Tag Archives: manufacturing

Unfettered ‘Access To Drug Innovation’ – An Oxymoron?

Posted on by
Reply

The mass paranoia, as it were, over Covid pandemic has now started fading with drug regulators’ ‘emergency approval’ of several Covid -19 vaccines, and its free of cost access to all, generally in most countries. As the endgame of the pandemic, supposedly, depends on the speed of Covid-19 vaccination, the drug industry’s public reputation in the interim period, driven by its rapid response to the crisis, got an unsurprising boost (62%). This was captured by the Harris Poll, released on March 15, 2021.

Interestingly, soon after the high of 62% approval rating, the decline began. It came down to 60% in May and then 56% in June 2021—and now down three more percentage points, according to the Harris Polls that followed. No wonder, why the FiercePharma article of August 24, 2021, carried a caption: ’Pharma’s reputation drops again. Could it foreshadow a return to the bottom?’

Further, in the new normal, especially when customer expectations and requirements from drug companies have significantly changed, MNC Pharma industry still appears to be in the old normal mode in this space. It still, reportedly, ‘believes that the need for innovation must be balanced with the necessity for more accessible medicines, within a robust IP and regulatory environment,’ in India.

The hidden purpose of the same could possibly be, as several industry watchers believe – availing benefits of greater access to one kind innovation, making access to other kind of innovation more difficult. Consequently, two critical points are reemerging, even in the new normal, as follows:

  • Aren’t Indian IP and regulatory ecosystems still conducive enough for MNC pharma players’ access to drug innovation?
  • In the name of greater access to pharma product innovation, are they creating barriers to pharma process innovation, delaying market access to complex generics and Biosimilar drugs – besides systematically eroding consumer confidence on such products?

In this article, under the above backdrop, I shall try to explore why the epithet – ‘access to drug innovation’ is considered an oxymoron – with contemporary examples from around the word, including India.

Aren’t Indian IP and regulatory ecosystems conducive to drug innovation? 

This allegation doesn’t seem to hold much water, as several successful local initiatives in Covid-19 vaccine development will confirm the same. Besides, already marketed Covaxin, developed by Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR) and Zydus Cadila’s ZyCov-D, there are several others waiting in the wings. These include domestic drug makers like, Hyderabad based Biological-E, Bengaluru-based medical pharma startup’s – Mynvax, and Pune-based Gennova Biopharmaceutical’s m-RNA vaccine candidates. However, only critical difference is – Indian made Covid vaccines are more affordable and accessible to patients, as against those manufactured by MNCs, such as, Pfizer, Moderna and J&J.

If we look back to the old normal, one will also find similar instances of new drug discovery in India, which deliberated in my article of September 02, 2013. Let me give just a couple of examples below:

  • Ranbaxy developed and launched its first homegrown ‘New Drug’ for malaria - Synriam, on April 25, 2012
  • Zydus Cadila announced in June 2013 that the company is ready for launch in India its first New Chemical Entity (NCE) for the treatment of diabetic dyslipidemia –Lipaglyn.

Hence, meager wherewithal for R&D notwithstanding, as compared to the MNCs, Indian pharma players don’t seem to find the country’s IP and regulatory ecosystems not conducive to innovation of affordable new drugs with wider patient access.

Off-patent drugs also involve another type of major innovation:

Discovering an NCE is, unquestionably, a product of drug innovation. Similarly, developing a new – cost-effective, non-infringing manufacturing process to market off-patent drugs, like biosimilars, also involve another type of major innovation. Intriguingly, when the MNC pharma industry talks about ‘access to innovation’, the latter type of innovation isn’t publicly acknowledged and included in their drug innovation spectrum. This practice, reportedly, remains unchanged in their advocacy campaign, even in the new normal.

However, the fact is, the manufacturers of off-patent drugs, such as biosimilars, also need to follow a major innovative process, for which they require access to innovation. This was also captured in an editorial of the newsletter – Biosimilar Development. The deliberation addressed the question - Do biosimilars fit into the innovation paradigm? The editor began by articulating – hardly anyone publicly argues that the development of new manufacturing process of Biosimilar drugs is not an innovation. The industry can’t call them as a copy of an existing innovation, either.

This is also vindicated in the Amgen paper, published on February 11, 2018. It acknowledges, “Unlike small molecule generic drugs, biosimilars are not identical to the reference biologic or to other approved biosimilars of the same reference biologic, because they are developed using different cell lines and undergo different manufacturing and purification processes.” Moreover, biosimilars also carry a different International Nonproprietary Name (INN), because of their molecular differences from the reference drug. This has been specified in the nonproprietary naming Guidance document of the US-FDA of January 2017.

From this perspective, the next question that logically follows: Is process innovation as important as product innovation?

Is process innovation as critical a capability as product innovation?

This question was unambiguously answered by a pharma industry-centric Harvard Business Review(HBR) article – ‘The New Logic of High-Tech R&D’, published in its September–October 1995, issue. The paper emphasized, for the commercial success of a product ‘manufacturing-process innovation is becoming an increasingly critical capability for product innovation.’

When to meet patient-needs ‘access to innovation’ an oxymoron: 

‘Access to innovation’ is an interesting epithet that is often used by many drug companies for meeting unmet needs of patients. However, the same is also often used to create barriers to meeting unmet needs of more patients with cheaper biologic drugs, like Biosimilars, immediately after their basic patent expiry. This is mostly practiced by creating a patent thicket. Hence, drug companies’ advocacy for greater access to innovation is an oxymoron to many.

The same was echoed in another article – ‘How originator companies delay generic medicines,’ published by GaBI. It wrote, such practices delay generic entry and lead to healthcare systems and consumers paying more than they would otherwise have done for medicines. These include the following:

  • Strategic patenting
  • Patent litigation
  • Patent settlements
  • Interventions before national regulatory authorities
  • Lifecycle strategies for follow-on products.

A very recent piece on the subject, published by Fierce Pharma on August 31, 2021, vindicates that the patent life extension through the patent thicket is happening on the ground – denying patients access to cheaper equivalent, especially of off-patent biologic drugs within a reasonable time period. It highlighted:

  • The exclusivity of AbbVie’s Humira, which hit the market in 2002 and generated nearly $20 billion in sales last year was extended by 130 patents.
  • The same company has applied for 165 patents for its another blockbuster Imbruvica. Launched in 2013, Imbruvica has already generated sales of $5.3 billion for AbbVie.

No wonder, why in February 2021, during a Senate Finance Committee hearing, Sen. John Cornyn blasted the company saying:

“I support drug companies recovering a profit based on their research and development of innovative drugs,” Cornyn said. “But at some point, that patent has to end, that the exclusivity has to end, to be able to get it at a much cheaper cost.”

More reports are also available on attempts to erode consumer confidence in Biosimilar drugs, as compared to the originals.

Work for innovation sans eroding consumer confidence in Biosimilars: 

Making affordable new drugs and vaccines available to patients with ‘access to innovation’, deserves inspiration from all concerned. Curiously, even in the new normal, some big companies continue trying to erode consumer confidence in off-patent drugs, especially Biosimilars and complex generics.

For example, an article on Biosimilars moving to the center stage, published in the Pharmaceutical Executive on August 12, 2021, quoted an interesting development in this space. The article highlighted that US legislators are now ‘eyeing measures to deter innovator promotional messages that disparage follow-on competitors.’ This initiative was spurred by US-FDA criticism of an Amgen promotional communication for undermining consumer confidence in Biosimilars to its Neulasta (pegfilgrastim) injection.

On July 14, 2021, US-FDA’s Office of Prescription Drug Promotion (OPDP) sent a letter to Amgen carrying a caption ‘FDA notifies Amgen of misbranding of its biological product, Neulasta, due to false or  misleading promotional communication about its product’s benefit.

The letter, as reported in the above article, criticized the company for making a false claim of greater adverse events with the injection system used by Biosimilars compared to the Amgen product. OPDP advised Amgen and other firms to “carefully evaluate the information presented in promotional materials for reference products, or Biosimilar products” to ensure correct product identification and avoid consumer confusion.

Conclusion:

When the point is, creating a conducive ecosystem to promote access to innovation, it should be patient-centric – always, and, more so in the new normal, considering changing needs and expectations of health care customers.

The innovation of usually pricey new molecular entities, no doubt, meets unmet needs of those who can afford these. Whereas, manufacturing process innovation expands access to the same molecule, particularly when they go off-patent, by making them affordable to a vast majority of the population.

But powerful industry lobby groups continue pressing harder for unfettered ‘access to innovation’ with greater relaxation of the IP and regulatory framework of countries, like India. The situation prompts striking a right balance between encouraging more profit by helping to extend patent exclusivity and encouraging greater access to off-patent cheaper Biosimilars as soon as the basic patent expires.

The bottom-line is, both need to be actively encouraged, even if it requires new laws to discourage practices like, creating patent thickets or undermining the use of generics or Biosimilars, and the likes. The good news is lawmakers have started deliberating on this issue – along with increasing public awareness, which gets reflected in the pharma industry’s current reputation ratings.

Left unresolved soon, such piggyback ride on ‘access to drug innovation’ bandwagon to serve self-serving interests, would continue denying speedy entry of cheaper Biosimilars. From this perspective, it isn’t difficult to fathom, why unfettered access to drug innovation is considered an oxymoron, by many.

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.

Taming Two Critical Covid Uncertainties For Pharma’s Sustainable Growth

Posted on by
Reply

The reasons behind a great urgency of the Governments, besides high expectations of the general public, to have the ‘ultimate solution’ very soon, against the ongoing pandemic, are understandable. However, various media-hyped narratives on their clinical trials, and timeframe for expected launch – ranging from November this year to anytime in 2021, are making many experts to raise eyebrows on the scientific processes followed for Covid vaccine development.

Exact answers to the ultimate efficacy standard, safety profile and dates of their availability to the entire population, are still not clear – not even to many domain experts. Besides, two other critical and fundamental questions in India, are related to huge financial resources and other wherewithal, such as, countrywide stringent cold-chain logistics network, required to achieve this goal.

While effective, safe and high-quality vaccines, as and when these will come, will be pivotal to contain the alarming spread of Covid-19 – and that too in a wave after wave manner. Alongside, the intense search for effective anti-Covid medicines are also expected to come to fruition. Doctors will then have in their arsenals a number of highly effective alternatives, that can predictably cure individuals, when infected by this lethal virus.

It causes a great concern when someone asks, when will those days of great relief to all come? For, those days may or may not be very soon – could well be for an indefinite period. No one seems to know the answer, yet.

Until then, pharma companies can’t afford to remain in a ‘quick-fix mode’ to address the problems related to Covid related market and consumer mindset changes. Choosing this path could eventually prove to be very costly, especially for the lost time in leveraging some key opportunities. Moving in that direction, would entail rebuilding the organization by creating a new work-culture – a mindset to be all-time ready for any disruptive changes in business. Most importantly, if or as and when it comes, the organization should not get as overwhelmed, as is happening during the current global pandemic.

In this article, I shall deliberate the following two critical and interrelated Covid-19 issues:

  • The uncertainty in achieving what everybody is expecting to get right away – getting a preventive vaccine or a cure for the infected patients.
  • Inordinate delay in getting prompt medical care by many patients for non-Covid related serious ailments, leading to complexity of the disease. How long this situation will continue still remains uncertain.

As things stand today, these uncertainties could continue for an indefinite period, making some of the Covid related changes irreversible. Thus, my aim will be, first to recap where we are today with these niggles. And then, focusing on the crucial need to pave a balanced pathway – uncharted by anyone, for destination success – in the new world order. Let me begin with the first issue first.

The uncertainty in achieving what everybody is expecting:

Although, some Covid vaccines, reportedly, will be ready by early 2021, uncertainties and delays are still anticipated on the way. Some the reasons may include the following:

  • A critical challenge: About 5.6 billion people worldwide would need to be immune in order to end the pandemic (NEJM). Thus, vaccination process may take years to achieve the coverage necessary for everyone to be protected.
  • Huge investment required: India would need to invest between Rs 3,000 -5,000 crore to create additional facilities for making a huge number of vaccines, required for the Indian population. Currently no one has the capacity to manufacture it for 1.3 billion Indian populations. Moreover, vaccine alone is not the solution to the COVID-19 problem, according to experts.
  • High vaccine cost in India: As these vaccines come from a very difficult platform its cost is going to be significantly higher than many other vaccines, so there is going to be a requirement to think about how we are going to fund this.
  • Coronavirus mutating, potentially evolving: As reported on September 24, 2020, Covid’s continual mutation may make it increasingly contagious. The study says, it’s possible that when our population-level immunity gets high, this Coronavirus will find ways to get around our immunity.
  • The logistical challenge of a lifetime: Getting billions of doses of COVID-19 vaccines around the world quickly, would require 15,000 flights and 15 million cooling boxes. Stringent temperature control requirements for the vaccine supply chain must not be compromised at any point, not even in rural India. It’s worth noting, some of these vaccines may need to be kept at temperatures as low as -80 degrees Celsius. Currently, even in the developed world, the most efficient medical supply chain conventionally distributes vaccines at +2–8°C.
  • Vaccines may not provide complete protection: If COVID-19 re-infections are common, “vaccines might not completely protect against the virus” and would instead require a design similar to seasonal flu shots to protect from new variants. Interestingly. India may, reportedly, approve covid-19 vaccines that show 50 percent efficacy in clinical trials.

Converting problems into opportunities:

Such uncertainties may not only aggravate people’s overall health risks, but also their exposure to Covid infection. Drug companies, drug authorities and various Governments have been working hard on these issues. However, as flagged earlier, amid this health crisis, there is also another growing concern of a very serious nature. It pertains to many people delaying their non-Covid related medical care and medical interventions, for various reasons.

Pharmaceutical companies can convert this problem into a golden business opportunity with ‘patient-centric’ innovative strategies having a cutting-edge, and from a number of platforms. Let me illustrate this point with an interesting example of an initiative taken by a global pharma major, in this area.

A pace setting initiative:

On September 22, 2020, Fierce Pharma reported, ‘J&J wants everyone to know that taking care of their health can’t wait—even during a pandemic.’ This effort is based on the findings of a recent Harris Poll commissioned by them. This study revealed, the COVID-19 pandemic has caused many Americans (68 percent) to delay healthcare treatment. It ranges from standard routine exams to important elective surgeries to ER visits – with physicians sharing concerns about the long-term impact of patients delaying care. The situation is expected to be no different in other countries of the world, including India.

Based on this finding Johnson & Johnson (J&J) have recently launched a US-based online initiative, aimed at giving both patients and physicians information and resources about health care options. This unique campaign has been named – “My Health Can’t Wait”.

By a statement J&J announced: “As the largest healthcare company in the world, we are committed to helping people live their healthiest lives, which means getting the care they need, when they need it.” It added: “Through My Health Can’t Wait, we hope to provide patients and healthcare providers with resources to help stay connected and prioritize their health care, both during this pandemic and in the future.” The point, especially take note of is, ‘both during this pandemic and in the future.’ This part of the above sentence of J&J, echoes the well-known management dictum – converting problem into opportunities, I add, even during the Covid pandemic.

I hope, many pharma players may also wish to pursue similar direction, responding to their own specific needs. But, not just to keep the head above water, in combating this unprecedented health crisis, but with a long-term strategic perspective – to rebuild the organization – for business excellence the new normal.

The concept reverberates:

I find the concept of ‘rebuilding the organization now, for business excellence the new normal’, reverberating in several expert voices. For example, The McKinsey ‘Briefing Note’ of September 16, 2020 – ‘COVID-19 and the great reset.’ It said: ‘The world anxiously awaits an effective COVID-19 vaccine that can be readily distributed. Until then, the priority is to re-energize organizations—to act rather than react. Even as the uncertainties of the COVID-19 crisis multiply, the goal must be to rebuild for the longer term.’

The authors emphasized, ‘a crisis has a way of bringing things to a head.’ Many believe, the coming months might be the best opportunity in memory for healthcare companies to pursue exponential innovation. This, according to McKinsey, ‘could create an additional $400 billion in value by 2025. And now is the time to claim the hundreds of billions of dollars that could be saved through productivity gains.’

Thus, I reckon, apart from creating a great business compulsion of working harder to neutralize the short-term operational constraints, Covid pandemic also provides a unique opportunity to pharma leadership. It gives a space for them for thinking long-term, and from a strategic perspective. The aim is to rebuild the organization, placing it at a higher trajectory for success, in an uncharted frontier, thus far.

Conclusion:

Meanwhile, as on September 27, 2020 morning, India had recorded a staggering figure of 5,992,532 of Coronavirus cases with 94,534 deaths. The virus’s unprecedented onslaught on the country still continues, unabated. Be that as it may, coming back to where I started from, I reckon, pharma companies, in general, could play a stellar role in converting the dual problems of uncertainties into a number of opportunities. In that process, they can create a win-win situation for all, in the health care space.

The uncertainties related to scientifically proven, safe and effective Covid drugs and vaccines will, hopefully, be addressed – sometime, by the scientists and medical researchers. However, as the above McKinsey paper wrote: ‘Until then, the priority is to re-energize organizations – to act rather than react. Even as the uncertainties of the COVID-19 crisis multiply, the goal must be to rebuild for the longer term.’ Thus, the second issue, needs to be creatively leveraged mostly by individual drug players, starting from now.

From this perspective, pharma leadership, will need to commit quality time of thinking people, supported by adequate resources, for conceiving and effectively implementing a ‘patient-centric’ strategy, that patients will fall for in the new normal. That being done, the top honchos, will require to roll up their sleeves to prioritize primary, secondary and tertiary action areas.

Instead of trying to do a little bit of everything, in all possible areas of Covid related changes in the market dynamics, ‘primary action areas’ ought to be the starting point, deploying all resources. And then, expand to the ‘secondary’ and ‘tertiary’ ones, in a well-calibrated manner. Evaluation of results and tightening the strategic loose knots, if any, should be an ongoing process. If implementation of the process requires handholding, so be it. Because, taming these two critical Covid related uncertainties, is intimately related to a sustainable growth for the pharma companies.

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.

 

Time For Predictive Rather Than Reactive Pharma Strategy

Posted on by
Reply

Traditionally, pharmaceutical industry, across the world, is mostly reactive – rather than proactive or predictive in its strategic approach – spanning across all its business domains. A large number of pharma players – both innovators and generic drug makers, formulate their business strategy – generally reacting to competition, changing market dynamics and patient/ doctor /other stakeholder preferences. The same is being witnessed even during Covid-19 pandemic. However, this trend seems to be more prevalent in India – as one looks around.

For example, in R&D – be it a statin drug, proton pump inhibitors and right up to monoclonal antibodies or cancer immunotherapies – after a first-in-class molecule comes, a plethora of ‘me-too’ – but patented molecules soon follow. A comparable trend in the generic drug categories is also all-pervasive, including fixed-dose combinations (FDCs).

Similarly, even in the good old days of sales and marketing, we have seen – after the first product detailing folder was successfully introduced by a leading pharma company in India, how competition lapped the concept up – considering this change as a magic wand for brand demand generation!

In recent days, a similar trend is surfacing for ‘Digitalization’ of pharma business, mostly reacting to the changing practices of key competitors, or involving patients or doctors’ preferences. It gets reflected in other business domains, as well. With this perspective, in this article, I shall deliberate on this area, especially in view of the current situation.

Traditional ‘safe sailing’ is no longer an option:

The Coronavirus pandemic could be a stronger catalytic factor for the drug industry to initiate the much-desired transition from being reactive to predictive in its strategic business approach- faster. Interestingly, way back in June 2007, the PwC Whitepaper titled “Pharma 2020: The vision”, had also articulated: ‘The social, demographic and economic context in which the pharmaceutical industry (Pharma) operates is changing dramatically.’

Some drug players have already opted to transform their organizations in sync with the changes in the operating environment. But, a vast majority of them preferred to stick to the traditional reactive mindset, for a safe sail, as it were. However, this doesn’t seem to be an option, any longer. Be that as it may, there is nothing wrong in being reactive in strategic business practices, although formulating a predictive or proactive growth strategy demands more cerebral prowess and is much different from the reactive ones.

The difference, I reckon, is similar to that of a leader and the followers, with nearly similar impact on overall corporate image and performance, besides a prime-mover advantage of the latter. Nevertheless, there could be a predictive approach even within a reactive approach to competition. To illustrate the point, let me cite an example related to ‘me-too’ – patented-drug development.

Making an overall reactive strategic approach proactive in nature: 

Among several examples of making a reactive strategic approach – proactive in nature with innovative goals, let me quote a very recent one. For decades, drug companies have been selling ‘me too’ but patented drugs, at prices similar to the original and ‘first-in-class’ drugs, which are successful and enjoying a market monopoly.

Moving away from this trend, a startup drug maker, reportedly, wants to disrupt the traditional pharma industry practices by delivering what most patients and healthcare stakeholders want. It has set a novel goal of becoming patient-centric in its offering by making innovative drugs available at affordable prices. The startup wants to achieve this objective ‘by changing long-held industry practices for developing, pricing, and selling slightly different versions of costly brand-name drugs.’

Accordingly, with a proactive or predictive approach within an overall ‘reactive’ trend, it wants to create a unique niche for itself. The entity ‘will focus on developing “me too” drugs, which imitate the biological functions of existing drugs, but use distinct molecular structures so they don’t infringe on existing drug patents.’

Evolving a new demand of value-based health care system:

During disruptive changes and uncertainties in the business environment, such as what is being experienced today, gaining actionable insight on how these changes will call for new strategies to excel, would require a predictive mindset. This is of critical importance, particularly when a new demand for a value-based health care system is fast unfolding. This subject was well deliberated also in the book – ‘Healthcare Disrupted: Next Generation Business Models and Strategies.’

About six years back what the authors of this book predicted, seems to be a reality today. They had said: The concept of “value” rules the day, undoubtedly. The transition from the old ‘fee-for-service’ to ‘fee for value’, is game changing. On the same subject, another article - Focus on Value 1: The “Tsunami of Change”, published in the ‘eye for pharma’ on March 22, 2026, quoted the authors of this book – explaining the scenario lucidly.

They said, today’s health care system is largely reactionary, as the health services react to the persistence of consumers, their phone calls, queuing for services, waiting in the waiting room and calls to healthcare insurers. Whereas, ‘tomorrow’s system would prompt the health care providers to answer a seemingly simple question: how will they become relevant to a customer group?

Even six years down the line, especially in the current global pandemic situation with an evolving demand of a value-based health care system, this concept remains so relevant, possibly more than ever before. That said, an unforeseen and unprecedented situation could also force a pharma player – already moving on a predictive strategic path, to choose a reactive path – mostly for survival and progress of business.

When a company moves into a ‘reactive’ path from a ‘predictive’ one:

Such instances are infrequent. But a major event like Covid -19 may give rise to such a situation. For example, in the Pharma and Biopharma R&D space, it happened and is still happening. As ‘Evaluate Vantage Covid-19 Report’ of April 16, 2020 highlighted, as follows:

‘Anyone thinking that 2020 might travel down a predictable path for the biopharma sector was swiftly disabused of this view in the opening weeks of the year. The Coronavirus pandemic has changed the focus for almost every drug developer, whether they are working on potential treatments or trying to keep their businesses on track – or both.’ Good or bad, this is the reality today.

However, many of these organizations are unlikely to jettison their well-thought out ‘predictive’ pathway and are expected to soon find ways to move back to it. Thus, the question that one may pose, how does a company move into a predictive pathway from a reactive one? And particularly considering, if Covid-19 pandemic has caused some irreversible changes, or even – a long-term change in the business environment.

Getting back to predictive strategic path from a reactive one:

This issue was also covered in the article – ‘Three Proactive Response Strategies to COVID-19 Business Challenges,’ published in the MIT Sloan Management Review, on April 17, 2020. It wrote, as organizations move from a reactive to a proactive approach to dealing with COVID-19, they should ask themselves the following three questions:

  • Can we offer a version of our products and/or services through an online channel? Going online is the closest equivalent to low-hanging fruit in the current environment.
  • Can we use our existing infrastructure to produce products and/or offer services that are in demand?  Many organizations have allocated infrastructure to produce goods and services to support the fight against COVID-19, but some strategic companies would think beyond the crisis to future changes in consumer needs.
  • How can we rapidly increase our capacity to produce and distribute on-demand products and/or services?  Turning to partnerships with other companies can boost capacity in a crunch situation, such as today.

The need for collaboration, in such extraordinary situation, has also been underscored by the European Pharmaceutical Review. It pointed out - how academia, government and the pharmaceutical industry can work together to potentially ‘repurpose drugs’ for the treatment of COVID-19. This is another example of formulating a predictive growth strategy to create a win-win situation, while being in the midst of a reactive one.

Conclusion:

Meanwhile, despite national Lockdowns at a very early stage on March 24, 2020, India has now climbed up to occupy the fourth highest position in terms of the number of Coronavirus infected cases. Continuing the steep ascending trend, as on June 14, 2020 morning, the recorded Coronavirus cases in the country reached 321,616 with 9,199 deaths.

During the current global pandemic of a humongous scale, drug companies are trying to respond to rapid challenges across their business operations, right from planned R&D programs to effectively maintaining supply chain, including manufacturing activities. If the current COVID-19 pandemic lasts for medium/long term, there could also be significant delays in the execution of various other ongoing projects/programs. This was the analysis of Deloitte in a paper, titled, ‘COVID-19 response for Pharma companies – Respond. Recover. Thrive’

While the full impact of the Coronavirus pandemic is still unknown, adopting a predictive strategy in the prevailing overall reactive environment, is expected to yield a significantly better business performance. As I said earlier, the core difference between adopting a ‘predictive’ and a ‘reactive’ business pathway, under the circumstances, is akin to the difference between a leader and a follower.

Unlocking the value innovation in all areas of pharma business is the name of the game, for excellence. Leveraging Artificial Intelligence (AI) based contemporary ‘predictive’ tools will help pharma players break the new ground, even in such trying times. Coming from this perspective, a ‘predictive’ strategy rather than a ‘reactive’ one, apparently, is the demand of time – where we all are in – today.

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.

Pharma Branding At Tough Times

Posted on by
Reply

“About two-thirds of drug launches don’t meet expectations. Improving that record requires pharmaceutical companies to recognize the world has changed and adjust their marketing accordingly.” This appeared in an article – “The secret of successful drug launches,” published by McKinsey & Company in March 2014. There isn’t any recent evidence, either, that this situation has improved now.

Even innovative drugs no longer guarantee a commercial success, as greater competition is building up there, as well. Today, the number of such drugs per indication has risen by 37 percent since 2006 making the task tougher, according to another article of McKinsey & Company, titled ‘Why innovative products aren’t enough for a successful pharma launch,’ brought out in August 2017.

Top marketers’ intimate involvement in these launches, backed by robust marketing strategies notwithstanding, large scale ‘brand failures’ or rather ‘branding failures,’ still remains unavoidable. Although, its telltale signs are more often visible immediately after launch, but may happen even several years after.

Pundits are just not scratching their heads, but doing extensive research to fathom why it happens. However, with changing times – the market dynamics and the research outcomes/inferences keep changing too. And that will be the focus of my today’s discussion in this article, while I explore various facets of the same.

Is pharma branding just a marketing exercise?

That pharma branding is not just a marketing exercise and its failure at any stage – from launch to even years after, I reckon, isn’t the sole responsibility of the pharma marketer. This is mainly because, doctors would ideally prefer to prescribe specific pharma brands and patients would feel confident to use those, because of successful construction of a positive brand bias. Which in turn creates a higher perceived efficacy and a low anticipated safety concern with the brand.

Although, it will be right to assume that good pharma marketers are solely responsible for the creation of this intangible brand asset, but the tangible intrinsic brand value should necessarily be ingrained into each dose of the same that patients consume, always.

Thus, tangible brand value creation, its maintenance, if not enhancement, span across many other functional domains of a drug company. Some of these include, unbiased reporting with expected disclosures of all clinical trial results, maintaining a robust and highly efficient supply chain network or high-quality manufacturing facilities, besides a few others. Evidences exist that irrational pricing could also result in a kind of brand failure. Considering these aspects in totality, creating a positive bias during a pharma brand-building process, is a collective responsibility, and not just of the marketers.

Why creating a positive brand bias is a collective responsibility?

There are ample examples to substantiate that creating a positive stakeholder bias during its brand-building process, is a collective responsibility. Let me illustrate this point by drawing a few examples of branded failures prompted by supply-chain network, disclosures on clinical development and of course perceived ‘irrational’ pricing that falls basically in the marketing domain. It is worth noting, similar incidents may also be related to the manufacturing process, even for top selling generic drugs.

Supply-chain: In the beginning of 2008, serious adverse drug events, some even fatal, were reported with Heparin (Baxter), which used to be widely used as an injectable anticoagulant. Around 80 people died from contaminated Heparin products in the U.S. The US FDA reported that such contaminated Heparin was detected from at least 12 other countries. The primary reason of the same was a serious breach in the supply-chain integrity.

Disclosures on clinical trial results: On 30 September 2004, Vioox (rofecoxib), a non-steroidal anti-inflammatory drug (NSAID) that had been on the market since 1999, was suddenly withdrawn by its manufacturer MSD, owing to concerns about its effect on cardiovascular health.

‘Irrational’ pricing: Like a lot of new cancer drugs, Zaltrap (aflibercept) wasn’t cheap carrying a price tag of USD 9,600 a month. But its price was quickly taken down. This followed some serious public flak, such as, doctors from Memorial Sloan-Kettering (MSK) wrote a blistering review for The New York Times in November 2012. They declared that MSK was taking the drug off the institution’s formulary, because less expensive and just as good alternative angiogenesis inhibitors were available. Although, Sanofi initially defended the price, it subsequently backed down, cutting down the price by half.

Manufacturing process: On September 13, 2019, the FDA announced that preliminary tests found low levels of N-nitrosodimethylamine (NDMA) in ranitidine (Zantac), a heartburn medication. Consequently, almost all companies, including Novartis (through its generic division, Sandoz), GSK, Apotex and many others announced its withdrawal from a large number of markets. Interestingly, these announcements came after a Connecticut-based online pharmacy informed the FDA that it had detected NDMA in multiple ranitidine products under certain test conditions. The NDMA impurity was believed to have been introduced by changes in the manufacturing process. There are several other well-reported examples, as well.

These examples vindicate that creating a positive brand bias remains a collective responsibility throughout the product lifecycle. And it involves several functional areas of drug companies. That said, let me now focus on the creation of a positive bias for pharma brands.

Creating a positive brand bias:

Skillful creation of a positive brand-bias, supported by high quality – tangible and intangible value offerings, is the net outcome of any successful branding process. It augments stakeholder confidence, leading to an increased prescription generation, alongside a favorable patient experience.

More often than not, a positive brand-bias successfully brings into being greater perceived brand-efficacy and higher perceived brand-quality, with lesser anticipated safety concerns. Consequently, the process invigorates an emotional bonding with customers for a long-term brand-loyalty. A positive brand-bias also creates a strong brand equity that often helps in working out a good pricing strategy for the company.

An interesting strategy prescribed – recently:

The October 8, 2019 issue of Fierce Pharma featured an article on creating a positive brand-bias with “Prime and prompt” marketing strategies, outlined by CMI/Compas.

According to Changing Minds: ‘Priming works by providing people with information that is easily brought to mind. The prompt that brings the information to mind can be an implanted and specific trigger or can be an associated term that will naturally bring back the primed information.’ Illustrating the point, it adds: ‘Prime-and-prompt can be a bit like firing a gun, where priming cocks and prompting pulls the trigger.’

Putting this concept in the pharma industry perspective, the CMI/Compas officials explained in the above article, ‘pharma marketers can create primes with product messages that condition people to recall their product when they need medicine or are diagnosed with a condition.’

Hence, a pharma marketer’s adroitness in the ‘priming’ strategy helps ‘prompt’ the desirable action, such as, going to a doctor to ask about a product. Hence, the persuasion technique is termed – ‘prime and prompt’, the paper explained. Naturally, the question that follows: what are the key principles behind this strategy?

Key principles behind ‘prime and prompt’ strategy:

As elucidated by the Changing Minds, when thinking and deciding, we are influenced by related information from the past. At that time, our memories would supply that information, which helps us understand, make sense, decide and act on the subject at hand. Thus, those things that come at the top of mind will have a more immediate and disproportionate influential effect, while those things which are long forgotten may have little or no effect.

It further adds: ‘Priming is driven by implicit memory, where recall is entirely unconscious as the person ‘just knows’ without having to think hard or otherwise put effort into remembering or working things out.’

How to apply the ‘prime and prompt’ strategy in pharma?

It’s no-brainer that to use ‘priming’ in the persuasion process, say for increasing prescription support, the marketers need to provide stakeholders with relevant information beforehand, and more importantly, in a different setting. And only thereafter, they need to focus on a normal brand persuasion strategy. One may most appropriately comment, this is easier said than done in the drug industry.

Taking a cue from the above interview with the CMI/Compas officials, some of the broad steps of the ‘prime and prompt’ strategy, I reckon, may be summarized as follows:

  • Consistent messaging through omnichannel media achieving target reach and frequency, as I had explained before.
  • For intended top of mind recall, a combination of print, digital, social, search, display at appropriate places and in TV, especially for OTC drugs, should consistently surround the target audience for ‘priming.’
  • According to a recent research, the most highly rated ‘priming’ spots for pharma ads for physicians are medical journals, conferences and the likes. Similarly, for patients, appropriate displays at doctors’ clinics and similar places also appeared to be one of the top-rated ‘priming’ spots.

Consequently, a well thought-out ‘priming’ strategy, skillfully executed – based on research findings, is expected to be effective. It will then help trigger desirable ‘prompts’ for the target-audience, augmenting a successful branding process. However, it comes with a caveat that the tangible intrinsic value of the brand, especially those which originate in other functional areas, don’t get compromised or changed in any way.

Conclusion:

Branding exercise in the pharma industry has never been more challenging, as it is today – both for innovative and generic drugs. As stated above, the number of innovative drugs per indication has risen by 37 percent since 2006, making the market competition tougher. Likewise, product proliferation with cut-throat pricing for branded generics, is also making the generic drug marketers grasping at straws, as it were.

In this challenging situation, creating a positive stakeholder bias for brands, as the net outcome of the pharma branding process, is a collective responsibility. Any non-marketing misstep in the tangible brand value offering, could sweep a brand away to oblivion – not just during launch, but at any stage of its life-cycle. Pharma marketers will of course be solely responsible to create the critical intangible brand assets, such as a positive stakeholder bias for brands.

At this tough time for pharma branding, several fresh marketing concepts like, ‘prime and prompt’ are now being seriously evaluated. Thus, I reckon, its also a time for astute marketers in the pharma industry to test the water, in pursuit of excellence.

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.

 

A New Facet of ‘Data Integrity’ With Novel Therapy… And Much Beyond

Posted on by
Reply

The peril of breach of data integrity involving a top Indian pharma player, jolted many, probably for the first time, on September 17, 2008. On that day, the USFDA, reportedly, issued two ‘Warning Letters’ and an ‘Import Alert’. These were related to deficiencies in the drug manufacturing process and deviations from U.S. current Good Manufacturing Practice (cGMP) at Ranbaxy’s Dewas and Paonta Sahib plants in India.

Since then, instead of demonstrable corrective measures, similar incidents had started ballooning – inviting more serious US-FDA actions, such as Import ban, consent decree, loss of market value, Loss of customer trust, among many others. The research article – ‘Overview of Data Integrity issues in the Pharmaceutical industry,’ published by the International Journal of Pharmaceutical Sciences Review and Research, in its May-June 2018 issue, also reflects the same trend.

Much reported instances of breach of ‘Data Integrity’ were specific to generic drugs and mostly manufactured by Indian companies, besides China. While this may be true at that time, it is now spreading much beyond generic drug manufacturing in India and China – making its way into the global clinical trial arena. I also wrote earlier that ‘Data Manipulation: Leapfrogging Dangerously Into Clinical Trial Domain.’ With greater focus, this article will discuss not just how ‘Data Integrity’ issue is cropping up into clinical trials of even modern, complex, highly innovative and exorbitantly priced lifesaving treatments. Going beyond that, I shall also point towards increasing attempts to exaggerate the success of many cancer drug trials due to strong bias. Nevertheless, let me start by rehashing the relevance of ‘Data Integrity’ on patients’ health interest.

Data Integrity ensures safe, effective and high-quality drugs for patients:

According to US-FDA: ‘Data integrity is an important component of industry’s responsibility to ensure the safety, efficacy, and quality of drugs, and of FDA’s ability to protect the public health.’ Thus, data integrity-related cGMP violations may lead to regulatory actions, including warning letters, import alerts, and consent decrees, as the drug agency notified. In other words, maintain all types of ‘Data Integrity’ is a key requirement in the pharma industry to demonstrate that the final products conform to the required quality parameters.

These requirements are known to all generic drug exporters catering to the regulated markets, including the local manufacturers in the United States. Curiously, it continues to happen despite their full knowledge of the grave consequences of violations. The June 12, 2019 paper – ‘An Analysis Of 2018 FDA Warning Letters Citing Data Integrity Failures,’ published in Pharmaceutical Online, brings out some interesting facts, related to drug manufacturing area.

From the analysis of 194 ‘Data Integrity’ associated ‘Warning Letters (WL).’ from 2008 to 2018, the top 5 countries in this regard came out as follows:

Rank

1

2

3

4

5

Country

China

India

United States

Europe

Japan

No. of WL

58

54

36

14

7
% to Total

29.8

27.8

18.6

7.2

3.6

Interestingly, over 76 percent of US-FDA Warning Letters (WL) are on manufacturing ‘Data Integrity’ and were issued to pharma companies located in China, India and the United States. Moreover, when it comes to all types WL related to various types of regulatory malpractices, India again featured as one of the top violators. Be that as it may, I shall now focus on the spread of this decay in other important drug safety related areas, such as clinical trials.

Ironically, breach of ‘Data Integrity’ in another crucial area, like clinical trials for new drugs, doesn’t seem to attract public attention as much, which I shall reason out below – also explaining why it’s so.

Breach of ‘Data Integrity’ in clinical trial – more crippling for the company: 

‘Data Integrity’ concern pertaining to clinical trials was recently expressed in an article, published by the Food and Drug Law Institute, in the April-May 2019 issue of its Update Magazine. The paper reiterated: ‘Good Clinical Practice (GCP) data integrity issues can at times be more crippling to a company than Good Manufacturing Practice (GMP) data integrity issues.’ Elaborating the point further, the authors highlighted, where such issues are severe, the drug regulatory agency may completely reject the data submitted in new drug applications, supplemental drug applications, and abbreviated new drug applications.

This outcome is quite akin to import bans for generic drugs into the United States, as it would cause a huge setback for the company, affecting clinical development programs for the new drug. Moreover, as the article says, such action would be ‘costing the sponsor substantial time, money, and reputational credibility, not to mention delaying patient access to new drugs.’

‘Dozens of recent clinical trials may contain wrong or falsified data’:

This is claimed by the research paper that was discussed in ‘The Guardian’ on June 05, 2017 carrying the headline - ‘Dozens of recent clinical trials may contain wrong or falsified data, claims study.’

In this study, John Carlisle, a consultant anesthetist at Torbay Hospital, reviewed data from 5,087 clinical trials published during the past 15 years in two prestigious medical journals, JAMA and the New England Journal of Medicine, and six anesthesia journals. In total, 90 published trials had underlying statistical patterns that were unlikely to appear by chance in a credible dataset, the review concluded.

As one of the top medical experts quoted in this paper, said: “It’s very scary that we may be treating patients based on false evidence.” He further added: “It may be the case that certain treatments may need to be withdrawn from use.”

Another October 01, 2013 report, citing a specific example of the same, wrote: ‘Japan’s ministry of health has concluded that studies based on clinical trials for Novartis’s blood pressure drug Diovan contain manipulated data.’ It also added: ‘Diovan was approved for use in Japan in 2000, but recently two universities who hosted and analyzed trials for Novartis – the Kyoto Prefectural University of Medicine and Jikei University School of Medicine – reported finding evidence of data fabrication.’

Thus, from available reports, it appears, just as the saga of ‘Data Integrity’ related drug manufacturing keeps continuing, the same related to clinical trials doesn’t seem to fall much behind. But, the valid question that may follow – why then reported instances of breach of clinical trial data integrity isn’t as many?

Breach of ‘Data Integrity’ found by USFDA is rarely reported: 

The answer to the above question may be found in The BMJ study, published on February 10, 2015. It brought to the fore – ‘Research misconduct found by FDA inspections of clinical trials is rarely reported in journal studies.’ This review was based on identified 57 published clinical trials for which an FDA inspection of one of the trial sites had found significant evidence of research misconduct, including falsification or the submission of false information, problems with adverse event reporting.

The researcher also noted that serious misconducts related to clinical trials, are rarely mentioned in subsequently published journal articles in the same area. More disturbing to note, this critical gap in the transparency of clinical trial reporting is now sneaking into even highly specialized treatment, such as ‘Gene Therapy’, and that too involving a Big Pharma name.

US-FDA has now raised this question even for a ‘Gene Therapy’:

A media report of September 09, 2019 highlights, that Novartis is facing an uproar over data manipulation involving USD 2.1 million gene therapy Zolgensma, which treats spinal muscular atrophy, a leading genetic cause of death in infants. According to this report, Novartis gave “detailed explanations” on Aug. 23 to the FDA about the company’s investigation into the data manipulation and addressed regulators’ questions over why the company waited until late June to make disclosures. However, quoting the FDA, the report indicates, ‘Novartis could face possible civil or criminal penalties.’

Prior to this, another report of August 13, 2019, stated that ‘documents referenced in a Form 483 by the FDA, which inspected the lab a month after it learned of the falsified records, also suggest the data-fudging began at least in early 2018 and could have been uncovered by managers at AveXis during several steps in the clinical outcome assessment.’ The gene unit of Novartis is called AveXis, which had announced the US-FDA approval of Zolgensma on May 24, 2019.

Such instances involving clinical trials with new, complex and highly innovative therapies, further reinforces already existing ‘Data Integrity’ related health safety concern. The cost of these new treatments being so high, it’s perplexing to fathom the necessity of cutting corners in clinical trials, if at all. More so, when these are avoidable to establish efficacy, safety and high-quality standard of the therapy to drug regulators for marketing approval.

Beyond ‘Data Integrity’ – in clinical trials:

Just as ‘Data Integrity’ issue in generic drug manufacturing has intruded in the clinical trial arena for novel treatments, yet another concern, also related to data, goes much beyond what is happening today in this area. This fast-emerging practice is related to ‘cherry-picking data’ for biased clinical trial reporting, adversely impacting public health safety, as brought by several research studies.

Very recently, this was vindicated by another paper published in The BMJ on September 18, 2019. It raised a serious concern of bias in clinical trial data submitted to regulatory agencies for marketing approval of even lifesaving drugs. The findings of the above paper concluded:

Between 2014 and 2016, almost half of the most pivotal studied forming the basis of European Medicines Agency (EMA) approval were judged to be at high risk of bias, based on their design, conduct or analysis. Accepting that some of these might be unavoidable because of complexity of cancer trials, it noted that regulatory documents and the scientific literature had gaps in their reporting. Journal publications also did not acknowledge the key limitations of the available evidence identified in regulatory documents. This concern too keeps growing.

Conclusion:

As discussed above, six broad and important points to note for any ‘breach of integrity’ or ‘cherry-picking’ of data in the pharma industry:

  • Takes place mostly in two known areas – manufacturing and clinical trials.
  • Involves both cheaper generic drug manufacturing, as well as, clinical trials of most innovative and highly expensive treatments – conducted even by Big Pharma constituents.
  • ‘Cherry-picking data’ for biased clinical trial reporting while obtaining marketing approval, involves even cancer drugs.
  • Any such avoidable malpractices with ‘data’, could seriously impact patients’ health interest, raising a public concern.
  • Instances of such malpractices usually become public, only when the perpetrators are caught by vigilant drug regulatory agencies, such as the US-FDA, or when external experts can trace their footprints through sophisticated analytical tools.
  • Multiple instances of wrongdoing of this nature, often by the same company, despite requisite regulations being in place, and also after facing penal actions, make it mostly a self-discipline issue of repeat offenders.

It’s a different discussion all together, whether or not ‘data’ is a new oil – air or water. But maintaining the sanctity of data, while generating, interpreting, presenting or even leveraging these, including for commercial considerations, must not be compromised, at any cost.

Today, breach of ‘Data Integrity’ and ‘Cherry-Picking of Data’ for biased reporting, are creeping into new drug clinical trial domain – from its usual habitat of generic drug manufacturing, posing a greater threat to patient safety. At the same time, none can say, either, that it’s happening with all drugs, at all the time and by all drug manufacturers. But, if and when it happens, it could lead to a catastrophic consequence both for patients and their family.

Be that as it may, country’s top drug regulators should strive harder for an ongoing and meaningful engagement with the pharma industry on this avoidable development. It could well be a carrot and stick approach, where repeat violations by any company would pose a risk of legal survival of the business.

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.

Pharma Stakeholder Sentiment: Back to Square One?

Posted on by
Reply

Is it fair to push out the core purpose of an important process, or rather a mission, unfairly? Whether we like it or not, it happened that way, over a period of time.

Way back on December 01, 1950, George W. Merck (President and Chairman Merck & Co., Inc.1925-1957), epitomized the core purpose of the drug innovation process. This is something, which apparently was possible only for him to articulate exactly the way he did.

On that day, while addressing the students and the faculty at the Medical College of Virginia, Richmond, George Merck said: “We try to remember that medicine is for the patient. We try never to forget that medicine is for the people. It is not for the profits. The profits follow, and if we have remembered that, they have never failed to appear. The better we have remembered it, the larger they have been.”

To many of us, it may sound more as an altruistic statement, and not really coming from a businessman who wants to excel in the financial performance of the organization. Interestingly, that was not the case, either. Merck removed any possible ambiguity in his statement by stating categorically: “In doing this, it will be as a business­ man associated with that area of the chemical industry which serves chiefly the worlds of medicine and pharmacy.”

In this article, I shall deliberate on whether or not the core purpose of drug innovation, as articulated by George Merck in 1950 has been pushed out of the mind of the stakeholders for good.

Management Guru – Peter Drucker’s similar observation:

It is worthwhile to recapitulate at this stage that around the same time, the Management Guru – Peter Drucker also made a similar observation, which is relevant even today. He said: “Because the purpose of business is to create a customer, the business enterprise has two – and only two basic functions: marketing and innovation. Marketing and innovation produce results; all the rest are costs. Marketing is the distinguishing, unique function of the business.”

Interestingly, when the word ‘customer’ is replaced with ‘patients’, George W. Merck’s iconic statement fits so well even in the realm of business management, including drugs and pharmaceuticals.

Signs of the core purpose of new drug discovery getting pushed out:

The core purpose of new drug innovation in pharma business, as articulated by a top industry pioneer – ‘Medicine is for the patient and not for the profits’, was pushed out eventually, regardless of its reasons. Today’s core purpose of the same process has seemingly become just the opposite of that – ‘Medicine is only for the patient who can afford it – to maximize profit.’

This change in the core purpose was visible in a large number of instances. For example, when the then Bayer CEO Marijn Dekkers reportedly said: ‘Our cancer drug is for rich westerners, not poor Indians.’  However, his exact wordings were “we did not develop this product for the Indian market, let’s be honest. We developed this product for Western patients who can afford this product, quite honestly.” If so,the question that comes up: why then Bayer fought so hard and spent so much of money, efforts and time to keep selling this specific product in India – exclusively?

In any case, this statement from the highest echelon of one of the top global pharma players is a contentious one, especially against George Merck’s articulation, or even Peter Drucker’s for that matter, on the same. By the way, Dekkers made this commentat the Financial Times Global Pharmaceutical & Biotech Conference in December in December 2013.

A wind of change?

The hope for a wind of change flickered when in an interview, Andrew Witty,the erstwhile global CEO of GlaxoSmithKline (GSK), signaled a totally contrasting view of his company. Witty said: “GSK is committed to offering all its new drugs in India at affordable prices.”

Much prior to this, on March 14, 2013 he told a conference on healthcare in London that: “It’s not unrealistic to expect that new innovation ought to be priced at or below, in some cases, the prices that have pre-existed them.” He further expressed: “The pharmaceutical industry should be able to charge less for new drugs in future by passing on efficiencies in research and development to its customers.”

Witty era is also over now. He retired from GSK at the age of around 53 on March 31, 2017. Perhaps his refreshing patient-centric thoughts would also not find any takers within the industry. Nonetheless, in March 2018, the same issue resurfaced in an interesting article, followed by a few other related developments.

Call for socializing drug development?

The issue, which is not just limited to high prices for new patented drugs, is much broader. An interesting article titled, “Developing drugs wasn’t always about profit, and it shouldn’t be now”, was published in Quartz- a news website owned by Atlantic Media, brings to the fore the same key point, yet again. It makes some profound observations, such as socializing drug development. The word ‘socializing’ may not be quite acceptable to many, though. Nevertheless, it raises some critical issues worth pondering over, such as:

  • Faith in the power of money pervades our modern medical system. Pharmaceutical companies aren’t evil (usually). They just choose to make the most profitable drugs, not the drugs of greatest value to society.
  • For example, despite antimicrobial resistance being a global threat, pharma companies have largely abandoned new antibiotic development on the eminently sensible principle that they are money-losers. Promising narrow-spectrum antibiotics – agents that precisely target pathogens and spare “good” bacteria - languish in development limbo because there is no hope that they might churn as much profit as several other drugs.

It’s high time, I reckon, to adequately address the dire need for a reliable supply of the medicines that make a vibrant modern society possible. All stakeholders, including the pharma industry, globally, would require putting their heads together in charting out a clear and time bound pathway for its effective resolution, soon. Otherwise, sheer gravity and the complexity of the situation may prompt the policy makers to move towards ‘socializing drug development,’ much to the dismay of many of us.

Hospitals creating nonprofit generic drug company:

On January 18, 2018, The New York Times (NYT), published an article titled “Fed Up With Drug Companies, Hospitals Decide to Start Their Own,” highlighted a novel initiative to address the prevailing situation, in their own way, without depending on others.

It reported, for many years, several hospital administrations have been expressing frustration when essential drugs like heart medicines have become scarce, or when prices have skyrocketed because investors manipulated the market. Now, about 300 of the country’s largest hospital systems are taking an aggressive step to combat the problem. They plan to go into the drug business themselves, in a move that appears to be the first on this scale.

‘The idea is to directly challenge the host of industry players who have capitalized on certain markets, buying up monopolies of old, off-patent drugs and then sharply raising prices, stoking public outrage’, the article elaborates.

‘Price of medications has soared, so have pharma profits’:

‘Big Pharma is jacking up prices for one reason – because it can,’ says a CNN Article, published on April 04, 2018. The article further emphasizes: “As the price of medications has soared, so have pharmaceutical company profits. Total sales revenue for top brand-name drugs jumped by almost $8.5 billion over the last five years. The Government Accountability Office (GAO) reported that 67% of drug manufacturers boosted their annual profit margins between 2006 and 2015 – with profit margins up to 20% for some companies in certain years.”

It further writes, “Not only have pharmaceutical companies reaped outsized profits from these price hikes, so have their CEOs. According to a USA Today analysis, the median compensation package for biotech and pharmaceutical CEOs in the Standard & Poor’s 500 was 71% higher than the median compensation for S&P 500 executives in all industries in 2015.”

Conclusion:

This is happening the world over. But its degree varies. In those countries where there are drug price regulators, only a small percentage of the total pharma market by value comes under price regulation, the rest of the products enjoy virtually free pricing freedom.

Would this ground situation change on its own any time soon? There is no specific answer to this question, yet. Moreover, there doesn’t seem to be none around in the pharma industry today with the stature and articulated vision like George Merck. He started from the very basic. Drawing the ‘square one’, he clearly defined the core purpose of discovery, manufacturing and marketing of medicines. Today’s pharma industry, by and large, seems to be charting in other newly drawn squares. Maximizing profit is now considered a key objective of achieving the core purpose – and not an outcome of achieving the core purpose of pharma business.

However, there are some very early signs of several stakeholders’ sentiment changing in this regard. Are they moving back to the basic – square one?

From the chronicles of the past several years on this issue, pharma industry does not seem to be on the same page with those stakeholders, just yet. If they do, a humongous health worry of a vast majority of the global population could be effectively addressed, as many believe.

The reverberations of this sentiment, though rather faint, can be felt in many countries, including the United States, and not just in the developing world, such as India.

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.

Why MNC Pharma Still Moans Over Indian IP Ecosystem?

Posted on by
Reply

Improving patient access to expensive drugs, paving the way for entry of their cheaper generic equivalents, post patent expiry, and avoiding evergreening, is assuming priority a priority focus area in many countries. The United States is no exception, in this area. The Keynote Address of Scott Gottlieb, Commissioner of Food and Drug at the 2018 Food and Drug Law Institute Annual Conference inWashington, DC by, on May 3, 2018, confirms this. Where, in sharp contrast with what the MNC Pharma players and their trade associations propagated, the US-FDA commissioner himself admitted by saying, “Let’s face it. Right now, we don’t have a truly free market when it comes to drug pricing, and in too many cases, that’s driving prices to unaffordable levels for some patients.”

Does US talk differently outside the country?

At least, it appears so to many. For example, in April 2018, the Office of the United States Trade Representative (USTR) released its 2018 Special 301 Report. In this exercise, the USPTO names the country’s trading partners for not adequately protecting and enforcing Intellectual Property (IP) rights or otherwise deny market access to U.S. innovators that rely on the protection of their IP rights.’ Accordingly, U.S. trading partners are asked to address IP-related challenges, with a special focus on the countries identified on the Watch List (WL) and Priority Watch List (PWL).

In 2018, just as the past years, India continues to feature, along with 11 other countries, on the PWL, for the so called longstanding challenges in its IP framework and lack of sufficient measurable improvements that have negatively affected U.S. right holders over the past year.

From Patient access to affordable drugs to Market access for Expensive Drugs: 

Curiously, the USTR Report highlights its concerns not just related to IP, but also on market access barriers for patented drugs and medical devices, irrespective of a country’s socioeconomic compulsion. Nevertheless, comparing it to what the US-FDA Commissioner articulated above, one gets an impression, while the US priority is improving patient access to affordable drugs for Americans, it changes to supporting MNC pharma to improve market access for expensive patented drugs, outside its shores.

Insisting others to improve global IP Index while the same for the US slides:

In the context of the 2018 report, the U.S. Trade Representative, reportedly said, “the ideas and creativity of American entrepreneurs’ fuel economic growth and employ millions of hardworking Americans.” However, on a closer look at the U.S. Chamber of Commerce’s annual Global IP Index for 2018, a contrasting fact surfaces, quite clearly. It shows, America, which once was at the very top of the overall IP Index score, is no longer so – in 2018, the world rank of the US in offering patent protection to innovators, dropped to 12thposition from its 10thglobal ranking in 2017. Does it mean, what the US is asking its trading partners to follow, it is unable to hold its own ground against similar parameters, any longer.

Should IP laws ignore country’s socioeconomic reality? 

MNC Pharma often articulated, it doesn’t generally fall within its areas of concern, and is the Government responsibility. However, an affirmative answer, echoes from many independent sources on this issue. No wonder, some astute and credible voices, such as an article titled “U.S. IP Policy Spins Out of Control in the 2018 Special 301 Report”, published by the Electronic Frontier Foundation on May 01, 2018, termed 2018 Special 301 Report – ‘A Tired, Repetitive Report.’ It reiterates in no ambiguous term: ‘The report maintains the line that there is only one adequate and effective level of IP protection and enforcement that every country should adhere to, regardless of its social and economic circumstances or its international legal obligations.

The ever-expanding MNC Pharma list of concerns on Indian IP laws:

The areas of MNC Pharma concern, related to Indian IP laws, continues to grow even in 2018. The letter dated February 8, 2018 of the Intellectual Property Owners Association, Washington, DC to the USTR, makes these areas rather clear. I shall quote below some major pharma related ones, from this ever-expanding list:

  • Additional Patentability Criteria – section 3 (d): The law makes it difficult for them to secure patent protection for certain types of pharma inventions.
  • TADF (Technology Acquisition and Development Fund)is empowered to request Compulsory Licensing (CL) from the Government:Section 4.4 of India’s National Manufacturing Policy discusses the use of CL to help domestic companies access the latest patented green technology.This helps in situations when a patent holder is unwilling to license, either at all or “at reasonable rates,” or when an invention is not being “worked” within India.
  • India’s National Competition Policyrequires IP owners to grant access to “essential facilities” on “agreed and nondiscriminatory terms” without reservation. They are not comfortable with it.
  • Regulatory Data Protection: The Indian Regulatory Authority relies on test data submitted by originators to another country when granting marketing approval to follow-on pharma products. It discourages them to develop new medicines that could meet unmet medical needs.
  • Requirement of local working of patents: The Controller of Patents is empowered to require patent holders and any licensees to provide details on how the invention is being worked in India. Statements of the Working, (Form 27),must be provided annually.Failure to provide the requested information is punishable by fine or imprisonment. It makes pharma patent holders facing the risk of CL, if they fail to “work” their inventions in India within three years of the respective patent grant.
  • Disclosure of Foreign Filings: Section 8 of India’s Patent Act requires disclosure and regular updates on foreign applications that are substantially “the same or substantially the same invention.” They feel it is irrelevant today.

Pharma MNCs’ self-serving tirade is insensitive to Indian patient interest:

Continuing its tirade against some developed and developing countries, such as India, the US drug manufacturers lobby group – Pharmaceutical Research and Manufacturers of America (PhRMA) has urged the office of the US Trade Representative (USTR) to take immediate action to address serious market access and intellectual property (IP) barriers in 19 overseas markets, including India, reports reported The Pharma Letter on February 28, 2018. It will be interesting to watch and note the level active and passive participation of India based stakeholders of this powerful US lobby group, as well.

Government of India holds its ground… but the saga continues:

India Government’s stand in this regard, including 2018 Special 301 Report, has been well articulated in its report released on January 24, 2018, titled “Intellectual Property Rights Regime in India – An Overview”, released by the Department of Industrial Policy and Promotion Ministry of Commerce and Industry (DIPP). The paper also includes asummary of some of the main recommendations, as captured in the September 2016 Report of the High-Level Panel on Access to Medicines, constituted by the Secretary-General Ban Ki-Moon of the United Nations in November 2015.  Some of these observations are as follows:

  • WTO members must make full use of the TRIPS flexibilities as confirmed by the Doha Declaration to promote access to health technologies when necessary.
  • WTO members should make full use of the policy space available in Article 27 of the TRIPS agreement by adopting and applying rigorous definitions of invention and patentability that are in the interests of public health of the country and its inhabitants. This includes amending laws to curtail the evergreening of patents and awarding patents only when genuine innovation has occurred.
  • Governments should adopt and implement legislation that facilitates the issuance of Compulsory Licenses (CL). The use of CL should be based on the provisions found in the Doha Declaration and the grounds for the issuance left to the discretion of the governments.
  • WTO members should revise the paragraph 6 decision in order to find a solution that enables a swift and expedient export of pharmaceutical products produced under compulsory license.
  • Governments and the private sector must refrain from explicit or implicit threats, tactics or strategies that undermine the right of WTO Members to use TRIPS flexibilities.
  • Governments engaged in bilateral and regional trade and investment treaties should ensure that these agreements do not include provisions that interfere with their obligations to fulfill the rights to health.

The DIPP report includes two important quotes, among several others, as follows:

Joseph Stiglitz, Nobel Prize for Economics (2001) – an American Citizen:

-       “If patent rights are too strong and maintained for too long, they prevent access to knowledge, the most important input in the innovation process. In the US, there is growing recognition that the balance has been too far tilted towards patent protection in general (not just in medicine).”

-       “Greater IP protection for medicines would, we fear, limit access to life-saving drugs and seriously undermine the very capable indigenous generics industry that has been critical for people’s well-being in not only India but other developing countries as well”.

Bernie Sanders, an American Citizen and Senior U.S. Senator:

-      “Access to health care is a human right, and that includes access to safe and affordable prescription drugs. It is time to enact prescription drug policies that work for everyone, not just the CEOs of the pharmaceutical industry.”

-      “Healthcare must be recognized as a right, not a privilege. Every man, woman and child in our country should be able to access the health care they need regardless of their income.”

Conclusion:

Why is then this orchestrated moaning and accompanying pressure for making Indian IP laws more stringent, which apparently continues under the façade of ‘innovation at risk’, which isn’t so – in any case. But, cleverly marketed high priced ‘me too’ drugs with molecular tweaking do impact patient access. So is the practice of delaying off-patent generic drugs entry, surreptitiously. Instead, why not encourage Voluntary Licensing (VL) of patented drugs against a mutually agreed fee, for achieving greater market access to the developing countries, like India?

Whatever intense advocacy is done by the vested interests to change Indian patent laws in favor of MNC pharma, the intense efforts so far, I reckon, have been akin to running on a treadmill – without moving an inch from where they were, since and even prior to 2005. The moaning of MNC Pharma on the Indian IP ecosystem, as I see it, will continue, as no Indian Government will wish to take any risk in this area. It appears irreversible and is likely to remain so, for a long time to come. The time demands from all concerned to be part of the solution, and not continue to be a part of the problem, especially by trying to tamper with the IP ecosystem of the country.

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.

For Improving Drug Quality in India – A Bizarre Intent

Posted on by
Reply

On January 16, 2017, quoting a Government source, a media report revealed, “India’s drug regulator is looking to inspect US pharmaceutical facilities, making critical medicines so that only high-quality products are imported from them.”

This intent follows a similar decision of the apex regulatory body – the Central Drugs Standard Control Organization (CDSCO), against some Chinese manufacturers on drug quality concern. The latest proposal to this effect was sent to the health ministry the previous week – the above report adds.

In this article, I shall explore the fundamental basis of this specific initiative. If it has any, I shall try to fathom whether it’s yet another case of misplaced priority of the decision makers, if not a bizarre one.

The current perspective:

About a couple of years ago, an article published in the global financial daily – the Financial Times, on September 9, 2015 titled, ‘Indian drugs: not what the doctor ordered’, articulated that the Indian pharma industry ‘now face a serious credibility crisis, as they battle to allay western regulators’ concerns about their manufacturing practices — especially the reliability of data from trials of their medicines.’

The report also pointed out: ‘Overseas regulators have been scrutinizing and banning products from some of India’s biggest and most reputable groups — including Sun Pharmaceuticals, IPCA, and Wockhardt – many of which have ongoing relationships with large multinational drug companies.’

Has anything changed now?

Nothing perceptibly seems to have changed in this area since then, to set our ‘own house in order’. Not even after witnessing a barrage of drug quality related ‘import bans’ by the US-FDA that involves Indian manufacturers of all sizes and scale. Instead, CDSCO turns its focus on setting-right ‘others’ manufacturing houses with its reportedly meagre manpower resources. Curiously, these initiatives include even those countries, which are globally acclaimed for having stringent regulatory frameworks well in place, such as the United States (US) and the European Union (EU).

Where a justifiable reason exists:

On Chinese API import by different countries, the article titled “Imports To Fuel India’s Active Pharmaceutical Ingredients’ Requirements,” published by Bloomberg | Quint on November 15, 2017 brings out a nice comparison. It says: ‘Among the top emerging and developing economies, India is a major importer of bulk drugs from China at 54 percent, followed by Indonesia at 24 percent, Brazil at 12 percent and South Africa at 8 percent.’ It also writes, in comparison, most of the developed markets of the world import in the range of just 2-3 percent from China.’

Going by this fact, Indian drug regulator’s inspection of some of the Chinese API plants is, by all means, understandable – mainly for two reasons. One, India is largely dependent on Chinese bulk drugs for formulations manufacturing and consumption in the country, besides exports. And the second, some incidents of compromised Chinese drug ingredients have already been reported. For example, citing quality issues, the Drug Controller General of India (DCGI) has recently, reportedly banned import of such questionable drug constituents from six major Chinese pharma companies. This is not a solitary instance. Similar incidents involving Chinese drugs were  reported in the past, as well.

An irony:

When international media agencies flash headlines, such as “U.S. and EU regulators urge Indian drug companies to step up standards,” Indian drug regulators decide to inspect overseas manufacturing plants, as well. Such a decision becomes intriguing, especially when it includes those countries, where from imports are meager, besides their stringent drug quality standards being globally acclaimed.

This is an irony, as the recent local media headlines like, “India among countries where 10% of drugs are substandard: WHO” or “… 27 medicines sold by top firms ‘fail’ quality tests in seven states”, unfold the veracity of drug regulatory laxity within the country.

The basis of the recent proposal becomes more incomprehensible, when the DCGI himself reportedly admits, even today that: “Substandard medicines are a major issue in India and we are looking out for ways to tackle the problem. As quality regulator, we are developing proper mechanisms to stop manufacturing and sale of counterfeit drugs so that they don’t reach the patients.”

The reasons cited for overseas plant inspection:

According to media reports, the reasons cited in the CDSCO proposal for Indian Drug Inspectors’ (DI) inspecting other overseas manufacturers, including those in the US and Europe, are broadly as follows:

  • Most of over 28 manufacturing sites registered in India from the US, manufacture critical formulations or critical new therapies, which are not available in other countries, as they fall into high-risk categories.
  • Inspections will not only result in compliance to the Drugs and Cosmetics Act and Rules, but also give exposure to Indian drugs inspectors to new technology adopted in the manufacturing and state-of-the-art facilities.
  • The sites will be inspected if they have made substandard drugs, received quality complaints, or faced action by other regulatory authorities.
  • Companies shortlisted for the proposed inspections include those making biologic and anti-cancer medicines.

Let me hasten to add, there is nothing wrong with this intent as such, but the moot point is: what’s the core issue that we are talking about? While addressing this point, let’s first have a quick look at India’s import of pharmaceutical product around the last two decades.

India’s import of pharmaceutical products – 1996 – 2018:

According to ‘Trading Economics’ (last updated in January of 2018), India’s import of pharmaceutical products decreased to USD 254.57 Million in 2016 from USD 795.34 Million in 2015. Average drug imports are shown as USD 645.06 USD Million from 1996 until 2016, reaching an all-time high of USD 1747.65 Million in 2012, and a record low of USD 64.32 Million in 1996.

Nonetheless, the micro- picture of India’s bulk drugs or API import isn’t quite the same. On December 19, 2017 in a written reply to the Lok Sabha, the Minister of State, Chemicals and Fertilizers gave details of India’s bulk drug imports from top five countries, as follows:

Country Import value Rs Crore Import value $ Million (Approx.)
China 12,254.97 1915 (66%)
United States 820.18 128 (4.5%)
Italy 701.85 110 (3.8%)
Germany 485.11 76 (2.6%)
Singapore 422.01 66 (2.3%)
Total 18,372.54 2871

It’s worth noting, although the overall value of API import has declined, including from China, its volume share still remains too high in India. More importantly, Indian drug import from the United States and the European countries, are not only very small, there doesn’t seem to be enough instances of substandard drugs imported from these countries to India, either.

The core issue:

Taking a serious note of the reported incidences of widespread substandard drugs by various reports, including the WHO, the core issue becomes rather obvious. What else could possibly be the core issue other than taking effective remedial regulatory measures to contain the menace of substandard drugs circulating within the country?

An article titled, “Correcting India’s Chronic Shortage of Drug Inspectors to Ensure the Production and Distribution of Safe, High-Quality of Medicines,” published by the International Journal of Health Policy and Management (IJHPM) on April 27, 2017, made an important observation in this regard.

It reiterated: Good drug regulation requires an effective system for monitoring and inspection of manufacturing and sales units. In India, despite widespread agreement on this principle, ongoing shortages of drug inspectors have been identified as a major hindrance to this effort by the national committees, since 1975. Rapid growth of India’s pharmaceutical industry and its large export market makes the problem more acute.

Thus, the major remedial measure that CDSCO needs to take on priority to effectively address this core issue, is the chronic shortage of competent drug inspectors in the country.

An assessment of the current situation:

On the ground, the above situation continues to prevail almost in every state of the country, with a varying degree, though. However, at this point, I shall quote just three such instances – only to illustrate the gravity of the situation.

Example 1 – Delhi:

The article titled, “Delhi’s pharmacy woes: Only 21 inspectors for city’s 25,000 chemists,” published by ‘India Today’ on November 25, 2017, well-captured the latest scenario in this regard, of India’s national capital – New Delhi.

It wrote, there’s no guarantee that the medicine you are buying from a pharmacy is safe. The drug regulatory body does not have enough manpower to conduct regular inspections of the city’s mushrooming chemist shops and wholesale units.

Against the sanctioned posts of 31 drug inspectors, the department has only 21 DI for keeping an eye on Delhi’s 25,000 medical stores, and blood banks. Quoting Government officials the report reiterated, while the number of DI has declined – or at best remained constant – over the past 40 years, the number of pharmacies has increased from 5,000 to 25,000.

Whereas, going by the Centre’s recommendation, Dr. Mashelkar Committee report and the Task Force Committee’s observation, there should be one drug inspector for every 50 manufacturing units. Considering the magnitude of the problem, the Drugs Technical Advisory Board (DTAB), in a recent meeting, reportedly suggested, there should be one official for every 200 sales outlets, and one official for every 50 manufacturing units.

Example 2 – Kerala:

Another report of July 08, 2017, with a similar headline – “Remedial action needed in medicine market”, focused on one more important state – Kerala. It wrote that the Kerala has just 47 drug inspectors to monitor the entire State drug market that has over 20,000 drug stores, excluding those located in the hospitals. “In Kerala – the consumer of about 15 to 20 percent of drugs manufactured in the country, there are no quality checks taking place owing to the manpower shortage” – the article cautioned.

Example 3 – Maharashtra:

Yet another national media report of March 16, 2017 carried a headline ‘FDA faces staff shortage again.’ It discussed the same issue for a major State where the financial capital of India is located – Maharashtra. Giving details, the article pointed out that out of 160 posts of drug inspectors across Maharashtra, only 90 have been filled so far and of the 250 food safety officer posts, just 180 have been filled. More than 50,000 pharmacies, 15,000 wholesalers and over 8,000 manufacturing units, are supposed to be properly governed as per the regulatory rules and godliness, to ensure high quality drug safety standards, by this meager DI staff strength of the State.

Conclusion:

Against the above backdrop, it appears absolutely minimum to expect that CDSCO would make the public know, how does it plan to make the drugs manufactured for domestic consumption of high quality standards, as a safeguard to patients’ health and safety.

This calls for strict quality audits by the DIs of the individual states, at pre-determined periodicity, just as what US-FDA does to ensure exactly the same, for patients in their own country. With dwindling resources of DI, CDSCO seems to be continually failing in achieving this critical goal. There doesn’t seem to be any specific and transparent accountability criteria in place, for the CDSCO to comply with.

In this situation, the plan to audit the overseas manufacturing plants located in the US and EU for drug quality assessment, carving out a slice from the existing DI manpower strength, appears rather foolhardy. Moreover, the safety-risk for those imported medicines is apparently low, not just due to meager quantity of drug import, but also for stringent regulatory environment prevailing in those countries.

In view of all this, the media report on CDSCO’s plan to inspect US and EU pharma facilities, making ‘critical’ drugs to ensure high product-quality, is interesting. If it holds any water, the initiative may be construed by many not merely a case of misplaced priority, but a bizarre one, to say the least.

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.