Sankar Sundaram, Professor of Pharmaceutical Sciences, JSS University, talks about data exclusivity and if effective then how it will impact the Indian pharm industry
Data exclusivity (DE) is the exclusion of data, generated by sponsors for supporting decision-making by regulatory authorities, for reaching the market-approval decisions, with regard to the product’s safety and efficacy, from its commercial exploitation by competitors.
DE in the US with relevance to pharmaceuticals generally concerns with the data generated from the four phases of clinical trials. In the first stage or the phase I stage of a clinical trial it is ascertained whether a treatment is safe for people to undergo, rather than to try to treat a disease condition, and to study the effect of the drugs in the human body and the effect of the human body on the drugs. Phase I study involves typically around 20-80 people and is usually done in healthy volunteers or sometimes in patients.
In the phase II stage of a clinical trial investigation, studies, for the safety and effectiveness of a potential therapy and for potential dose regimes are done. Phase II stage involves typically between 100 and 300 people and is usually done in patients.
Phase III stage of clinical trials involves a patient population ranging from a few hundred to several thousand patients, and is spread between different hospitals and different states. Phase III studies are done to ascertain whether a drug is safe and effective over a wider range of population. Usually after the successful completion of these three phases a sponsor can apply for a marketing authorisation.
In the phase IV stage of clinical trials, post-marketing studies are done to gather additional information including the drug’s risks, benefits and optimal use. These studies are designed to monitor effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use of the product.
DE in the US with relevance to agrochemicals generally concerns with the data generated by suitable animal model studies carried out for the determination of the particular product’s oncogenicity, teratogenicity, neurotoxicity, effects on reproduction etc.
History of undisclosed information protection
Article 39.3 of the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement requires the World Trade Organization (WTO) member states to protect undisclosed test data which originates from new chemical entities and those which require considerable efforts to generate. It would be clear from a 2002 South Centre publication paper of Dr Carlos Maria Correa, of the University of Buenos Aires, Argentina – who had participated in the negotiations of TRIPS during the Uruguay Round – that TRIPS negotiators specifically considered and rejected language requiring grants of exclusive rights to test-data and hence the member countries are not obligated under Article 39.3 of TRIPs to confer exclusive rights on the originator of marketing approval data.
Surmounting the data exclusivity: Reinventing the wheel?
As DE provisions implementation would prevent the disclosure of the test data, the generic approval seekers have to carry out their own trial studies. This would render the marketing approval seeking process a very costly and time consuming procedure. Perhaps by the time the study has been completed, the product in question would itself be out of the DE restrictions. Viewed from an end user’s perspective this repetition procedure would inflict unnecessary anxiety, would prove too costly and practically wouldn’t lend itself amenable for a treatment intervention. It is worth mentioning at this juncture that Indian health authorities are actively considering the waiver of phase III clinical trials, for those drugs for which the authorities in public interest could place reliance upon the clinical trial data available from other countries.
DE is not an intellectual property, as it doesn’t involve the application of the intellect. It is a clause imposed for ensuring that the access to the trial’s data, gathered as above, is excluded from the competing commercial interests. If the competitor so wishes, he is free to repeat the same procedure and accumulate his own trial data.
Now, the chances of a path breaking drug, being discovered, its safety and efficacy established and its launch be found patient-acceptable in India is somewhat unpredictable. But, we are ostensibly the world leaders for reverse engineering of an already proven medicine and to work out a more affordable process, so that any patient worldwide would accept this reverse engineered medicine as the first drug of choice, in terms of the bang for the buck. If DE is effected, then, till the exclusivity period is over, no Indian company can rely on the regulatory-submission data of the big pharma. With the leeway proffered in the WTO legend, interpretation suits- similar to the Markman hearings – perhaps in the Dispute Settlement Board, are likely to become the preferential route to limit the regulatory authorities’ decisions. Alternatively, we have to transgress ethical practices and resort to a re-inventing process. A similar drama is likely to unfold in the agrochemicals sector too.
Making overkill?
A preliminary comparison would show that, for those diseases affecting our Indian population, there has been very few treatment modalities made available by the US manufacturers. Once again, there are the small molecule drugs and the biopharma drugs. Currently, the biopharma drugs are very costly for an average Indian citizen. The trend in the US market is towards the marketing of biopharma drugs. Very few US companies currently show interest in small molecule drugs’ launching. This is because the 1984 Hatch-Waxman act has almost delivered what it was intended to deliver, in terms of bring an affordable pharma product quickly to the patients. This is a situation, where all the low-hanging fruits have already been plucked — in this case the small molecule drug segment.
Borrowing a quote from Heather Behanna, analyst for Wedbush Securities of the US “Big Pharma is running low on innovation.” So, now, the big pharma lobbyists are actively considering the expansion of data exclusivity — for the drug products when they acquire marketing approval in India and elsewhere and apart from their patent protection — as a fortified means of protection for their markets. This over-protection is clearly perceptible from a 15th of March Bill introduced in the US House of Representatives calling for the Promoting Access for Treatments Ideal in Enhancing New Therapies (PATIENT) Act, 2015 invoking an extra two year protection extension for the already three-year DE protecting the newer version of a previously market approved drug. A similar situation is likely to be prevalent in the agrochemicals trial study data too.
Can DE provisions destroy the accessibility and affordability?
DE provisions generally don’t compel an originator to launch the product immediately in Indian market. Hypothetically, a product could be launched towards the end of its patent term too. If Indian government was to confer DE protection, then, there is also a possibility that an attempt would be made to extend the product’s patent protection term until the completion of its DE period. This would further complicate a patient’s accessibility for medicines and a farmer’s accessibility for agrochemicals.
Globally, there have been rare but real instances where, as in the case of an arthritis treatment drug, the only mainstay market command was based its clinical DE, without the support of even its extended patent term, which had expired due to regulatory delays in securing its market approval. Contrarily, if the originator doesn’t launch a product under the prevalent — non DE ? conditions, then, the originator’s product could automatically be launched by a generic company in India, subjected to other compliance conditions.
Another argument against DE is that even those products which are not new and inventive enough — in other words not deserving enough to be patent protected — could be extended commercial protection by the implementation of DE provisions and would create a barrier to generic entry. Unlike a patent protection which can be worked-around, a DE provision is airtight. Similarly, if a product is protected by DE provisions and that product is not worked-up by the innovator company for a time period of a few years, even then, a generic company can’t launch the product, as the generic-company has no compulsory-licensing clause to invoke for the launch of the product. This is because of the likely-nature of DE provision making a product, competition-eligible only after the expiry of its DE period.
Likewise, as DE is automatically conferred on a product — as soon as it gets marketing approval — it now becomes the duty of the regulatory authorities to protect the private rights of the originator, a fiduciary responsibility. So, the innovator hardly incurs any litigation costs at all. Also the strain on the regulatory authority would be overstretched, as now the regulatory authority also has to divert its time and resources in policing every industrial application for commercial launch. Also, through a back door entry, non-patentable subject matter also could be conferred DE protection. The scope of challenging the DE of a drug on the grounds of patient-care afforded in any court of law is very limited. Then again, a slew of data exclusivities, as for example, DE for a new-use of an already product, a DE for a product with a different mode of administration etc could be demanded. These also need special efforts from the regulatory authority’s side. Another danger of DE is that pending any incentivisation, there is a possibility that the generic manufacturer’s absence in the industry would create a monopolistic situation, when, even during a national emergency, there may be an acute shortage of a particular product.
The cultural influence on DE implementation
There are many reasons cited for the non-recognition of the indigenous Indian drug discovery. One major reason is the indifferent attitude of Indian patients, for new chemical entities(NCEs) discovered indigenously. Indian patients need to appreciate that quality medicines discovered and produced from India, would essentially have to comply with official standards and specifications. The Indian mindset needs to undergo a sea-change and for the change there is the urgent need to revamp the setup, beginning from the work culture upward, to the infrastructure upward till the patient-care endpoint. In the absence of a renewed business-model, implementing the TRIPS-plus DE provisions is a surefire method of suffocating the Indian reverse engineering potential. If there is no DE, the current position of bioavailability and bioequivalence testing would maintain their status quo.
The role of clinical trial data in drug development
A policy paper from the Health Action International which is an independent, global network, striving to increase access to essential medicines and improve their rational use through research excellence and evidence-based advocacy, has in 2013 citing a few examples had argued that “it is the withholding of clinical study reports that pose the greater risk to public health compared to non-disclosure.” There have been many instances even in the regulated-markets of the world where incorrect clinical trials reporting had led to an incomplete patient care. Eminent scholars have opined that the publicly generated clinical trial data need to be available for the drug discovery industry for its proactive use, in return of a consideration.
Could a modified Adaptive Pathways Approach alleviate the problem?
The European Medicines Agency(EMA) had launched a pilot project in 2014 called as the Adaptive Pathways Approach. Here, those medicines, addressing life-threatening conditions were to be given conditional approval. The authorisation of a medicine, was to be granted on the basis of the demonstration of a positive benefit/ risk balance. From the patient registries and pharmacovigilance tools, post-approval data on the medicine’s use were to be collected and the marketing authorisation was to be extended to enable the access of this medicine to a broader patient population. On iterative evaluation of the post-approval data, the changes to the status of the product’s authorisation, was to be made. Whereas the EMA declared that data protection and other relevant legal provisions remained the same in the Adaptive Pathways Approach, relevant modifications, tailored to suit Indian situations could certainly make it more adaptable for regulatory purposes especially in the arena, where unmet medical need exists.
The other side of the coin
India is a country with more mouths to feed. The same is true for treating diseases too. So, if and when the DE provisions are implemented, the clinical trials costs would directly have to be borne by the end users. Although in the long term, this would breed competency in new discovery, in the short-span these trials would likely cause a rush for unnecessary amassing of medicines/ agrochemicals among certain strata and would cause frustration among certain strata of the society. Indigenous discovery would flourish in the long run. The invention-based industry (in contrast to being a manufacturing hub) would be established and a lot of new regulations which are inconceivable now would be in promulgation. Instead of being a mere manufacturing-hub, catering mainly to the export markets of the world, our industry would concentrate more on her own citizens. Our indigenous industry would be given a jump start.
Recent political moves
The January 2015 US Trade Representative (USTR) Michael Froman’s statement at a US Congressional hearing assuring that the USTR has been able to “secure commitments from India in the 2014 Trade Policy Forum on a broad range of Intellectual Property (IP) issues of concerns to the US and its stakeholders” sounds an alarm in the minds of the generic manufacturers in India. Also, it has been recently cited in a SpicyIP article, by Swaraj Paul Barooah, about the Government of India’s intention to table the “Pesticides (Amendment) Bill” in the Parliament during the current session. The Bill purportedly includes DE provisions to be introduced in the area of agro-chemicals for a period of five years, based on the recommendations of the Standing Committee Report. It remains to be seen whether these DE provisions would slowly be extended to include pharma products also.
Conclusion
A recent statement of New York’s Attorney General, though pertaining to a different context, sums it up all: One commercial entity trying to “squeeze every last dollar out of its drug franchise with no concern about the effects on highly vulnerable patients,” is a replete reminder of the situation, should India adopt the DE provisions, in the short term. Again, keeping in mind the welfare of Indian citizens above everything else and weighing the tangible and intangible give-and-takes of the dialogue involving India’s diplomacy, the Indian government is the best authority to implement the level of regulations in the pharma and agrochemical industry.
From one side, the argument is for implementing the DE provision but from the opposite side it is a plea for freeing the access to data. Either way the government has to take cautious measures to safeguard its citizen’s interest in an efficacious, accessible and affordable way. As a recent Wall Street Journal article by Geeta Anand had opined, it is very important for the Indian government to reach the balance to stimulate innovation by rewarding it against the imperative of making life-saving inventions accessible to people, at this moment of time. India was never against intellectual property protections and never would be. But the data exclusivity provision is altogether a different ballgame.
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