In the realm of medicine, consensus is rare, but through persistent research and systematic synthesis of available data, a broad agreement can often be achieved. However, one topic that has remained controversial and unresolved is the debate between branded and generic medicines.
For decades, fish farmers have used chemicals like formalin and potassium permanganate to prevent infections. However, when antibiotics such as chloramphenicol and tetracycline became available, these became the preferred options. So, what does this have to do with the debate between generic and branded medicines?
Branded medications are developed and marketed by pharmaceutical companies under exclusive patent protection, while generic drugs offer cheaper alternatives with the same active ingredient, dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use.
The issue of high prices for brand-name medicines has long been a concern. Governments and elected officials worldwide have addressed this matter, leading to increased competition from generic manufacturers. However, brand-name pharmaceutical companies often resist this competition.
In 1949, Parke-Davis, a US-based company, introduced Chloromycetin (branded chloramphenicol), a highly effective drug for treating typhoid. It became a blockbuster, generating annual sales exceeding $100 million. Several generic versions were ready to enter the market once the patent expired in 1966. However, the company requested the USFDA (regulator) not to allow generics without clinical trial data, citing potential differences in raw materials and manufacturing processes that could affect the effectiveness of generic chloramphenicol compared to Chloromycetin.
Public opinion supported the need for generics, leading to their approval. Generic chloramphenicol was significantly cheaper, leading to its increased use. A dealer who had been using Chloromycetin for his fish decided to switch to generic chloramphenicol. To his surprise, the generic capsule did not dissolve as expected (failed dissolution test in today’s parlance).
This observation led to further tests conducted by Parke-Davis and later by the FDA. The results revealed that three generic versions of chloramphenicol were inadequately absorbed into the bloodstream, a critical finding considering the life-saving nature of the medication. Consequently, the FDA suspended the authorisation of generic chloramphenicol, granting the company extra time of market exclusivity.
This event led to enactment of the Hatch-Waxman Act in 1984. The legislation established regulatory requirements for generic drug approval, including the need for bioequivalence studies comparing the generic version to the branded product.
The Indian perspective
Many differences exist between branded and generic drugs, but in principle, a generic drug should work as well as a branded one. In India, we also see branded generics — different companies market their generics under their own brand names.
Struggling with high medicine prices, India passed the Drugs & Cosmetics Act in 1970, allowing domestic companies to manufacture drugs using different processes. This led to the growth of the generic drug industry. Originator companies, often multinational corporations, attempted to prevent generics from entering the market. A significant milestone was achieved when Cipla provided affordable anti-AIDS medicines to Africa, despite resistance from Big Pharma. Efforts to counter Indian generic drug-makers would ultimately lead India to shift to the “product-patent” regime under the WTO-GATT-TRIPS Agreement in 1995.
One argument against generic medicines is the perception of inferior quality. However, generics must demonstrate equivalence through clinical studies before entering the market. In India, the regulator (CDSCO) evaluates the quality, safety and efficacy of generics by reviewing data on the active ingredient, manufacturing processes, formulation, and stability. The advantages of using generic medicines are many, and cost savings of up to 80 per cent have been reported.
While generic medicines are generally safe and effective, concerns have been raised by the European Medicines Agency (EMA) about bioequivalence studies conducted by certain Contract Research Organisations (CROs), including those in India. Similarly, in 2021, the USFDA notified that studies conducted by certain CROs were deemed “not acceptable” due to concerns about data integrity. While Europe suspended the marketing authorisations of the products, the USFDA categorised them as “BX”, meaning they are approved but not recommended as automatic substitutes for the brand-name drugs — a much softer penalty.
Similar issues have been raised in the past, accusing the USFDA of being too lenient with drug companies, failing to detect problems during inspections, withholding information about problematic drugs, and not banning such drugs. Building trust is of utmost importance. Quality control plays a vital role in the regulatory landscape.
An analysis of the past six months of CDSCO’s findings on drugs of substandard quality reveals that about 4.5 per cent of medicines, all of which are generics, failed to meet one or more criteria. Several reasons contribute to these failures, including problems with assay, dissolution, sterility, and the presence of toxins. It remains unclear if branded products have been subjected to this testing by the regulator, as they do not appear in the lists published by the CDSCO.
A recent PGI study has shown that adequate drug levels of an antifungal drug itraconazole were achieved in only 29 per cent of patients receiving generic itraconazole, and in 73 per cent of those who received branded medicine. What’s important to note is that even the branded product is not 100 per cent successful — such is the complexity of drug-patient interaction along with the multifaceted inter-play of various other factors.
Shortcuts taken by some organisations serve to enhance profits. However, the question of profiteering from the suffering of fellow human beings is no longer even debated, although examples exist where discoverers of significant drugs (e.g. insulin) have willingly given up patents for the betterment of society.
India not only has a large domestic market for generic drugs, valued at around $25 billion, but also plays a significant role as a global supplier, with a substantial share in the $400 billion global market. In 2008, the government launched the Jan Aushadhi scheme, aiming to provide quality generic medicines. In 2016, the Medical Council of India (now NMC) recommended that physicians prescribe generic drugs, which are typically 30-80 per cent cheaper than their brand-name counterparts.
Switchability of generics
While generic drugs are generally considered safe and effective alternatives to branded drugs, there are certain situations where it may be advisable to avoid switching from a branded drug. It is important to note that healthcare providers make individualised decisions based on their clinical judgment and patient-specific factors. Open communication between healthcare providers and patients is crucial in determining the appropriateness of switching to generic drugs.
India, with its large and diverse population, faces unique challenges in providing accessible and affordable medications to its citizens. Generic drugs have emerged as a game-changer in the healthcare system. The CDSCO mandates adherence to Good Manufacturing Practices (GMP) for all manufacturers and conducts regular inspections. All stakeholders, including regulators, manufacturers, prescribers, civil society, and patient advocacy groups, must work together to achieve the goal of providing good-quality generic drugs to patients.
On paper, Indian laws are at par with the developed nations of the world. In implementation, there is scope for improvement.
— The writer is head of PGI’s Department of Pharmacology. Views expressed are personal
MYTHs AND FACTS
What are generic medicines?
Replicas of branded drugs that have been marketed, they are expected to provide similar therapeutic benefits.
Why are generic medicines cheaper?
Branded medicines are developed after years of expensive research and the companies want to recover their expenditure. Another argument given is that high costs are required to ensure that there is money to develop newer drugs. Manufacturers of generic drugs do not need to duplicate all the research before obtaining approval for marketing, and thus, sell their medicines at cheaper rates.
How is a generic drug approved?
The Central Drugs Standard Control Organization (CDSCO), under the Ministry of Health and Family Welfare, oversees the approval and regulation of generic drugs. The manufacturers must submit an Abbreviated New Drug Application (ANDA), providing comprehensive data on the active ingredient, manufacturing processes, formulation, stability, and bioequivalence studies.
Do generic drugs differ in appearance?
Yes, as companies use different excipients, colouring materials, casts and other manufacturing parts.
Do they cause more adverse effects?
Adverse effects usually occur due to the active ingredient — since both are same and in equal amounts in both branded and generic drugs, the incidence of adverse effects is expected to be the same. However, some excipients can cause adverse effects, albeit rarely, and since excipients are different, there may be some differences.
Are generic drugs less effective?
The efficacy of a medicine depends on the active ingredient, and since both have the same active ingredient, the efficacy must be the same. However, inappropriate dissolution may lead to reduced absorption and less efficacy. The regulatory authority assures that this does not happen.
Things to keep in mind
- For certain medications, small variations in dosage can significantly impact their effectiveness and safety.
- Switching to a generic version with a different formulation could alter the drug’s release characteristics, potentially impacting its efficacy.
- It is important to review the composition of both the branded and generic drugs to ensure there are no potential allergens.
- In some cases, patients may prefer a branded drug due to familiarity, perception, or personal experience.
- Certain medical conditions or specific patient factors may require close monitoring and individualised treatment.
- Healthcare providers may choose to maintain patients on branded drugs to ensure consistent management and minimise potential risks
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