“Bottle Of Lies Exposes The Dark Side Of The Generic-Drug Boom” – re-emphasized the book, released in May 2019. This confirms, the raging debate on the questionable quality of many generic drugs manufactured in India and involving several top domestic pharma companies, is a never-ending one. Numerous articles also ascribe many different reasons to this saga, leaving an overall impression – as if, blindfolded persons are trying to describe an elephant, touching and feeling different parts of the animal’s body, each at a time.
Let me illustrate the point with the Bloomberg article of January 31, 2019. It reported, “Culture of ‘Bending Rules’ in India Challenges U.S. Drug Agency.” And further commented: ‘The FDA confronts creative improvisation in the world’s largest generic-drug exporter.’ Curiously, according to the above report it seems to be a general belief among many, even within India.
This article will take into account the above apprehension – specifically raised against Indian drug manufacturers of both branded and non-branded generics. Accordingly, my focus will be on just three points – as possible causative factors for this critical issue:
- Is it an India specific concern – thus related to ‘Indian cultural mindset’? or it’s a global issue, involving both Indian multinational drug manufacturers.
- Is it a systematic attempt to create a perception bias against low-cost generic drugs, worldwide?
- Are generic drug makers resorting to such unacceptable shortcuts due to increasing margin pressure?
Having deliberated these points, I shall try to outline a set possible remedial measures to address this issue in a holistic way, ensuring a win-win outcome. Let me first explore, whether or not this issue is specific to India, involving Indian drug manufacturers.
Is the issue India specific?
Is the issue of questionable quality of generic drugs, irrespective of whether they carry a brand name or not restricted to the shores of India? One can find its answer in the same report, as quoted above. A yearlong investigation by Bloomberg News into the generic-drug industry concluded, ‘FDA inspections at factories from West Virginia to China have found reason to doubt the data meant to prove drugs are safe and effective.’
One possible reason for such perception could be, since India is predominantly a branded generic market, voices decrying ‘questionable’ safety and efficacy of cheaper non-branded generic drugs, are too loud. Nevertheless, amidst all this, who’s who of branded generic manufacturers continue getting caught on the wrong foot by overseas regulators in the quality quagmire. Ironically, multinationals are also included in it.
Multinationals are also included in such quality quagmire:
There are several examples of non-compliance to requisite drug quality standards by multinational drug companies. Let me illustrate the point with an example that involves a top global pharma player.
The March 04, 2019 ‘Warning Letter’ of US-FDA for the Irungattukottai (Tamil Nadu) plant of Pfizer in India, clearly said: “Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture.”
This is not a solitary example of Pfizer’s generic hospital injectables manufactured in this plant. According to a media report dated July 17, 2018, twice before US-FDA had cited manufacturing and testing issues in this facility, containing 11 observations of the regulator, such as, workers “manipulated test sample weights to obtain passing results” for both batches of raw materials and finished product. It is a different matter that the company, later on, decided to close this plant for commercial reasons. Be that as it may, negative perception of generic drug quality is indeed an issue that needs to be addressed without further delay, holistically.
Studies have captured negative perception of generic drugs:
That this is a perception, has been well – elucidated along with its implications, in several studies. A few of which are as below:
A BMJ article concluded: “A significant proportion of doctors, pharmacists and lay people hold negative perceptions of generic medicines. It is likely these attitudes present barriers to the wider use of generics.” It further added, “Negative perceptions of medicine quality along with other drivers contribute towards choosing more expensive medicines in the private sector.”
Endorsing this point, yet another BMJ article inferred: “Negative perceptions of generic medicines and preferential promotion of branded medicines over generics by pharmaceutical companies could influence prescriber behavior and affect trust in healthcare provided in public services. To succeed, access to medicine programs need to systematically invest in information on the quality of medicines and develop strategies to build trust in healthcare offered in government health services.”
Again, in a separate survey of over 2700 physicians on perceptions of generic drugs, more than 23 percent of respondents expressed negative perceptions about their efficacy and nearly 50 percent. reported negative perceptions of generic drug quality. In the same survey, patients also expressed concerns that the lower cost of generics is associated with reduced medication quality.
Although, the above survey was conducted in the United States, the current situation in India, I reckon, is no different, but with one caveat. Here, preferential promotion of branded generic medicines over cheaper non-branded equivalents, by the respective drug manufacturers, could significantly influence prescriber behavior. Therefore, the question that follows: Is this perception-creation based on facts?
Is the negative perception fact-based?
Although, even the US-FDA clearly states that: ‘A generic medicine works in the same way and provides the same clinical benefit as its brand-name version”, I did try to find some conclusive evidence depicting brand name drugs are superior to their cheaper generic equivalents. While doing literature searches, two types of results emerged – there are studies that do not find any significant difference between generic drugs and their branded equivalents. At the same time, a few other studies do suggest that there is a difference between these two, but admitting that these studies are not conclusive. Let me give below examples of each.
No quality difference found between generic drugs and the branded variants:
I shall quote here three studies, out of which one is India specific. The analysis reported in the above BMJ article, found that ‘the generic and branded variants of the medicines tested were of comparable quality.’
Another study, published by PLOS Medicine on March 13, 2019 also said, “In this study of 8 drug products conducted using 2 large US commercial insurance databases, we observed that use of generics provided comparable clinical outcomes as the brand products.”
An India specific researchon the same also reported, most generic and branded drug users believed that their drugs were effective in controlling their ailments with no significant difference in reported adverse effects and drug adherence.
Slightly different results were also reported with generics, but not conclusive:
One such study questioned, whether generic drugs are truly equivalent to the brand-name versions.This article was published on January 2019 by Harvard Health Publishing with the title, “Do generic drugs compromise on quality?”
This article quoted a Canadian study, published in the October 2017 issue of ‘Circulation: Cardiovascular Quality and Outcomes’, which found that patients who took generic versions of three different blood pressure medications in the months after the generic drugs became available saw increased rates of drug-related side effects.
Was it due to a perception bias?
To ascertain whether or not there is a perception bias, let us look into the following details of the same study along with its conclusion.
In this study, the researchers ‘looked at the numbers of emergency room visits and hospitalizations for 136,177 individuals ages 66 and over (60% of them women) who used any of three blood pressure medications: losartan (U.S. brand name Cozaar), valsartan (Diovan), and candesartan (Atacand). The investigators examined data for the periods 24 months before and 12 months after the generic versions of these medications went on the market. And found that before the generic versions became available, about one in 10 people taking the blood pressure drugs had to go to the emergency room or be hospitalized each month. In the month after each of the generics went into use, the rates of these adverse events went up: 8% for losartan, almost 12% for valsartan, and 14% for candesartan.’ The study authors commented, this might suggest performance differences between the brand-name and generic drugs.
However, analyzing this study, the Harvard article suggested further probe on the question: Did it result from quality problems with the generic versions of these medications or were there other factors that occurred in this time frame?
Another research, aimed at finding, whether patients are more adherent to generic statins than brand-name statins (lovastatin, pravastatin, or simvastatin) and whether greater adherence improves health outcomes, also concluded, “An 8% reduction in the rate of the clinical outcome was observed among patients in the generic group versus those in the brand-name group.” This also wasn’t a conclusive one, either.
Nevertheless, the key point of a ‘perception bias’, is captured in a separate study, where the researchers did find higher rates of psychiatric hospitalization for patients taking generic and AG escitalopram and sertraline, compared with those who initiated the brand-name product. Importantly, they noted that these outcomes were likely due to either residual confounding or generic perception bias.
No quality difference also found between branded and non-branded generics in India:
There are studies, which captured no quality difference between branded generics and non-branded generics in the country. One such India specific study concluded: “Quality of branded-generics is same as for their branded version. The study highlights the need to modify the drug price policy, regulate the markups in the generic supply chain, conduct and widely publicize the quality testing of generics for awareness of all stakeholders.”
Thus, so far, we have seen in this article that concern on quality of generic drugs is neither India specific, nor is it related to ‘Indian cultural mindset.’ And this is, undoubtedly, a global issue, involving both Indian and multinational drug manufacturers. There are also ample evidences available that a systematic attempt is being made to create a perception bias against low-cost generic drugs, worldwide. Let us now look at the third possible causative factor, as I listed above.
Is it due to margin pressure on generic drugs?
The answer to this question was deliberated in an article titled, ‘Generic drug makers feel pinch as prices crumble,’ published in the Financial Times on August 17, 2017. Quoting a top global financial analyst, it reported – global generic drug industry, where Indian manufacturers are major players,has maintained roughly 30 per cent operating margins over a long period of time, with improvements year on year. But, since last few years, there has been a margin degradation, which may possibly further go down – even lower than what it is today.
The article further highlighted, a round of consolidation among their main customers in the US: the wholesalers, have escalated the problem. Many of these groups have clubbed together to form “mega buyers”, known as general purchasing organizations, that can command large discounts. Moreover, for the US market, another area of ‘concern’ is that the US-FDA has identified boosting competition in the generics market as one of its main priorities. As this reform opens up, it could squeeze the generic drug margins further.
Many envisage that intense cost cutting measures, could have transgressed in the drug quality assurance area, aggravating this issue. Although, it needs to be verified through credible studies, curiously, some signs of improvement in this area has recently been reported.
That said, there appears to be a strange coincidence between recent reports on Indian drug makers showing improvement in USFDA inspection outcomes and attempts to increase generic drug companies and some of their top executives slapped with price-fixing lawsuits in the U.S.This needs to be studied further.
The way forward:
The negative perception of generic drugs, in general, and non-branded generic drugs, in particular, is most likely a well-crafted business issue, rather than a genuine patient safety concern. It calls for an immediate two-pronged approach:
- Vigorous awareness and educational campaigns on safety and efficacy of generic drugs targeted to patients, medical and paramedical professionals.
- New regulatory measures, especially the following five:
- No pricing pressure or price control in any form of generic drugs
- Abolish brand names for generic drugs
- Make generic prescription compulsory to boost intense competition and thereby reducing the price.
- Restrict the number of ingredients in FDC not more than two or three
- Make Uniform Code of Pharmaceutical Marketing Practices (UCPMP) mandatory.
Thus, the questionable quality of generic drugs is not an India specific concern and involves both Indian multinational drug manufacturers. This is also evident from the analysis, as quoted above, that underscores, ‘FDA inspections at factories from West Virginia to China have found reason to doubt the data meant to prove drugs are safe and effective.’ Many studies have revealed that there is a systematic attempt to create a perception bias against low-cost generic drugs, worldwide.
A sequence of remedial measures, as described above, also include fostering competition, instead of introducing government controls on prices of generic drugs with stringent regulatory oversight being in place.
Thus, the so called ‘belief’ that the ‘culture of bending Rules’ is culpable for dubious generic drug quality in India, is more akin to a strong perception, prevailing in India, rather than based on any scientific analysis related to this issue. This ought to change with a well-coordinated intervention – for patients’ health interest sake.
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.