The proposed regulatory pathway for ‘emergency use’ authorization of new drugs

Last month, the Ministry of Health invited comments on a proposed amendment to the New Drugs and Clinical Trial Rules, 2019 in order to create a new regulatory pathway for patients in private hospitals to access unapproved experimental drugs under a new compassionate use policy. The existing rules already provide for such a pathway to provide drugs to patients being treated in government hospitals. Our feedback to the government can be accessed over here.

It is not clear why private hospitals were excluded from the original 2019 rules and why the government has deemed it necessary to amend the rules now to include even private hospitals. As always, a draft set of rules was published without an explanatory note or a whitepaper. We can however safely presume that the government wanted to create a legal pathway to allow certain patients to access drugs that are not approved in India. Such a policy is prudent to a certain extent because there maybe life-saving therapies that are literally the last resort for some patients who cannot wait until clinical trials have been completed by the pharmaceutical company, often outside India. This however does pose an ethical dilemma for policymakers. Should patients who are already in a precarious medical position be given drugs whose benefit-risk ratio has not been established and what exactly should the safeguards be to protect these patients from unscrupulous hospitals and pharmaceutical companies? What if the drug worsens the patient’s condition?  

In the Indian context, new drug approvals is an area rife with controversies given how the DCGI has a history for approving drugs which have not been approved in any other country. In many cases the Ministry of Health has had to step in and prohibit the manufacture of such drugs. In this environment, seeking to drop existing regulatory thresholds to allow for the manufacture and sale of experimental drugs is worrisome. Yet there is a public interest in doing so, provided the government puts in place rules to protect the interests of patients.

In our opinion, the framework put in place by the government via these draft rules does not do enough to protect patients. To begin with, for the purpose of import, the rules require the medical institution to submit an application to the DCGI explaining the rationale for using this drug, data about the drug’s toxicity etc.  If this application is approved by the DCGI, the drug can be imported even if it is not approved for sale in India. In our opinion, these rules are problematic for two reasons. First, it does not mention any requirement for the medical institution to take the informed consent of the patient and to maintain records of such documentation. Second, these rules do not require an Ethics Committee to oversee the process within the medical institution. We think it is crucial that the process undertaken within the clinical establishment to prepare the application to for the DCGI be subject to a debate by an Ethics Committee that has external representation so as to counter any possible conflicts of interest.  In addition, we make recommendations for ensuring greater transparency throughout the entire process. For example, the medical institution and the recommending doctors should be required to disclose any conflicts of interest vis-à-vis the pharmaceutical manufacturer or importer or distributor of the experimental therapy. Similarly, the medical institution itself must make a disclosure regarding its margins (financial incentive) on such procurement. This is vital because hospitals in India do profiteer from the sale of the medicine. We also believe that the DCGI should be required to publish clear and cogent reasons while disposing such an application. Such reasons should be published in the Gazette of India.  

The second set of amendments proposed by this draft pertains to the manufacture of this drug domestically within India. The rules propose that the manufacturer seek the informed consent of the patient and secure approval from the Ethics Committee of the medical institution before submitting the application to the DCGI for its approval.

In our opinion, it is a bad idea to ask the manufacturer to get informed consent from the patient, given that the manufacturer is the one seeking to financially benefit from the sale of a drug to a vulnerable patient. This is a text book example of a conflict of interest. We therefore recommend against the manufacturer having to do anything with the process of informed consent. It would be more prudent for the Ethics Committee to oversee this process.

A second concern pertains to the manner in which the DCGI intends to validate the manufacturing process for the domestic manufacture of an unapproved drug. It is unlikely that enough information will be publicly available for experimental drugs in order to validate their manufacturing process. For example, with new drugs that are approved, a monograph is usually published in the pharmacopeia and reference samples are available for bioequivalence studies. How does the government expect to validate unapproved drugs when such information is not likely to be available? We therefore recommend that the government sort out this question before going ahead with this proposed framework. The last of our concerns pertain to special labeling measures for such drugs wherein the packaging indicates that the drug is not approved and is meant only as an experimental therapy under medical supervision. We also recommend that the government address issues such as patient privacy because most experimental therapies are given on the condition that their data is being shared with the manufacturer.  Further on the issue of compensation, there is complete silence in the proposed amendment. We argue for a compensation regime similar to the regime put in place for patients enrolled in clinical trials. At the end of the day, both patients are being administered unapproved therapies with incomplete information on their benefit-risk ratio. It is only fair that both sets of patients are protected equally under the law.

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