Before a new drug, biologic or medical device is approved and authorized for market launch, it has to undergo a long and complex process involving extensive testing and clinical trials to ensure its safety and efficacy. However, for patients who have exhausted all other options, sometimes an unapproved or pre-approved or investigational drug could be the only hope. There are ways and means to access unauthorized medicines or treatment options, most obviously through participating in a clinical trial. But if even clinical trials are not possible, Managed Access Programs (“MAPs”) can help. This note discusses MAPs and their regulation in India.
Managed Access Programs
Managed Access Programs, or MAPs, are programs under which investigational medicines, or medicines for which market authorization is pending, may be made available to patients who cannot enroll in clinical trials. The term is used interchangeably with programs such as Compassionate Use (“CU”), “Expanded Access”, and “Named Patient Supply” programs.
These programs do not fit into standard definitions, and different jurisdictions and groups have chosen to interpret and understand them differently. For example, the World Health Organization says that such programs could involve:
“use of an unproven treatment outside of a clinical trial, that is usually being evaluated in clinical trials, for the clinical benefit of an individual with a serious or life-threatening disease or condition, and no other reasonable alternatives”.
“use of an investigational intervention for patients outside of an ongoing clinical trial.”
The European Medicines Agency describes CU programs as “a treatment option that allows the use of an unauthorized medicine. Under strict conditions, 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.”
The US Food and Drug Administration (“FDA”), which prefers the term “Expanded Access”, defines it as a “potential pathway for a patient with an immediately life-threatening condition or serious 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.”
Given the definitional variance, and the range of regulatory controls they operate under, the design of MAPs tend to vary too, but some basic features are usually common. Typical pre-conditions for MAPs that apply in most jurisdictions include the following:
- the patient has a serious, life-threatening or severely debilitating disease;
- the patient is unable to participate in a clinical trial due to ineligibility or otherwise;
- no satisfactory or comparable alternative treatments are available;
- sufficient evidence supports that the potential benefit to the patient justifies the potential risk;
- the drug in question must be available in adequate supply to support both clinical trials and pre-approval access; and
- pre-approval access must be allowed under local country laws and regulations.
Requests for accessing such programs must be made to the competent regulatory authority of the concerned country, and in some cases, especially programs classified as CU programs, drugs may be provided to the patient free of cost. Drug shipments are also delivered to the concerned hospital or institution only, and not directly to the patient.
Under the Named Patient Supply (“NPS”) program, a doctor requests supply of an unauthorized medicine directly from the manufacturer to treat an individual patient, provided that such supply is allowed under local laws. This is usually undertaken on an individual basis, under the direct responsibility of the doctor, and the patient bears the costs of the drug.
Regulating MAPs in India
Drugs and medical devices are regulated under the Drugs and Cosmetics Act, 1940 (the “DC Act”) and the Drugs and Cosmetic Rules, 1945 (the “DC Rules”) in India. While the DC Act is silent on CU, the DC Rules have some relevance to MAPs. These rules allow for drugs to be imported either by doctors and hospitals, or by individuals themselves, under certain conditions.
Rule 33A allows government hospitals or autonomous medical institutions to import certain drugs, which is otherwise prohibited under the DC Act, for the treatment of patients. As per this Rule, small quantities (100 average doses per patient) of a new drug may be imported for treating patients of life threatening diseases, or diseases causing serious permanent disability, or diseases requiring therapies for unmet medical needs. The hospital or institution in question must apply to the Drug Controller General of India (DCGI) for access to the drug.
Rule 36 provides that small quantities of drugs, the import of which is otherwise prohibited, may be imported for personal use. There are two ways to do this: imported via personal baggage, or imported otherwise. Where the drugs form part of a passenger’s bona fide personal baggage, they must be for the exclusive personal use of that passenger; the quantity of the drug must not exceed 100 average doses (although, in exceptional cases, this limit may be waived); and the drugs must be declared to the Customs department, if directed. Drugs imported for personal use but not part of personal baggage may be imported if, upon an application made in this regard, the licensing authority is satisfied that the drugs are for bona fide personal use, the quantity to be imported is reasonable, and are covered by prescription.
Additionally, Rule 36A allows the importation of small quantities of a drug or a medical device donated to a charitable hospital for the treatment of patients free of cost may also be allowed by the DGCI.
Regulatory controls around MAPs in India may change in the future, and potentially become simpler. For example, draft rules (New Drugs and Clinical Trials (Amendment) Rules) issued in 2020, intend to permit CU for any new unapproved drug by hospitals and medical institutions for patients that require them, if the drugs are under Phase III clinical trial in India or abroad. The draft also allows a manufacturer to apply to the Central Licensing Authority (CLA) for a license to manufacture new drugs for CU. Note that these amendments are only still in draft form, and there has been no further development in this regard.
MAPs in action in India
Many patients and hospitals have successfully obtained access to unapproved drugs in India through various MAPs. Examples include, anti-tuberculosis medications like Bedaquiline and Delamanid have been made available to individual patients under CU programs like the National Tuberculosis Control Program (“NTCP”) services, with the preapproval of the DGCI upon request from treating physicians. In both cases, the physician needs to submit patient details for accessing the drugs from their respective manufacturers (Jensen and Otsuka).
Through the pandemic, the Central Drugs Standard Control Organisation approved injectable formulations of Remdesivir for treating patients with severe COVID-19 infection and Favipiravir tablet for CU for treatment of mild to moderate COVID-19 infection. Both drugs were supplied for use only to the hospital/institutions, and informed consent of the patient or their representatives was mandatory before treatment.
The way forward
India’s burgeoning population comes with many concerns, equal and adequate access to healthcare being one of them. Even as the internet has made information around cutting-edge developments in medicine available, access to these developments is not always simple. Strict regulatory control around MAPs means that accessing unapproved drugs is not straightforward. Compliance requirements and paperwork to obtain such drugs can slow down access. Sometimes, patients and doctors may also not be aware of the options at their disposal. A robust functioning of MAPs would require a combination of increased awareness and simplified access procedures, with regulatory intention to eventually speed up clinical trials and market approvals of new drugs and devices, to ensure that everyone has a fair right to health.