- DBT 2002 • Preconception and Prenatal Diagnostic Techniques Act, 2003 • Drugs and Cosmetics (3rd Amendment) Rules 2011 for Cord Blood Stem Cells • Guidelines for Stem Cell Research and Therapy, ICMR DBT 2007 are now the Guidelines for Stem Cell Research 2012

9. Guidelines for Stem Cell Research 2012 • Guidelines for Stem Cell Research and Therapy 2007 modified as Guidelines for Stem Cell Research 2012 • Emphasis on research and proof on concept before the stem cells are put to therapeutic applications. • Prescribe strict procedures for sourcing and use of stem cells by research institutions • Provide ethical direction to scientists working in the field. • Scope of Guidelines extended to all stakeholders’ involved with basic and clinical research on all types of stem cells from humans with or without manipulation.

10. Policy on Stem Cell Research (2012) Some Salient Features: • All stem cell therapy in India considered experimental, except BM; • SCR legalized for cells from adults, BMs or fetal cord blood. • Emphasis on basic research involving preclinical, clinical trials and clinical research to prove efficacy, safety and utility of the cell types used. • New class of human induced pluripotent stem cells (iPSC) added • New chapters added on preclinical and clinical trials, clinical research, Tissue Engineering and Scaffolds in SCR • Scope of Banking Standards of Biological tissues and distribution of Cell lines defined • Addressed issues on Import / Export of Stem Cells and Public Participation The Guidelines are silent on legal measures on unethical use of cells, Rights of donors of cells for basic R&D and protection and safeguards of recipients.

11. Recent Steps Initiated by GOI to Regulate laws for Stem Cell Therapy The Government of India has initiated steps towards regulating stem cell therapies. • Drugs and Cosmetics (3rd Amendment) Rules 2011 enacted for Manufacture of Blood Products and Collection, Processing, Testing, Storage, Banking and Release of Umbilical Cord Blood Stem Cells; • High Powered Committee (2013) set up to regulate stem cell and other cell based therapies; • Apex Court directed DGHS to file affidavit on different aspects of Clinical trials of new chemical entities in particular the deaths and adverse impacts; • Apex Court directed robust system for regulating clinical trials in ethical manner; • Transparency in payments by companies to investigators for conduct of clinical trials; • Drugs and Cosmetics (Amendment) Act, 2013 introduced in Parliament to regulate clinical trials and exports; • Report by Prof. RanjitRaiChaudhuri, 2013 on formulation of policy and guidelines for approval of new drugs, clinical trials and banning of drugs; • Bill to set up Central Drugs Authorityintroduced in RajyaSabha, August, 2013

12. The salient features of Drugs and Cosmetic (Amendment) Bill 2013 • Definition of “New Drug” include all vaccines, rDNA products, LMOs, mAb, stem cells, gene therapeutic products and xenografts intended for use as drugs; • Word “Manufacture” w.r.t. human blood/components include collection process, processing, storage, packing, labeling and testing for its use, sale, export or distribution for transfusion in human beings. • Prior permission from the Central Licensing Authority (CLA) mandatory for manufacture of any new drug • Central Drugs Authority represented by Secretaries/Officials of GOI, experts, state nominees of DCGI; would specify regulations, guidelines, norms, structures and requirements for Central Licensing Authority; have power to review, suspend or cancel any permission, license or certificate; would register all clinical trials for new drug or IND after permission of CLA • Includes Penalties and Punishments for violation and non-complianceconduct of clinical trials • Injury/death during clinical trial, compensated by developer as decided by DCGI / any other authority appointed for this purpose • Penalty: Injury ; Jail 3-5 yrs, fine rupees 10 lakhs, Death; Jail up to 10 yrs, fine rupees 20 lakhs

13. Laws for Stem Cell therapy ? Some Considerations? • Ban advertising/publicity in electronic/print media or otherwise any therapy for anti-aging, health and beauty benefits; • Allow therapeutic use of cells only after thorough testing for purity, sterility, viability, cytogenic stability and biological potency; • Make mandatory for commercial centre to obtain license from Drug Controller Authority for specific treatment / indication; • Regular reporting by FDA officers on inspection of clinical facilities for manufacture of stem cells;

14. Laws for Stem Cell Therapy ? Contd. • Enforce monitoring of treated patients for minimum five years or more by the treating doctors/clinics/institutions before the treatment is advertised for general public and proper data bank is prepared on its long term safety; • Maintain central registry of total information on patients having Stem Cell therapy including type of cells used, indications in which used, side effects noted etc.; • Make government officer/department responsible in case of gross violation of the Act if takes place by the doctor/clinic/institution situated in their jurisdiction.