India Proposes To Regulate Stem Cells As Drugs; To Require Clinical Trials, Licenses

Chandigarh: New rules proposed by India's health ministry promise to put an end to shady medical practitioners promising stem cell-based miracle cures to desperate patients, who have so far operated out of the ambit of the law.

The draft Drugs and Cosmetics (Amendment) Rules of 2018, issued for stakeholder consultation in April, seek to regulate stem cells as well as stem cell-based products as drugs, bringing them firmly under the Drugs and Cosmetics Act of 1940.

This means all clinical use of stem cells (for treatment) and their products will have to first be backed by clinical trials to prove safety and efficacy, and will then require licenses for manufacture and sale. No clinics or hospitals that have not first met the rigorous standards prescribed for clinical trials to prove that their stem cell-based therapies work will be able to administer these treatments.

Stem cells in plants and animals are undifferentiated cells whose offspring cells can either continue as stem cells or become differentiated (or specialised) to produce various tissues and organs. This property of stem cells to differentiate has been the subject of much medical research--and some limited therapeutic applications--for their potential to replace defective or damaged cells and thus treat a variety of degenerative diseases such as Parkinson's, injuries such as to the spine, and even cancer.

However, regulators around the world have struggled to understand the complexity of stem cell research and potential therapies in order to regulate them. As a result, developed and developing countries alike have seen a proliferation of clinics and doctors promising stem cell-based treatments and cures.

The Indian health ministry's proposed rules are aimed at regulating self-styled clinics and hospitals--estimated to number 300--that have been offering a range of untested and unproven stem cell "therapies", usually charging patients significant sums of money.   

All stem cells and stem cell-based products involving more than "minimal manipulation"--defined as "ex-vivo [outside of the organism] alteration in the cell population... which is expected to result in alteration of function”--will be termed as drugs and would hence have to follow the regulatory protocols mandated for new drug development, namely, establishing safety and efficacy through clinical trials, and then obtaining licenses to manufacture and sell.

Current status

Over the past two decades, numerous hospitals and clinics have mushroomed around the country claiming to offer stem cell-based "treatments" without preclinical evidence of their efficacy and safety, operating under the regulatory radar as existing legislation and rules do not apply to them.

Last year, the Department of Biotechnology and the Indian Council of Medical Research released the National Guidelines for Stem Cell Research 2017 that made it clear that all clinical use and research with stem cells could be conducted as clinical trials only--free of charge for patients, and with all requisite approvals from the regulator, the Central Drugs Standard Control Organization.

In addition to putting a stop to use of stem cells in authorised facilities, the guidelines also put a stop to advertisements by clinics offering unapproved therapies.

Clinical (therapeutic) use of only 'haematopoietic stem cell transplantation' was allowed, but only for specified conditions for which its efficacy and safety is recognised globally.

Haematopoietic stem cell transplantation involves intravenous injection of the receiver's own or another person's stem cells collected from bone marrow, peripheral blood (blood circulating in the body), or umbilical cord blood to treat bone marrow or immune system damage or defects. The guidelines allowed this for some 30 specified conditions including acute myeloid leukemia and Burkitt's lymphoma.

The Indian Medical Association had welcomed the guidelines, saying they would provide procedural clarity.

However, numerous clinics have continued to offer stem cell treatments for a wide range of clinical conditions including muscular dystrophy, cerebral palsy, Alzheimer’s disease, Parkinson’s disease and spinal cord injury, with apparently little oversight, Shashank S. Tiwari, a U.S.-based scholar of science and technology studies with a PhD in the ethics and governance of stem cells in India, told IndiaSpend.

Unlike in the U.S., Germany and Japan where adverse effects including deaths have been recorded, no patients have come forward to report cases of harm in India and therefore, no action has been taken against doctors offering such treatments.

Draft rules

"This is the first time that regulatory action has been proposed to be included in the Drugs and Cosmetics Act and Rules thereunder for stem cells and stem cell-based therapies,” Rajdutt Shekhar Singh, partner at law firm Singh & Associates, told IndiaSpend. The proposed rules would apply to both autologous stem cells--from the patient's own body--and homologous stem cells--from another human.

Singh said some businesses he advises have suggested an exemption for autologous cells in their comments to the ministry, as is the case in some large and significant jurisdictions such as the EU and Australia. There, autologous cells and their manipulation are outside the purview of regulation.

However, such use has been problematic, and in the US, the Federal Drugs Administration has cracked down on some clinics offering autologous cell "treatment".

Allowing minimally manipulated stem cell-based therapies would result in these being "administered in vulnerable patients without any oversight", Tiwari warned. "The experience in the US suggests that a majority of stem cell therapies in India will continue to be unregulated," he said, "Most clinics in India use autologous stem cells, which require minimal manipulation. A similar categorisation by the US FDA allowed unproven stem cell therapies to mushroom there, especially as they did not require pre-market authorisation."

The Indian Council of Medical Research has already been reported to have opposed waiver from regulation for minimally manipulated stem cells, arguing that many of the uses that minimally manipulated stem cells are put to are unproven.

Keeping these out of regulatory oversight will leave patients and their families open to exploitation, health activists warn.

It remains to be seen what shape the final rules will take, but the health ministry must strike a balance between supporting indigenous research and drug development on the one hand and protecting patient safety and interest on the other.

(Singh is a contributing editor with IndiaSpend.)

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