Generic drugs - The Indian scenario.

Introduction

A generic drug is a medication created to be the same as an existing approved brand name drug in dosage form, safety, strength, route of administration, quality, and performance characteristics.[1]

Beginning of Generics

On September 24, 1984, in the 98th United States Congress, the act named The Drug Price Competition and Patent Term Restoration Act was passed, informally known as the Hatch-Waxman Act, encouraging the manufacture of generic drugs by the pharmaceutical industry and established the modern system of government generic drug regulation in the United States.[2]

The requirement was an abbreviated new drug application (ANDA) to be submitted by the pharmaceutical companies to the regulatory authorities for getting the approval to market a generic drug. ANDA process does not require the manufacturer to carry out repeat testing of generics in animals which is often time-consuming, as their branded versions have already been tested and approved for the safety and effectiveness. They are formulated when patent and other exclusivity rights of the innovator have expired.[3]

Generic drug manufacturers do not have to spend extra money for drug discovery and preclinical and clinical trials. Generics are available at a lower cost; they provide an opportunity for savings in drug expenditure in a country.

Indian Scenario

As India is one of the highest per capita out-of-pocket expenditures’ country, such generics will save a lot of money which can be used for other health issues.[4] In all the countries, use of generic drugs has increased significantly in recent years.[56]

The regulations governing the approval of generic drugs are somewhat the same world over, with very few differences in developing countries, as in this part of the world it is not mandatory to undergo bioequivalence (BE) studies for getting approval for generics, and the gold standard considered for regulation in this field is United States.[3]

In 2008, the Government of India, through the Department of Pharmaceuticals, started a new initiative “Jan Aushadhi” (a Hindi word literally translated as “Medicine for People”). This program envisaged making unbranded quality medicines available to poor people in the country at a reasonable and affordable price through retail outlets’ setup with the help of the government. It has taken ownership of setting up Jan Aushadhi stores, which are pharmacies selling only generic name medicines to the extent possible, giving preference to pharmaceutical public sector undertakings too.[7] Until March 15, 2018, 3200 Jan Aushadhi stores were operating in more than 33 states/union territories across India.[8] There are not enough Jan Aushadhi stores, possibly 3200 against more than 8 lakh retail pharmacies in existence, with many rural areas still underserved.[8]

The Medical Council of India, in an amendment to the code of conduct for doctors in October 2016, has recommended that every physician should prescribe drugs with generic names legible and he or she shall ensure that there is a rational prescription which promotes the use of generic drugs.[9] In future, the Government of India may bring a legal framework under which doctors will have to prescribe generic medicines to patients.[5]

Quality Issues

Generic medicines are typically 30%–80% cheaper than originator equivalents.[5] The question raised quite often is “Whether the quality and performance of generic drugs is comparable to the brand drugs?” The proponents of generic drugs claim that they are equally effective as brand or innovator drugs.[4] Subsequent to this claim, the Drugs Technical Advisory Board of India in May 2016 considered amending Rule 65 (11A) of the Drugs and Cosmetics Act, 1940, so that pharmacists can dispense generic name medicines and/or equivalent brands against prescriptions in brand names. However, skeptics have stated that the use of generic drugs may lead to prolongation of illness or even therapeutic failure as the bioavailability (BA) of a generic drug may not be as good as that of the prescribed brand.[9]

Hence, the critical issues that affect the quality of generic drugs are purity, potency, stability, and drug release, and these should be controlled within an appropriate limit, range, or distribution to ensure the desired drug quality.

Road Blocks

The government should ensure uniform quality across all the generics, and experts in the field of medicine say only then will doctors prescribe them willingly and with confidence.

One of the main reasons for lack of confidence in generic drugs among doctors (and even patients) has been the absence of stringent regulatory requirements for the quantity of the drug in its generic version and the permissible impurities in it.[10] But since 2016, clear-cut guidelines have been formulated which state that there should be 90% confidence interval of generic-drug-to-brand-drug ratio for key pharmacokinetic parameters [maximum concentration (Cmax) and area under curve] to lie between 80% and 125% of 1.00.[11] BEs (in vivo) are required by the regulators to ensure that the pharmaceutical equivalent reference product is therapeutically equal to the standard reference product. In certain situations, in vitro dissolution study is sufficient for showing equivalence between two drug products. But for highly water-soluble Biopharmaceutics Classification System (classes 1 and 3), immediate release products using currently available excipients and manufacturing technology, an in vivo–in vitro correlations, may not be possible.[12] Tramadol, paracetamol, levofloxacin, memantine, moxifloxacin, and temozolomide were given BE waiver by Indian regulator as this drug substances were highly soluble and highly permeable.[13]

To ensure that the quality of generic drugs is equivalent to its branded version and that this equivalence is scrupulously maintained, the government should also bring legislation to ensure compliance in generic drug manufacturing and testing.[11]

The Way Forward

Currently, undergraduate medical students learn the concept of generic drugs during their second MBBS teachings in pharmacology. Beyond this initiation, the importance of generic drugs in reducing patient expenses is not adequately emphasized during their further undergraduate and postgraduate training. Experts who formulate medical education curriculum would have to address this lacuna to ensure that future practicing physicians are well versed and comfortable in prescribing generic drugs[14]

Pharmacies and drug stores other than in government-run hospitals and clinics hardly stock unbranded generic drugs. When a generic drug is prescribed, it is likely that the pharmacist would dispense his favorite branded generic. Unless the prescribers are sure about the quality of generic drugs, compulsory prescribing in generics holds no breath in it.[10] Central Drugs Standard Control Organization is a licensing authority in India which has recently released guidelines for BA/BE studies.[11] It has given a checklist for submission of documents before undertaking BA/BE study, but is not clear whether they will ensure bioequivalence of each and every molecule. Confidence and habit of generic prescribing need to be inculcated into our medical fraternity by providing information and education particularly in areas of bioequivalence, regulatory aspects, and dispelling myths, fears, doubts, or false ideas about generic medicines. Only providing guidelines will not enhance quality drugs in market and prescribing. On the other hand, ensuring quality with strict regulatory mandate and providing updated information regarding the generic drugs (as given by United States Food and Drug Administration in its Orange Book) will eventually enhance prescription of generic drugs. The Orange Book provides information of approved drug products with therapeutic equivalence evaluations on a monthly basis.[15] It serves as public information to state health agencies, prescribers, and pharmacists to promote public education in the area of drug product selection.[15]

Godman et al[16] have proposed a 4”E” (Education, Engineering, Economics, and Enforcement) methodology for promoting generic drug utilization and development in Europe[16]; and the same can be replicated in India. The 4”E” include: (i) “Education” - design programs to influence generic prescribing by disseminating educational materials; (ii) “Engineering” - Focus on organizational interventions to evolve agreements on the price and volume of existing drugs in relation to disease management programs; (iii) “Economics”: Increase generic drug utilization through the use of positive and negative incentives for physicians and patients (iv) “Enforcement”- initiate regulatory or law enforcement methods which may include mandatory generic substitution laws to which pharmacists must adhere.[16] Well-designed survey studies should be planned especially taking in consideration patients, community pharmacists, and physicians to infer a general picture relevant to attitudes in generic drug prescribing.

Healthcare expenditure continues to rise in countries where healthcare is not a priority. Healthcare providers and policymakers need to keep drug prices affordable. Generic drugs offer an important tool for reducing the overall healthcare expenditure.[17] As more and more patents expire, the generic versions of the pharmaceutical market are expected to continue for increased sales. A sample list of generic drugs available in India along with their indication is depicted in Table 1.

Table 1

Cost price of a few generic drugs

Name of the generic drug	Indication	Price
Paracetamol	Fever	Rs. 9.80/10 tablets
Cefixime	Bacterial infection	Rs. 225/10 tablets
Amoxicillin	Bacterial infection	Rs. 30.77/10 tablets
Ofloxacin	Diarrhea	Rs. 92/10 tablets

With the availability and usage of generic drugs, the experience with these drugs will increase and it will be possible to compare the real-time effectiveness of generic drugs vis-à -vis brand drugs.

Only after real-time effectiveness of generic drugs is documented and made published, will physicians be able to easily convince patients, including the wealthy, to take generic drugs.[18] Our government can achieve this goal, if the regulator maintain high standards for safety, efficacy, and quality in the review of generic drugs.

If sponsors, healthcare providers, and regulators work together effectively, then effective use of generic drugs will make medical costs cheaper and also ensure sound treatment options for the patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.