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OTC Drugs in India: ‘Where Art Thou?’

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It is now a widely accepted fact that responsible self-medication plays an important role in health care, facilitating greater access to medicines and reducing overall health care cost. With continued improvement in people’s education, general knowledge and socioeconomic conditions, self-medication has been successfully integrated into many health care systems, throughout the world.This was emphasized in the paper “The benefits and risks of self-medication,” published by the World Health Organization (WHO) based on a presentation of the WHO Coordinator, Quality Assurance and Safety: Medicines, way back in March 2000.

Which is why, calibrated deregulation of prescription drugs for ‘Over the Counter (OTC)’ sale, are helping many countries to expand drug access in a cost-effective manner, facilitating overall health care, through responsible self-medication.

In this article, I shall try to explore the OTC drug issue in India, against the backdrop of the veracity of dangerous and virtually uncontrolled self-medication in the country. It will be interesting to recap where India stands in this area, despite the enactment of so many relevant laws and rules to eliminate this menace. In tandem, it will be worthwhile to fathom why is India still keeping away from promoting responsible self-medication through OTC drugs? Even when this is widely considered as one of the effective ways to improve access to drugs for specified common ailments at a reduced treatment cost for patients.

OTC Drug in India: ‘Where Art Thou?’ – becomes a relevant question in this context. Let me pick up the thread of this discussion from the general belief among a large number of domain experts that OTC drugs facilitate responsible self-medication.

OTC drugs facilitate responsible self-medication:

For greater clarity in this area, it will be worthwhile to first recapitulate the definition of self-medication. The W.H.O has defined itas, ‘the practice whereby, individuals treat their ailments and conditions with medicines which are approved and available without prescription, and which are safe and effective when used as directed.’

Whereas, self-medication with prescription drugs is not only an irresponsible act, it can often be dangerous to health for the users. On the other hand, OTC drugs facilitate responsible self-medication, as the drug regulators of respective countries have included under this category, with clear guidelines, only those medicines, which:

  • Are of proven safety, efficacy and quality standard.
  • And indicated only for conditions that are self-recognizable, and some common chronic or recurrent disorders.
  • Should be specifically designed for the purpose, will require appropriate dose and dosage forms and necessarily supported by information, which describes: how to take or use the medicines; effects and possible side-effects; how the effects of the medicine should be monitored; possible interactions; precautions and warnings; duration of use; and when to seek professional advice.

Since, OTC drugs facilitate responsible self-medication, it will be interesting to know how the constituents of Big Pharma, such as Pfizer, view the social impact of legally recognized OTC drugs.

Social impact of self-medication with OTC drugs:

Like many other large global pharma players, Pfizer also believes: “OTC medicines provide easier access to treatment options for common conditions, offering not only convenience, but also timely treatment and relief for sudden symptoms or minor ailments.” The company also acknowledges, OTC medicines, as classified so by the drug regulators of a country, “provide consumers safe and effective treatments for commonly occurring conditions, saving them time and money that might otherwise be invested in other, more expensive health services.”

To substantiate the point, Pfizer communique referred to the U.S. study, which by analyzing the seven most common acute and chronic, self-treatable conditions found that 92 percent of those who use OTC medicines in a given year are likely to seek more expensive treatment elsewhere, if OTCs were not available.

The above may be construed as a generally accepted view of both, the drug regulators and a large number of drug companies, globally. Thus, it won’t be a bad idea to quickly have a glance at the process followed by the drug regulators of the major countries, such as US-FDA, for OTC classification of medicines.

US-FDA classification of OTC medicines:

In most countries of the world, as many of us would know, those who are permitted to sell drugs under a license, can sell two types of drugs, namely: prescription drugs and nonprescription drugs. OTC medicines, obviously, fall under the nonprescription category.

Briefly speaking, US-FDA defines OTC drugs as “drugs that are safe and effective for use by the general public without seeking treatment by a health professional.”The Agency reviews the active ingredients and the labeling of over 80 therapeutic classes of drugs, for example, analgesics or antacids, instead of individual drug products. For each category, an OTC drug monograph is developed and published in the Federal Register. OTC drug monographs are a kind of ‘recipe book’ covering acceptable ingredients, doses, formulations and labeling.

Many of these monographs are found in section 300 of the Code of Federal Regulations. Once a final monograph is implemented, companies can make and market an OTC product without the need for FDA pre-approval. These monographs define the safety, effectiveness and labeling of all marketing OTC active ingredients. While this is the scenario in the United States and a large number of other countries, let’s have also a glimpse of this aspect in India.

‘OTC drugs’ in India:

As on date, legally approved as OTC drugs along with the guidelines, for responsible self-medication during pre-defined common illnesses, doesn’t exist in India. Accordingly, neither drugs & Cosmetics Act, 1940 nor the Drugs & Cosmetics Rules, find any mention of OTC drugs, as yet. While even responsible self-medication is not legally allowed or encouraged in the country, ‘self-medication’ of all kinds and of all nature are rampant in India, possibly due to gross operational inefficiency on the ground.

Several research papers vindicate this point. One such study that was done with 500 participants, reported 93.8 percent self-medication with no gender difference. The most common reasons for self-medication were found to be – 45.84 percent for fever, 18.34 percent for pain, and 10.87 percent of headache, among others. While the common medications used were listed as nonsteroidal anti-inflammatory drugs 49.4 percent, followed by antibiotics 11.6 percent, besides other drugs.

Among those participants who took self-medication were of the opinion that self-medication resulted in quick cure of illness – 50.75 percent, saved their time – 17.46 percent, and gave them a sense of independence – 17.06 percent. The most common source of information was found to be a local chemist/pharmacy – 39 percent.

Raising a flag of concern that indiscriminate self-medication is dangerous for the population, the study suggested that public health policies need to find a way of reducing unnecessary burden on healthcare services by decreasing the visits for minor ailments. One such way is a well-defined OTC category of medicines, as are being created in many countries, including the United States. However, it appears, the Indian drug regulators are still apprehensive about giving a formal recognition of OTC drugs in the country, to prevent self-medication that is, unfortunately, rampant in the country, even otherwise.

Self-medication rampant, although illegal in India:

Regardless of all drugs laws and rules being in place to prevent self-medication with prescription drugs, these seem to be just on paper, the ground reality is just the opposite in India. In the absence of a clearly defined category of OTC drugs with guidelines, most medicines falling under the drug act, are prescription drugs, except a few drugs on the Schedule K of the Drugs & Cosmetics Act. Currently, non-pharmacy stores can sell a few Schedule K drugs classified as ‘household remedies’ onlyin villages with less than 1,000 populations, and where there is no licensed dealer under the Drugs and Cosmetics Act.

Primarily to prevent self-medication and also to ensure maintenance of specified storage conditions, among others, the D&C Act requires all other drugs to be sold by a retail drug license holder and sold only against the prescriptions of registered medical practitioners. Such drugs are labeled with a symbol ‘Rx’ on the left-hand corner of the pack and the symbol ‘NRx’, if drugs fall under Narcotic Drugs and Psychotropic Substance Act.

Additionally, these are also labeled with a warning – ‘To be sold on the prescription of a registered medical practitioner only.’ All retailers, pharmacy/medical store are supposed to strictly abide by this directive. But in reality, who cares? One can possibly get most prescription drugs that one wants, without a doctor’s prescription.

The same holds good for virtually unregulated advertising of some self-categorized ‘OTC drugs’, many of which fall under the prescription drug category. I re-emphasize, the terminology of OTC drugs does not exist, at all, in the D&C Act of India, not as yet.

Virtually uncontrolled advertisements of some so called ‘OTC’ drugs: 

Media reports indicate, widespread complaints received in the drug controller general of India (DCGI)’s office that vitamin tablets and capsule formulations are being marketed in the country as dietary/food supplements to circumvent the Drugs Price Control Order (DPCO).

Curiously, to resolve this issue – way back on July 24, 2012, the Drugs Technical Advisory Board (DTAB), the highest authority in the union health ministry on technical matters, deliberated on the OTC drug issue in India. After detailed discussion, the DTAB has given its green signal to amend Schedule K of the Drugs and Cosmetics Rules in this regard.

But Food safety watchdog Food Safety and Standards Association of India (FSSAI) did act promptly on this matter. On September 24, 2016, FSSAI), reportedly, issued new guidelines clearly specifying that health supplements should not be sold as medicines and also fixed the permissible limits of various ingredients used in the products. It further said: “Every package of health supplement should carry the words health supplement as well as an advisory warning not for medicinal use prominently written.

“The quantity of nutrients added to the articles of food shall not exceed the recommended daily allowance as specified by the Indian Council of Medical Research and in case such standards are not specified, the standards laid down by the international food standards body namely the Codex Alimentarius Commission shall apply,” FSSAI added.

The juggernaut moves on:

The point worth noting here that all laws, rules and regulations are in place to discourage both, self-medication and surreptitious way to sell products sans medicinal values, as medicines. Despite the enacted laws and rules being reasonably robust to achieve the intended objective, inefficient implementation of the same keeps the juggernaut moving, perhaps gaining a momentum.

Is OTC Drug Category coming now or just another good intent?

The good news is: On September 18, 2017, the Drug Consultative Committee (DCC), in principle approved to amend rules on Drugs and Cosmetics Act to include a separate schedule for OTC drugs for minor illnesses like fevers, colds and certain types of allergies. However, in the meeting of February 20, 2019, the DCC constituted another subcommittee under the chairmanship of Drugs Controller, Haryana to examine the report on OTC drugs. The final decision is still awaited without any prescribed timeframe for the same.

Conclusion:

Creation of separate schedule for OTC drugs in India, is still a contentious issue for some. Nonetheless, such a long overdue amendment in the D&C Act, along with well-regulated OTC guideline as and when it comes,I reckon,will expand drug access to patients. Alongside, the drug makers must ensure that these OTC medicines are safe, effective and offering good value for money.

As the author of the above W.H.O articled emphasized: ‘High ethical standards should be applied to the provision of information, promotional practices and advertising. The content and quality of such information and its mode of communication remains a key element in educating consumers in responsible self-medication.’ Thus, in the Indian context, it will be equally essential for drug companies to make sure that OTC medicinesare always accompanied by complete and relevant information that consumers can understand without any ambiguity.

Be that as it may, I agree, even responsible self-medication is not totally risk-free – not even with OTC drugs, just as many other things that we choose to do in life. The risks associated with the use of OTC medicines may include, risks of misdiagnosis, excessive drug consumption and for a prolonged duration, precipitating drug interactions, side-effects and polypharmacy.

This discussion will remain theoretical until the D&C law and rules are appropriately amended to accommodate much awaited OTC category of medicines. Till then one can possibly ask in India: ‘OTC drugs, where art thou?’

By: Tapan J. Ray   

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

 

Generic Drug Quality: Cacophony Masks An Important Note, Creates A Pariah

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In the ongoing debate between branded-generics and generic drugs without brand names, the concern about drug quality is occupying the center stage, with the former generally being painted in white, and the later in black – with no shades of gray in-between. Interestingly, many large domestic companies manufacture and sell both these genres of generic medicines, and the marketing approval process of both is no different, in a relative yardstick. The degree of difficulty in testing their quality standards, across the country, is no different, either.

On February 25, 2017, even the USFDA, reportedly, raised concerns, for the first time, on the quality and efficacy of medicines, in general, being sold within India. The news report further highlighted: ‘Over the past two years, many domestic majors, including Sun Pharma, Dr. Reddy’s, Cipla and Zydus Cadila have faced regulatory ire over quality of medicines exported from here and sold in the US and other overseas markets’.

It is undeniable, if prescriptions in generic names are made mandatory, there could be direct job losses within the industry, just as loss of significant business clientele of many professional service providers for branded generic business, directly or indirectly. Its net impact needs to be factored-in too, while taking a final decision on this subject.

Lack of enough credible scientific data establishing superiority of branded-generics over their non-branded equivalents are also striking, so are few instances of doctors filing Pharmacovigilance reports with the DCGI on the inferior quality of non-branded generic drugs. Neither is the most competent body in this area – the Central Drugs Standard Control Organization (CDSCO), has concurred with any such claims, so far. Without these, the whole debate based on seemingly over the top claims of superiority of branded generics as a class, is based no more than a matter of conjecture.

I discussed most of these points in one of my earlier articles published in this blog on April 24, 2017. Thus, in this article, I shall focus mostly on an important generic-drug-quality related amendment, very recently made in the Drugs and Cosmetics Act of India, which hasn’t received as much attention as it deserves. This finer note in the drug regulatory playbook, in fact, got nearly masked in the high-decibel cacophony of arguments and counterarguments on Prime Minister Modi’s recent hint on making prescriptions in generic drug names mandatory.

The core issue remains the same, both for non-branded and branded generics:

In the marketing approval process of any branded generic or a non-branded generic drug, Bioequivalence (BE) studies hold immense scientific importance. It ascertains whether the generic equivalent possesses similar efficacy and safety profile as the original molecule for interchangeability. Which is why, in most countries, including Europe and the United States, BE testing is mandatory for approval of any generic drug. Even the large buyers of these drugs, such as the World Health Organization, buy only those generics with proven BE.

Nonetheless, like many other nations, in India, as well, the marketing approval standards for all generic drugs, with or without a brand name, are exactly the same. However, this approval process gets alarmingly relaxed, for both these generic types, with the passage of time, which is the core issue.

New drug definition in India:

According to section 122-E of Drugs and Cosmetics Rules, 1945 (D&C Rules) new drugs will include unapproved drugs, modified or new claims, such as, indications, dosage forms (including sustained release dosage form) and route of administration of already approved drugs and combination of two or more drugs. A new drug shall continue to be considered as new for a period of four years from the date of its first approval or its inclusion in the Indian Pharmacopoeia, whichever is earlier.

BE studies necessary only for ‘New Drugs’:

For all such new drugs and their Fixed Dose Combinations (FDC), including those which are not covered by a patent, if introduced for the first time in India, would necessarily require its applicant to submit the marketing approval documents well-supported by phase III clinical trial data, which includes BE studies against the original molecules. BE of a drug product is achieved if its extent and rate of absorption do not show statistically significant differences from those of the reference product when administered at the same molar dose.

After the 4-year period BE tests not necessary:

Interestingly, after the 4-year period, D&C rules allow subsequent manufacturers of similar drugs to generally rely on the data generated by other pharma companies to obtain marketing approvals for their drugs. In other words, after this 4-year period, manufacturers of branded or non-branded generic drugs are not required to establish comparable safety and efficacy of their formulations with the original molecule through BE and other studies. It is worth noting here, unlike India, BE tests are mandatory for approval of all generic drugs at any time, in most countries across the world.

How would a doctor select only those branded-generics with BE studies?

As there isn’t any easy way to know and identify, both by the doctors and also the patients, which branded or non-branded generics were introduced without BE studies, both these categories pose equal risks to patients – not just the cheaper generic drugs sans brand names.

Changes recommended:

This laxity in the regulatory framework in India did create a lot of uneasiness about the quality of branded and non-branded generic medicines approved by the drug regulators and sold in the country. Responding to this issue, Professor Ranjit Roy Chowdhury Committee Report recommended in July 2013 to make BE and bio­availability studies mandatory for all types of generic drugs, even after the 4-year period.

Cacophony masks an important note:

The good news is, on April 3, 2017, by a Gazette Notification, Indian Government enacted amendments to the Drug and Cosmetics Act (1940) requiring mandatory BE studies for marketing approval of all generic drugs even beyond the 4-year period of the ‘new drug’ definition. It says, “The applicant shall submit the result of bioequivalence study referred to in Schedule Y, along with the application for the grant of a license of the oral dosage form of drugs specified under category II and category IV of the biopharmaceutical classification system.”

Biopharmaceutics Classification System:

The Biopharmaceutics Classification System (BCS) is a scientific framework to differentiate the drug formulations based on their aqueous solubility and intestinal permeability, and mainly depends on two factors:

  • How well the drug dissolves in the stomach and intestinal fluids (drug solubility)
  • How readily the drug passes through the intestinal wall into the blood flow (drug permeability)

The BCS was introduced by Gordon L. Amidon in 1995 to classify drugs into the four categories based on these parameters, as follows:

  • Class I: High Solubility – High Permeability
  • Class II: Low Solubility – High Permeability
  • Class III: High Solubility – Low Permeability
  • Class IV: Low Solubility – Low Permeability

CDSCO still needs to find the right answer to a key question:

Interestingly, this so important note in the regulatory playbook of India got masked in the high-voltage cacophony on branded and non-branded-generics. However, CDSCO would still require finding out the right answer to a key question: how would a doctor or a patient possibly know on which branded and non-branded generic drugs BE tests were not carried out, before the above amendment came into force.

Reported data on substandard drugs in India:

Quoting CDSCO data, the September-October 2015 issue of the ‘Indian Journal of Endocrinology and Metabolism’ summarized that ‘during the years 2011-2014, the regional laboratories tested samples at 91 percent of the installed capacity, but their overall detection rate of sub-standard drugs were only 3.6 percent’. Many have expressed doubts about these numbers though, nevertheless, these are Government data, and don’t fall in the realm of any conjecture.

In any case, the Union Ministry of Health doesn’t seem to concur that the issue of substandard drugs in India, that includes both the branded and non-branded generics, has assumed a public health menace in India or even alarming.

No qualms on value added branding of generic drugs, but fix the loophole for all:

It is understandable, when generic drugs are branded for tangible value-added product differentiation even within the identical or the same drug molecules. There are no qualms on such branding per se, though it comes at a high cost.

Marketing approval requirements being the same for all branded and non-branded generic drugs with the same pitfalls of no mandatory BE-testing requirement after the 4-year period, branding should add commensurate tangible value. Otherwise, why should most patients pay a significantly extra amount for heavily promoted branded-generics? Is it to help the pharma companies fighting with each other to increase their respective pies of revenue and profit on an essential commodity? Instead, stakeholders should now focus on easy detection of all those branded and non-branded generic drug formulations that avoided mandatory BE studies, prior to April 3, 2017.

In conclusion:

Despite CDSCO’s statistical data on substandard drugs, the general concern regarding the efficacy and safety of medicines manufactured in India is often raised both inside the country, as well as by some well-respected overseas drug regulators. Curiously, when raising the same concern CDSCO banned hundreds of branded FDCs, as these drugs came to the market without carrying out required scientific tests due to some major lacunae in the regulatory system, there was a huge protest in the country raised by almost the same people, as business interests prevailed over patients’ health interest.

Interestingly, displaying a sharp contradiction in today’s cacophony, patients’ health interest has been put in the forefront to protect business interests, especially when the CDSCO has raised no such concern, whatsoever.

The reverberating claims on superior drug quality for branded-generics as a class, over their cheaper non-branded equivalents, with the former generally being painted in white, and the later in black – with no shades of gray in-between, as I said before, is based mostly on conjecture rather than enough hard facts. Thus, the question comes up, who is responsible for ensuring drug efficacy and safety for the patients in India – CDSCO or non-fact based claims being raised mostly by those who have a direct or indirect financial interest in branded-generic business?

Keeping this in perspective, it is indeed intriguing, why such an important regulatory step of April 3, 2017 requiring mandatory BE studies for marketing approval of all generic drugs, even after the 4-year period, is getting masked in the cacophony, mostly favoring the branded-generics as a category. However, it’s no-brainer to understand that this din would continue, projecting all generic drugs sans brand names – a pariah!

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.