(debug: legal) The Pharma Legal Handbook: India

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The Pharma Legal Handbook: India answers essential questions about the legal and regulatory environment for pharmaceuticals in India. It is a must-have for any company operating in the country or looking to enter the market.

Prepared in association with Nishith Desai Associates, a leading Indian law firm, it should answer any questions linked to regulation, pricing, clinical and preclinical trials, marketing, manufacturing, trademarks and patents.

January 2024

1. Regulation, Pricing and Reimbursement Overview: India

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All about regulation, pricing and reimbursement in Indian pharma. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. What are the regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in your country?

The following authorities are responsible for the regulation drugs, biologics and medical devices in India:

(i) Central Drugs Standard Control Organization (“CDSCO”), headed by Drugs Controller General of India (“DCGI”) under the Ministry of Health and Family Welfare

The CDSCO regulates import, manufacture, marketing and clinical trials of drugs, biologics and medical devices for the entire territory of India.

(ii) State-level licensing authority (“SLA”)

Each State, through SLAs (who are the state-level Food and Drug Administration), independently regulates manufacture and sale of drugs, biologics and medical devices within the territory of that State.

In certain cases, there is an overlap of function between DCGI and SLAs. In such cases, SLAs operate under the direction of DCGI.

(iii) National Pharmaceutical Pricing Authority (“NPPA”) under the Department of Pharmaceuticals

NPPA fixes prices of certain essential drugs, biologicals and medical devices for entire territory of India. It monitors price movements other drugs, biologicals and medical devices to ensure that the prices do not increase more than 10% year on year. NPPA also monitors the availability of drugs and takes remedial steps to prevent shortage.

(iv) Controller of Legal Metrology

Each State, through its Controller of Legal Metrology, regulates packaging and labelling of medical devices. The Controller of Legal Metrology does not have jurisdiction over drugs and biologicals.

(v) Review Committee on Genetic Manipulation (“RCGM”) under the Department of Biotechnology (“DBT”)

The RCGM, under the Ministry of Science and Technology to evaluate safety related aspects of on-going research involving Genetically Modified Organisms.

(vi) Genetic Engineering Approval Committee (“GEAC”)

The GEAC, under the Ministry of Environment, Forests and Climate Change regulates research, testing, safe use and handling of Genetically Modified Organisms and their products from an environment safety perspective.

2. What is the regulatory framework for the authorization, pricing and reimbursement of drugs, biologicals and medical devices?

AUTHORIZATION/LICENSING

The Drugs and Cosmetics Act, 1940 (“D&C Act”) along with the Drugs and Cosmetics Rules, 1945 (“D&C Rules”) and The Medical Device Rules, 2017 (“MDR”) governs the authorization, import, manufacture, distribution and sale of drugs, biologicals of medical devices.

The MDR regulates only certain categories of medical devices specifically notified for regulation by the Ministry of Health and Family Welfare. Medical devices are categorised into one of four classes under the MDR on the basis of increasing risk, from Class A to Class D.

At the time of enactment of the MDR, only 15 categories of medical devices were regulated under the rules. 14 additional medical devices were notified and included within the regulatory framework in 2018 and 2019 with effect from different points of time in 2019, 2020 and 2021.

Subsequently, on 11 February 2020, the Ministry of Health and Family Welfare published a notification (which came into force on 1 April 2020) effectively bringing all medical devices under the ambit of the MDR. The notification notified an expansive and catch-all definition of medical devices (rather than notifying an individual or category of medical devices), so that all medical devices were notified and consequently brought under the ambit of the MDR.

To provide a transition period for the medical device industry to undertake the compliance requirements under the MDR, the Ministry of Health and Family Welfare has also provided a temporary exemption from adhering to the compliance requirements for a period of 30 months for Class A and B devices and 42 months for Class C and D devices. The exemption commenced on February 11, 2020 and is conditional on the manufacturer/importer of the medical device registering their device on the Online System for Medical Devices established by the CDSCO for this purpose.

PRICING

The Drugs (Price Control) Order, 2013 (“DPCO”) under the Essential Commodities Act 1954 (“ECA”) regulates the pricing of drugs, biologicals and notified medical devices in India.

REIMBURSEMENT

India currently does not have a mechanism for reimbursement of drugs, biologics and medical devices. Out-of-pocket expenditure by patients is the primary means of financing of drugs, biologicals and medical devices. For more details on India’s healthcare system, please refer to Chapter 1 Question 7.

3. What are the steps to obtain authorization to develop, test, and market a product?

DEVELOPMENT

There is no authorization required to develop a product in India. However, once a product starts showing properties that qualify it to be called as drug, then a license is required to import or manufacture it.

A product in development becomes a drug when it starts satisfying the criteria for what is considered a drug for the purposes of the D&C Act, which includes:

“all medicines for internal or external use of human beings or animals and all substances intended to be used for or in the diagnosis, treatment, mitigation or prevention of any disease or disorder in human beings or animals, including preparations applied on human body for the purpose of repelling insects like mosquitoes;
such substances (other than food) intended to affect the structure or any function of the human body or intended to be used for the destruction of vermin or insects which cause disease in human beings or animals, as may be specified from time to time by the Central Government by notification in the Official Gazette;
all substances intended for use as components of a drug including empty gelatine capsules; and
such devices* intended for internal or external use in the diagnosis, treatment, mitigation or prevention of disease or disorder in human beings or animals, as may be specified from time to time by the Central Government by notification in the Official Gazette, after consultation with the Board”

TESTING

Any processing activity carried out on a drug, biological or medical devices requires a manufacturing license from the CDSCO or SLA, as the case may be. Testing of product amounts to processing. Therefore, a manufacturing license for the purpose of examination, test or analysis is required to be obtained from the SLA. If a product on which testing is to be carried out is to be imported, then a separate import license for the purposes of test and analysis is required from CDSCO. Please note that the import license is to be obtained in addition to the manufacturing license.

MARKETING

If the drug or biological qualifies as a “new drug” or if a notified medical device qualifies as an “investigational medical device” or “new In Vitro Diagnostic Device”, then a marketing permission from the CDSCO is required to be obtained in respect of such drug, biological or medical device before its manufacture or import, respectively.

The definition of investigational new drug is as follows:
“investigational new drug” means a new chemical or biological entity or substance that has not been approved for marketing as a drug in any country”

The definition of new drug is as follows:
“new drug” means, –

a drug, including active pharmaceutical ingredient or phytopharmaceutical drug, which has not been used in India to any significant extent, except in accordance with the provisions of the D&C Act and the rules, as per conditions specified in the labelling thereof and has not been approved as safe and efficacious by the CDSCO with respect to its claims; or
a drug approved by the CDSCO for certain claims and proposed to be marketed with modified or new claims including indication, route of administration, dosage and dosage form; or
a fixed dose combination of two or more drugs, approved separately for certain claims and proposed to be combined for the first time in a fixed ratio, or where the ratio of ingredients in an approved combination is proposed to be changed with certain claims including indication, route of administration, dosage and dosage form; or
a modified or sustained release form of a drug or novel drug delivery system of any drug approved by the CDSCO; or
a vaccine, recombinant Deoxyribonucleic Acid (r-DNA) derived product, living modified organism, monoclonal anti-body, stem cell derived product, gene therapeutic product or xenografts, intended to be used as drug;

The drugs, other than drugs referred to in sub-clauses (iv) and (v), are considered to be new drugs for a period of four years from the date of the marketing authorization and the drugs referred to in sub-clauses (iv) and (v) shall always be deemed to be new drugs;

The definition of investigational medical device is a notified medical device:

“which does not have its predicate device as defined in clause (zm); or
which is licenced under sub-rule (4) or sub-rule (6) of rule 20, sub-rule (1) of rule 25, or sub-rule (1) of rule 36 and claims for new intended use or new population or new material or major design change;
and is being assessed for safety or performance or effectiveness in a clinical investigation.”

Next, depending on whether the product will be importer or manufactured in India, appropriate license is required to be obtained from the CDSCO or SLA.

The said marketing permission is give only when the DCGI is satisfied about the safety and efficacy of the product. Where the safety and efficacy of the product cannot be established with available data, then a clinical trial (in case of drugs) or clinical investigation (in case of medical devices) is required to be conducted in India to generate safety and efficacy data of the product on Indian population. A permission is also required to undertake clinical trial/clinical investigation in India.

Thus, for a product which qualifies as a new drug or investigational medical device, the steps needed to be taken to start manufacturing or import of the product in India are:

Obtain permission to conduct clinical trial from DCGI
Obtain permission to market product from DCGI on the basis of safety and efficacy data generated from the clinical trial
Obtain import/manufacturing license to start import/manufacture of the product.

If the drug or biological does not qualify as a “new drug” or if the notified medical device does not qualify as an “investigational medical device”, then the product may be marketed in India after obtaining import/manufacturing license.

4. What are the approximate fees for each authorization?

The fees for each authorization are summarized in the table below:

Type of Authorization		Fee (in INR)
Clinical Trials (Drugs)	Phase I	300,000
	Phase II	200,000
	Phase III	200,000
	Phase IV	200,000
Manufacture of New Drug	Original application	500,000
Manufacture of New Drug	Subsequent application by same applicant for the drug (but with modified dosage/new claims)	300,000
Import of New Drug	Original application	500,000
Import of New Drug	Subsequent application by same applicant for the drug (but with modified dosage/new claims)	300,000
Clinical Investigation (Medical Devices)	Pilot investigation	100,000
Clinical Investigation (Medical Devices)	Pivotal investigation	100,000
Clinical Performance Evaluations		25,000
Import or manufacture a medical device which does not have a predicate device (i.e. if the device is first of its kind).		50,000

5. For how long are marketing authorizations/registrations valid? How are marketing authorizations/registrations renewed?

Marketing authorizations for new drugs, investigational new drugs investigational medical devices and new IVDs are valid in perpetuity. Therefore, they do not need to be renewed.

6. How does the authorization process differ between brand-name products and generic products? Are there differences for local manufacturers versus foreign-owned manufacturers?

The drug and medical device regulatory framework does not make a distinction for authorizations between generic and brand name products or between local and foreign owned manufacturers.

In certain cases, there may be relaxations granted based on approvals/authorizations received from a foreign jurisdiction. For more information on the status of foreign marketing authorizations see Chapter 3 Question 6.

7. How are combination products (drug + drug, drug + biologic, drug + device, biologic + device, drug + biologic + device) regulated?

Combination products introduced into the Indian market for the first time are deemed to be ‘new drugs’, which means that a permission of the DCGI is required before they can be marketed in India. This deeming fiction continues for a period of four years, which means that any other importer or manufacturer of the combination product during the four-year period would also be required to obtain the permission of the DCGI for marketing of the said combination product.

After expiry of period of four years, combination products may be sold in India with appropriate manufacturing or import license from DCGI or SLA, without the requirement of obtaining a marketing permission from DCGI.

8. How is compliance with regulation monitored and evaluated? Is the regulatory regime comparable with the U.S. Food and Drug Administration or the European Medicines Agency expectations and requirements?

The CDSCO along with the SLAs is responsible for ensuring compliance with the requirements of the D&C Act. The CDSCO is primarily responsible for regulating and monitoring clinical trials and import of drugs, biologics and medical devices. The state drug licensing authorities primarily deal with licensing for manufacture, stocking and sale of drugs. The also carry out pre-licensing and post-licensing inspections and oversee the manufacturing process for drugs manufactured in their respective state units. The CDSCO and the state drug licensing authorities can inspect the premises of any manufacturing license holder without giving prior notice to ensure compliance with applicable laws. If non-compliance to any condition of the license or provision of the D&C Act is observed, the license can be suspended or cancelled, after providing an opportunity for the manufacturer to show cause as to why the license should not be cancelled or suspended.

With respect to clinical trials, the DCGI and Ethics Committee are the primary bodies exercising control over monitoring and enforcement. Any change in clinical trial protocol or serious adverse events occurring during the clinical trial must be notified to the Ethics Committee and the CDSCO.

Though the Indian regulatory framework is broadly comparable with U.S. Food and Drug Administration or the European Medicines Agency, India has its own unique and independent legislations governing the drug and medical device sector.

9. What is the potential range of penalties for noncompliance?

Penalties for non-compliances with the requirements of the D&C Act have been summarized in the tables below:

Import Related Contraventions

Offence	Penalty for First Offence		Penalty for Subsequent Offence		Comments
Offence	Imprisonment	Fine (in INR)	Imprisonment	Fine (in INR)	Comments
Import of adulterated or spurious drugs	Up to 3 years	5,000	Up to 5 years	10,000	The penalties can be imposed individually or together.
Import of prohibited drugs or import of drugs in contravention of the D&C Act	Up to 6 months	500	Up to 1 year	1,000	The penalties can be imposed individually or together.
Import of drug or cosmetic in contravention of a notification issued by the Central Government which prohibits import of drugs and cosmetics in public interest	Up to 3 years	5,000	Up to 5 years	10,000	The penalties can be imposed individually or together.

Manufacture/Sale Related Contraventions

Offence	Imprisonment	Fine
Manufacture or sale of adulterated and spurious drugs which may cause grievous hurt	Up to 10 years	Between 10,00,000 to three times the value of the drugs confiscated, whichever is more
Manufacture or sale of adulterated drugs (not causing grievous hurt) or manufacture of drugs without a valid license	Between 3 to 5 years	INR 1,00,000 to three times the value of the drugs confiscated, whichever is more.
Manufacture or sale of drugs in contravention of any other provision in the D&C Act	Between 1 to 2 years	INR 20,000

10. Is there a national healthcare system? If so, how is it administered and funded?

India does not have a national healthcare system on the lines present in the United Kingdom and other developed countries. The government operates a fair number of primary, secondary and tertiary healthcare centres around the country. However, a majority of health care providers in India operate privately.

The government operates several schemes under which beneficiaries can avail care facilities from private healthcare providers. For example, the Central Government Health Scheme (“CGHS”) extends medical coverage to central government employees, pensioners and their dependents. The Employee State Insurance Scheme (“ESI Scheme”) makes it mandatory for employers who employ more than a certain number of employees in the organized sector, to participate in an insurance scheme for employees that covers the employees against the events of sickness, maternity, disablement and death due to employment injury and to provide medical care to the insured employees and their families.

Having said that, it is a fact that a major chunk of Indian population does not have a health insurance. To address the situation, A National Health Policy was introduced in 2017, with the objective of providing health insurance coverage to poor and backward population of India the tune of INR 500,000 per year. Any healthcare provider who wishes to participate and offer its services under the National Health Policy is required to register itself with the concerned department. As a precondition of registration, the service provider has to agree to a fixed set of charges for its services that are pre-determined by the government. In furtherance of the policy, the Government in the Union Budget of 2018 announced ‘Ayushman Bharat’, a National Health Protection Mission funded through Union Budget allocations. INR 12 billion (approximately USD 1.8 billion) was allocated to set up one hundred and fifty thousand Health and Wellness Centres as well as hospitalization cover for approximately 100 million poor and vulnerable families with INR 500,000 (approximately USD 7,700) per family, for secondary and tertiary care hospitalization.

11. How does the government (or public) healthcare system function with private sector healthcare?

For the most part, public healthcare and private healthcare systems function within their own spheres. The cost of care at Government hospitals is fixed by the Government while the market determines cost in the private sphere. However, it has been observed that an increase in quality of public hospitals is concomitant with a decrease in cost of care at private hospitals. Certain primary health and secondary centers run by the Government provide free treatment to patients who are otherwise unable to afford it.

12. Are prices of drugs and devices regulated and, if so, how?

The prices of all drugs and notified medical devices are regulated in India. All drugs and notified medical devices have been identified as “essential commodities” and their prices are regulated like prices of other essential commodities under a law called Essential Commodities Act, 1955 (“ECA”) and an order called Drugs (Prices Control) Order, 2013 (“DPCO”).

The ECA and DPCO segregate drugs and notified medical devices under two categories – scheduled formulations and non-scheduled formulations, depending on whether the drug or notified medical device appears in the schedule of the DPCO. The prices of scheduled formulations are fixed by an agency called National Pharmaceutical Pricing Authority (“NPPA”). The schedule to the DPCO is based on the National List of Essential Medicines, which is amended from time to time. The NPPA uses a formula to fix prices that essentially averages the prices of the same drug or medical device sold under various brands in the market. The government does not fix prices for non-scheduled formulations. However, government has mandated that the price of non-scheduled formulations should not increase by more than 10% between any 12-month period. The NPPA is tasked with the duty of monitoring prices of non-scheduled formulations.

13. How are drugs and devices used by patients paid for? What roles do public and private payers play?

There are three main modes of financing available to patients— out of pocket, beneficiary of government scheme or insurance. Out-of-pocket payment methods, however, remain the primary means of payment as India suffers from low insurance penetration. Reportedly, only 12.78% of Indians have some form of Government insurance, while only 2.47% of Indians have private insurance. There are also certain Non-Governmental Organizations that provide free medication to patients who are otherwise unable to afford them.

14. Who dispenses drugs and devices to patients and how are those dispensers compensated?

Licensed pharmacies and pharmacists are the only persons permitted to dispense drugs to patients in India. The pharmacists are usually compensated by way of salary for their services as part of employment. It is unethical for pharmacists to charge commission from pharmaceutical and medical device companies for sale of drugs and devices to patients.

15. What are the professional and legal responsibilities of those who dispense drugs and devices? What role do they play in providing patient care, information, and safety?

Pharmacists are governed by the Pharmacy Act, 1948 (“Pharmacy Act”) and Pharmacy Practice Regulations, 2015 (“PPR”) issued under the Pharmacy Act. The Pharmacy Act lays down minimum qualifications and mandatory registration requirements for any person intending to practice the profession of pharmacy in India. The role and responsibilities of pharmacists are laid down under the PPR. The PPR defines the practice of pharmacy to mean:

“Interpretation, evaluation and implementation of medical orders; dispensing of prescriptions, drug orders
Participation in drug and device selection, drug administration, drug regimen reviews and drug or drug
Provisions of patient counseling and the provision of those acts or services necessary to provide pharmaceutical care in all areas of patient care including primary care; and
Responsibility for Compounding and labeling of drugs and devices (except labeling by a manufacturer, redistributor of non-prescription drugs of drugs and devices and maintenance of proper records for them.”

The responsibilities of registered pharmacists include:

Dispensing medication only on the basis of the prescription of a registered healthcare practitioner, and not substituting the prescription;
Compounding, preparing, mixing, dispensing and/or supplying medication on the basis of the prescription of a registered medical practitioner.
Counselling patients by personally initiating discussion on matters that will enhance or optimize drug therapy with each patient. The topics for the discussion may include special directions or precautions for administering the drug, common side effects of the drug and its proper storage.
Reviewing patient record history and prescription for identifying drug-disease interactions, drug-drug interactions and drug-allergy interactions;
Maintaining records of drugs dispensed and records of prescriptions for a minimum period of 5 years;
Maintaining confidentiality of information received;

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2. Preclinical and Clinical Trial Requirements: India

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Preclinical and clinical trial requirements in India. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?

If the drug or biological satisfies the definition of new drug (see Chapter 1 Question 3 above for definition), or if a notified medical device satisfies the definition of investigational medical device (see Chapter 1 Question 3 above for definition), then a clinical trial is required to be conducted locally as a pre-condition for marketing approval, in order to prove its safety and efficacy on Indian population.

However, if the investigational medical device is imported from United States of America, United Kingdom, Australia, Canada, Japan or the European Union, then the requirement to undertake local clinical trial may be waived on the submission of a free sale certificate from the relevant jurisdiction.

In all other cases, there is no requirement to undertake clinical trial before marketing of products in India.

2. How are clinical trials funded?

The clinical trials may be funded directly by the sponsor of the trial, irrespective of whether the sponsor is incorporated in India or not. The clinical trials are run by a team of investigators chosen by the sponsor, and the team is led by a principal investigator who is also chosen by the sponsor. The sponsor is permitted to pay the investigators directly for their services. The sponsor also selects a site for trial to provide in-patient and other facilities. The sponsor is permitted to make payment to the site as well. Sometimes, when the investigators are employees of the site, the sponsor makes payment directly to the site and the site then redistributes the payment to the investigators.

3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?

The preclinical trials (or studies on animals) are regulated by The Prevention of Cruelty to Animals Act, 1960 (“PCA Act”) and The Breeding of and Experiments on Animals (Control and Supervision) Rules, 1998 (“BEACS Rules”) made under the PCA Act. The BEACS Rules stipulate that any protocol for preclinical studies must ensure that

animals lowest on the phylogenetic scale which may give scientifically valid results should be first considered for any experimental procedure
the experiment should be designed using minimum number of animals to give statistically valid results at 95% degree of confidence,
replacement alternatives not involving experiments on animals have been given due and full consideration
sound justification is provided where alternatives not involving experiments on animals, though available, are not used

Before conducting any experiment animals, an experiment specific permission of the Committee for Purpose of Control and Supervision of Experiments on Animals (“CPCSEA”) or an Institutional Animals Ethics Committee (“IAEC”) recognized by CPCSEA is required. The CPCSEA or IAEC reviews each protocol for meeting the requirements stipulated above, amongst other things.

With respect to clinical trial protocols, the New Drugs and Clinical Trial Rules, 2019 (“CT Rules“) – a set of rules framed under the D&C Act prescribes a lot of requirements. The format of the protocol, along with the requirements, is published under Table 2, Third Schedule of the CT Rules – a set of rules framed under the D&C Act.. Some of the notable requirements are study rationale, study design, subject eligibility, study treatment and background of the principal investigator.

The protocol is submitted to the DCGI along with the application for permission to conduct the clinical trial. The ethics committee of the trial is also required to approve the clinical trial prior to its commencement. You may note that any change or update to the clinical trial protocol is required to be approved by the ethics committee before it can be implemented as part of the trial, except when such change in necessary to be implemented in the interest of the patient health and safety.

4. What are the requirements for consent by participants in clinical trials?

Voluntary informed consent is an essential requirement of the subject recruitment process. Prior to obtaining consent from a study subject, the investigator is required to provide information about the study in an easy-to-understand, non-technical manner, both verbally and by using a Patient Information Sheet (“PIS”). The consent of the study subject is required be obtained in writing in an ‘Informed Consent Form’ (“ICF”), the format for which is prescribed under the D&C Rules. The ICF is required to be submitted to the DCGI as part of the application for permission to conduct the clinical trial, while the ethics committee is also required to accord its approval prior to commencement of the trial.

In instances where the participants are unable to give consent (such as unconscious persons or minors), the legal representatives of the study subjects may do so on their behalf. If the subject or the legal representative is unable to read/write, an impartial witness is required to be present during the process and their signatures should be recorded on the form too.

Appendix V to Schedule Y of DCR enlists all the essential information the study subject or his legal representatives must be provided with prior to obtaining consent. The list of essential information includes explanation with respect to the purpose and duration of the study, any expected risks or discomfort the subject may face, alternate procedures or therapies available to the subject and anticipated payment if any

The D&C Rules also mandate audio-visual recording of the informed consent process in case of vulnerable subjects who volunteer to participate in trial involving a new chemical or molecular entity. The recording must contain the entire process of obtaining consent including the process of providing information and any questions that the prospective study subject may ask. However, in cases of clinical trials for anti-HIV drugs and anti-Leprosy drugs, only an audio recording of the process shall suffice.

Vulnerable subjects include those who are part of a hierarchical structure (e.g. prisoners, armed forces personnel, staff and students of medical, nursing and pharmacy academic institutions), patients with incurable diseases, unemployed or impoverished persons, patients in emergency situation, ethnic minority groups, homeless persons, nomads, refugees and minors.

5. May participants in clinical trials be compensated?

Participants in clinical trials may be compensated. If any compensation is to be paid to the prospective study subject, such study subject must be made aware of it while obtaining consent. However, the Ethical Guidelines for Biomedical Research on Human Subjects state that compensation “should not be so large or the medical services so extensive as to induce prospective subjects to consent to participate in research against their better judgment.”

21. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?

The sponsor of a clinical trial is responsible for paying compensation to a study subject or his/her legally acceptable representatives in case the study subjects suffers an injury or death which is related to the trial and arose because of:

Adverse effects of the investigational product;
Violation of the approved protocol, scientific misconduct or negligence by the sponsor or his representative or the investigator;
Failure of investigational product to provide intended therapeutic effect, where, the standard care, though available, was not provided to the subject as per the clinical trial protocol;
Use of placebo in a placebo-controlled trial where, the standard care, though available, was not provided to the subject as per the clinical trial protocol;
Adverse effects due to concomitant medication excluding standard care, necessitated as part of approved protocol;
For injury to a child in-utero because of the participation of parent in clinical trial;
Any clinical trial procedures involved in the study.

The sponsor is also obligated to provide for medical management to the study subject for all injuries suffered by the study subject during the course of the trial until it is proven that the injury was not connected to the clinical trial.

Most sponsors obtain a clinical trial insurance to gives the protection against claims for compensation from study subjects or their legally acceptable representatives.

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3. Marketing, Manufacturing, Packaging & Labelling, Advertising: India

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An essential legal guide to marketing, manufacturing, packaging & labelling and advertising in Indian pharma. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?

For information of the marketing authorization process for new drugs, investigational new drugs, investigational medical devices and new IVDs, please refer to Chapter 1 Question 3.

The import, manufacture and sale of drugs (both prescription and non-prescription) and notified medical devices require a license from the CDSCO or SLA, as the case may be.

2. What is the authorization process for the marketing of generic versions of these products?

Marketing authorizations are only required for new drugs, investigational new drugs new In Vitro Diagnostic devices (“IVD”) and investigational medical devices. Generic versions of drugs and medical devices require a license for manufacture, import and sale from the CDSCO or SLA, as the case may be.

3. What are the typical fees for marketing approval?

For information on the fee for marketing approval please see Question 4 in the Regulatory, Reimbursement and Pricing Overview.

4. What is the period of authorization and the renewal process?

Marketing authorizations are valid in perpetuity. However, for a period of four years from the date of a marketing authorization issued for a new drug, subsequent applicants for the manufacture, import and sale of the new drug is also required to apply for marketing authorization. Upon expiry of the four-year period, the drug can be manufactured, imported and sold with a license from the CDSCO or SLA, as the case may be, without a marketing authorization. For more information on the definition of a ‘new drug’ see Chapter 1 Question 3.

5. What are the requirements, if any, for post-approval pharmacovigilance?

Subsequent to the approval of a new drug, the applicant is required to furnish Periodic Safety Update Reports (“PSUR”) to report all the relevant new information, summarize status of market authorization in different countries and to indicate whether changes should be made to product information to optimize use. From the day of receipt of marketing permission, the PSUR must be submitted every six months for the first two years and then once a year for the remaining two years. If any serious adverse events occur post marketing, details of the event must be furnished to the authority within 15 days.

6. Are foreign marketing authorizations recognized?

A drug whose safety and efficacy is not established on the Indian population is considered to be a new drug, irrespective of whether the drug has received foreign marketing authorizations or not. For drugs discovered outside India that have been granted foreign marketing authorizations, Phase I clinical trials need not be conducted locally and the relevant data from foreign trials may be submitted but Phase II and Phase III clinical trials must be conducted in India to obtain marketing authorization. Additionally, if a drug has been marketed in foreign countries for a few years and there is adequate published evidence with respect to its safety, the DCGI may also relax or modify submission requirements.

The CT Rules permit the CDSCO to waive the local clinical trial requirements in the event the drug has been approved in a country specified by the Ministry of Health and Family Welfare for this purpose. However, no countries have been notified so far.

The rules governing notified medical devices are different in this aspect. Devices which have been granted a free sale certificate in Australia, Canada, Japan, the European Union and the United States of America can be imported without carrying out a clinical trial on Indian population. Permission to import or manufacture devices medical devices without a predicate device can also be granted without providing results of clinical investigations if the device has been marketed for at least two years in the above mentioned countries.

7. Are parallel imports of medicines or devices allowed?

Parallel imports are permissible in India under the Patents Act as well as the Trademarks Act. India follows the principle of ‘international exhaustion’ i.e. if the first sale has been made validly either by the patent holder or someone authorized by such patent holder, the patent holder cannot control the conditions of a subsequent sale or profit from such sale. The same principle applies to trademarks as well. In cases where the goods were acquired legally or were placed on a worldwide market by the trademark owner. However, the importer may be required to communicate to the buyer that the goods are imported. The principle of international exhaustion will not apply in cases the goods were either not lawfully acquired or were changed or materially altered after their acquisition.

8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?

The Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations 2002 (“MCI Code”) and the Revised Dentists (Code of Ethics) Regulations 2014 (“DCI Code”) regulate the interaction of medical and dental practitioners respectively with pharmaceutical, medical device and allied healthcare companies. The MCI Code and DCI Code prohibit medical and dental practitioners from:

Accepting gifts;
Accepting travel facilities from pharmaceutical and allied healthcare companies for attending conferences, seminars, workshops and so on as a delegate;
Accepting hospitality from pharmaceutical and allied healthcare companies under any pretext;
Accept any cash or monetary grants from pharmaceutical and allied healthcare companies in an individual capacity.

However, both the MCI Code and the DCI Code permit medical and dental practitioners to be engaged by pharmaceutical and allied healthcare companies as a consultant, researcher or in another professional capacity.

Apart from the restrictions placed on medical and dental practitioners under the above regulations, the Central Civil Services (Conduct) Rules 1964 and similar state-level rules requires that medical practitioners who are government servants cannot place themselves under any financial or other obligation to any individual or organization that may influence them in the performance of their official duties.

In the same way, the Uniform Code of Pharmaceutical Marketing Practices (“UCPMP”) prohibits medical device and pharmaceutical companies from:

Accepting gifts, pecuniary advantages or benefits in kind;
Providing travel facilities to healthcare practitioners for attending conferences, seminars, workshops and so on as a delegate.
Providing hospitality to healthcare practitioners under any pretext.
Providing any cash or monetary grants to healthcare practitioners in an individual capacity.

However, the UCPMP is currently a voluntary code and does not have the force of law. The Government is reportedly planning to make the UCPMP mandatory in some form of legislation.

9. How is the manufacturing of medicines and devices regulated and by which agencies?

A license to manufacture drugs must be obtained from the SLA of the state where the manufacturing facilities are located. A separate license must be obtained for each plant. In case of certain drugs and medical devices such as new drugs, investigational new drugs and investigational medical devices, a license from both SLA and CDSCO, as the case may be, is required. If drugs are sought to be manufactured for use in a clinical trial, then a separate license to manufacture for test purposes must be obtained from SLA. For manufacturing ‘new drugs’ or ‘investigational new drugs’ (refer to Chapter 1 Question 3 for definition), a marketing authorization needs to be obtained from the CDSCO after completion of clinical trials prior to applying for a manufacturing license.

With respect to license for manufacturing notified medical devices, it depends on the risk classification of notified medical devices. Notified medical devices are divided into Class A to Class D in terms of increasing risk. A license to manufacture a Class A or Class B device is given by the state licensing authorities while a license to manufacture Class C or Class D devices will be given by the CDSCO. A separate license must be obtained for each manufacturing plant. If a notified medical device is sought to be manufactured for use in a clinical trial, then a separate license to manufacture for test purposes must be obtained.

10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the U.S. Food & Drug Administration and/or the European Medicines Agency?

India has independent Good Manufacturing Practices (GMPs), which have been prescribed under Schedules M, M-II and M-III of the D&C Rules. India also has a separate set of GMPs that apply to Ayurveda, Siddha and Unani medicines.

The standards for manufacturing for medical devices have been prescribed in the Quality Management System (“QMS”) in the MDR. They lay down requirements for documentation, management responsibilities, resource management and monitoring. Violation of QMS can lead to cancellation of license.

11. What is the inspection regime for manufacturing facilities?

An inspection of the manufacturing facilities is mandatorily carried out before grant of license. The foreign manufacturing facilities may or may not be inspected, at the discretion of the DCGI prior to grant of license. After grant of license, manufacturing facilities may be inspected by DCGI, State Licensing Authorities at any point without prior notice. If the manufacturing facilities are in violation of the law, a show cause notice is issued to the company and an opportunity for hearing is provided before arriving at a decision.

12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?

Yes, domestic manufacturing facilities are open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA provided the manufacturer has applied for registration of the manufacturing facility before foreign authorities or has already registered the manufacturing facility with the foreign authorities.

13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?

A license must be obtained to stock drugs and a separate license is required for each of the premises where the drug is stored. The storage premises should be adequate in size and should be equipped with proper storage and accommodation for preserving the properties of the drugs. A person who has prescribed qualifications and is competent in the opinion of the licensing authority to supervise and control the sale, distribution and preservation of drugs must always be present on the storage premise.

Stocks which have expired should not be stored along with stocks which are yet to expire. Storage handling and packaging requirements for different types of products has been specified differently. Storage specifications for vaccines, human blood and umbilical cord blood have been specified in the D&C Act. The CDSCO has also come out with Good Distribution Practices, which, although voluntary, provide guidelines for the storage, packing and transport of drugs.

14. What information must be included in medicine and device labeling?

DRUGS

The following must be included in the labelling:

Date of manufacture
Date of expiry.
Name, address and license details of manufacturer
Batch or lot number
Net content in terms of weight, measure, volume, number of units of contents, number of units of activity
The content of active ingredients.

The generic name of the drug must be printed in double the font size of the brand name or in cases of drugs in the Indian Pharmacopoeia or the National Formulary of India then the name as specified therein.

The labelling requirements also specify that the prescription drugs must have the symbol Rx on them. Other drugs must include the warning that the drug must be taken under medical supervision. The CDSCO continues to update labelling norms through notifications.

MEDICAL DEVICES

The following particulars must be on the medical device:

name of the medical device
the details necessary for the user to identify the device and its use
name of manufacturer and address of manufacturing premises where the device has been manufactured
statement as to the net contents (in terms of weight or measure)
license number, date of manufacture
date of expiry (alternatively, its shelf life)
applicable storing and handling conditions, warnings and precautions
the batch number, as well as the manufacturing license number under which it is manufactured (if manufactured in India).

Imported products must display the import license number, name and address of the importer, address of the actual manufacturing premises and the date of manufacture.

The Legal Metrology (Packaged Commodities) Rules, 2011 (“LM Rules”) apply to medical devices in addition to the MDR. The LM Rules have prescribed labeling and packaging requirements. The label of any commodity covered by the LM Rules are required to have the following declarations:

Maximum retail price (“MRP”);
Name and address of the manufacturer or importer;
Net quantity,
Common or generic name of the commodity;
Country of origin;
Month and year in which the commodity is manufactured or packed or imported;
Name, address, telephone number, e-mail address of the person who can be or the office which can be contacted, in case of consumer complaints;
Actual corporate name and complete address of domestic manufacturer or importer or packer;

15. What additional information may be included in labeling and packaging?

Provided the mandatory declarations are made on the label/package and the information is not prohibited under applicable law, any additional information as required by the manufacturer is permitted to be included.

16. What items may not be included in labeling and packaging?

The same restrictions that are applicable to advertisement of drugs and medical devices apply to the label and package of drugs/medical devices as well, as claims made on the label or package are considered to be advertisements under the DMRA.

Please refer to Chapter 3 Question 17 for information on restrictions applicable to advertisements of drugs and medical devices.

17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?

There are multiple provisions in the D&C Rules as well as the DMR Act relating to the advertisement of drugs.

Prescription Drugs (Schedule H and H1) and Psychotropic substances (Schedule X) cannot be advertised without the previous sanction of the Central Government. However, this rule is only applicable to manufacturers.
Drugs purporting to prevent or cure diseased and ailments mentioned in Schedule J of the D&C Rules such as blindness, baldness, asthma, cancer, obesity and sexual impotence cannot be advertised.
The DMR Act prohibits advertisement of drugs in a manner suggesting that such drugs may be used for

the procurement of miscarriage in women or prevention of conception in women
the maintenance or improvement of the capacity of human beings for sexual pleasure
the correction of menstrual disorder in women
curing or preventing any illness specified in the Schedule to the DMR Act.

The Government may, however, advertise a drug in exercise of its discretion. Additionally, drugs may be advertised to a registered medical practitioner in a confidential manner. The document containing the advertisement must bear a prominent message at the top stating “For the use only of registered medical practitioners or a hospital or a laboratory”.

Apart from the rules and provisions mentioned above, advertising in India is self-regulated as there is no central authority to monitor or approve advertisements. The Advertising Standards Council of India (“ASCI”), a non-profit organization comprising media, advertising agencies, advertisers, has published a code regulating the publishing of advertisements in India. The ASCI Code applies to advertisements relating to drugs as well.

The UCPMP, a voluntary opt-in guideline issued by the Department of Pharmaceuticals, also has directions on what promotional materials should contain. The directions are as follows:

The name of the drug
Name and address of the authorization holder
Recommended dosage and route of administration
Adverse reactions and relevant contraindications.

The UCPMP also states that any promotions arranged in journals by pharmaceutical companies must be marked as such and should not appear to be editorial in nature.

18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?

Licenses issued for the retail sale of drugs and notified medical devices are premise specific. Therefore, medicines and notified medical devices can only be sold from registered pharmacies, by registered pharmacists. Further, the PPR states that drugs must be dispensed by a registered pharmacist to the patient or the caretaker of such patient directly. Therefore, it is challenging to sell or deliver medicines and notified medical devices via post.

19. What are the restrictions and requirements for electronic marketing and advertising via email, by Internet, social media, and other channels?

There are currently no specific laws to governing advertising of drugs over the internet. The same regulatory framework that applies to advertisement of drugs generally will apply to advertising over the internet as well.

However, the government is reportedly in the process of amending the D&C Rules in order to incorporate specific requirements for the online sale of drugs. For more information, please refer to Chapter about Regulatory Reforms, Question 1.

20. May medicines and devices be advertised or sold directly to consumers?

Medicines and devices that are covered under the advertisement restrictions specified under the DMRA and the D&C Act, cannot be advertised directly to consumers. For details, please refer to Chapter 3 Question 17.

With respect to sale, pharmaceutical companies cannot sell medicines directly to consumers unless it possesses a retail license. Retail licenses are provided to pharmacies which have been set up in accordance with the requirements prescribed under the D&C Rules.

21. How is compliance monitored?

The SLAs (and CDSCO, in certain cases) are tasked with monitoring of certain compliances. Inspectors appointed by SLA have powers to enter and search premises when there may be reason to believe that an offence under relevant law has been committed. The Inspector also has the power to seize a violating advertisement or examine a record or document to obtain evidence for the same.

22. What are the potential penalties for noncompliance?

Advertising a drug in contravention of the DMR Act or the D&C Rules may be punishable with imprisonment or fine. On a first conviction, the person may be punished with imprisonment up to six months or with fine or both. For a subsequent offence, imprisonment may extend up to one year with or without fine. Contraventions relating to non-compliance with a condition prescribed in a license (manufacture, import or marketing authorization) may also lead to the cancellation or suspension of the license by the relevant authority.

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4. Traditional Medicines and OTC Products: India

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A guide to the legal requirements for traditional medicines and OTC products in India. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 19.

1. What are the regulatory requirements for traditional, herbal, complementary, or alternative medicines and devices?

Traditional medicines are categorized under the D&C Act broadly into Ayurveda, Siddha and Unani (“ASU”) drugs and Homoeopathic medicines.

Ayurveda, Siddha and Unani

ASU drugs are those which are manufactured exclusively in accordance with the formula prescribed in the Ayurveda, Siddha and Unani Tibb systems of medicine as specified in the D&C Act.

The State Licensing Authority is responsible for issuing licensing with respect to manufacture of ASU drugs. A different license must be obtained for each premise Manufacturing facilities must comply with Good Manufacturing Practices (specified in Schedule T of the D&C Act) as a precondition to obtain a license.

It is an offence to manufacture adulterated or spurious ASU drugs or drugs that are not in accordance with prescribed standards. Depending upon the specific offence, the penalty levied ranges from imprisonment between three months to three years and fine between INR 500 to INR 5,000. Subsequent offences of a similar nature carry a greater penalty.

Homoeopathic Medicines

Homoeopathic medicines include drugs which are recorded in Homoeopathic provings and whose therapeutic efficacy has been established through long clinical experience as recorded in the authoritative Homoeopathic literature of India and abroad. It must be prepared according to the techniques of Homoeopathic pharmacy and also includes a combination of drugs.

A New Homoeopathic Medicine (“NHM”) is one which is not specified in the Homoeopathic Pharmacopoeia of India, USA, UK or Germany or not recognized as efficacious in authoritative Homoeopathic literature under the conditions prescribed. A combination of two Homoeopathic drugs not mentioned in authoritative literature is also included.

An import license is required for importing Homoeopathic medicines. A special permission is required from the CDSCO for importing NHMs.

A license needs to be obtained for manufacturing or selling Homoeopathic medicines. If drugs are being manufactured, stocked or sold at more than one place a separate license needs to be obtained for each individual facility. Licenses are valid for a period of five years. Applications are made to the State Licensing Authority for manufacture of Homoeopathic medicines and to the Central Licensing Authority for manufacture of NHMs. Drugs may be manufactured in small quantities for test or analyses if the manufacturer holds the appropriate licenses.

2. Can these traditional, herbal, complementary, or alternative products be advertised directly to the public?

Traditional drugs can be advertised directly to the public, subject to the restrictions imposed by the DMR Act and the D&C Rules. For restrictions placed the DMR Act and D&C Rules see Question 17 in the Manufacturing, Marketing, Labeling and Packaging overview.

The Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy (“AYUSH”) has signed a Memorandum of Understanding with the ASCI where they have agreed that ASCI will comprehensively monitor and identify potentially misleading advertisements in the AYUSH Sector and process complaints through its Customer Complaint Council (“CCC”).

3. What health, advertising, and marketing claims may be made for traditional, herbal, complementary, or alternative products?

Schedule J of the D&C Act and the DMR Act states that drugs purporting to prevent or cure certain ailments is prohibited. For advertisement restrictions placed by the DMR Act and D&C Act see Question 17 in the Manufacturing, Marketing, Labeling and Packaging overview.

4. What are the regulatory requirements for over-the-counter (non-prescription) medications?

The D&C Act or the Rules do not specifically mention OTC drugs. The two broad categories envisaged by the Act are prescription and non-prescription drugs. Prescription Drugs are those specified in Schedules H, H (1) and X of the D&C Act but there is no specific schedule enlisting the non-prescription drugs. There are certain drugs, however, which can be sold in non-drug licensed stores i.e. in non-pharmacies. These drugs are specified in Schedule K of the D&C Act and include drugs such as quinine and other anti-malarial drugs and household remedies such as Aspirin tablets, Paracetamol and Gripe water.

5. Are there any limitations on locations or channels through which OTC products may be sold?

Non-prescription drugs specified in Schedule K can also be sold in non-pharmacies as there is no license requirement to sell them. Therefore, OTC drugs can be sold through additional locations than other drugs.

6. What health, advertising, and marketing claims may be made for OTC products?

There are no specific advertising regulations for non-prescription drugs and the regulations applicable to drugs generally are applicable. For information on the rules concerning advertising in India see Question 17 in the Manufacturing, Marketing, Labeling and Packaging overview.

7. Can OTC products be marketed or advertised directly to the public?

OTC products as identified in Question 4 cannot be marketed or advertised directly to the public.

8. What is the mechanism by which a prescription-only product can be converted to an OTC product?

There is currently no mechanism in place for prescription-to-OTC switches. However, the Central Government has the power to frame rules to give effect to the provisions of the D&C Act. To that end, the Central Government may include or exclude a drug from the relevant schedules thereby changing the degree of regulatory compliance required to manufacture and/or sell the drug.

9. What are the requirements for the importation of either traditional medicines or OTC products?

An import license is required to import homoeopathic medicines and an additional special permission is required from the CDSCO for the import of NHMs. Medicines with less than 60% of their shelf life remaining are not allowed to be imported unless the licensing authority has allowed it in writing. The drugs must also meet the standards of strength, quality and purity that may be prescribed for them. The packaging and labelling requirements applicable to domestically manufactured Homoeopathic Medicines are also applicable to imported drugs.

Drugs whose import is otherwise prohibited may be imported in small quantities for test purposes. The Licensing Authority may inspect the premises where such drugs are stored to ensure they are being used in accordance with the license requirements.

If the Customs Collector has reason to believe that drugs are imported in contravention of the provisions of the Act he may forward them to the Director of a laboratory appointed for this purpose. If the drugs are found to be not of standard quality, the import must either export them back to the country of manufacture or forfeit them to the Central Government to be destroyed.

India also requires the importer to have an Import Export Code (“IEC”) prior to importing any item. The IEC is a ten-digit code issued by the Director General Foreign Trade with a lifetime validity. The customs authorities require an IEC prior to clearing any shipment.

The requirements for importing OTC products is the same as that of other drugs.

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5. Product Liability: India

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An insight into product liability in India. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. What types of liability are recognized in your jurisdiction?

Manufacturers, distributors and retailers can be held liable either under D&C Act or under India’s penal laws. Generally, manufacture, import, sale of drugs and devices that are spurious or of poor quality or contravene any of the requirements of law is punishable under Indian law. The D&C Act allows manufacture and sale of certain controlled substances which is otherwise prohibited under India’s anti-drug laws. Manufacture of those drugs illegally can lead to criminal prosecution under the Narcotic Drugs and Psychotropic Substances Act 1985 (“NDPS”) in addition to penalty under the D&C Act. The Indian Penal Code (“IPC”) specifically identifies adulteration of drugs and sale of adulterated drugs as an offence.

In addition to the criminal liabilities prescribed above, the Consumer Protection Act, 2019 (“CPA”) also applies as a means of obtaining compensation. Manufacturers and retailers can be held liable under the CPA under two primary grounds viz. sale of defective goods and unfair trade practice. Deficiency is any shortcoming, fault or imperfection in the quality or nature of the good as compared to the standard prescribed for that good. Unfair trade practice means an unfair or deceptive practice used for promoting the good. Manufacture or sale of spurious drugs will be construed as an unfair trade practice.

2. How do these types of liabilities apply to the manufacturers of medicines and devices?

Currently, for deficiencies in the quality of drug, the manufacturer can be held responsible under the D&C Act, IPC as well as the CPA. However, the D&C Rules have been amended such that liability for quality of drugs is imposed not only on the manufacturer but also on the marketer the drug. This was necessitated because a DCGI investigation revealed that many big pharmaceutical companies market unapproved drugs or drugs not of standard quality. However, those drugs are manufactured by third party contractors and therefore the company marketing the drug escapes liability.

Manufacture of a drug in Schedule X of the D&C Rules without a valid license is an offence under the NDPS Act.

The CPA states that the manufacturer can be held liable in a product liability claim in the following cases:

the product contains a manufacturing defect;
the product is defective in design;
there is a deviation from manufacturing specifications;
the product does not conform to an express warranty regardless of whether the manufacturer was negligent in making such express warranty; or
the product fails to contain adequate instructions of correct usage to prevent any harm or any warning regarding improper or incorrect usage.

3. Does potential liability extend to the manufacturer only or could claims extend to corporate executives, employees, and representatives?

The D&C Act and the NDPS Act specify that when an offence has been committed by a company the persons in charge of the affairs of the company (key personnel) can be held liable for those acts. Key personnel includes directors, secretaries and managers of the company and any other officer who was responsible for the conduct of the company’s affairs.

The IPC applies to offences committed by persons and companies. Therefore, all persons involved in either the adulteration of drugs or sale of adulterated drugs will be held guilty.

4. How can a liability claim be brought?

In case of an offence committed under the IPC, a criminal complaint can be filed with the relevant police station to seek redressal. For offences under the D&C Act, a complaint may be made to the licensing authority.

The CPA establishes district, state and national commissions to exercise jurisdiction over consumer disputes and provide redressal. A complaint before the above mentioned forums can be filed even without the help of a lawyer. The appropriate forum to file a complaint depends on the total value of the goods and compensation claimed. If the value is below INR 10,000,000, the complaint must be filed in the District Forum. If the value is between INR 1,00,00,000 to 10,00,00,000, the complaint must be filed in the State Consumer Forum. If the value exceeds INR 10,00,00,000 the complaint must be filed at the National Forum.

5. What defenses are available?

The key personnel will not be held liable if they can prove that the offence was committed without their consent. However, it must be also be shown that they exercised all due diligence to prevent the commission of the offence. Therefore, if the offence was committed owing to the negligence of the director or manager the defense mentioned above will not be available to them.

Under the CPA, the manufacturer may take the following defenses.

The complainant is not a ‘consumer’ under the CPA as the complainant has either obtained the goods or avails services for any commercial purpose or has availed the service free of charge.
Even if the product was defective, no ‘harm’ caused to a consumer by the use of the defective product.
In case of a claim against a product manufacturer for not having provided adequate warning or instructions, the product manufacturer shall not be liable if:

- The product was purchased by an employer for use at the workplace and the product manufacturer had provided warnings or instructions to such employer.
- The product was sold as a component or material to be used in another product and necessary warnings or instructions were given by the product manufacturer to the purchaser of such component or material, but the harm was caused to the complainant by use of the end product in which such component or material was used.
- The product was one which was legally meant to be used or dispensed only by or under the supervision of an expert or a class of experts and the product manufacturer had employed reasonable means to give the warnings or instructions for usage of such product to such expert or class of experts.
- While using the product, the complainant was under the influence of alcohol or any prescription drug which had not been prescribed by a medical practitioner.

iv. The product manufacturer would not be liable for failure to instruct or warn about a danger which is obvious or commonly known to the user or consumer of such product or which, such user or consumer, ought to have known, taking into account the characteristics of such product.

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6. Patents and Trademarks: India

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Vital info on patents and trademarks in Indian pharma. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. What are the basic requirements to obtain patent and trademark protection?

India’s Intellectual Property Law is TRIPS compliant. The Patents Act, 1970 and the Trademarks Act, 1999 provide protection and regulate patents and trademarks in India.

PATENTS

The requirements to obtain a patent are:

An application for grant of patent may be made by the inventor or the legal representatives and assignees of such inventors.
The application must be made to the Controller of Patents.
The application must contain the complete specification of the invention describing the invention and the subject matter to which it relates. A complete specification must detailed enough that a person possessing average skill and average knowledge of the art to which the invention relates should be capable of working that invention.
The application will then be examined by an examiner who shall inquire into whether the invention is patentable under the provisions of the Act or has been already been published or disclosed in any manner.
Depending upon the decision of the examiner, the patent shall either be granted by the Controller or, in case the patent is refused or an amendment to the application is required, the applicant shall be given an opportunity to be heard before a decision is made.

Patents are valid for 20 years from the date of filing the application.

TRADEMARK

Any person who has either been using the trademark of proposes to use the trademark may file an application with the Registrar of Trademarks to register the trademark.
Indian is a contracting party to the Madrid Protocol and follows the Nice Agreement Concerning the International Classification of Goods and Services for the Purposes of Registration of Trademarks. Therefore, a single application may be filed to register a trademark in multiple categories of goods.
The Registrar may admit the application in full or partially or reject it in entirety. In the latter two cases, an opportunity for hearing must be provided.

Trademarks are registered for a period of ten years from date of registration and can be renewed thereafter.

2. What agencies or bodies regulate patents and trademarks?

The Office of the Controller General of Patents, Designs and Trademarks is the regulatory body for patents and trademarks.

3. What products, substances, and processes can be protected by patents or trademarks and what types cannot be protected?

PATENTS

An invention to be patentable must be new, inventive and useful. The three requirements may be elaborated as follows:

Firstly, the invention must not be patented in India and should not be common knowledge.
Secondly, it must involve an inventive step i.e. the invention should be non-obvious to the person skilled in the art. The standard for this is that if a person skilled in the art is in the workshop, such person would not be able to arrive at the invention using existing knowledge. This necessitates that the invention technical advance as compared to existing knowledge and/or has economic significance.
The third requirement is that the invention is useful i.e. capable of industrial application. It may be noted that computer programs are not considered inventions but can be copyrighted.

A patent may not be registered if the invention is frivolous or contrary to well established natural laws or the primary use of such invention is contrary to public order and morality or is harmful to human, animal or plant life and the environment. The Act also states that “any process for the medicinal, surgical, curative, prophylactic, diagnostic, therapeutic or other treatment of human beings or any process for a similar treatment of animals to render them free of disease or to increase their economic value or that of their products” is not patentable.

TRADEMARKS

A trademark is defined as “a mark capable of being represented graphically and which is capable of distinguishing the goods or services of one person from those of others and may include shape of goods, their packaging and combination of colors”. Therefore, any mark fitting the above definition may be registered as long as the registration of such a mark is not prohibited under any other provision of the Act. For instance, a trademark may not be registered if it is deceptively similar to an already registered trademark, scandalous in nature, or if the trademark is merely an indication of the quality, quantity, intended purpose or the geographical origin of the goods.

4. How can patents and trademarks be revoked?

PATENTS

After a patent has been published but before it has been granted, any party may make an opposition to the grant of patent to the Controller. Depending upon the representations made by the parties, the Controller main maintain the patent or order that the application be amended or revoked. This is known as pre-grant opposition. The patent technically cannot be revoked in this proceeding as it has not been granted yet. Revocation of patent may be done on the petition of an interested party, the Central Government or in a case where infringement proceedings have been filed the defendant may be plead that the patent is invalid and should therefore be revoked.

Essentially, a patent may be revoked if it does not fulfil the requirements of invention as specified above or has been obtained by someone not entitled to file the application or the grant of patent is in contravention of the interests of the true inventor. Patents granted on the basis of incorrect, false, misleading or incomplete specification can also be revoked. Lastly, if the invention is already claimed in a valid claim or complete specification of an earlier date or if it is discovered that the patent has been published prior to the application date, then the patent will be revoked.

TRADEMARKS

Similar to patents, trademarks can also be opposed both prior to and after registration. Any person may within three months from the advertisement of the trademark but before such registration make a representation to the Registrar to oppose grant of the trademark. The Registrar will arrive at a decision after hearing both parties.

Trademarks may be cancelled by the Registrar on the following grounds.

The registered used has used the mark in a way that is likely to cause confusion or deception
The proprietor or the registered user misrepresented or failed to disclose some fact material to the application for registration
Circumstances have changed in such a manner that were the trademark were to be registered on the date of application for cancellation, the trademark would not have been granted.
Registration ought not to have been affected having regard to rights vested in the applicant by virtue of a contract in the performance of which he is interested

5. Are foreign patents and trademarks recognized and under what circumstances?

India is a signatory to the Patent Cooperation Treaty 1970 (PCT). Therefore, patent applications filed under the PCT will be considered as valid applications as long as a corresponding application has been filed before the Controller in India. The relevant date for the application will be the international filing date accorded under the PCT.

India is a Contracting party to the Madrid Protocol. Therefore, trademarks made through the international application are recognized in India. India also recognizes the concept of well-known marks. Therefore, a foreign well-known mark will not be permitted to be registered in India irrespective of whether such well known mark has been registered or used in India.

6. Are there any non-patent/trademark barriers to competition to protect medicines or devices?

A drug will continue to remain a new drug for four years after it has been approved. To import or market a new drug, the permission of the marketing authorization holder must be obtained. The rationale behind this is that the drug can thereby be studied in safe and controlled environment. However, it also gives the holder of the marketing authorization a window within which to maximize the profits from selling the drug.

For more information on what constitutes a new drug see Question 3 in the Regulatory, Reimbursement and Pricing Overview.

7. Are there restrictions on the types of medicines or devices that can be granted patent and trademark protection?

A new form of a known drug will not be patentable unless an increase in efficacy can be shown. Additionally, mere discovery of any new property or new use for a drug is also not patentable.

Please note that India has a robust compulsory licensing policy for drugs and devices. Under the Patents Act the Controller may grant any person a license with or without the consent of the patent holder if:

The reasonable requirements of the public with respect to the patented invention are not being satisfied
The patented invention is not available to the public at a reasonable price
The patented invention is not worked in the territory of India
3 years have expired from the date of grant of patent

The terms of grant of the compulsory license will be determined by the Controller. Before making a decision, the Controller must look into whether the applicant for compulsory license is capable of undertaking risk, providing capital and working the invention to public advantage.

There are no restrictions on the types of medicines which may be granted trademark protection.

8. Must a patent or trademark license agreement with a foreign licensor be approved or accepted by any government or regulatory body?

While there were certain exchange control approval requirements in the case of foreign technology collaborations, the approval requirements were liberalized in 2009. A prior approval of a government/regulatory body is currently not required in case of a patent of trademark license agreement.

However, it is to be noted that with respect to patents, a person who acquires a share, title or interest in a patent, whether by license or otherwise, is required to apply to the Controller of Patents for registration of such title or interest.

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7. Regulatory Reforms: India

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Upcoming regulatory reforms affecting Indian pharma. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. Are there proposals for reform or significant change to the healthcare system?

E-pharmacy regulations

The Government has recently released draft regulations that propose to create a streamlined system of licensing e-pharmacies and governing the sale of drugs online. The rules grant legal recognition to e-pharmacies and prescribes duties with respect to handling of prescriptions and protection of sensitive patient data. It states that while the data shall be kept confidential, it may be shared with the Government for public health purposes. However, e-pharmacies will not be permitted to sell psychotropic drugs i.e. drugs in Schedule X. Any complaints against e-pharmacies can be made to the State Drug Licensing Authorities.

Companies Marketing Products liable for quality

The D&C Rules have been amended with effect from March 01, 2021 such that the companies marketing the drugs will be held responsible in addition to the manufacturer. Currently, big pharmaceutical companies escape liability with respect to the quality of their drugs by contracting out manufacturing to third parties. This amendment seeks to incentivize big pharmaceutical companies marketing the drug to ensure that the manufacturer of the drug being marketed is in compliance with the law.

2. When are they likely to come into force?

Comments from the public were accepted in respect of the e-pharmacy regulations and the rules are in the process of being finalized.
The amendment that seeks to make marketing companies liable for product quality will come into effect on March 31, 2020.

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8. Cannabinoid Drugs, Medicinal Cannabis & Opioid Drugs: India

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Cannabinoid drugs, medicinal cannabis & opioid drugs in India – a comprehensive legal overview. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

CANNABINOID DRUGS

Global Comment: For the purpose of this chapter, we will assume that Cannabinoid Drugs are preparations made out of extract or tincture of Cannabis. If a drug contains cannabinoids which have been synthetically manufactured, they would be regulated as drugs, except for drugs containing Tetrahydrocannabinol (THC). THC is regulated as a psychotropic substance in India. We have assumed that a drug that that contains only, or mostly, THC that is synthetically manufactured will not be called as a Cannabinoid Drug.

1. Are Cannabinoid Drugs authorized in your country?

Cannabinoid Drugs can be sold in India in accordance with the requirements laid down by law. Cannabinoid Drugs which are an extract or tincture from cannabis require a licensed under Narcotic Drugs and Psychotropic Substances Act 1985 (“NDPS Act”), Narcotic Drugs and Psychotropic Substances Rules 1985 (“NDPS Rules”), Drugs and Cosmetics Act,1940 (“D&C Act”) and the Drugs and Cosmetics Rules, 1945 (“D&C Rules”) for sale in India.

2. What are the regulatory authorities with jurisdiction over Cannabinoid Drugs?

The following authorities have jurisdiction with respect to all narcotic drugs including Cannabinoid Drugs:

Central Bureau of Narcotics (“CBN”) operates under the Department of Revenue, Ministry of Finance and is in charge of enforcement of the NDPS Act, which is India’s primary anti-drug abuse legislation. The CBN is headed by the Narcotics Commissioner.
Narcotics Control Bureau (“NCB”) operates under the Ministry of Home Affairs and exercises the function of the Central Government under the NDPS Act. The NCB is also in-charge of coordinating between various government authorities under the NDPS Act, Customs Act 1962 and Drugs & Cosmetics Act 1940 (“D&C Act”).
Central Drugs Standard Control Organisation (“CDSCO”) headed by the Drugs Controller General of India (“DCGI”) under the Ministry of Health and Family Welfare regulates clinical trials import, manufacture, marketing and clinical trials, biologics and medical devices in the territory of India.
State-level Licensing Authorities (“SLA”) are established in each Indian state and independently regulate the manufacture and sale of drugs, biologics and medical devices within the territory of their respective state.

3. Is there a specific regulatory framework for the authorization, pricing, and reimbursement of Cannabinoid Drugs?

There is no specific regulatory framework regulating the authorization, pricing and reimbursement of Cannabinoid Drugs.

AUTHORIZATION

As indicated in the first response, a Cannabinoid Drug can be sold after obtaining appropriate licenses under the NDPS Act and NDPS Rules, as well as D&C Act and D&C Rules.

PRICING

There is no specific pricing framework for Cannabinoid Drugs in India. However, since cannabinoids drugs would be regulated under the larger framework applicable to medicinal drugs in India, they would be subject to price control.

Under the Drugs Price Control Order,2013 (“DPCO”) the National Pharmaceutical Pricing Authority (“NPPA”) is empowered to fix prices of drugs that qualify as ‘essential’. As of now, to our knowledge, no Cannabinoid Drug has been listed as an essential drug. However, even non-essential drugs are subject to price control, as they are not permitted to increase prices by more than 10% in any 12-month period.

REIMBURSEMENT

There is no specific regulatory framework for the reimbursement of drugs, including cannabinoid drugs, in India.

4. Which are the cannabinoid drugs that have received market approval to date?

So far, to our knowledge, no cannabinoid drugs have received market approval.

5. Who can prescribe Cannabinoid Drugs?

The persons who are permitted to prescribe cannabinoid drugs vary from state to state. But, at the least, the following persons can prescribe cannabinoid drugs:

A person who holds a qualification recognized under National Medical Commission Act, 2019 and is registered with a medical council;
A person registered as a dentist under the Dentists Act, 1948 (in some States with approval of the government);
A person who is registered in the practice of veterinary medicine and who possesses qualifications approved by the government (in some States with approval of the government)

6. Is there a list of doctors authorized to prescribe Cannabinoid Drugs?

No. There is no such list of doctors authorized to prescribe Cannabinoid Drugs.

7. What approvals or notifications are required to prescribe Cannabinoid Drugs?

At the minimum, the following authorizations are required to sell Cannabinoid Drug in India –

License from the Narcotics Commissioner to manufacture the Cannabinoid Drug
License from State Licensing Authority to manufacture Cannabinoid Drug
Marketing Permission from DCGI, if the Cannabinoid Drug has not been used in India to any significant extent under the conditions prescribed, recommended or suggested in the labelling thereof and has not been recognised as effective and safe by the DCGI.

8. Which organizations are authorized to sell/distribute Cannabinoid Drugs available?

The following entities are authorized to sell/distribute cannabinoid drugs –

Licensed vendors and druggists;
Hospitals, dispensaries and veterinary dispensaries working under Government supervision;
Other medical institutions authorised by the state government;
Dispensary owned by a registered medical practitioner where no prescriptions except his own are dispensed, provided that the registered medical practitioner is registered with the State Government.

9. Is there a list of retailers/ distributors authorized to sell Cannabinoid Drugs?

No. There is no publicly available list of retailers/distributors authorized to sell Cannabinoid Drugs.

10. Are there proposals for reform or significant change to the regulation of Cannabinoid Drugs?

No. There are currently no proposals for reform or significant change to the regulation of Cannabinoid Drugs.

11. When are they likely to come into force?

The question is not applicable.

MEDICINAL CANNABIS

Global Comment: For the purpose of this chapter, we have assumed that Medical Cannabis means use of Cannabis in its original form, i.e. not in form of extracts or tinctures, for medicinal purposes.

12. Is Medicinal Cannabis authorized in the country?

No, the sale of cannabis to patients for medicinal purposes is not permitted in India.

13. What are the regulatory authorities with jurisdiction over Medicinal Cannabis?

The following authorities have jurisdiction with respect to all narcotic drugs including Medicinal Cannabis:

Central Bureau of Narcotics (“CBN”) operates under the Department of Revenue, Ministry of Finance and is in charge of enforcement of the
Narcotic Drugs and Psychotropic Substances Act 1985 (“NDPS Act”), which is India’s primary anti-drug abuse legislation. The CBN is headed by the Narcotics Commissioner.
Narcotics Control Bureau (“NCB”) operates under the Ministry of Home Affairs and exercises the function of the Central Government under the NDPS Act. The NCB is also in-charge of coordinating between various government authorities under the NDPS Act, Customs Act 1962 and Drugs & Cosmetics Act 1940 (“D&C Act”).
Each Indian State has the power to regulate the cultivation of any cannabis plant, production, manufacture, consumption, transport, import inter-State, export inter-State, sale, purchase, consumption or use of cannabis.

14. What is the regulatory framework for the authorization, pricing, and reimbursement of Medicinal Cannabis?

Medicinal Cannabis cannot be prescribed as a drug for the use of Indian citizens.

15. How is the production and import of Medicinal Cannabis regulated and by which agencies/authorities?

MANUFACTURE

Cultivation of Medicinal Cannabis may be done for scientific or research purposes under a license granted by the State Government and a separate license granted by the Narcotics Commissioner.

IMPORT

Cannabis, including Medicinal Cannabis, can only be imported into India for the following purposes:

i. Scientific requirements including analytical requirements of any Government laboratory or any research institute in India or abroad.

ii. Very limited medical requirements by a foreigner by a duly authorised person of a hospital or any other establishment of the Government especially
approved by that Government.

iii. De-addiction of drug addicts by Government or local body or by an approved charity or voluntary organisation or by such other institution as
may be approved by the Central Government.

iv. Restraining or immobilising wild animals by or under the authority of the Government and approved by that Government.

In order to import cannabis for above purposes, a permission from the Narcotics Commissioner is required.

Persons authorised to import cannabis for the above mentioned purposes are required to maintain records concerning the acquisition and use of the cannabis for at least two years.

16. What approval or notifications are necessary to produce or import Medicinal Cannabis?

Medicinal Cannabis can only be imported by duly authorised person of a hospital for very limited medical requirements of foreigners under a valid import permission granted by the Narcotics Commissioner.

17. What is the regulatory framework for the marketing and distribution of Medicinal Cannabis?

Medicinal Cannabis cannot be marketed and distributed in India.

18. How can patients obtain Medicinal Cannabis?

Indian patients cannot obtain medical cannabis. However, eligible foreign patients can import medical cannabis under an import permission from Narcotics Commissioner.

19. Who can prescribe Medicinal Cannabis?

Medicinal Cannabis cannot be prescribed in India.

20. Is there a list of doctors authorized to prescribe Medicinal Cannabis?

There is no list of doctors authorized to prescribe Medicinal Cannabis.

21. What approvals or notifications are required to prescribe Medicinal Cannabis?

Medicinal Cannabis cannot be prescribed in India.

22. Where is Medicinal Cannabis available?

Medicinal Cannabis can only be imported in India for specific uses. Please refer to Question 15 above for more information.

23. Is there a list of retailers authorized to sell Medicinal Cannabis?

There is no publicly available list of retailers authorized to sell Medicinal Cannabis.

24. Are there proposals for reform or significant change to the regulation of Medicinal Cannabis?

There are currently no proposals for reform or significant change to the regulation of Medicinal Cannabis.

OPIOID DRUGS

25. Are Opioid Drugs authorized in your country?

Yes, opioid drugs are authorized for marketing in India. Any person intending to market opioid drugs must obtain a license under the Narcotic Drugs and Psychotropic Substances Act 1985 (“NDPS Act”), Narcotic Drugs and Psychotropic Substances Rules 1985 (“NDPS Rules”), Drugs and Cosmetics Act, 1940 (“D&C Act”) and Drugs and Cosmetics Rules, 1945 (“D&C Rules”).

26. What are the regulatory authorities with jurisdiction over Opioid Drugs?

The regulatory authorities that have jurisdiction over Cannabinoids have jurisdiction over Opioid Drugs as well.

27. Is there a specific regulatory framework for the authorization, pricing, and reimbursement of Opioid Drugs?

There is no specific regulatory framework regulating the authorization, pricing and reimbursement of Opioid Drugs.

AUTHORIZATION

An Opioid Drug can be sold after obtaining appropriate licenses under the NDPS Act and NDPS Rules, as well as D&C Act and D&C Rules.

PRICING

There is no specific pricing framework for Opioid Drugs in India. However, since Opioid Drugs would be regulated under the larger framework applicable to medicinal drugs in India, they would be subject to price control under the Drugs Price Control Order, 2013 (“DPCO”). The DPCO gives power to the National Pharmaceutical Pricing Authority (“NPPA”) to fix prices of drugs that qualify as ‘essential’. Some opioids such as morphine and fentanyl have been dentified as essential medicines and their prices are now fixed by NPPA. The drugs that do not qualify as essential are not permitted to increase prices by more than 10% in any 12-month period.

REIMBURSEMENT

There is no specific regulatory framework for the reimbursement of drugs, including opioid drugs, in India.

28. Which are the Opioid drugs that have received market approval to date?

The following Opioid Drugs can be marketed in India:

Methyl Morphine (commonly known as Codeine) and Ethyl Morphine and their salts (including Dionine), all dilutions and preparations except those which are compounded with one or more other ingredients and containing not more than 100 milligrams of the drug per dosage unit and with a concentration of not more than 2.5 % in undivided preparations and which have been established in therapeutic practice.
Fentanyl and its salts and preparations, admixtures, extracts or other substances containing any of these drugs.
Dihydrocodeinone (commonly known as Hydrocodone), its salts esters, salts of its esters, and preparations, admixtures, extracts or other substances containing any of these drugs.
Methadone, its salts, and all preparations, admixtures, extracts or other substances containing any of these drugs.
Morphine , its salts and all preparations containing more than 0.2 per cent. of Morphine.
Dihydroxy Codeinone (commonly known as ‘Oxycodone and Dihydroxycodeinone), its salts, its esters, salts of its esters and all preparations, admixtures, extracts or other substances containing any of these drugs.

29. Who can prescribe Opioid Drugs?

Opioid Drugs that have been identified in the response above fall under the Essential Narcotic Drug (“END”) list and can be prescribed by any medical practitioner who is:

registered as a medical practitioner or a dentist; and
has undergone training in pain relief and palliative care for prescription of ENDs for pain relief and palliative care or training in opioid substitution therapy for prescription of ENDs for treatment of opioid dependence.

30. Is there a list of doctors authorized to prescribe Opioid Drugs?

No. There is no such list of doctors authorized to prescribe Opioid Drugs.

31. What approvals or notifications are required to prescribe Opioid Drugs?

No. There are no specific approvals or notifications that are required to prescribe Opioid Drugs.

32. Which organizations are authorized to sell/distribute Opioid Drugs available?

Dealers and chemists who have obtained a license from the State Government to sell narcotic drugs on the END list can sell/distribute Opioid Drugs.

33. Is there a list of retailers/ distributors authorized to sell Opioid Drugs?

No. There is no public list of retailers/distributors authorized to sell Opioid Drugs.

34. Are there proposals for reform or significant change to the regulation of Opioid Drugs?

There are currently no proposals for reform or significant change that have been made to the regulation of Opioid Drugs.

35. When are they likely to come into force?

This question is not applicable.

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9. Orphan Drugs & Rare Diseases: India

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Want to know more about orphan drugs & rare diseases in India? Read on! Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. What is the definition of Rare Diseases in your country?

India does not have a definition of rare diseases. The National Policy on Treatment of Rare Diseases, 2020 (“NPTRD”), which is currently in the draft form, highlights the necessity of coming up with a definition of rare diseases that fits India’s needs but does not provide one.

The government had solicited comments from the general public early 2020 in respect of the NPTRD and is in the process of finalizing the document.

2. Does the designation of ‘Orphan Drug’ exist in your country? (Does it correspond with the definition of Rare Diseases?)

Yes. Orphan Drugs have been defined in the New Drugs & Clinical Trial Rules 2019 (“New Drugs & CT Rules”) as a drug “intended to treat a condition which affects not more than five lakh (500,000) persons in India”.

3. What is the regulatory framework for the authorization of an Orphan Drug? (Is this regulatory framework based on Rare Disease status or can it alternatively be based on Orphan Drug foreign status?)

Clinical Trials

The regulatory framework for the clinical trial of an Orphan Drug is similar to the clinical trial process of other drugs apart from a few relaxations that are granted to Orphan Drugs. The relaxations are as follows:

The Central Drugs Control Standards Organization (“CDSCO”), India’s apex drug regulatory agency, can dispense with the requirement of conducting local clinical trials in the case of Orphan Drugs.
The sponsor of a clinical trial of an orphan drug can request the CDSCO to expedite the review process for approval of such Orphan Drug.
No application fee is required to be paid for the conduct of a clinical trial of an Orphan Drug.

Authorization

The entity seeking to market any new drug in India, including an orphan drug, must obtain authorization from the CDSCO to import or manufacture such drug. A new drug is a drug whose safety and therapeutic efficacy has not been tested on the Indian population.

4. Does your country have provisions for relaxed clinical trial/scientific evidence requirements in respect of Orphan Drugs as compared to other drugs?

Please see response to Question 3.

5. Is there an expedited pathway for Orphan Drugs?

Yes, there is an expedited review process for approval of Orphan Drugs after clinical development.

6. Are foreign marketing authorizations recognized in your jurisdiction for Orphan Drugs? If yes, marketing authorizations from which countries are recognized?

India recognizes foreign marketing authorizations of new drugs (including orphan drugs) from countries recognized by the CDSCO (under Rule 101 of the New Drugs & CT Rules). The CDSCO is yet to notify any countries under Rule 101. In the event the CDSCO recognizes marketing authorizers from a particular country, the drug will not be required to undergo local clinical trials for obtaining marketing authorization. Nonetheless, a separate marketing authorization will be required to be obtained in respect of the new drug. However, unlike other drugs, requirements for post-marketing surveillance for Orphan Drugs may be relaxed at the discretion of the CDSCO.

7. Can Orphan Drugs be reimbursed? If so, is there a specific reimbursement procedure for Orphan drugs?

India has a financial assistance program in place for treatment of rare diseases.

The Union Health Ministry as well as the various state health ministries have set up technical committees known as the Central Technical Committee (“CTC”) and the State Technical Committee (“STC”) respectively, to review applications by patients requesting financial assistance for treatment of rare diseases. The relevant patient or caregiver can apply to the STC or the CTC directly to request assistance. It may be noted that the CTC will convey its decision only to the relevant STC. In the event the CTC considers the case favorably, the relevant State can claim 60% of the approved cost of treatment from the CTC.

The NPTRD has also proposed a financial assistance scheme for treatment of rare diseases. The scheme divides rare diseases into three categories and provides financial assistance as follows:

Group A: Disorders amenable to a one-time curative treatment e.g. Adrenoleukodystrophy, Wiskot Aldrich Syndrome, Tyrosinemia, Fabry’s disease. For diseases in group A, the Central Government has proposed providing financial support of up to INR 15,00,000 (USD 20,300). Approximately 40% of the Indian population is eligible for financial assistance under this initiative.
Group B: Diseases requiring long term or lifelong treatment which have relatively lower cost of treatment and for which benefit has been documented in literature. Annual or more frequent surveillance may be required to treat such diseases. Group B diseases include Tyrosinemia type 1 and 2, Homocystinuria, Propionic Acidemia and Isovaleric Acidemia. The NPTRD does not specifically provide for financial assistance for Group B disorders. Instead, financial assistance for diseases in Group B has been made the purview of State Governments.
Group C: Diseases for which definitive treatment is available but challenges exist in terms of high cost, lifelong therapy and issues relating to optimal patient selection. Group C diseases include Gaucher Disease, Hurler Syndrome, Hunter Syndrome, Spinal Muscular Atrophy, Cystic Fibrosis, and Duchenne Muscular Dystrophy. The Central Government has proposed setting up a digital platform to crowdfund the cost of treatment for diseases in Group C. Individual and corporate donors are permitted to contribute to the fund which shall be used to cover the cost of treatment of individuals suffering from Group C diseases at designated government hospitals equipped for treating rare diseases.

8. How are the prices of Orphan Drugs regulated?

Orphan Drugs, as identified by the Health Ministry from to time, are exempt from price regulation.

9. In case of reference price based on a basket of countries, what countries are included?

India does not follow a system requiring a reference price based on a basket of countries.

10. Have there been any significant legal/judicial developments in relation to Orphan Drugs in your country?

The constitutional obligation of the state to ensure access to life saving drugs has been formally recognized by the Delhi High Court in Mohd. Ahmed (Minor) v. Union of India & Ors W.P.(C) No. 7279 of 2013 (“Mohd. Ahmed Case”). In the Mohd. Ahmed Case, the Delhi High Court directed the Delhi Government to provide the Mohd. Ahmed (minor patient in question) with enzyme replacement therapy worth INR 600,000 (USD 8,334) per month as a treatment to gaucher. The petitioner was represented through his father who was a rickshaw-puller and could not afford the exorbitant cost of treating his minor child Mohd. Ahmed. Therefore, the parents of the minor patient had approached the Delhi High Court to request the Court to direct the Delhi Government to offer financial assistance with respect to the treatment of the rare disease.

11. Are there proposals for reform or significant change to the regulation of Orphan Drugs? If yes, when are they likely to come into force?

The finalization of the NPTRD is the primary regulatory reform expected in the orphan drug space.

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10. Localization: India

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The key facts about the localization in Indian Pharma. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. Are there any rules or regulations requiring and/or encouraging localization in your country? What is the legal framework defining these localization rules and policies?

There are no specific legislations or regulations requiring and/or encouraging localization in India. The relevant localization policies have been elaborated upon in the answers provided below.

2. Have there been any recent significant changes involving localization rules?

Yes, there have been significant changes involving localization rules.

3. If yes, when did they take place and what did they involve?

Exemption from Drug Price Control

The Department of Pharmaceuticals by way of an order (“Order”) extended a price control exemption that was earlier granted only to manufacturers of new drugs and medical devices protected through a product patent (“Patented New Drugs”) developed through indigenous research and development to all Patented New Drugs regardless of the country in which such drugs are developed (“New Drug Exemption”). The New Drug Exemption was effective from January 03, 2019.

Prior to the Order, the scope of price control exemption was limited to only those manufacturers who were producing Patented New Drugs that were (i) developed through indigenous (i.e. local) research and development and (ii) not produced elsewhere. However, the New Drug Exemption removes all localization requirements. Therefore, even manufacturers, importers and marketers of Patented New Drugs developed and manufactured outside India are now eligible for price control exemption for a period of five years from the start of its commercial marketing. Conversely, domestic manufacturers who marketed Patented New Drugs in India and outside India have also become eligible for price control exemption, which was not the case earlier.

Prices of all drugs and medical devices in India are controlled under the Drugs (Prices Control) Order, 2013 (“DPCO”). The National Pharmaceutical Pricing Authority (“NPPA”) set up under the DPCO is empowered to fix ceiling prices of drugs and medical devices that are listed in the schedule appended to the DPCO (“Scheduled Formulations”). The drugs that are not part of the schedule to the DPCO (“Non-Scheduled Formulations”) are under strict price surveillance. The prices of Non-Scheduled Formulations cannot be increased by more than 10% in any 12 month period.

Exemption from Conducting Local Clinical Trials

The New Drugs and Clinical Trial Rules, 2019 (“New Drugs & CT Rules”) empowers the Central Drugs Standard Control Organisation (“CDSCO”)- India’s apex drug controller- to exempt a drug approved in foreign jurisdiction specified by the CDSCO from undergoing local clinical trials to obtain marketing authorization in India. The New Drugs & CT Rules came into force on March 19, 2019. For more information, please see Question 6.

4. Is the process of obtaining a marketing authorization impacted by localization policies in your country?

Yes, the process of obtaining marketing authorization is impacted by localization policies in India.

5. If yes, how so (what are the incentives received or the requirements)?

Drugs

As a matter of rule, new drugs are required to undergo local clinical trials before being granted marketing authorization in India to determine whether such drug is safe and efficacious for the Indian population. A new drug includes the following:

A drug, including a bulk drug substance, which has not been used in India to a significant extent and whose safety, efficacy and therapeutic value has not been established in India;
A drug which is already approved which is now proposed to be marketed with modified or new claims such as indication, dosage, dosage forms or route of administration;
A Fixed Dose Combination (“FDC”) of two drugs individually approved earlier but which are now proposed to be changed for the first time or if the ratio of drugs in an FDC is sought to be changed;
A modified or sustained release form of a drug or novel drug delivery system of any drug approved by the CDSCO; and
All vaccines and Recombinant DNA (r-DNA) derived drugs, unless certified otherwise.

However, a local clinical trial may not be required at all if the new drug is approved and marketed in countries specified by the CDSCO and if:

No major adverse events have been reported;
There is no probability or evidence of difference in (a) the enzymes or gene involved in the metabolism of the new drug and, (b) safety and efficacy of the new drug between the Indian population and the population the drug was tested on; and
The applicant has undertaken to conduct comprehensive post-marketing surveillance to establish and effectiveness of the new drug as per a study design that has been approved by the CDSCO.

Medical Devices

Generally, medical devices that have not been approved by the CDSCO (“Investigational Medical Devices”) are required to undergo clinical investigations before they can be manufactured or imported for sale or distribution in the country. Submission of such clinical investigation data is a pre-requisite to obtaining a manufacturing or import license in respect of such medical device.

However, when a free sale certificate has been issued in respect of any medical device by the national regulatory authority of Australia, Canada, Japan, European Union countries or the United States of America, an import or manufacturing license can be granted without carrying out a clinical investigation.

6. Is the pricing process for pharmaceutical products impacted by localization policies in your country?

Yes, the pricing process of pharmaceutical products is impacted by localization policies.

7. If yes, how so (what are the incentives received or the requirements)?

For more information, please see Question 3.

8. Is the reimbursement of pharmaceutical products impacted by localization policies in your country?

The reimbursement of pharmaceutical products is not impacted by localization policies in India as India does not have a reimbursement policy for pharmaceutical products.

9. If yes, how so (what are the incentives received or the requirements)?

Not applicable.

10. Is the access to public or public tenders of pharmaceutical products impacted by localization policies in your country?

Yes, access to public tenders of pharmaceutical products is impacted by localization policies.

11. If yes, how so (what are the incentives received or the requirements)?

As part of the ‘Make in India’ policy, the Indian Government gives preference to ‘local supplier’ of pharmaceutical products and medical devices for public procurement purposes by all government procuring entities. The Public Procurement Policy of India stipulates the eligibility criteria to obtain preferential status in case of tenders.

To qualify as a local supplier of pharmaceutical products, the minimum local content shall be 75% for all products manufactured in India and 10% for all products manufactured outside of India. The local content requirements are slated to increase every financial year until they reach 90% and 30% respectively for fiscal year 2023-25.

For medical devices, the minimum local content is as follows:

Category of Medical Devices	% of Local Content
Medical disposables and consumables	50%
Medical electronics, hospital equipment, surgical instruments	25%
Implants	40%
Diagnostic Reagents/IVDs	25%

Separately, the Indian Government has also amended the General Financial Rules, 2017 (“GFR”) – a compilation of rules and orders to be followed by Government Departments when dealing with matters involving public finances – restricting bids for public tenders from bidders based in countries which share a land border with India (“Bordering Countries”). The amendment requires bidders from Bordering Countries to register with the Department for Promotion of Industry and Internal Trade (“DPIIT”) to be eligible to bid for public procurement of goods, services or works carried out by government bodies (including public sector banks and enterprises).

12. Are import tariffs, importation and/or exportation permits, trade and/or taxation of pharmaceutical products impacted by localization policies in your country?

Yes, import tariffs, importation and/or exportation permits, trade and/or taxation of pharmaceutical products is not impacted by localization policies in India.

13. If yes, how so?

Import tariff exemption is granted for some pharmaceutical products by the Finance Ministry of India. However, after the introduction of the Make in India policy, the Central Government has withdrawn tariff exemptions granted to over 70 drugs including life-saving drugs used for HIV with a view to boost production of pharmaceutical products in India.

14. Are there any other incentives or advantages offered by the current local localization rules in your country?

Yes.

15. If yes, what are they?

India offers tax incentives in the form of tax deductions for in-house R&D expenditures.

16. Are there discussions about the possibility of implementing localization policies in your country?

None.

17. If yes, what are the proposed reforms and when should they come into place?

None.

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11. Biosimilars & Biologics: India

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An insight into biosimilars & biologics in Indian Pharma. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

1. Are biosimilar medicines considered the same as generic medicines in your country?

Biosimilar medicines are not regulated in the same manner as generic medicines in India. While biosimilars and generic medicines are classified as drugs under the Drugs & Cosmetics Act 1940 (“D&C Act”) (India’s primary drug control legislation), clinical trial requirements for biosimilars are stricter than those applicable to generic medicines. Once a drug formulation has received marketing authorization from the Central Drugs Standard Control Organisation (“CDSCO”) – India’s apex drug regulator – subsequent manufacturers of the drug formulation are not required to undertake clinical trials in respect of the same drug formulation, if the drug formulation has been marketed for over four years. However, biologics such as vaccines, recombinant deoxyribonucleic acid (“rDNA”) derived products and living modified organisms are required to undergo clinical trials even if another entity has been manufacturing the same biologic. As a result, unlike generic drugs, every iteration of a biologic must undergo clinical trials.

2. Are all biologic medicines, including biosimilar medicines patentable in your country?

Biologic medicines as well as biosimilars are patentable in India (subject to certain exceptions) as long as such biologic or biosimilar (i) is novel/new (ii) involves an inventive step/is non-obvious and (iii) has utility/industrial application.

Biologics

Biologics comprising living organisms that are not naturally occurring i.e. have been developed by humans may be patented. However, biologics comprised of a living organism already occurring in nature cannot be patented as the mere “discovery of any living thing or non-living substance occurring in nature” is not patentable under the Patent Act 1970. It may be noted that India does not grant patent protection to (i) the mere discovery of a new form of a known substance if it does not result in the enhancement of the known efficacy of that substance or (ii) mere discovery of any new property or use for a known substance.

Biosimilars

Biosimilars are not eligible for product patents (as the end product is the same as an already patented/known reference biologic) but are eligible for process patents as long as the process fulfils the other criteria for patentability. However, India does not grant patent protection to the mere use of a known process unless such known process results in a new product or employs at least one new reactant.

3. Is there a specific regulatory framework for the marketing authorization of biosimilar medicines in your country?

Yes, India has a specific regulatory framework for the marketing authorization of biosimilar medicines.

4. If yes, what is the regulatory framework for the authorization of biosimilar medicines?

Biosimilar medicines in India are regulated under:

The Drugs & Cosmetics Act 1940;
Drugs & Cosmetics Rules 1945 (“D&C Rules”) (framed under the D&C Act govern the process for clinical trials, import and manufacture of all drugs including biologics and biosimilars);
New Drugs & Clinical Trial Rules, 2019 (“New Drugs & CT Rules”) (framed under the D&C Act govern the procedure for the conduct of clinical trials of all drugs including biologics and biosimilars);
Guidelines on Similar Biologics: Regulatory Requirements for Marketing Authorization in India, 2016 (“Biosimilar Guidelines”) (guidelines that stipulate the pre-clinical trial requirements for biosimilars);
Rules for Manufacture, Use, Import, Export and Storage of Hazardous Microorganisms/Genetically Engineered Organisms or Cells, 1989 (“Genetically Engineered Microorganisms Rules”) notified under the Environment (Protection) Act, 1986 (applicable to manufacture, import and storage of microorganisms and gene-technological products as well as genetically engineered microorganisms, microorganisms and cells);
Regulations and Guidelines on Biosafety of Recombinant DNA Research and Biocontainment, 2017 (“rDNA Guidelines”) (cover the regulation on biosafety of rDNA research and handling of hazardous microorganisms and GE organisms or cells);
Guidelines for Generating Pre-clinical and Clinical Data for rDNA Vaccines, Diagnostics and other Biologicals, 1999 (“Clinical Data Guidelines”) (cover preclinical and clinical evaluations. Their objective is to generate preclinical and clinical data with respect to the safety, purity, potency and effectiveness of rDNA vaccines, diagnostics and other biologicals);
CDSCO Guidance for the Industry, 2008 (“Guidance for the Industry”) (provides guidance to clinical trial sponsors regarding the submission of clinical trial applications under the D&C Act and GCP Guidelines);
Guidelines and Handbook for Institutional Biosafety Committee, 2011 (“IBSC Guidelines”) (provides guidance to the Institutional Biosafety Committees (“IBSC”) that are required to be set up to oversee the preclinical trials of biologics and biosimilars in India);
Guidance Document for Industry: Submission of Stability Data and Related Documents for Review and Expert Opinion for Granting Post-approval Changes in Shelf Life of Recombinant Biotherapeutic Products and Therapeutic Monoclonal Antibodies published by the National Institute of Biologicals 2016 (“Post-Approval Guidelines”) (provides guidance and recommendations to holders of marketing authorization of biologics who intend to make post approval changes in the shelf life of the product).

The authorities responsible for overseeing the approval process are:

Institutional Biosafety Committee (a committee that is required to be constituted by every organisation engaged in research, handling and production activities related to genetically modified organisms (“GMO”). The IBSC is the nodal point for interaction within an organisation for implementation of the biosafety regulatory framework);
Review Committee on Genetic Manipulation (“RCGM”) (a regulatory/approval committee established under the Genetically Engineered Microorganisms Rules to monitor the safety related aspect in respect of on-going research projects or activities involving hazardous microorganisms, GMOs and cells and products thereof);
Genetic Engineering Appraisal Committee (“GEAC”) (a body established by the Ministry of Environment, Forest and Climate Change (“Environment Ministry”) to appraise activities involving large scale use of hazardous microorganisms, GMOs or cells in research, industrial production and experimental field trials); and
The Central Drugs Control Standards Organisation (the apex regulatory body with respect to clinical trials, import and manufacture of all drugs in India including biologics and biosimilars).

5. What kind of data package is needed to obtain approval for a biosimilar drug?

The approval process for biosimilar drugs is divided into pre-clinical trial, clinical trial and post clinical trial stages with each stage having different data package requirements. Data packages may also differ based on the risk classification assigned to the GMOs) under the Genetically Engineered Microorganisms Rules, as prior authorisation from the IBSC and subsequent approval of the RCGM is required for conducting experiments involving LMOs classified in risk categories 3 or higher.

In addition to RCGM permission, the approval of the GEAC is also required for activities involving large scale use of hazardous microorganisms and recombinants in research and industrial production. The GEAC is also responsible for approval of proposals relating to release of GMOs and products into the environment including experimental field trials.

Pre-clinical Trial Stage

Data packages must demonstrate the consistency of process and product, product characterisation, and product specifications to comply with RCGM requirements. The application to the RCGM should be accompanied by approval of the IBSC and the approval of the Institutional Animal Ethics Committee (“IAEC”) along with details of the personnel involved such as study director, principal investigator, pathologist, other investigators and quality assurance officer.

The information in the data package may include the following.

Basic Information about Reference Biologic

Information about drug, route of administration, absorption and elimination rate, therapeutic index, dose, vehicle, mode of administration, dose response etc.
Bioequivalence range, if available,
Tissue-specific localisation, if available,
Available toxicity data on reference biologic, and
Mode of action.

Basic Information about the Similar Biologic

Known/proposed clinical use,
Target population (age, sex, pregnancy, lactating, children etc.),
Dosage units (frequency and intervals),
Route/alternate routes of administration,
Final formulation of adjuvants and additives including toxicity data of such adjuvants and additives,
Diluents, and
Presentation e.g. pre-filled syringe, cartridge, vial.

Quality Attributes

To establish similarity, the quality attributes of a biosimilar may be considered in two categories:

Critical Quality Attributes (“CQA”): these attributes have a direct impact on the clinical safety or efficacy. All attributes that directly impact the known mechanism(s) of the molecule fall in this category.
Key Quality Attributes (“KQA”): are those attributes which are not known to impact clinical safety and efficacy but are considered relevant from a product and process consistency perspective.

Attributes that do not impact the known mechanism(s) of action of the molecule fall in this category. While KQAs must necessarily be controlled within acceptable limits, it may be acceptable to have slight differences in comparison to the reference biologic.

Other Information

Details of pharmacodynamic study design (both in-vitro and in-vivo studies). The in-vitro studies should establish comparability between the reference biologic and the biosimilar.
Details of toxicology study design such as in vivo toxicity studies on a pharmacologically relevant animal involving three levels of doses (1X, 2X and 5X of human equivalent dose) for repeat dose toxicity studies.
Immune responses in animals i.e. antibody response, immune toxicity.
Safety pharmacology, reproductive toxicity, mutagenicity and carcinogenicity studies are not generally required unless warranted by the results of repeat dose toxicological studies.

Clinical Trial Stage

Based on successful evaluation of pre-clinical study reports, the RCGM may recommend that the Drugs Controller General of India (“DCGI”) (head of the CDSCO and apex drug regulator of India) allow the sponsor to conduct appropriate phase of clinical trial as per CDSCO requirements. A clinical trial typically takes place over four stages. The New Drugs & CT Rules, which have replaced the erstwhile clinical trial rules under Part X-A and Schedule Y of the D&C Rules, govern the conduct of clinical trials in India. The clinical trial data requirements for biosimilars are the same as for drugs apart from a few differences.

Overview of Clinical Trial Regulation

While a clinical trial is typically conducted over four phases, the DCGI is empowered to expedite the approval process with respect to a drug taking into account the severity, rarity and prevalence of the disease. For instance, the requirement for submission of studies relating to animal toxicity, reproduction, tetrogenic, perinatal, mutagenicity and carcinogenicity may be waived if the CDSCO is satisfied that there is adequate published evidence regarding the safety of the drug.

Additionally, a local clinical trial may not be required at all if the new drug is approved and marketed in countries specified by the CDSCO and if:

No major adverse events have been reported,
There is no probability or evidence of difference in (a) the enzymes or gene involved in the metabolism of the new drug, (b) pharmacokinetics (“PK”) and pharmacodynamics (“PD”), safety and efficacy of the new drug between the Indian population and the population the drug was tested on,
The applicant has undertaken to conduct Phase IV clinical trials (post-marketing studies) to establish and effectiveness of the new drug as per study design that has been approved by the CDSCO.

Additional Data Requirements for Biosimilars

Comparative PK and PD studies: PK and PD studies are conducted in the first phase of the clinical trial. PK studies should be conducted to demonstrate comparability in both single dose and multi-dose PK studies. For biosimilars that is proposed to be used in a multi-dose regimen, multiple-dose, comparative, parallel arm steady state PK studies are required. Comparative PD studies are also recommended when the PD properties of the reference biologic are well characterised with at least one PD marker validated for a clinical outcome of the molecule.
Confirmatory safety and efficacy studies: In order to eliminate any residual risk, a comparative safety and efficacy study (typically conducted in the third phase of the clinical trial) are required. The requirement of safety and efficacy study may be waived only in exceptional cases if there are no uncertainties left after comparing the biosimilar and reference biologic at the analytical, non-clinical and PK/PD level and if a comprehensive post-marketing risk management plan has been presented to the CDSCO. Wherever, phase III trial is waived, the immunogenicity that should have been gathered in the PK/PD study will also need to be generated during post-approval phase IV study.

Post-Clinical Trial Stage

Post-marketing surveillance is particularly important in the case of biosimilars, as a biosimilar is approved based on a reduced pre-clinical and clinical trial data package. Therefore, a formal Risk Management Plan must be established to monitor and detect both known inherent safety concerns and potential unknown safety signals that may arise from the biosimilar. A comprehensive pharmacovigilance plan must also be put into place which shall include the submission of periodic safety update reports (“PSUR”).

In the event phase III clinical trials are not carried out, immunogenicity studies must be conducted in phase IV. Additional safety data may need to be collected after market approval through a pre-defined single arm study of over 200 evaluable patients. The study should preferably be completed within 2 years of receipt of marketing permission/manufacturing license unless otherwise justified.

6. Is this any different to the requirements for the original Biologics drug?

The data package requirements for biologics drugs are similar to those of biosimilars. The notable differences are:

The data collected for an original biologics drug will not be in reference to a pre-existing product. For instance, the PK/PD data collected will not be in reference to another product but will be directed towards assessing the PK/PD of the original biologics drug.
Phase III clinical trial must be conducted as the original biologic will be licensed on the basis of a full safety, efficacy and quality data as opposed to the reduced data package employed when licensing a biosimilar.

7. What are the requirements for the choice of the reference comparator product?

The requirements for choice of comparator product are as follows:

reference comparator product should be licensed / approved in India or a country that follows the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (“ICH”)
reference comparator product should be the innovator’s product as another biosimilar cannot be the reference biologic as the comparator product should be licensed based on a full safety, efficacy and quality data.

8. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?

The comparator product can be imported from another regulatory jurisdiction regardless of whether such product is beingmarketed in India. The only requirement is that the comparator product be approved in an ICH country. However, the acceptance of an innovator product as comparator product for evaluation of a biosimilar does not imply approval for the use of such comparator product in India.

9. How are the prices of biosimilar medicines regulated? Is this any different to the requirements for the original Biologics drug?

The Drugs (Prices Control) Order 2013 (“DPCO”) governs pricing for both original biologics and biosimilars in the same manner. The National Pharmaceutical Pricing Authority (“NPPA”) is empowered by the DPCO to fix ceiling prices of drugs (including biologics) that are listed in the schedule to the DPCO (“Scheduled Formulations”). The Scheduled Formulations include biologics such as vaccines and sera. The DPCO clarifies that all biologicals irrespective of variation in source, composition and strengths and all the products of the same vaccine/sera/immunoglobulin considered as part of the schedule to the DPCO.

10. What is the reimbursement policy for biosimilar medicine? Is this any different to the requirements for the original Biologics drug?

India currently does not have a mechanism for reimbursement of biologics or biosimilar medicines. Out-of-pocket-expenditure is the primary source of healthcare financing in India as India suffers from a low level of both private and government insurance penetration. In addition to the above, the Indian government runs schemes that provide free or highly subsidized care to Indian citizens. There are also Non-Governmental Organisations that provide free medication to patients who are otherwise unable to afford them. All of these methods are however, applicable for all drugs, biologics and medical devices.

11. Does biosimilar competition impact the reimbursement policy of the originator reference products?

India does not have a reimbursement policy in place.

12. What is the legal framework for biosimilar medicines prescribing (clinical decision maker) and dispensing (pharmacy level, hospital or retail)? Is this any different to the requirements for the original Biologics drug?

In India, doctors are required to prescribe all drugs, including biologics by their chemical names i.e. the name of pharmaceutical formulation. There is no difference in requirements for prescribing or dispensing an original biologic and a biosimilar.

Prescribing

A valid prescription shall:

Be in writing and be signed by a medical practitioner registered under the Indian Medical Degrees Act, 1916, the Indian Medical Council Act, 1956 or the Dentists Act, 1948 among others (“Registered Medical Practitioner”),
Specify the name and address of the person for whose treatment it is given, and
Indicate the total amount of medicine to be supplied and the dose to be taken.

Dispensing

Biologics or biosimilars can only be dispensed by registered pharmacists on the basis of a valid prescription signed by a registered medical practitioner.

13. Is the system considering physician-led switching and/or pharmacy-level substitution (without involvement of the clinical decision maker)?

Pharmacy level substitutions of a biosimilar for a biologic are possible as doctors in India are required to prescribe medicines using their chemical name. Moreover, a biosimilar can be approved for all the clinical indications the reference biologic has been approved if:

Similarity with respect to quality and preclinical assessment has been proven to reference biologic,
Clinical safety and efficacy is proven in one indication,
Mechanism of action is same for other clinical indications,
Involved receptor(s) are same for other clinical indications.

14. What are the post – authorisation requirements (including pharmacovigilance, risk management plans, post-approval studies) for biosimilar medicines? Is this any different to the requirements for the original Biologics drug?

Pharmacovigilance

Entities marketing biosimilars are obliged to undertake pharmacovigilance for a period of four years from the launch of the drug. Under the pharmacovigilance system, the marketer must have a risk management plan in place which provides brief details of safety concern and necessary action taken by the marketer to mitigate these safety concerns. PSURs must be submitted to the CDSCO every six months for the two years after the biosimilar has been granted approval. Thereafter, the PSUR must be submitted annually for two more years.

Post-approval Studies

Post-approval studies for biosimilars must be conducted in more than two hundred patients in continuation to demonstrate comparability between the biosimilar and the original biologic. In the event permission was obtained to not undertake safety and efficacy study, immunogenicity data that should have been gathered in the PK/PD study will need to be generated in the post-approval phase. However, if pre-approval immunogenicity studies were conducted on more than 100 patients, then the number of patients in the post-approval study may be modified such that safety data (from both immunogenicity and post-approval study) is derived from a minimum if 300 patients treated with the similar biologic.

15. Are there specific policies and requirements in terms of biosimilar medicines labelling in the event of second medical use patents? Is this any different to the requirements for the original Biologics drug?

India does not recognise second medical use patents as the Patents Act, 1970 (“Patents Act”) – India’s patent regulatory framework- excludes the discovery of a new use for a known substance from the definition of invention.

16. Have there been any significant legal/judicial developments in relation to biosimilars in your country? (Including but not limited to IP, procurement, competition, misleading information campaign, access to reference comparator product)

The Delhi High Court held that the predecessor to the Biosimilar Guidelines published in 2012 is enforceable in law in the case of Roche Products (India) Pvt. Ltd. & Ors v. Drugs Controller General of India & Ors. [MIPR 2016 (2) 217] (“Roche Judgement”). The court held that guidelines are in the nature of directions issued by the government and as long as the guidelines are not in contradiction but merely in addition to already existing rules and regulations, the guidelines will have legal validity. Even though the Roche Judgement was in context of the previous version of the Biosimilar Guidelines, the same principle should apply to the current Biosimilar Guidelines as well.

17. Are there proposals for reform or significant change to the legal, regulatory, procurement of biosimilars? If yes, when are they likely to come into force?

There are currently no proposals for reform or significant change to the legal, regulatory or procurement framework of biosimilars.

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12. Digital Health: India

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An insight into digital health in Indian Pharma. Prepared in association with Nishith Desai & Associates, a leading law firm in India, this is an extract from The Pharma Legal Handbook: India, available to purchase here for GBP 119.

151. Is the term ‘digital health’ defined in your jurisdiction? If no, how is the term generally understood?

The term digital health is not specifically defined in India. It is generally understood to include tools and services that use information and communication technologies (ICT) for purposes connected to health. These purposes may include improving accuracy of diagnosis, monitoring chronic diseases more closely and improving treatment outcomes for patients.

152. What digital health tools are specifically recognized and regulated in your jurisdictions?

Telemedicine is the only digital health tool specifically recognized and regulated. The government is currently in the process of regulating online pharmacies as well.

153. What is the regulatory framework applicable to the above-mentioned digital health tools? Who are the regulators with jurisdiction over these areas?

The Telemedicine Practice Guidelines (“TPG”) regulate telemedicine in India. The TPG is administered an enforced by the National Medical Commission (“NMC”) – the apex regulatory body governing medical education and the medical profession in India.

It should be noted that the TPG is only binding on healthcare practitioners licensed to practice in India. This is because the TPG are framed as part of the code of ethics to be followed by healthcare practitioners when practising medicine.

154. How is health data regulated in your jurisdiction? Is there a separately regulatory framework governing health data?

Health data is regulated under India’s data protection and privacy legislation, the Information Technology Act, 2000 (“IT Act”) and the Information Technology (Reasonable security practices and procedures and sensitive personal data or information) Rules, 2011 (“SPDI Rules”) framed thereunder. India does not have a separate regulatory framework governing health data at the moment.

Under the SPDI Rules, information relating the physical, physiological or mental health condition, and medical records and history of a individual are considered to be sensitive personal data or information (“SPDI”). Accordingly, the collector of this information is required to undertake certain compliances during the collection and processing of data to safeguard the privacy of the provider of information.

You may note that India is presently in the process of putting in place a new data protection and privacy framework. See response to question 157 for more details.

155. What are the obligations of entities collecting, storing, or otherwise processing health data in your jurisdiction?

The collector of information is required to adhere to the following broad compliances under the SPDI Rules.

Publish a terms of use and privacy policy on the website which is available to the provider of information;
Obtain express consent from the provider of the information regarding the purpose of usage before such information is collected;
Only collect information which is necessary for undertaking the function or activity of the body corporate;
Take reasonable steps to inform the provider of information of the fact for which the information is being collected, the purpose for which the information is being collected, the intended recipients of the information and the name and address of the agency that will collect and/or retain the information;
Provide an option at the time of collecting information to not provide the data or information;
Use the information only for the purpose for which it has been collected;
Not retain the information for longer than is required for the purpose for which the information may be lawfully used or longer than required by law;
Follow reasonable security practices and procedures including documented information security programme and information security policies commensurate with the information assets being protected. Body corporates implementing the standard ISO 27001 on “Information Technology – Security Techniques – Information Security Management System – Requirements” are deemed to have put in place reasonable security practices provided such security practices are duly audited by an independent, recognised auditor once a year or as and when the body corporate undertakes a significant upgradation of its process and computer resource. Nonetheless, a separate security standard may be agreed to upon by the provider of information and the collector of information.
Appoint a grievance officer to address any discrepancies and grievances of the provider of information with respect to processing of information in a time bound manner.

156. Can health data be transferred abroad in your jurisdiction? What restrictions (if any) are applicable to cross-border transfer of health data?

Yes, health data may be transferred outside of India provided the following conditions are fulfilled:

The transferor ensures that the receiver of the information implements the same level of data protection in respect of the data as the transferor; and
The transfer is necessary for the performance of a lawful contract between the body corporate and the provider of information or where the provider of the information has consented to the transfer.

157. Are there proposals for reform or significant change to digital health regulation? If yes, when are they likely to come into force?

India is presently in the process of finalising a new data protection and privacy legislation. The Personal Data Protection Bill, 2019 was introduced in the Indian Parliament in December 2019. Subsequently, the bill was referred to a Joint Parliamentary Committee under the Chairpersonship of Meenakshi Lekhi for the committee to examine the bill and provide recommendations. The committee has reportedly made extensive amendments to the bill. The report of the committee is likely to be released during the Monsoon Session of the Indian Parliament in 2021.

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Legal & Regulatory

(debug: legal) The Pharma Legal Handbook: India

1. Regulation, Pricing and Reimbursement Overview: India

1. What are the regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in your country?

2. What is the regulatory framework for the authorization, pricing and reimbursement of drugs, biologicals and medical devices?

3. What are the steps to obtain authorization to develop, test, and market a product?

4. What are the approximate fees for each authorization?

5. For how long are marketing authorizations/registrations valid? How are marketing authorizations/registrations renewed?

6. How does the authorization process differ between brand-name products and generic products? Are there differences for local manufacturers versus foreign-owned manufacturers?

7. How are combination products (drug + drug, drug + biologic, drug + device, biologic + device, drug + biologic + device) regulated?

8. How is compliance with regulation monitored and evaluated? Is the regulatory regime comparable with the U.S. Food and Drug Administration or the European Medicines Agency expectations and requirements?

9. What is the potential range of penalties for noncompliance?

10. Is there a national healthcare system? If so, how is it administered and funded?

11. How does the government (or public) healthcare system function with private sector healthcare?

12. Are prices of drugs and devices regulated and, if so, how?

13. How are drugs and devices used by patients paid for? What roles do public and private payers play?

14. Who dispenses drugs and devices to patients and how are those dispensers compensated?

15. What are the professional and legal responsibilities of those who dispense drugs and devices? What role do they play in providing patient care, information, and safety?

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2. Preclinical and Clinical Trial Requirements: India

1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?

2. How are clinical trials funded?

3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?

4. What are the requirements for consent by participants in clinical trials?

5. May participants in clinical trials be compensated?

21. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?

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3. Marketing, Manufacturing, Packaging & Labelling, Advertising: India

1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?

2. What is the authorization process for the marketing of generic versions of these products?

3. What are the typical fees for marketing approval?

4. What is the period of authorization and the renewal process?

5. What are the requirements, if any, for post-approval pharmacovigilance?

6. Are foreign marketing authorizations recognized?

7. Are parallel imports of medicines or devices allowed?

8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?

9. How is the manufacturing of medicines and devices regulated and by which agencies?

10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the U.S. Food & Drug Administration and/or the European Medicines Agency?

11. What is the inspection regime for manufacturing facilities?

12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?

13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?

14. What information must be included in medicine and device labeling?

15. What additional information may be included in labeling and packaging?

16. What items may not be included in labeling and packaging?

17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?

18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?

19. What are the restrictions and requirements for electronic marketing and advertising via email, by Internet, social media, and other channels?

20. May medicines and devices be advertised or sold directly to consumers?

21. How is compliance monitored?

22. What are the potential penalties for noncompliance?

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4. Traditional Medicines and OTC Products: India

1. What are the regulatory requirements for traditional, herbal, complementary, or alternative medicines and devices?

2. Can these traditional, herbal, complementary, or alternative products be advertised directly to the public?

3. What health, advertising, and marketing claims may be made for traditional, herbal, complementary, or alternative products?

4. What are the regulatory requirements for over-the-counter (non-prescription) medications?

5. Are there any limitations on locations or channels through which OTC products may be sold?

6. What health, advertising, and marketing claims may be made for OTC products?

7. Can OTC products be marketed or advertised directly to the public?

8. What is the mechanism by which a prescription-only product can be converted to an OTC product?

9. What are the requirements for the importation of either traditional medicines or OTC products?

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5. Product Liability: India

1. What types of liability are recognized in your jurisdiction?

2. How do these types of liabilities apply to the manufacturers of medicines and devices?

3. Does potential liability extend to the manufacturer only or could claims extend to corporate executives, employees, and representatives?

4. How can a liability claim be brought?

5. What defenses are available?

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6. Patents and Trademarks: India

1. What are the basic requirements to obtain patent and trademark protection?

2. What agencies or bodies regulate patents and trademarks?

3. What products, substances, and processes can be protected by patents or trademarks and what types cannot be protected?

4. How can patents and trademarks be revoked?

5. Are foreign patents and trademarks recognized and under what circumstances?

6. Are there any non-patent/trademark barriers to competition to protect medicines or devices?

7. Are there restrictions on the types of medicines or devices that can be granted patent and trademark protection?

8. Must a patent or trademark license agreement with a foreign licensor be approved or accepted by any government or regulatory body?

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7. Regulatory Reforms: India