Stem cell research and therapy in India: General awareness for the public and stem cell therapy providers

Caroline Mathen; Neeta Devi Sinnappah-Kang

doi:10.4103/cjhr.cjhr_91_19

REVIEW ARTICLE

Year : 2020 | Volume : 7 | Issue : 2 | Page : 90-94

Stem cell research and therapy in India: General awareness for the public and stem cell therapy providers

Caroline Mathen¹, Neeta Devi Sinnappah-Kang²
¹ Clinical R & D, OCT Therapies and Research Private Limited, Mumbai, Maharashtra, India
² Betty Cowan Research and Innovation Centre, Christian Medical College and Hospital Brown Road, Ludhiana, Punjab, India

Date of Submission	21-Aug-2019
Date of Decision	04-Apr-2020
Date of Acceptance	20-May-2020
Date of Web Publication	8-Oct-2020

Correspondence Address:
Neeta Devi Sinnappah-Kang
Betty Cowan Research and Innovation Centre, Christian Medical College and Hospital Brown Road, Ludhiana - 141 008, Punjab
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/cjhr.cjhr_91_19

Abstract

The rapidly evolving field of stem cell research and therapy, along with changing regulations requires clarity both for stakeholders and patients who take recourse as a last resort. If one was to do a search for a paper on public awareness in this area, there are very few, more so for India. The main objective of this article is to help the lay public and also those interested in providing stem cell therapy understand the current rules and requirements in India. This article provides important information in a concise, to the point and nontechnical way.

Keywords: Central Drug Standard Control Organization, Indian regulations, National Apex Committee for Stem Cell Research and Therapy, stem cell research, stem cell therapy

How to cite this article:
Mathen C, Sinnappah-Kang ND. Stem cell research and therapy in India: General awareness for the public and stem cell therapy providers. CHRISMED J Health Res 2020;7:90-4

How to cite this URL:
Mathen C, Sinnappah-Kang ND. Stem cell research and therapy in India: General awareness for the public and stem cell therapy providers. CHRISMED J Health Res [serial online] 2020 [cited 2023 Mar 31];7:90-4. Available from: https://www.cjhr.org/text.asp?2020/7/2/90/297585

Introduction

Stem cells serve a unique function in the human body that is to repair damaged tissues and regenerate new cells to replenish those that die during their normal lifespan. It is widely recognized that stem cell therapies have been expected to revolutionize healthcare and offer hope for patients suffering from numerous diseases and injuries that have limited or no therapeutic options. Given the significant investment of research resources and finances, it is important to understand the clinical trial (CT) outcomes.^{[1],[2],[3],[4],[5],[6],[7],[8]} It is imperative to monitor the outcomes on a continuous basis to comprehend the timeframe needed to achieve a successful product and monitor if a product causes collateral loss because it is unable to satisfy the regulatory guidelines and CT output. There are several reports that have reviewed the outcome of the use of different types of stem cells in various CTs.^[9],[10] A few examples of stem cell research cover wound healing,^{[11],[12],[13]} stroke,^{[14],[15],[16],[17]} cardiac regeneration,^{[18],[19],[20],[21],[22]} type I diabetes,^[23],[24] multiple sclerosis,^[25],[26] spinal cord injury,^[27] osteoarthritis,^[28] hepatic repair,^[29],[30] graft-versus-host disease,^{[31],[32],[33]} and more recently therapeutic strategies for the management of COVID-19 patients.^[34],[35]

In India, public understanding, knowledge and awareness about stem cell research and therapy is either very limited or nonexistent. Most of the time, the factor that drives families into stem cell therapies is the hope that there may be a chance that it may work for an ailing family member when conventional approaches fail and all other hope is lost. Due to the involvement of large financial costs, it becomes an ethical issue.

The main objective of this article is to help the lay public and also those interested in providing stem cell therapy understand the current rules and requirements in India. It is important to understand the ethical issues that have caused some cautionary measures to be set in place to limit certain activities and assertions related to stem cell therapies. As per the latest National Guidelines for Stem Cell Research (NGSCR) (2017)^[36] by the Indian Council of Medical Research (ICMR) and Department of Biotechnology, “every use of stem cells in patients outside of an approved clinical trial is considered unethical and shall be considered as malpractice”. This rule is not known by a lay person. ICMR puts the responsibility of communicating information to patients about CTs involving stem cells on the Principal Investigators, i.e., assuming the CT has been approved and registered with the Government of India (GoI). However, in many scenarios, the therapy is being offered by those whose laboratories are not registered and whose protocol has not been linked to any approved CT. In the latter case, the general public is left to look for information on their own which can be a daunting task. With the stakes being high, scientific misconduct may range from outright data fabrication to violation of ethical norms.^{[37],[38],[39]}

Government agencies in India and around the world^[40] continue to engage with all stakeholders involved to improve the safety and efficacy of using stem cells. The paper brings together information in a very concise manner, highlighting the important points to note for the general public and those who are interested in providing stem cell-based therapy. It is hoped that the information provided will help in ensuring that only those CTs that are well regulated and approved may be offered as therapy.

What Should the Lay Public Understand When They Are Seeking Stem Cell Therapy?

Stem cells are living cells, unlike a pill or chemical liquid. The regulation and quality control governing harvesting, propagation, stability and administration of stem cells are critical. Laboratories involved in research and/or CTs using stem cells must have a registered Institutional Committee for Stem Cell Research (IC-SCR) and be approved by the National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT). The links to the various information provided at the NAC-SCRT website are listed in [Table 1]. The public can verify the approval of the institution/clinic/private company easily via the website.

Table 1: Useful links at the National Apex Committee for Stem Cell Research and Therapy and Indian Council of Medical Research websites

Click here to view

The involved laboratories must be good manufacturing practice (GMP) and good laboratory practice (GLP) certified facilities. Without these certifications, the quality and safety of the products (i.e., stem cells or their derivatives) will be compromised. A patient information sheet must be provided with details about the CT, possible benefits and risks; and its expected outcome.

As of now, umbilical cord blood banking is permitted and licensed by the Central Drug Standard Control Organization (CDSCO). “Commercial banking of other biological materials (is) not permitted until further notification” by NGSCR. A violation of the rules of CDSCO can result in the registration of IC-SCR being withheld. The list of these companies is also available on the NAC-SCRT website [Table 1] along with those seeking renewal, under review or requiring clarifications/compliance with guidelines, and requiring resubmission.

For Private Start-Ups, Hospitals or Clinics Interested in Providing Treatment, How Should They Prepare?

Human stem cell research, especially involving translational research, has led to a new type of medical intervention using living entities. The seemingly endless potential and ability of this new type of drug has shaped modern therapeutic modalities. From the regeneration of damaged tissues to personalized medicine, all that cannot be treated using conventional medicine now seems squarely within reach. This “living medicine” which is fast being used throughout the world, is more biocompatible and manifests fewer side effects.

However, cell-based products are not classified as chemical entities, and thus the CDSCO (India's regulatory authority) has published the new Drugs and CTs Rules in March 2019 (as per G. S. R. 227 (E) Gazette notification).^[41],[42] Along with the 2017 NGSCR, this notification has brought much-needed clarity to the process of obtaining cell-based products and derivatives and delivering them to the bedside in a clinically safe, efficacious, and relevant manner.

Types of accreditation

Firstly, one must form an IC-SCR (as per the NGSCR, 2017). The aim of IC-SCR is to examine the scientific, technical, ethical, legal, and social issues in the stem cell research. This institutional-level body is self-regulatory. Thus, it must be an independently functioning body without any interference, bias, or undue influence. In fact, the quality and independence of the IC-SCR goes a long way in establishing its credentials as a local regulatory body.

In order to function smoothly, the committee must consist of at least 11 medical and nonmedical representatives. It should ideally include experts in stem cell research, cell and molecular biology, clinical medicine, hematology, immunology, developmental biology, assisted reproduction technology, toxicology, related disciplines (as per the requirements of the research undertaken), ethics, social sciences, and law. A lay person must also be included. Depending on the need, a subject expert may be invited (without voting rights) to present their views and enable the IC-SCR members to take an informed decision.

It is crucial to ensure that whenever a meeting is convened, the voting members do not have any conflict of interest (COI). If any COI exists, it must be recorded, and the concerned member must abstain from the decision-making process. The only member of the IC-SCR who can be affiliated to its institute is the Member Secretary. This person should preferably not belong to the scientific or clinical team which is proposing the research activity, so as to avoid any potential or implicit COI. All research proposals must necessarily be vetted by the IC-SCR, and the quorum should include the Chairperson/Vice-Chairperson, Member Secretary, experts from law, ethics, and social sciences, community/lay person, and two stem cell/cell and molecular biology experts – all with no COI. All IC-SCR members are expected to be familiar with the current bioethical and stem cell research guidelines, and Good Clinical Practices. All members must also sign a confidentiality agreement, and strive to attend all IC-SCR meetings.

The IC-SCR must be registered with NAC-SCRT. This is an online process and generally takes between 8 and 12 months. Although most criteria are attainable, it isn't easy to identify stem cell experts without any potential COI.

The NAC-SCRT has been set up by the Department of Health Research (Ministry of Health and Family Welfare, GoI) as an independent apex body of experts from different areas of biomedical research, relevant government agencies, and other stakeholders [Tables 1, no. 2]. It comprises a monitoring mechanism at the national level.

Registering the laboratory with Government of India

Allogenic products

The institute carrying out stem cell research has to first apply for a Test License with Form CT-10, which will allow it to carry out research activities for tests and analyses. The drug-development process is similar. The institute has to apply for the No Objection Certificate (NOC) from the CDSCO. This is followed by a joint inspection by CDSCO and the local Food and Drug Agency. The inspection report, along with the CDSCO's NOC, can help in applying for the Test License, which is granted in CT-11 as per the new rules.

This license allows the institute to manufacture stem cells or stem cell derivatives, which can be used for preclinical testing. This includes all characterization data, stability studies, efficacy studies, and safety studies. The studies have to be carried out in compliance with GMP/GLP. This means that the manufacturing facility has to uphold GMP norms, and the testing facility (especially for safety studies) has to be a GLP-accredited laboratory. Apart from IC-SCR, one will need the hospital IEC approvals (for obtaining tissue source), the documented informed consent, and the approvals from the Institutional Animal Ethics Committees for small animal studies. If larger animals or nonhuman primates are involved in testing, then additional approval from The Committee for the Purpose of Control and Supervision of Experiments on Animals is required.

The next step would entail CTs. For this, the institute has to apply for Test License for CTs (not the License for sale). The protocol for the CT is as per the template described in Annexure II of the NGSCR (2017), the application is made in Form CT-04 or CT-4A to the CDSCO, and the permission is granted in Form CT-06.

Autologous products

For minimally-manipulated products or more than minimally-manipulated products, there are inherent limitations to carrying out preclinical studies. For example, it may not be feasible to carry out stability or safety studies. However, for unapproved indications, CTs would still be a requirement to establish the safety and efficacy of the cell-based products. Thus, the other regulatory compliances of IC-SCR, IEC and NAC-SCRT approvals would be mandatory. Currently, the only approved indications include those using Hematopoietic Stem Cell Therapies for the malignant and non-malignant conditions described in Annexure III of the NGSCR (2017).

Registering the clinical trial

The sequence of events is as follows:

Obtain IC-SCR approval
Obtain NAC-SCRT approval (the proposal will be evaluated by the Cell Biology-Based Therapeutic Drug Evaluation Committee (CBBTDEC), which will then place the proposal before the NAC-SCRT
Obtain hospital IEC and IC-SCR approvals for the trial sites
Register the trial on ctri.gov.in at http://ctri.nic.in/Clinicaltrials/login.php
Establish a separate Data Safety Monitoring Board for each CT to monitor any adverse events. The members should not have any COI and the functioning should be independent of the IC-SCR and IEC.

Additional information to assist you

The entire process of commercializing cell-based products or derivatives has been streamlined and offers greater clarity when compared to the earlier guidelines. For example, the Technical Evaluation Committee has been eliminated, as this was an additional step between the evaluation by the CBBTDEC and the NAC-SCRT. Moreover, combined Phase I and II trials are acceptable for stem cell CTs. An encouraging shift has been the provision of conditional approval of cell-based products for unmet needs, if the process or product shows demonstrable safety and efficacy characteristics.

Database on Clinical Studies

An example of a registry that compiles a broad range of publicly and privately funded clinical studies from around the world is ClinicalTrials.gov. It is a resource provided by the U. S National Library of Medicine. They put the onus of the safety and scientific validity of the clinical studies on the sponsors or funders and the investigators. Please read their disclaimer carefully.

On the main page, a search can be carried out using the keywords. For example, under “Condition or disease” and “Country,” if the terms “spinal cord injuries” and “India” are inserted, nine studies are listed (as of December 17, 2019). Then based on the information provided, a patient can have discussions with their health care provider. As a “Condition or disease” is typed within the box, a dialog menu appears below and helps by suggesting related words. This registry covers clinical studies on different conditions or diseases from September 2008 onwards. It is an excellent resource.

Summary

The main aim of this article is to provide a brief overview to the lay public, hospitals, clinics, and start-ups about what they need to know before seeking or providing stem cell-based therapies. It is also important to understand that guidelines are set in place to protect all involved from undesirable outcomes. The concise information provided in the article is meant to assist in decision-making, but this information may be updated periodically by the assigned government agencies in India. Thus, it is important to verify before proceeding forward.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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