The Indian Council of Medical Research has objected to amendments proposed by the Ministry of Health and Family Welfare to the Drugs and Cosmetics Rules, 1945 on the regulation of stem cells procedures. The amendments seek to exclude certain kinds of processed stem cells, called minimally manipulated stem cells, from being defined as new drugs. Such an exclusion will man that these cells will not have to be tested in clinical trials for efficacy and safety before they receive market approval. If passed, these amendments may legitimise the use of unproven stem cell therapies in India.

The proposed amendments were notified on April 4, with 45 days until May 20 given for objections and comments. The Indian Council of Medical Research submitted its objections on April 29.

Stem cells are cells that are derived from parts of the body like the embryo and umbilical cord that can grow into different kinds of specialised cells in the body, like nerve cells or blood cells. Stem cells derived from bone marrow have been successfully used for treating blood cancers including leukemia. Donation may be autologous, in which a patient is treated with his or her own stem cells, or allogenic, in which a patient gets stem cells from another donor. Many other stem cell therapies are still in clinical trials and their efficacy and safety are yet to be proven.

In India, there is no law to regulate the use of stem cells. The Indian Council of Medical Research has issued guidelines that recognise stem cell therapies only for certain treatments and say that other types of treatments are unproven and should not be offered as therapy.

The health ministry seeks to change this by amending the rules of the Drugs and Cosmetics Act, which regulates the approval and use of drugs in India. At present, stem cells are not classified as drugs. If the amendments are accepted, stem cells will be classified as drugs and will come under the jurisdiction of the Drugs Controller General of India. Crucially, however, the proposed amendment excludes stem cells that are “minimally manipulated” from the definition of a new drug.

Stem cells are described as being minimally manipulated when they are retrieved from an individual, subjected to minor procedures like rinsing, cleaning and resizing and do not undergo any other processing steps that may alter their function before being re-implanted into the same individual.

The amendment contradicts the guidelines issued by the ICMR. On April 29, ICMR submitted its objections, suggesting that minimally manipulated stem cells should also fall under the definition of a drug. By excluding “minimally manipulated” stem cells, the proposed amendment may allow doctors to offer many unproven and unregulated stem cell therapies.

“Even if minimally manipulated stem cells are to be used for clinical application, our guidelines mandate that necessary permissions from the Central Drugs Standard Control Organisation and the Institutional Committee for Stem Cell Research need to be taken,” said Dr Geeta Jotwani, deputy director general, Indian Council of Medical Research.

The ICMR guidelines say that any stem cell use in patients, apart from those already approved, must only be done as an approved and monitored clinical trial with the intent to advance science and medicine, and should not be offered as therapy.

Several Indian doctors offer stem cell procedures for to treat conditions like autism, muscular dystrophy, spinal cord injuries, cerebral palsy without having adequate clinical data to show that the therapy has benefits in improving the condition of patients.

The Drugs Controller General of India Dr S Eswara Reddy defended the proposed amendments, which he said his office had been mulling over for more than a year. “The amendments are proposed to bring uniformity and clarity on stem cell products in India,” he said.

However, suspicion is being raised on why the DCGI did not wait for the report of the sub-committee formed by its advisory body, the Drug Technical Advisory Board. The sub-committee was formed to deliberate on regulating stem cell on January 31, 2017. But a member of the sub-committee told that they never met. “Even we didn’t know about this draft notification,” said the member.

Valid distinction?

In 2001, at around that time at United States President George W Bush restricted federal funding for stem cells obtained from human embryos, the Indian government started looking into regulating the growing stem cell industry in India. The health ministry asked the ICMR and the DCGI to to draw up guidelines. The latest edition of stem cell research guidelines by the ICMR were issued in 2017.

Neurons (green) that have been developed from human induced pluripotent stem cells; the cell nucleus is depicted in blue. (Photo: The Scripps Research Institute)

A senior official from the office of the DCGI said that guidelines are “not mandatory”. The same official added that the guidelines were not being followed. “The only way we can regulate the industry is by having a legislation which clarifies what is and what is not allowed,” added the official who did not want to be named.

However, a senior ICMR official told that the proposed amendments are only a cover for doctors to offer unproven stem cell therapies for exorbitant fees.

In its comments on the health ministry’s proposed amendments, the ICMR has objected the exclusion of minimally manipulated stem cells from being called drugs.

The health ministry notification says that only those stem cells that undergo “substantial or more than minimal” manipulation need to be regulated. But the ICMR wants the use of minimally manipulated stem cells also to require approval before they are offered as clinical therapy.

Last year, the ICMR had asked doctors offering stem cell procedures to submit clinical data demonstrating the efficacy of these therapies but the research body did not receive any submissions of importance. “Some doctors submitted us hypothesis on stem cells,” said an official from ICMR. “No one had any scientific data to show us [that the therapies were effective].”

Capacity of the regulator

Health activists and researchers said that the regulatory difficulties cannot be an excuse to not regulate the industry. Dr Anant Bhan, a researcher of bioethics and global health and policy, pointed out that patients will be more vulnerable to exploitation in the absence of a regulatory authority. “We have already seen cases where families have paid heavy sums to get these so called magical stem cell therapies and haven’t been benefited,” he said. “There are concerns about the safety and utility of stem cell therapies and [having] no regulation would only bring bad name to the industry and increase distrust.”

Not surprisingly, doctors working on stem cell therapies have welcomed the proposed amendments.

“It is an extremely proactive step from the regulator,” said Dr Abhjit Bopardikar, director of Reelabs, a company dealing in stem cell banking and therapies.

Speaking to Economic Times, Stem Cell Society of India president Dr Alok Sharma called the changes progressive and in line with developments in countries like Japan, Korea and the US.

“This amendment will facilitate growth of cell therapies in India and will also make these therapies available to lakhs of patients who are currently suffering with incurable diseases,” he said.