A clause in a draft free trade agreement text being negotiated between India and the European Free Trade Association (EFTA) — Switzerland, Iceland, Lichtenstein and Norway — could delay access to affordable, generic versions of patented drugs in India by a minimum of six years, according to documents viewed by The Hindu.

A leaked draft of the Trade and Economic Partnership Agreement (TEPA), available on the website bilaterals.org, an organisation that tracks international free trade agreements, says that within six months of the trade agreement being signed, signatories (in this case the countries) should include a “specific duration” during which applicants (pharmaceutical companies) applying to their country’s regulators for permission to sell a drug would not rely on “undisclosed test data” (in this case data on the drug’s efficacy and impact on people) to gain market approval for at least six years.

There is also a line that suggests this should apply not only to ‘new’ chemical drugs but also a class of drugs called ‘biologics drugs,’ — monoclonal antibodies, vaccine formulations — that involve complex mixtures of organic and inorganic entities, and are harder to make copies of. Many Indian biotechnology companies are developing biologics drugs.

The Hindu has independently confirmed the existence of this clause from sources following international bilateral negotiations.

India, which has over decades, mushroomed a thriving generics drug industry has resisted attempts by foreign pharmaceutical companies to extend monopoly rights over patented drugs. This is mostly because India’s generic drug industry has over the years made affordable versions of expensive drugs and become a large global supply itself. The Indian pharma industry is the third largest in the world and produces over 60,000 generic drugs across 60 therapeutic categories and had an annual turnover of ₹3.4 lakh crore, Minister of State (Chemicals and Fertilizers) Bhagwant Khuba told Parliament in July 2023. It is also the bulwark of the government’s Jan Aushadhi Scheme that allows free drugs to be made available to the poor.

“These effectively means that drugs such as bedaquiline (for TB) under provisions of data exclusivity wouldn’t be available,” said Gopa Kumar, legal researcher, Third World Network. Medicine Sans Frontiers, which works on enabling access to medicines, has written to Prime Minister Narendra Modi on February 9 pointing out concerns over these provisions in the draft TEPA.

In the most recent round of EFTA negotiations that were held in Delhi from January 8-13, media reports suggest that officials from both delegations have moved closer to a deal.

“Balanced solutions”

Swiss Economy Minister Guy Parmelin, who heads the EFTA, posted on X last month after he flew to India on a “last-minute” invitation of India’s Commerce Minister Piyush Goel for negotiations on the TEPA, following which they had reached “balanced solutions” to concerns around the agreement.

While details of these solutions are not public, intellectual property (IPR) concerns are a major sticking point. In an interview to The Hindu in December, Helene Budliger Artieda, Swiss Director of the State Secretariat for Economic Affairs (SECO), and Norwegian Trade Minister Jan Christian Vestre said Minister Goyal had been told that securing the “best possible deal in IPR was a ‘bread and butter issue’“ for EFTA countries. “At this stage we do not wish to comment on the ongoing negotiations. We hope for the agreement to be concluded as soon as possible,” a spokesperson for the Norwegian Embassy told The Hindu.

Patented drugs give exclusive marketing rights to the inventor, or whoever files for the patent first, for 20 years. This has often resulted in essential drugs and medicines being unaffordable in several countries, including in India. Under internationally accepted provisions of compulsory licensing, Indian law allows drug maker to reverse-engineer and sell generic, or copy-cat versions of the drug, after only three years of it being patented in India. This is provided if there is a convincing case that the drug is necessary and unavailable to those who need it because it is too expensive.

‘Data exclusivity’

However this conflict between original inventors of drugs — several of whom have been European pharmaceutical giants — and Indian drug manufacturers, who have largely grown on reverse-engineering these drugs, has frequently played out as contentious litigation. Discovering effective drugs is expensive and time-consuming and pharma companies in the business of drug discovery, have moved to extend the period over which they can claim exclusive rights, and thus profitability, over their most valuable drugs. While claiming new methods of manufacture and furnishing new combinations of the underlying active chemical ingredient of a blockbuster drug are the familiar approach to extend such patentability, an emerging approach is in claiming ‘data exclusivity.’

That means all the data generated during testing the safety and efficacy of a drug — an expensive and time-consuming process — and that usually becomes public knowledge, becomes exclusive to the company. This means the current practice, whereby generic drug makers make a copy-cat, establish that it’s for all practical purposes the same drug and rely on the published clinical trial data to prove that it is safe and effective, ceases to be legal.

This could, say experts, even extend to drugs that have not been patented in India and require generic manufacturers to either wait out the exclusivity period or repeat expensive clinical trials.

For instance, Colchicine, a traditional medicine used for gout saw its price rise by 5000% in the United States after one company was granted data exclusivity rights blocking other companies’ rights to manufacture it.

“Over the last two decades, the fact that India did not have data exclusivity in its law facilitated the affordable entry of new drugs for HIV, tuberculosis (TB) and viral hepatitis, which we have been able to use to treat people in our care. Implementing data exclusivity now has the potential to jeopardise access to essential drugs in general, as well as to delay the approval of generic versions of newer medicines, such as paediatric formulations for new TB drugs for which patents have expired,” said Leena Menghaney, Global IP Adviser, Médecins Sans Frontières (MSF), and an expert on intellectual property laws governing drugs.

The India EFTA text is a broad-ranging agreement that is being negotiated between India and the four countries since 2008 to increase investment by these countries in India and reduce tariffs, on a range of exports from these countries.

(With inputs from Suhasini Haidar)

Thursday evening saw the end of a half-month stand-off between the National Medical Commission (NMC), India’s regulatory body guiding medical professionals and the Indian Medical Association (IMA), a national voluntary organisation of physicians with over three lakh members.

(For top health news of the day, subscribe to our newsletter Health Matters)

The two had locked-horns over one of the provisions of the NMC’s notification on August 2 asking registered medical practitioners (RMP) to prescribe generic medicines only. The Health Ministry now seems to have bought time for both parties.

In its latest notification the NMC has suspended proposed regulations until further notifications. “The NMC Registered Medical Practitioner (Professional Conduct) regulations, 2023 are hereby held in abeyance with immediate effect,’’ noted the Commission.

Said Dr. Sharad Agarwal, national president, IMA: “This is a grand victory as the entire regulations have been held in abeyance. Medical community has prevailed for the good of the people.’’

The previous NMC’s Ethics and Medical Registration Board notification reads: “Every RMP should prescribe drugs using generic names written legibly and prescribe drugs rationally, avoiding unnecessary medications and irrational fixed-dose combination tablets.’’

The IMA had demanded its withdrawal stating that it should not be enforced till there is assurance that the medicines meet quality standards.

Generic is much cheaper

Explaining its stand the Commission has said out-of-pocket spending on medication remains very high, and with generic medicines being 30 % to 80 % cheaper than branded drugs, prescribing generic medicines may bring down health care cost and improve access to quality care.

The IMA on the other hand raised objection to this provision in the notification and expressed their fear that the alleged poor quality of generic medicines available in India would adversely impact patient health and treatment. They even met with Union Health Minister Mansukh Mandaviya to put across their strong objection. The other arguments against the move include – leaving sales in the hands of chemists in an ecosystem where generic medicines available have wildly varying MRP and huge profit margins on the same combination drugs manufactured by different companies. Unregulated proliferation of pharma companies making generic drugs and lack of choice for patients are also fears.

Even though doctors were required to prescribe generic drugs earlier, there are no penal provisions mentioned.

The suspended notification, however, said that case of violations, a doctor may be given a warning to be more careful about the regulations or instructed to attend a workshop or academic programme on ethics, personal and social relations, and/or professional training and on repeated violations, the doctor’s license to practice may be suspended for a particular period.

K. Senthil, State president, T.N. The Government Doctors Association said that this was not a new idea: a proposal to prescribe generic drugs has existed since 2016. “The only difference now is the quantum of punishment prescribed,” he said.

Pharmacists can choose

The problem, he explained, was that even if doctors did give generic drug prescriptions, pharmacists/chemists were under no such obligation and could give branded drugs to patients. “Also, prescribing combination drugs is not possible through generics,” he said.

On quality of drugs, he pointed to the dismal shortage of manpower in most States in the Drug Controller’s offices, and asked how it was possible to ensure good quality drugs in such a situation. Drugs available in India fall under the following categories – branded under-patent drugs, branded generic (a branded generic drug is one which has come off patent and is manufactured by drug companies and sold under different companies’ brand names. These drugs may be less costly than the branded patent version but costlier than the bulk-manufactured generic version of the drug) and lastly generic drugs. Generic drugs are defined as a “drug product that is comparable to brand/reference listed product in dosage form, strength, route of administration, quality and performance characteristics, and intended use”.

There is less regulatory control over the prices of these “branded” generic drugs and this is also what has the doctors worried and they warn that any change in drug — especially for patients with chronic illnesses and critical care — may mean patients do not get the full benefit of a particular drug. There is no concrete evidence to show that generic drugs are equal to branded drugs, with respect to bioavailability, potency, efficacy, and impurity content.

There can be complications and some of the ailments and diseases can go out of control, doctors argued.

Quality is an issue

Pointing out that the bioavailability of a generic drug molecule is not assured by quality control or clinical trials, C.N. Manjunath, director of the state-run Sri Jayadeva Institute of Cardiovascular Sciences and Research, said the very fact that the same company that is manufacturing a branded drug also manufactures a generic drug means that there is a shift in quality.

He said one should not compromise on the quality of drugs, particularly in the critical care sector, including cardiac emergencies. Sundar Sankaran, who formerly headed the Indian Society of Nephrology (Southern Chapter) said maintaining stable drug levels in transplant recipients is vital. “Branded drugs and non-branded generic drugs may have variations in their formulation and potency which can potentially affect drug levels and outcomes for transplant patients. Lifesaving drugs like Tacrolimus and cyclosporine, which have a narrow therapeutic window, require careful monitoring and consistency in brand usage. Swapping between different generic brands could lead to variations in drug levels, putting the transplanted kidney at risk,” said the doctor, who is also the Director of Aster Institute of Renal Transplantation in Bengaluru.

Rajeev Jayadevan, member, Public Health Advisory Panel, Kerala State IMA, adds that the primary aim of the doctor is to ensure the complete recovery and well-being of the patient. Doctors’ prescribing patterns are established through years of practice and patient feedback. This is a relationship no pharmacy or medical shop can have with patients. “When only a generic name is written on the prescription, even if a better quality version is available, the pharmacy salesperson will be encouraged to dispense those products with the highest profit margin. The quality control, storage, distribution and dispensation of drugs is not yet uniform in the country which is the main area of concern for doctors. If this is worked out — generic medicines will work well in India,’’ he said.

Rules for prescribing

NMC had in its notification also listed out the manner in which prescriptions have to be made and stated :”Prescribe drugs with generic, non-proprietary, pharmacological names only but in the case of drugs with a narrow therapeutic index, biosimilars, and similar other exceptional cases, this practice can be relaxed.

“Prescribe drugs rationally and optimally, both overprescribing and under prescribing are to be avoided keeping in mind possible drug interactions and fixed-dose combinations are to be used judiciously. Besides this only approved and rational fixed-dose combinations are to be prescribed,’’ NMC has noted.

It also advised hospitals and local pharmacies to stock generic drugs, prescribe only those generic medicines that are available in the market and accessible to the patient, avoid prescribing “branded” generic drugs and encourage patients to purchase drugs from Jan Aushadhi Kendras and other generic pharmacy outlets.

In the recently concluded G-20 health summit the Health Ministry maintained that for India — healthcare is not just a sector, but a mission and that the country is currently supplying around 60% of the world’s vaccine needs and 20-22% of generic exports. Its $50 billion drug-manufacturing industry exports medicines to over 200 nations, as per some reports.

Committed to affordability

“The country is dedicated to providing affordable, high-quality drugs and contributing to global accessibility,’’ Union Health Minister Mansukh Mandaviya said while speaking alongside Ernst Kuipers, Health Minister of the Netherlands. He said medicines manufactured in India saves lives in Netherlands, in Europe and across the world.

Budi Gunadi Sadikin, Indonesian Health Minister, added that India’s Jan Aushadhi Kendra model is the best in the world in terms of providing quality, accessibility and affordability of medicines to the people.

Also just last month the Health Ministry directed regulatory authorities to conduct risk-based inspections and audits of manufacturing plants adding that Schedule M shall be made compulsory for the Micro, Small and Medium Enterprises (MSME) pharma sector in a phased manner. The move is aimed at helping in quality assurance and reduce compliance burden. Schedule M of Drugs and Cosmetics Act 1940 deals with ‘Good Manufacturing Practices’ that should be followed by pharmaceutical manufacturing units in India.

Meanwhile, individual doctors and healthcare activists have expressed their views on the stand-off between NMC and IMA. In a social media post S.P. Kalantri, director professor of MGIMS and Medical Superintendent of Kasturba Hospital said: “The NMC’s bid to cut links between medical professionals and the pharma industry is sending shockwaves through India’s healthcare. But is this strict approach the solution? Bioequivalence testing is important because it shows that a generic drug works the same way as the original one tested in trials. Hence, should every drug—be it generic or branded—go through this before hitting the market? Is the NMC’s proposal too ambitious? Is it possible to untangle deep-rooted ties between doctors and the drug world?

Gopal Dabade, president of Drug Action Forum, Karnataka, said: “we welcome the NMC notification. Use of generic drugs will make healthcare affordable and cut out of pocket expenses for patients.’’ Disputing claims by the medical fraternity that switching to generic drugs may harm the patients, he said there was no scientific evidence to prove this.

(With inputs from Afshan Yasmeen in Bengaluru, Zubeda Hamid in Chennai and C. Maya in Tiruvananthapuram)

Bindu.p@thehindu.co.in