|Year : 2015 | Volume
| Issue : 5 | Page : 541-545
Only generics (drugs/names): Is India ready?
Puneet Dhamija1, Parmod K Sharma2, Sanjay Kalra3
1 Department of Pharmacology, AIIMS, Rishikesh, Uttarakhand, India
2 Department of Pharmacology, AIIMS, Jodhpur, Rajasthan, India
3 Department of Endocrinology, BRIDE Hospital, Karnal, Haryana, India
|Date of Web Publication||19-Aug-2015|
Department of Pharmacology, AIIMS, Rishikesh, Uttarakhand
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Dhamija P, Sharma PK, Kalra S. Only generics (drugs/names): Is India ready?. Indian J Endocr Metab 2015;19:541-5
| Introduction|| |
Branded versus generic medicines is a topic of debate and discussions among physicians, drug regulators, and policy makers across the world. Endocrinologists face a situation where chronic therapy is to be provided at a minimum financial burden to the patient with a minimum margin of error as far as control of disease process is concerned.
It is important to understand the underlying pharmaceutical concepts about branded and generic medicines which may affect all stakeholders in the field of health-care. This editorial will explore this issue so as to allow informed decision making for the benefit of patients and society alike. Conventional medical curriculum does not address this important aspect of rational prescription writing. This is especially relevant for endocrinology as chronic disease require long-term use of drugs some of which have narrow therapeutic index like levothyroxine and peptides like insulin and hormones which come under the heading of biologicals for which entirely separate set of regulations exist.
| Nomenclature of Drugs|| |
The English dictionary defines the word generic as: "Not protected by trademark registration; Nonproprietary or any product, as a food, drug, or cosmetic that can be sold without a brand name".  Briefly, it pertains to the salt name or active ingredient of a drug delivery form, e. g., tablet "obimet" has active ingredient is "metformin" the chemical name of which is 1,1-dimethylbiguanide monohydrochloride. Chemicals are given nonproprietary name by World Health Organization (WHO) which is the unique name of drug. Brand names are registered and are protected by law. [Table 1] clarifies the nomenclature of drugs.
| The Concept of 'Generic Drugs'|| |
According to WHO, "A generic drug is a pharmaceutical product, usually intended to be interchangeable with an innovator product that is manufactured without a license from the innovator company and marketed after the expiry date of the patent or other exclusive rights".  To understand this definition a brief review of drug development process is required. 
Whenever a new potential pharmaceutical product is identified, the inventor (individual or company) files for protection of their intellectual property. This pharmaceutical product is now patent protected and no one can produce it without permission (or license) from a patent holder. Patents are transferable following a legal process involving payment of royalty. Innovator Company is the first one to identify or develop and market the pharmaceutical product. Once the duration of patent protection expires (usually 20 years unless specified), , the product can be manufactured and marketed by anyone without permission from the innovator provided it shows bioequivalence with the innovator's product. These products are called generics and manufacturers called generic manufacturers while those from innovator companies are called "branded". The term "biosimilar" is distinct from "generic" and applies to medications obtained from living organisms which can be humans, animals or bacteria.
| Branded Versus Generic|| |
The branded versus generic debate is an ongoing one, with various stakeholders actively involved in it. The relative merits of branded and generic drugs have been discussed, with varying opinions. Quality, efficacy, safety, and economy are some aspects which are presumed to differ between branded and generic formulations. , [Table 2] summarizes the contrast between these classes of drugs.
| Approval Process of Generic Drugs|| |
As discussed above, following expiry of patent of drug for innovator, it can be manufactured and marketed by any pharmaceutical company. Before marketing the drug, generic manufacturers need to obtain permission from relevant drug regulatory authorities. First, any drug manufactured should follow good manufacturing practices guidelines, the enforcement of which is the responsibility of drug regulators. The manufacturing units should obtain certification in this regard from drug regulators of the respective state. 
Second, there is a requirement for in-vitro dissolution and in-vivo bio-availability and bio-equivalence (BA-BE) testing of new brand (from generic manufacturer) which compares the release of active pharmaceutical ingredient (API) on certain dissolution and liberation characteristics and pharmacokinetic parameters (Cmax , Tmax , and area-under-the-curve) with those from reference standard.  If dissolution and BA-BE of API is within acceptable range only then, the new brand is approved for marketing. This ensures that the quality of drugs marketed by generic manufacturers is as good as the one marketed by the innovators. In-vivo BA-BE studies are required only at the time of seeking approval for marketing and not after that while in-vitro studies can be performed anytime.
| Economy|| |
An innovator company needs to invest money into new drug development and initial marketing of concept and molecule. Patent protection is primarily intended to provide financial security and assure decent financial returns to innovators so that research and development needs in future can be taken care of. The average cost of developing a new drug is calculated to be US $ 2.6 billion. This estimate includes opportunity cost and price of failure.  The clinical development phase of a drug is the most expensive. Also with stricter regulatory requirements, the number of clinical trials required for generating evidence of efficacy and safety has increased with consequential increase in cost of development of the new drug. All these considerations (and many more) decide the cost of a drug from an innovator, which sets the benchmark. On the other hand, generic manufacturers need not replicate most of the experiments and clinical trials thus saving a lot of money and reducing their cost. Once off-patent competition brings down the cost of drug marketed by the innovator in many cases.
Governments usually do not invest in drug development as aggressively as corporate sector. As far as India is concerned, centchroman is the only new drug identified and marketed by an Indian public sector undertaking.  Hamycin, an antifungal drug, is another Indian discovery, which was earlier produced by Hindustan Antibiotics Limited.
| Quality Assurance|| |
As discussed above, many manufacturers are available for off-patent drugs. Drug regulators across the globe use different strategies including sampling of products, document verification, and site visits to assure quality. , All dimensions of drug-related data pertaining to the manufacture and clinical trials conducted are inspected and audited to ensure authenticity and acceptability of data. Some of these strategies are listed in [Table 3].
|Table 3: Strategies used by drug regulators for quality assurance of manufactured drugs|
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| Indian Scenario|| |
In India, the pharmaceutical sector is regulated by the bodies and acts mentioned in the [Table 4]. The regulation of manufacture, sale and distribution of drugs is primarily the concern of state authorities while central authorities are responsible for approval of new drugs and clinical trials, laying down the standards for drugs, control over the quality of imported drugs, coordination of the activities of State Drug Control Organizations providing expert advice with a view of bring about the uniformity in the enforcement of the Drugs and Cosmetics Act. Central Drugs Standard Control Organization (CDSCO) under Ministry of Health and Family Welfare is the pivotal agency dealing with all drug related issues. This organization deals with all new drug approvals, review of new safety information regarding approved drugs, approval and safety review of fixed-dose combinations, medical devices, and implants. All endocrine and metabolic drugs are covered by these organizations and acts. Food supplements (including many herbal products) are regulated by separate laws since they are legally not considered drugs. 
In India, drug testing laboratories are located at central and regional levels which are entrusted with the job of ensuring production and availability of quality medicines. During the years 2011-2014, the regional laboratories tested samples at 91% of the installed capacity but their overall detection rate of sub-standard drugs was only 3.6%. [Table 5] summarizes the activity of drug quality control laboratories in India during this period. 
|Table 5: Details of samples tested by Central and Regional Drug Testing Laboratories in India from 2011 to 14|
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The total number of samples tested was 43,387 over a period of 3 years. This number though impressive still lags significantly in terms of detection rate and especially when corrected for growth in the number of pharmaceutical companies over this period. In addition, with its manpower of 327 employees in 2012, CDSCO is grossly understaffed to perform its assigned duties of protecting the general population from sub-standard, spurious, and counterfeit medicines.  The 2014 episode of death of 13 women and illness of 138 following tubectomy and prescription of poor quality ciprofloxacin is a clear indicator of the deficiencies in our system which makes available poor quality medicines. ,
| Generic Drugs Versus Generic Names|| |
The recent directive of Medical Council of India under code of medical ethics 1.5 which states "Every physician should as far as possible, prescribe drugs with generic names and he/she shall ensure that there is a rational prescription and use of drugs" creates confusion between terms "generic drugs" and "generic names."  By default, most drugs sold in India are generic. However, they are marketed under a brand name given by the manufacturer. This directive passes the onus of selecting the brand name of drug and manufacturer to the pharmacist. This guidance puts the health of patients in the hands of pharmacist instead of the physician. Laudable theoretically, this guidance does not fit in the not so robust drug regulatory system of our country which is struggling to provide quality medicines from all manufacturers. Once the regulatory apparatus is empowered with adequate manpower and facilities, this directive will be a welcome contribution toward rational prescription writing.
| Endocrinologist's Perspective|| |
The practice of endocrinology makes ample use of generic medicines and recombinant hormones. Endocrine and metabolic pharmaceutical preparations may be more complex than those used in other fields of medicine. Metformin-sustained release and gliclazide modified release (MR) have pharmacokinetic properties which are different from immediate release formulations. MR formulations for generic molecules are used extensively in endocrinology and in many cases generic formulations may not be able to mimic the characteristics of innovator formulations. This aspect must be kept in mind while crafting prescriptions.
Generic counterparts of biological agents are called biosimilars. European Medicines Agency defines "A similar biological or "biosimilar" medicine is a biological medicine that is similar to another biological medicine that has already been authorized for use." As discussed previously biological medicines are medicines that are made by or derived from a biological source, such as a bacterium or yeast. They can consist of relatively small molecules such as human insulin or erythropoietin, or complex molecules like monoclonal antibodies.  The issues related to biosimilars will be discussed in the separate editorial.
Endocrinology also utilizes other hormones which are available as both innovator and generic products. L-thyroxine is one such frequently used molecule. There are serious bioavailability issues and significant brand-to-brand variation in case of levothyroxine where interchanging brands is not advisable. A joint statement by American Association of Clinical Endocrinologists, The Endocrine Society of America, and American Thyroid Association recommends use of same brand of levothyroxine in patients. , The directive by Medical Council of India, Government of India or any other regulatory body promoting writing of generic names only should be evaluated carefully by practicing clinician. Patient safety must be given paramount importance. Every effort should be made by professional bodies to achieve syncretism with government regulations based on an in-depth understanding of issues involved.
| Proposed Solutions|| |
The solution to the problem of branded versus generic lies in strengthening the existing quality control structure of the country. The strategy can be two pronged with an increase in the capacity of existing laboratories and opening up of new laboratories in government colleges. Pharmacology departments of existing medical colleges can play a big role in this direction.
The public sector ("jan aushadhi" scheme, hospitals etc.,) should procure medicines from firms which quote lowest price (existing practice) along with in-house quality control reports of each batch of medicines supplied. These firms must be subject to external audit and quality control as well. Physicians should be allowed choice of writing generic or branded products as they are best placed to monitor efficacy and safety of drug therapy. Pharmacists should also be involved in informed decision making, as should members of patient organizations. With the burden of endocrinopathy increasing rapidly, the need for endocrinologists to contribute to such decision making is also important. This editorial hopes to sensitize our specialties to play a proactive role in ensuring rational use of branded and generic drugs.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]