Advances in drug research over the years have resulted in the development of blockbuster drugs, which have increased the life expectancy of mankind. In the past decade, scores of patients across the globe suffering from rare or chronic ailments had limited treatment options due to unavailability / pending approval of life-saving drugs in their countries. From a legal standpoint, a drug is only permitted to be obtained and used by a patient once such drug has been granted the requisite approvals from the requisite drug regulatory authorities of such country after following proper clinical trial protocols that establish safety and efficacy of such drugs. With rising costs of drug trials, not every drug is submitted for approval in every country yet disease conditions that warrant use thereof still exist. Following representations from medical professionals and stakeholders to cater to such situations, drug regulators realized the need to ensure that such drugs are made available to those who need them irrespective of approval status. Currently, numerous expressions such as ‘usage on compassionate grounds’, ‘expanded access’ and ‘preapproval use’ exist to describe this concept and are used interchangeably[1].
The European Medicines Agency describes the expression ‘compassionate use’ as a treatment option that allows the use of an unauthorized medicines under strict conditions, wherein products in development can be made available to groups of patients who have a disease with no satisfactory authorised therapies and who cannot enter clinical trials.[2] Similarly, in the US, the Food and Drug Administration has coined the expression ‘expanded use’, which refers to a potential pathway for a patient with a serious or immediately life-threatening disease or condition to gain access to an investigational medical product (drug, biologic or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.[3]
In India, the Drugs and Cosmetics Act, 1940 (“D&C Act”) read with the Drugs Rules, 1945 (“Drugs Rules”)set out the regulatory regime surrounding the import, manufacture, and sale of drugs. As a general rule, a drug can only be sold to treat indications for which it has been approved. Any use thereof for the treatment of unapproved conditions (off-label use), is consequently prohibited. Every drug that is imported, sold, manufactured, and marketed in India is required to be accompanied by a package insert that has information pertaining to the approved therapeutic indications of the drug, method of administration thereof, contra-indications, warnings, interactions with other drugs, contra-indications in relation to pregnancy and ability to operate machinery/ vehicles, side effects and possible remedies in case of overdose thereof. Such package insert is also required to contain information pertaining to the excipients, drug incompatibilities, shelf life in packaged/ dilution/ reconstituted state, storage precautions including container specifications and instructions for use/ handling. In addition to the above, certain packaging related instructions/ conditions may also be prescribed by the licensing authorities on a case-to-case basis. All of the above form a part of the conditions, albeit not exhaustive, that are required to be adhered to for issuance of applicable licenses.
In addition to the prohibition on off-label use, pharmaceutical companies are also not permitted to be involved in any kind of marketing/promotional activities involving ‘off-label’ indications of approved drugs or unapproved drugs, as the case may be. The penalties for non-compliance of the above conditions as prescribed include imprisonment, fines, confiscation of drugs, and cancellation of license.[4]
The above said, there exist certain exceptions, built into the regulatory regime itself, that come to the aid and benefit of those who need life-saving drugs that may otherwise not be approved for use in India. In particular:
(a) Import by Individuals: Small quantities of ‘drugs’, the import of which are otherwise prohibited under the D&C Act, may be imported by individuals as part of their bona fide baggage for their exclusive personal use or for their bona fide personal use, subject to the prescribed conditions.
(b) Import by Government Hospitals / Government Medical Institutions upon application to the regulator: An application to import a ‘new drug’ (as defined under the New Drugs and Clinical Trial Rules, 2019), which has not been permitted for usage in India but approved for marketing in the country of origin for treatment of a patient suffering from a life-threatening disease or a disease causing serious permanent disability or a disease requiring therapies for unmet medical needs, may be made by the Medical Superintendent of a Government hospital or Head of the Government medical institution; and
(c) In the ‘research during humanitarian emergencies and disasters’ section of the National Ethical Guidelines for Biomedical and Health Research involving Human Participants, 2017, published by the Indian Council of Medical Research (ICMR), provisions have been made for monitored emergency use of unregistered and experimental interventions (MEURI) under specific conditions.[5]
In June 2020, the Ministry of Health and Family Welfare (“MoFHW”) proposed an amendment to the law, which provided for permission to import unapproved new drugs on grounds of compassionate use for treatment of patients by hospitals/medical institutions. Under this proposed exemption, medical officers of a hospital or medical institution may import a new drug for on grounds of compassionate use for treatment of patients suffering from a life-threatening disease, a disease causing serious permanent disability or a disease requiring therapy for an unmet medical need, which has not been permitted in the country but are under Phase-III clinical trials in India or in any other country. However, this exemption is still in the draft stage and has not been incorporated as part of the regulatory regime.
It is undeniable that a vast majority of the patients suffering from life-threatening diseases, which have no approved drug/therapy in India, struggle for their survival as their health consistently deteriorates. While the MoFHW has endeavored to propose and incorporate exceptions to the general laws regarding the usage of unapproved drugs in the country, it is apparent that the regulatory regime governing usage of drugs on compassionate grounds necessitates a regulated and structured framework. The framework provides scope for further reduction in the timelines in relation to the clinical trials and approval process, albeit with necessary checks and balances in place, so as to enable the patients/hospitals access to such drugs with informed consent as soon as possible. Inspiration for drafting a regimented framework for the usage of drugs on compassionate grounds and off label usage may be drawn from the extant guidelines and policies prevalent in other jurisdictions across the world, including the EU and US, where the concepts of usage of drugs on compassionate grounds have been assimilated into the regulatory regime of the country. It is also essential that the drug regulators work in tandem with the pharmaceutical companies and other stakeholders in order to create awareness through engagement and mitigate the increasing number of issues pertaining to the accessibility to life-saving drugs faced by the patient population at large.
[1] https://www.ijp-online.com/text.asp?2020/52/3/163/291391
[2] https://www.ema.europa.eu/en/human-regulatory/research-development/compassionate-use
[3] https://www.fda.gov/news-events/public-health-focus/expanded-access
[4] Refer Section 13 and Section 27(b) of the D&C Act and Rules 58 and 66 of the Drugs Rules.
[5] https://ethics.ncdirindia.org/asset/pdf/ICMR_National_Ethical_Guidelines.pdf
For further information, please contact:
Ashwin Sapra, Cyril Amarchand Mangaldas
ashwin.sapra@cyrilshroff.com
