A CRITICAL ANALYSIS OF INDIA’S PROBABLE DATA EXCLUSIVITY/
by Brook Baker
A CRITICAL ANALYSIS OF INDIA’S PROBABLE DATA EXCLUSIVITY/
DATA COMPENSATION PROVISIONS
Professor Brook K. Baker, Health GAP
October 20, 2006
I. INTRODUCTION
According to recent reports, on August 6, 2006, the Committee for the Protection of Undisclosed Information under Article 39.3 of the TRIPS Agreement, under the chairpersonship of Ms. Satwant Reddy, Secretary, Ministry of Chemicals and Fertilizers, finalized a proposal for a 5-year term of data exclusivity for India. Although the precise terms of the proposal have not yet been released to the public, an earlier version discussed at an Inter Ministerial meeting on May 22, 2006, is likely to have been adopted. Thus, it is important to analyze the severity of the wound India is about to inflict upon itself and its own population in terms of future access to affordable generic versions of new medicines. Likewise, it is important to analyze the knock-on affect that reduced access in India will have on poor consumers in other developing countries that have historically relied on low-price Indian generic medicines of assured quality, particularly in response to the global AIDS pandemic.
It would be logical to wonder why drug companies want data exclusivity rights in India since they have recently won product-patent rights that grant 20 years of patent protection, which ordinarily block generic competition. The answer is in fact fairly straight forward – smaller research entities and even major drug companies have not always filed patent application on drug innovations of uncertain value, especially in developing country markets.(1) Patent applications are expensive because of translation and filing fees and because annual patent maintenance fees. Since an innovator will ordinarily file its patent application long before safety and efficacy is established via clinical trials, the innovator may not want to waste patent fees on what may be a dead-end product. Whereas universities, small research companies, and even big pharma firms are willing to pay patent application and maintenance fees in large markets to hedge their bets and to preserve their monopoly interests, they are less willing to do so in smaller markets. Moreover, because India did not granted product patents until very recently, some drug companies responded by delaying introduction of a newer medicine on the market. In essence, traditional data exclusivity rules would have allowed drug companies to exclude competitors even where they had not sought or been permitted to patent their products.
Data exclusivity provisions, if added to the Indian Drugs and Cosmetic Act, will prevent India’s drug regulatory agency from referencing or otherwise relying on registration data previously filed by innovator drug companies in order to gain regulatory approval for therapeutically equivalent generic versions. Under data exclusivity rules, the Indian drug regulatory agency will have to pretend that the safety and efficacy of identical follow-on products cannot be established via proof found in the originator’s earlier submission. As a consequence, generic companies would be forced to repeat time-consuming, expensive, and unethical studies in order to receive regulatory approval during the five-year period of exclusivity. These added and unnecessary costs, delays, and ethical concerns virtually guarantee that no generic company will seek registration until the exclusivity period has expired.
Even with safeguard exceptions for data compensation (discussed further below), there might still be procedural delays and litigation bottlenecks that could impede access and/or increase the costs of essential generic products. India could avoid some of these consequences were it to adopt a simple, non-appealable formula for data percentage-based royalties. However, under more complex market-share compensation rules with required negotiations, market-share assessments, and opposition and appeal procedures, generic drugs could take years to come onto the market, and medicines would be more expensive in the interim. Either form of compensation adds to the eventual cost of medicines. On this ground and on the ground that India can and should be a leader in avoiding TRIPS-plus measures, India should avoid data-exclusivity even with a compensation option.
The WTO TRIPS Agreement does not require data exclusivity, and thus India is not obligated to adopt TRIPS-plus data exclusivity laws. The relevant portion of the TRIPS Agreement, Article 39.3,(2) only requires protection of expensive, undisclosed data submitted to drug regulatory agencies against “unfair commercial use” – basically theft or commercial espionage. Nowhere does TRIPS state that exclusive rights must be provided for a given period. In fact, TRIPS makes clear that countries may decide for themselves what constitutes “unfair commercial use” and that there are many possible approaches to satisfy this requirement. Permitting a drug regulatory authority to do its job – assuring the quality, safety, and efficacy of medicines – is not unfair commercial use; it is a mandated public service.(3)
The World Health Organization’s Commission on Intellectual Property Rights, Innovation, and Public Health recently reinforced the view that TRIPS does not require data exclusivity:
Article 39.3, unlike the case of patents, does not require the provision of specific forms of rights. It does not create property rights, nor a right to prevent others from relying on the data for marketing approval of the same product by a third party or from using the data except when unfair (dishonest) commercial practices are involved.
Prior to 1994, the U.S. tried to get its strict version of data exclusivity into the TRIPS Agreement and failed – developing country negotiators simply rejected its proposal. This “legislative history” of failure, by itself, should be enough to scuttle U.S.-inspired arguments that data exclusivity is required. Moreover, many countries have rejected data exclusivity as requirement of data protection and have instead adopted or continued more minimal forms of TRIPS-compliant data protection. These countries have never been challenged with a WTO complaint and for good reason – such a complaint would surely be considered unmeritorious. If more proof is required, the historic WTO Doha Declaration on the TRIPS Agreement and Public Health ensures the primacy of public health and further ensures that intellectual property rules do not interfere with promoting “access to medicines for all.” Even under U.S. law, the Trade Promotion Authority Act of 2002 § 2102(b)(4)(C), the U.S. is required to uphold the Doha Declaration.
The dangers of data-exclusivity on access to medicines is clear – poor consumers in India and throughout the developing world will have reduced access to the newest life-saving and life-enhancing medicines that is routinely available to their rich counterparts. Even though data exclusivity would not apply to all drugs, it would apply to the newest medicines (those involving “new chemical entities”), many of which represent therapeutic breakthroughs, such as Atazanavir, an important second-line AIDS medicine, and Tamiflu, a medicine believed to be effective against avian/human influenza. If implemented in the manner proposed, data exclusivity would apply to most of the important new medicines brought to market in India in the future. Moreover, the USTR and the R&D drug industry will continue to seek a shorter period of data exclusivity, usually three years, for new formulations and new uses of known medicines.(4) There’s no reason that Indians should not have access to affordable versions of the newest and most effective medicines even if those drugs are relatively few in number.
II. CRITIQUE OF INDIA’S FIVE-YEAR DATA EXCLUSIVITY PROPOSAL
According to available reports, India’s new data exclusivity proposal contains several safeguard provisions and exceptions:
(1) Application to “new chemical entities only”;
(2) exclusivity period running from the date of first approval anywhere in the world;
(3) requirement that a registration application be filed in India within one year of first approval elsewhere;
(4) an exception for emergencies and public health crises;
(5) an exception for drugs of mass consumption, including for HIV/AIDS, upon payment of a reasonable royalty;
(6) a compensation exception where repeat clinical trials would be unethical;
(7) an exception for reliance on data submitted elsewhere (rare);
(8) a Bolar provision allowing applications for marketing approval even during the period of data exclusivity;
(9) price control assurances;
(10) termination of exclusivity following a grant of a voluntary license by the data originator; and
(11) termination of exclusivity upon patent-term expiration.
This section will analyze and critique each of these so-called safeguard provisions.
1. Application to “new chemical entities only”
By its express provisions, Article 39.3 requires data protection only for “new chemical entities.” However, that term is not defined in TRIPS and it is subject to broader or narrower interpretations.
Under broader interpretations, “newness” would be considered only in the context of whether chemical entity has previously been approved in a pharmaceutical product in the Indian market. Under a stricter or narrower interpretation, “newness” would be considered in reference to any previous approval or commercialization anywhere in the world. Likewise, newness could be interpreted liberally or strictly with respect to variations in the form of the chemical entity. Overly liberal definitions of new chemical entities would encourage evergreening of data exclusivity by introduction of minor variations in the base chemical entity. Strict definitions would provide data exclusivity only once and only for truly unique chemical entities.
India’s current regulatory scheme with respect to registration is wholly inadequate.(5) Nonetheless, India remains free to adopt its own interpretation of “new chemical entity” and could wisely choose the narrowest possible definition,(6) such as the following:
A new chemical entity means a drug that contains no active moiety and which has not been known to exist previously in India or any other part of the world. For the purpose of this rule, active moiety means the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance.
However, even this narrow definition could not prevent a likely period of marketing exclusivity for many new and important pharmaceutical products.
2. Exclusivity from the first date of approval anywhere in the world
The May 22 data-exclusivity proposal contained a provision that the period of data exclusivity would commence from the date of first approval of the new chemical entity for pharmaceutical use anywhere in the world. Drug companies at present routinely introduce their products first to rich-country markets in the United States, Europe, and Japan. This stop-the-clock provision would promote early introduction of the new product to the Indian market by penalizing drug companies for their own controllable delays in seeking product registration and marketing approval in India. Although this clause would not eliminate the total five-year period during which Indian consumers would not have access to the newest medicines, it would ensure that they did not suffer interminable delays – long delays in seeking approval followed by five long years of data exclusivity.
3. Requirement that a registration application be filed within one year of first approval anywhere in the world
A related provision requires that a drug company file its registration application within one year or thereby lose its right to claim that the chemical entity is new. In many respects, this provision would operate like the one-year rule in the Paris Treaty, which allows innovators a one-year grace period during which to file patent applications elsewhere in the world after their initial, first filing. The one-year patent grace period allows the patent applicant to claim novelty and to solve the inevitable bureaucratic difficulties of multiple filings.
Although it is a positive restriction to grant drug companies a one-year-only grace period rather than let them avoid a market for a long time and then still seek data exclusivity long after the drug has been in use elsewhere in the world, the one-year, use-it-or-lose-it grace period does not ultimately shorten the five-year period of exclusivity.
4. An exception for emergencies and public health crises
The proposal is likely to have an express exception for publicly declared emergencies and public health crises. Of course, there will be questions about who or which agencies will be permitted to declare such emergencies or crises and about their duration, but the larger question is why this exception should be limited to extreme circumstances. It would be much preferable if the data exclusivity provision, if any, would include an express exception for any circumstance in which a compulsory license or government use order has been issued in compliance with the India Patent Act as amended in 2005. That Act permits specials procedures for compulsory licenses granted to addressed emergencies and matters of extreme urgency, but it also allows compulsory licenses on many other grounds: government, non-commercial use, public health needs, competition, and export to countries lacking domestic manufacturing capacity. None of these flexibilities should be forestalled because of data exclusivity.
5. An exception for drugs of mass consumption, including for HIV/AIDS, upon payment of a reasonable royalty
A compensation exception limited to medicines of mass consumption simply does not make sense. The Gleevec case is a perfect example of a medicine critical to the survival of a small number of cancer patients and where monopoly pricing rendered treatment unaffordable except for the richest minority. In fact, drug prices are often set higher for drugs with small consumer bases. Patients suffering from relatively rare diseases have the same interests as patients of pandemics in accessing affordable medicines.
If a compensation system makes sense at all – a contested issue – it only makes sense if it is potentially available, and affordable, across a broad range of products through an easy to administer system.(7) The major justification for such a compensation system – even though it would be TRIPS-plus – would be to counteract drug companies’ claims that their investments are being “taken” without just compensation. The easiest to administer system would be one involving a modest percentage royalty fee based on Indian domestic sales without regard to the drug company’s R&D investment. A more complicated, and far less desirable, compensation scheme could require computation of relevant research and development expenditures and further calculations of market shares, and might even involve requirements for royalty negotiations, opposition procedures, and appeals. Such complex compensation schemes, even ones involving arbitration, can be laborious and slow.(8) They also raise a troubling degree of uncertainty about future costs that can greatly complicate economic forecasting and market entry by generic companies.
Any and all royalty or cost-sharing compensation schemes are problematic when compared to a baseline, TRIPS-compliant right to avoid data exclusivity altogether. As a preliminary matter, it is well established that major drug producers recoup their research and development expenditures in rich country markets in the U.S., Europe, and Japan.(9) Drug company profits continue to soar and continue to exceed R&D investments even though there has not been data exclusivity or compensation in most developing countries. Moreover, what drug companies call necessary and related research and development is a highly contested matter. Much drug research is focused on me-too drugs, on efforts to increase market share, and on efforts to make misleading claims for expanded use. Finally, research and development incentives from Indian market sales are insignificant on a global scale – the entire subcontinent comprises less than 1.3% of global pharmaceutical sales. Indeed, Africa and Asia combined total only 5.1% of global sales and all developing countries lumped together total roughly 11% of the global market.
In sum, the most desirable outcome would be no data exclusivity and no data compensation. India should be a global leader in resisting TRIPS-plus measures, particularly on a voluntary basis. If India stands up and resists U.S.-sponsored pressure for data exclusivity that will embolden other developing countries, including those involved in U.S. free trade negotiations.
6. A compensation exception where repeat clinical trials would be unethical
The truth of the matter is that clinical trials for generic equivalents of previously approved pharmaceutical products will always be unethical. Clinical trials are only justified where there is a legitimate scientific inquiry concerning the safety and efficacy of an investigational new product. However, once that safety and efficacy of the new product has been established the only scientifically valid studies of the follow-on equivalent are whether it is produced according to required quality standards and whether it is therapeutically equivalent to the original product, usually via bio-equivalence studies. The clinical-trial exception makes it sound like there is some subset of medicines where unnecessary and duplicative trials are ethical. To the contrary, exposing human subjects to placebo-based clinical trials when the drug being investigated is already known to be safe and effective is a gross violation of human rights and investigational ethics and enormous waste of medical and economic resources. It should not be tolerated let alone condoned.
7. A rare exception for reliance on data submitted elsewhere
India may well be advised to amend its drug regulatory scheme to permit more reliance on previous registration by stringent drug regulatory authorities or even on WHO pre-qualification. Vicarious reliance on the work of other highly capable drug regulatory authorities would reduce the burden on Indian regulators and also speed up the approval process. At present, India requires separate clinical trials on Indian patients, but this requirement seems unnecessary in the vast majority of cases. There is little need for India-specific studies to establish safety and efficacy for Indian people whose human biological diversity (and fundamental similarity) closely matches that in the rest of the world.
Reliance on foreign registration may certainly be beneficial in circumstances where a pharmaceutical product has not yet been brought to the Indian market and a generic producer stands ready to produce, import, or sell the product in India. (Note: the product’s patent status in India may adversely affect such an effort.) Alternatively, an importer could be seeking to use parallel importation rights to import a previously unregistered brand-name product. These producers or importers who are striving to bring new drugs to the Indian market should not be forestalled by the originator’s reluctance or delay in seeking approval in India. Thus, the idea that this should be a rare exception is probably misguided, though it is also true that data exclusivity would not be an issue if there were a more than one year delay in an Indian application for data exclusivity (see point 3 above).
8. A Bolar provision allowing applications for marketing approval even during the period of data exclusivity
The proposal is likely to contain a research exception and an exception to permit applications for marketing approval during the period of data exclusivity even though the actual grant will not occur until after the period expires. Clearly, it is desirable to allow follow-on producers to conduct research on product formulation, conduct stability experiments, and undertake bioequivalence studies. This advance work can permit the generic company to prepare a registration dossier for submission to the drug regulatory agency even during the period of exclusivity. Under the proposal the drug regulatory authority will be permitted to examine the application and rely on data previously filed by the data originator, but the drug regulatory authority will only be permitted to grant tentative approval. Final approval will be granted only after the period of exclusivity expires, but at the very least the new product might be brought onto the market very quickly rather than having to wait for an additional period of regulatory delay.
9. Vague price control assurances
Under the proposal, the Government says it will create a suitable mechanism to ensure that the prices of such new drugs continue to remain reasonable so that there is a wider coverage as far as the patients are concerned. The details of this mechanism are unspecified, and without specifications the threat of price controls offers little protection against the threat of rising drug prices, especially since the record of Indian price controls is not entirely reassuring. Moreover, since Indians continue to pay for the majority of drug costs out-of-pocket, higher prices will inevitably lead to lower usage, especially for poor Indian who live on less than $2/day.
10. Termination of exclusivity following a grant of a voluntary license by the data originator
Any authorization of a generic by the data exclusivity holder would automatically terminate data exclusivity for all producers. Whether the authorization applies only to voluntary licensees or whether it also covers the data holder’s launch of a generic version of its own product is uncertain. In the U.S., drug companies are beginning to launch official generic versions of their own drugs shortly before patent expiration in order to gain market share in the generic and in some instances to prevent a competing generic from gaining six months of exclusivity under U.S. law. There is no comparable, first-generic entrant rule in India, but the proposed provision is designed to prevent de facto market share control by the data holder and therefore to encourage entry by multiple generic competitors. This competition will have a favorable impact on prices.
11. Termination of the period of data exclusivity upon termination of the patent term.
India is proposing to ensure that the period of data exclusivity never extends beyond the term of patent protection. This clause could be significant for products that enter the market very late in their patent term – a condition that may apply in the short term to drugs in the Indian “mailbox” if there are additional long delays in granting patents (post-1995 innovations have been held in India’s mailbox until the new 2005 Patent Act Amendments.) This provision directly contradicts terms that the U.S. is seeking in its free trade agreement negotiations, so India might receive blow-back from U.S. authorities and PhRMA officials.(10)
III. CONCLUSION
India has attempted to soften the perverse effects of its unnecessary adoption of data exclusivity by engrafting multiple safeguard provisions and exceptions. Although it is true that these provisions ameliorate the harshest features of the proposal and grant some exceptions to data exclusivity, individually and collectively they do not mean that India is making a wise policy choice. The TRIPS Agreement does not require a grant of data exclusivity nor does the interest of India’s own pharmaceutical industry, which does not currently invest strongly in new chemical entity research and which can recoup its investments through data exclusivity granted in the U.S. and Europe. By granting data exclusivity, even with safeguards, India is allowing another form of monopoly market protection that will inevitably result in higher prices. Even worse, in some identified circumstances, it will prevent effective utilization of TRIPS-compliant flexibilities by preventing domestic registration of medicines for which compulsory licenses have been granted. Although the adverse policy consequences of this self-inflicted wound will fall primarily on poor Indian consumers, the adverse consequences could be felt in other developing countries as well. To the extent that Indian generic producers rely on marketing rights in India in order to produce medicines for exportation, domestic data exclusivity rules can deter generic entry into the production-for-export market. Likewise, since some countries require registration in the manufacturing country before granting marketing approval for an imported drug, data exclusivity in India may further delay life-saving access to generic medicines in other developing countries.
The best outcome would be for patients, public health and human rights practitioners, AIDS activists, and other progressive political forces in India to combine forces in opposing the adoption of data exclusivity. International activists should support Indian opponents in their campaign to resist U.S. and drug company pressure on India and to defeat data exclusivity during the legislative process. This is a matter of urgency as lives are at stake.
Endnotes:
(1) See, Shoibal Mukherjee, Here’s a penny for your pill (8 August 2006) available at http://www.hindustantimes.com/onlineCDA/PFVersion.jsp?article=http://10.81.141.122/news/181_1764059,00020008.htm#.
(2) Article 39.3 of the trips Agreement reads:
Member when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products with utilize new chemical entries, the submission of undisclosed test or other data, the origination of which involves a considerable effort, shall protect such data against unfair commercial use. In addition, Members shall protect such data against disclosure, except where necessary to protect the public or unless steps are taken to ensure that the data are protected against unfair commercial use.
(3) Carlos Correa, Protection of Data Submitted for the Registration of Pharmaceuticals: Implementing the Standards of the TRIPS Agreement (2002); cf. Aaron X. Fellmeth, Secrecy, Monopoly, and Access to Pharmaceuticals in International Trade Law: Protection of Marketing Approval Data under the TRIPS Agreement, 45 Harv. Int’l L.J. 443 (2004); contra G. Lee Skillington & Eric M. Solovy, The Protection of Test and Other Data Required by Article 39.3 of the TRIPS Agreement, 24 Nw. J. Int’l L. & Bus. 1 (2003).
(4) Drug companies justify getting data exclusivity for new uses and new formulations of old chemical entities to incentivize clinical trials into expanded uses of previous medicines and into development of more patient-friendly formulations. In some countries, such new uses and new formulations will be patentable, but not under India’s 2005 Patent Act, unless they show significant therapeutic advantages. Accordingly, gaining three-year exclusivity will be a high priority goal for the pharmaceutical lobby and its USTR proxies – it will be the only way they can gain monopoly status and market exclusivity for some of their unpatentable products.
(5) Under Rule 122-E of the DCA Rules (1945), a “new drug” is defined as: (a) a bulk drug substance which has not been used in the country to any significant extent and has not been recognised as safe and effective by the licensing authority; (b) a drug that is already approved by the licensing authority which is now proposed to be marketed with modified or new claims, namely, indications, dosage, dosage form (including sustained release dosage form), route of administration; or (c) a fixed dose combination of two or more drugs, individually approved for certain claims, which are now proposed to be combined for the first time in a fixed ratio, or if the ratio of ingredients in an already marketed combination is proposed to be changed, with certain claims, namely, indications, dosage, dosage form (including sustained release dosage form), and route of administration. For the purpose of the Rules, all vaccines shall be new drugs unless otherwise certified and a new drug shall continue to be considered a new drug for a period of four years from the date of first approval or its inclusion in the Indian Pharmacopoeia, whichever is earlier.
(6) See, Initiative for Medicines, Access & Knowledge, The Impact of Article 39.3 in India: A Practical Perspective, 30 (2006); cf. http://www.fda.gov/cder/about/smallbiz/exclusivity.htm.
(7) Judit Rius Sanjuan, James Love & Robert Weissman, A cost sharing model to protect investments in pharmaceutical test data, CPTech Policy Brief No. 1 (Revised: 18 May 2006).
(8) I-MAK, supra note 6, has listed the following questions and concerns:
• How royalty standards are set. This would include identifying and explicitly setting out the costs that would be subject to compensation. For example, guidelines should be provided that clarify whether costs relating to failed trials form part of an assessment for compensation.
• What mechanisms would be utilised for government verification of originator claims, possibly including the creation of a specific authority set up under the Ministry of Health and/or Drug Controller General in India.
• How to catalyse access to undisclosed information relating to the cost of clinical trials and market-share data.
• What laws exist relating to the discovery of costs of clinical trials and market share data.
• How to devise mechanisms that will monitor effectively the amount of compensation the originator will receive, and whether the amount exceeds the original investment.
• What cap should be set on compensation and the percentage of original investment that can be recouped by originator, e.g. 80% as suggested by Fellmeth. Effectiveness and Procedural Aspects of Arbitration/Litigation
• How to ensure that production of medicines is permitted during arbitration and litigation so that extended administrative procedures do not become a bar to competition.
• Whether a specialist arbitration panel composed of public health experts is needed for such arbitration.
• How to prevent delay by expediting arbitration and litigation in compensation cases.
• How and whether appeals can be made from arbitration decisions.
• What the relative bargaining position of different market players is likely to be at the commencement of arbitration, and how this will affect competition.
• How to prevent “gaming” of a market share system—for example, where an originator refrains from selling a drug after obtaining marketing approval, the generic company pays 100% of the costs of the data for that drug.
• What the impact of artificial barriers will be to market entry on economic growth.
• Whether Indian industry is able to share in the costs of original investment, given that clinical trials will often have been conducted in the United States or Europe where costs are much greater, and whether the expense for Indian manufacturers would be prohibitive.
• How market share will be measured, and when will it be measured, because if assessments are not predictable, Indian manufacturers will not be able to assess risks or costs/benefits and make informed business decisions.
• Which Ministry will be responsible for monitoring implementation of the cost-sharing model, and other significant administrative aspects of this model, and how cumbersome these burdens will be to implement in practice.
To this list one could add questions about whether market share will be based on dollar volume of sales or pill volume of sales and how India would acknowledge or assess market share of later entrants?
(9) See Donald W. Light & Joel Lexchin, Foreign Free Riders and the High Prices of U.S. Patented Drugs, 331 British Med. J, 958-60 (2005).
(10) One of the primary rationales for data exclusivity from the U.S. perspective is that it allows a guaranteed period of market exclusivity and monopoly pricing even if a patent was never filed or if a granted patent has expired.
A CRITICAL ANALYSIS OF INDIA’S PROBABLE DATA EXCLUSIVITY/
DATA COMPENSATION PROVISIONS
Professor Brook K. Baker, Health GAP
October 20, 2006
I. INTRODUCTION
According to recent reports, on August 6, 2006, the Committee for the Protection of Undisclosed Information under Article 39.3 of the TRIPS Agreement, under the chairpersonship of Ms. Satwant Reddy, Secretary, Ministry of Chemicals and Fertilizers, finalized a proposal for a 5-year term of data exclusivity for India. Although the precise terms of the proposal have not yet been released to the public, an earlier version discussed at an Inter Ministerial meeting on May 22, 2006, is likely to have been adopted. Thus, it is important to analyze the severity of the wound India is about to inflict upon itself and its own population in terms of future access to affordable generic versions of new medicines. Likewise, it is important to analyze the knock-on affect that reduced access in India will have on poor consumers in other developing countries that have historically relied on low-price Indian generic medicines of assured quality, particularly in response to the global AIDS pandemic.
It would be logical to wonder why drug companies want data exclusivity rights in India since they have recently won product-patent rights that grant 20 years of patent protection, which ordinarily block generic competition. The answer is in fact fairly straight forward – smaller research entities and even major drug companies have not always filed patent application on drug innovations of uncertain value, especially in developing country markets.(1) Patent applications are expensive because of translation and filing fees and because annual patent maintenance fees. Since an innovator will ordinarily file its patent application long before safety and efficacy is established via clinical trials, the innovator may not want to waste patent fees on what may be a dead-end product. Whereas universities, small research companies, and even big pharma firms are willing to pay patent application and maintenance fees in large markets to hedge their bets and to preserve their monopoly interests, they are less willing to do so in smaller markets. Moreover, because India did not granted product patents until very recently, some drug companies responded by delaying introduction of a newer medicine on the market. In essence, traditional data exclusivity rules would have allowed drug companies to exclude competitors even where they had not sought or been permitted to patent their products.
Data exclusivity provisions, if added to the Indian Drugs and Cosmetic Act, will prevent India’s drug regulatory agency from referencing or otherwise relying on registration data previously filed by innovator drug companies in order to gain regulatory approval for therapeutically equivalent generic versions. Under data exclusivity rules, the Indian drug regulatory agency will have to pretend that the safety and efficacy of identical follow-on products cannot be established via proof found in the originator’s earlier submission. As a consequence, generic companies would be forced to repeat time-consuming, expensive, and unethical studies in order to receive regulatory approval during the five-year period of exclusivity. These added and unnecessary costs, delays, and ethical concerns virtually guarantee that no generic company will seek registration until the exclusivity period has expired.
Even with safeguard exceptions for data compensation (discussed further below), there might still be procedural delays and litigation bottlenecks that could impede access and/or increase the costs of essential generic products. India could avoid some of these consequences were it to adopt a simple, non-appealable formula for data percentage-based royalties. However, under more complex market-share compensation rules with required negotiations, market-share assessments, and opposition and appeal procedures, generic drugs could take years to come onto the market, and medicines would be more expensive in the interim. Either form of compensation adds to the eventual cost of medicines. On this ground and on the ground that India can and should be a leader in avoiding TRIPS-plus measures, India should avoid data-exclusivity even with a compensation option.
The WTO TRIPS Agreement does not require data exclusivity, and thus India is not obligated to adopt TRIPS-plus data exclusivity laws. The relevant portion of the TRIPS Agreement, Article 39.3,(2) only requires protection of expensive, undisclosed data submitted to drug regulatory agencies against “unfair commercial use” – basically theft or commercial espionage. Nowhere does TRIPS state that exclusive rights must be provided for a given period. In fact, TRIPS makes clear that countries may decide for themselves what constitutes “unfair commercial use” and that there are many possible approaches to satisfy this requirement. Permitting a drug regulatory authority to do its job – assuring the quality, safety, and efficacy of medicines – is not unfair commercial use; it is a mandated public service.(3)
The World Health Organization’s Commission on Intellectual Property Rights, Innovation, and Public Health recently reinforced the view that TRIPS does not require data exclusivity:
Article 39.3, unlike the case of patents, does not require the provision of specific forms of rights. It does not create property rights, nor a right to prevent others from relying on the data for marketing approval of the same product by a third party or from using the data except when unfair (dishonest) commercial practices are involved.
Prior to 1994, the U.S. tried to get its strict version of data exclusivity into the TRIPS Agreement and failed – developing country negotiators simply rejected its proposal. This “legislative history” of failure, by itself, should be enough to scuttle U.S.-inspired arguments that data exclusivity is required. Moreover, many countries have rejected data exclusivity as requirement of data protection and have instead adopted or continued more minimal forms of TRIPS-compliant data protection. These countries have never been challenged with a WTO complaint and for good reason – such a complaint would surely be considered unmeritorious. If more proof is required, the historic WTO Doha Declaration on the TRIPS Agreement and Public Health ensures the primacy of public health and further ensures that intellectual property rules do not interfere with promoting “access to medicines for all.” Even under U.S. law, the Trade Promotion Authority Act of 2002 § 2102(b)(4)(C), the U.S. is required to uphold the Doha Declaration.
The dangers of data-exclusivity on access to medicines is clear – poor consumers in India and throughout the developing world will have reduced access to the newest life-saving and life-enhancing medicines that is routinely available to their rich counterparts. Even though data exclusivity would not apply to all drugs, it would apply to the newest medicines (those involving “new chemical entities”), many of which represent therapeutic breakthroughs, such as Atazanavir, an important second-line AIDS medicine, and Tamiflu, a medicine believed to be effective against avian/human influenza. If implemented in the manner proposed, data exclusivity would apply to most of the important new medicines brought to market in India in the future. Moreover, the USTR and the R&D drug industry will continue to seek a shorter period of data exclusivity, usually three years, for new formulations and new uses of known medicines.(4) There’s no reason that Indians should not have access to affordable versions of the newest and most effective medicines even if those drugs are relatively few in number.
II. CRITIQUE OF INDIA’S FIVE-YEAR DATA EXCLUSIVITY PROPOSAL
According to available reports, India’s new data exclusivity proposal contains several safeguard provisions and exceptions:
(1) Application to “new chemical entities only”;
(2) exclusivity period running from the date of first approval anywhere in the world;
(3) requirement that a registration application be filed in India within one year of first approval elsewhere;
(4) an exception for emergencies and public health crises;
(5) an exception for drugs of mass consumption, including for HIV/AIDS, upon payment of a reasonable royalty;
(6) a compensation exception where repeat clinical trials would be unethical;
(7) an exception for reliance on data submitted elsewhere (rare);
(8) a Bolar provision allowing applications for marketing approval even during the period of data exclusivity;
(9) price control assurances;
(10) termination of exclusivity following a grant of a voluntary license by the data originator; and
(11) termination of exclusivity upon patent-term expiration.
This section will analyze and critique each of these so-called safeguard provisions.
1. Application to “new chemical entities only”
By its express provisions, Article 39.3 requires data protection only for “new chemical entities.” However, that term is not defined in TRIPS and it is subject to broader or narrower interpretations.
Under broader interpretations, “newness” would be considered only in the context of whether chemical entity has previously been approved in a pharmaceutical product in the Indian market. Under a stricter or narrower interpretation, “newness” would be considered in reference to any previous approval or commercialization anywhere in the world. Likewise, newness could be interpreted liberally or strictly with respect to variations in the form of the chemical entity. Overly liberal definitions of new chemical entities would encourage evergreening of data exclusivity by introduction of minor variations in the base chemical entity. Strict definitions would provide data exclusivity only once and only for truly unique chemical entities.
India’s current regulatory scheme with respect to registration is wholly inadequate.(5) Nonetheless, India remains free to adopt its own interpretation of “new chemical entity” and could wisely choose the narrowest possible definition,(6) such as the following:
A new chemical entity means a drug that contains no active moiety and which has not been known to exist previously in India or any other part of the world. For the purpose of this rule, active moiety means the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance.
However, even this narrow definition could not prevent a likely period of marketing exclusivity for many new and important pharmaceutical products.
2. Exclusivity from the first date of approval anywhere in the world
The May 22 data-exclusivity proposal contained a provision that the period of data exclusivity would commence from the date of first approval of the new chemical entity for pharmaceutical use anywhere in the world. Drug companies at present routinely introduce their products first to rich-country markets in the United States, Europe, and Japan. This stop-the-clock provision would promote early introduction of the new product to the Indian market by penalizing drug companies for their own controllable delays in seeking product registration and marketing approval in India. Although this clause would not eliminate the total five-year period during which Indian consumers would not have access to the newest medicines, it would ensure that they did not suffer interminable delays – long delays in seeking approval followed by five long years of data exclusivity.
3. Requirement that a registration application be filed within one year of first approval anywhere in the world
A related provision requires that a drug company file its registration application within one year or thereby lose its right to claim that the chemical entity is new. In many respects, this provision would operate like the one-year rule in the Paris Treaty, which allows innovators a one-year grace period during which to file patent applications elsewhere in the world after their initial, first filing. The one-year patent grace period allows the patent applicant to claim novelty and to solve the inevitable bureaucratic difficulties of multiple filings.
Although it is a positive restriction to grant drug companies a one-year-only grace period rather than let them avoid a market for a long time and then still seek data exclusivity long after the drug has been in use elsewhere in the world, the one-year, use-it-or-lose-it grace period does not ultimately shorten the five-year period of exclusivity.
4. An exception for emergencies and public health crises
The proposal is likely to have an express exception for publicly declared emergencies and public health crises. Of course, there will be questions about who or which agencies will be permitted to declare such emergencies or crises and about their duration, but the larger question is why this exception should be limited to extreme circumstances. It would be much preferable if the data exclusivity provision, if any, would include an express exception for any circumstance in which a compulsory license or government use order has been issued in compliance with the India Patent Act as amended in 2005. That Act permits specials procedures for compulsory licenses granted to addressed emergencies and matters of extreme urgency, but it also allows compulsory licenses on many other grounds: government, non-commercial use, public health needs, competition, and export to countries lacking domestic manufacturing capacity. None of these flexibilities should be forestalled because of data exclusivity.
5. An exception for drugs of mass consumption, including for HIV/AIDS, upon payment of a reasonable royalty
A compensation exception limited to medicines of mass consumption simply does not make sense. The Gleevec case is a perfect example of a medicine critical to the survival of a small number of cancer patients and where monopoly pricing rendered treatment unaffordable except for the richest minority. In fact, drug prices are often set higher for drugs with small consumer bases. Patients suffering from relatively rare diseases have the same interests as patients of pandemics in accessing affordable medicines.
If a compensation system makes sense at all – a contested issue – it only makes sense if it is potentially available, and affordable, across a broad range of products through an easy to administer system.(7) The major justification for such a compensation system – even though it would be TRIPS-plus – would be to counteract drug companies’ claims that their investments are being “taken” without just compensation. The easiest to administer system would be one involving a modest percentage royalty fee based on Indian domestic sales without regard to the drug company’s R&D investment. A more complicated, and far less desirable, compensation scheme could require computation of relevant research and development expenditures and further calculations of market shares, and might even involve requirements for royalty negotiations, opposition procedures, and appeals. Such complex compensation schemes, even ones involving arbitration, can be laborious and slow.(8) They also raise a troubling degree of uncertainty about future costs that can greatly complicate economic forecasting and market entry by generic companies.
Any and all royalty or cost-sharing compensation schemes are problematic when compared to a baseline, TRIPS-compliant right to avoid data exclusivity altogether. As a preliminary matter, it is well established that major drug producers recoup their research and development expenditures in rich country markets in the U.S., Europe, and Japan.(9) Drug company profits continue to soar and continue to exceed R&D investments even though there has not been data exclusivity or compensation in most developing countries. Moreover, what drug companies call necessary and related research and development is a highly contested matter. Much drug research is focused on me-too drugs, on efforts to increase market share, and on efforts to make misleading claims for expanded use. Finally, research and development incentives from Indian market sales are insignificant on a global scale – the entire subcontinent comprises less than 1.3% of global pharmaceutical sales. Indeed, Africa and Asia combined total only 5.1% of global sales and all developing countries lumped together total roughly 11% of the global market.
In sum, the most desirable outcome would be no data exclusivity and no data compensation. India should be a global leader in resisting TRIPS-plus measures, particularly on a voluntary basis. If India stands up and resists U.S.-sponsored pressure for data exclusivity that will embolden other developing countries, including those involved in U.S. free trade negotiations.
6. A compensation exception where repeat clinical trials would be unethical
The truth of the matter is that clinical trials for generic equivalents of previously approved pharmaceutical products will always be unethical. Clinical trials are only justified where there is a legitimate scientific inquiry concerning the safety and efficacy of an investigational new product. However, once that safety and efficacy of the new product has been established the only scientifically valid studies of the follow-on equivalent are whether it is produced according to required quality standards and whether it is therapeutically equivalent to the original product, usually via bio-equivalence studies. The clinical-trial exception makes it sound like there is some subset of medicines where unnecessary and duplicative trials are ethical. To the contrary, exposing human subjects to placebo-based clinical trials when the drug being investigated is already known to be safe and effective is a gross violation of human rights and investigational ethics and enormous waste of medical and economic resources. It should not be tolerated let alone condoned.
7. A rare exception for reliance on data submitted elsewhere
India may well be advised to amend its drug regulatory scheme to permit more reliance on previous registration by stringent drug regulatory authorities or even on WHO pre-qualification. Vicarious reliance on the work of other highly capable drug regulatory authorities would reduce the burden on Indian regulators and also speed up the approval process. At present, India requires separate clinical trials on Indian patients, but this requirement seems unnecessary in the vast majority of cases. There is little need for India-specific studies to establish safety and efficacy for Indian people whose human biological diversity (and fundamental similarity) closely matches that in the rest of the world.
Reliance on foreign registration may certainly be beneficial in circumstances where a pharmaceutical product has not yet been brought to the Indian market and a generic producer stands ready to produce, import, or sell the product in India. (Note: the product’s patent status in India may adversely affect such an effort.) Alternatively, an importer could be seeking to use parallel importation rights to import a previously unregistered brand-name product. These producers or importers who are striving to bring new drugs to the Indian market should not be forestalled by the originator’s reluctance or delay in seeking approval in India. Thus, the idea that this should be a rare exception is probably misguided, though it is also true that data exclusivity would not be an issue if there were a more than one year delay in an Indian application for data exclusivity (see point 3 above).
8. A Bolar provision allowing applications for marketing approval even during the period of data exclusivity
The proposal is likely to contain a research exception and an exception to permit applications for marketing approval during the period of data exclusivity even though the actual grant will not occur until after the period expires. Clearly, it is desirable to allow follow-on producers to conduct research on product formulation, conduct stability experiments, and undertake bioequivalence studies. This advance work can permit the generic company to prepare a registration dossier for submission to the drug regulatory agency even during the period of exclusivity. Under the proposal the drug regulatory authority will be permitted to examine the application and rely on data previously filed by the data originator, but the drug regulatory authority will only be permitted to grant tentative approval. Final approval will be granted only after the period of exclusivity expires, but at the very least the new product might be brought onto the market very quickly rather than having to wait for an additional period of regulatory delay.
9. Vague price control assurances
Under the proposal, the Government says it will create a suitable mechanism to ensure that the prices of such new drugs continue to remain reasonable so that there is a wider coverage as far as the patients are concerned. The details of this mechanism are unspecified, and without specifications the threat of price controls offers little protection against the threat of rising drug prices, especially since the record of Indian price controls is not entirely reassuring. Moreover, since Indians continue to pay for the majority of drug costs out-of-pocket, higher prices will inevitably lead to lower usage, especially for poor Indian who live on less than $2/day.
10. Termination of exclusivity following a grant of a voluntary license by the data originator
Any authorization of a generic by the data exclusivity holder would automatically terminate data exclusivity for all producers. Whether the authorization applies only to voluntary licensees or whether it also covers the data holder’s launch of a generic version of its own product is uncertain. In the U.S., drug companies are beginning to launch official generic versions of their own drugs shortly before patent expiration in order to gain market share in the generic and in some instances to prevent a competing generic from gaining six months of exclusivity under U.S. law. There is no comparable, first-generic entrant rule in India, but the proposed provision is designed to prevent de facto market share control by the data holder and therefore to encourage entry by multiple generic competitors. This competition will have a favorable impact on prices.
11. Termination of the period of data exclusivity upon termination of the patent term.
India is proposing to ensure that the period of data exclusivity never extends beyond the term of patent protection. This clause could be significant for products that enter the market very late in their patent term – a condition that may apply in the short term to drugs in the Indian “mailbox” if there are additional long delays in granting patents (post-1995 innovations have been held in India’s mailbox until the new 2005 Patent Act Amendments.) This provision directly contradicts terms that the U.S. is seeking in its free trade agreement negotiations, so India might receive blow-back from U.S. authorities and PhRMA officials.(10)
III. CONCLUSION
India has attempted to soften the perverse effects of its unnecessary adoption of data exclusivity by engrafting multiple safeguard provisions and exceptions. Although it is true that these provisions ameliorate the harshest features of the proposal and grant some exceptions to data exclusivity, individually and collectively they do not mean that India is making a wise policy choice. The TRIPS Agreement does not require a grant of data exclusivity nor does the interest of India’s own pharmaceutical industry, which does not currently invest strongly in new chemical entity research and which can recoup its investments through data exclusivity granted in the U.S. and Europe. By granting data exclusivity, even with safeguards, India is allowing another form of monopoly market protection that will inevitably result in higher prices. Even worse, in some identified circumstances, it will prevent effective utilization of TRIPS-compliant flexibilities by preventing domestic registration of medicines for which compulsory licenses have been granted. Although the adverse policy consequences of this self-inflicted wound will fall primarily on poor Indian consumers, the adverse consequences could be felt in other developing countries as well. To the extent that Indian generic producers rely on marketing rights in India in order to produce medicines for exportation, domestic data exclusivity rules can deter generic entry into the production-for-export market. Likewise, since some countries require registration in the manufacturing country before granting marketing approval for an imported drug, data exclusivity in India may further delay life-saving access to generic medicines in other developing countries.
The best outcome would be for patients, public health and human rights practitioners, AIDS activists, and other progressive political forces in India to combine forces in opposing the adoption of data exclusivity. International activists should support Indian opponents in their campaign to resist U.S. and drug company pressure on India and to defeat data exclusivity during the legislative process. This is a matter of urgency as lives are at stake.
Endnotes:
(1) See, Shoibal Mukherjee, Here’s a penny for your pill (8 August 2006) available at http://www.hindustantimes.com/onlineCDA/PFVersion.jsp?article=http://10.81.141.122/news/181_1764059,00020008.htm#.
(2) Article 39.3 of the trips Agreement reads:
Member when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products with utilize new chemical entries, the submission of undisclosed test or other data, the origination of which involves a considerable effort, shall protect such data against unfair commercial use. In addition, Members shall protect such data against disclosure, except where necessary to protect the public or unless steps are taken to ensure that the data are protected against unfair commercial use.
(3) Carlos Correa, Protection of Data Submitted for the Registration of Pharmaceuticals: Implementing the Standards of the TRIPS Agreement (2002); cf. Aaron X. Fellmeth, Secrecy, Monopoly, and Access to Pharmaceuticals in International Trade Law: Protection of Marketing Approval Data under the TRIPS Agreement, 45 Harv. Int’l L.J. 443 (2004); contra G. Lee Skillington & Eric M. Solovy, The Protection of Test and Other Data Required by Article 39.3 of the TRIPS Agreement, 24 Nw. J. Int’l L. & Bus. 1 (2003).
(4) Drug companies justify getting data exclusivity for new uses and new formulations of old chemical entities to incentivize clinical trials into expanded uses of previous medicines and into development of more patient-friendly formulations. In some countries, such new uses and new formulations will be patentable, but not under India’s 2005 Patent Act, unless they show significant therapeutic advantages. Accordingly, gaining three-year exclusivity will be a high priority goal for the pharmaceutical lobby and its USTR proxies – it will be the only way they can gain monopoly status and market exclusivity for some of their unpatentable products.
(5) Under Rule 122-E of the DCA Rules (1945), a “new drug” is defined as: (a) a bulk drug substance which has not been used in the country to any significant extent and has not been recognised as safe and effective by the licensing authority; (b) a drug that is already approved by the licensing authority which is now proposed to be marketed with modified or new claims, namely, indications, dosage, dosage form (including sustained release dosage form), route of administration; or (c) a fixed dose combination of two or more drugs, individually approved for certain claims, which are now proposed to be combined for the first time in a fixed ratio, or if the ratio of ingredients in an already marketed combination is proposed to be changed, with certain claims, namely, indications, dosage, dosage form (including sustained release dosage form), and route of administration. For the purpose of the Rules, all vaccines shall be new drugs unless otherwise certified and a new drug shall continue to be considered a new drug for a period of four years from the date of first approval or its inclusion in the Indian Pharmacopoeia, whichever is earlier.
(6) See, Initiative for Medicines, Access & Knowledge, The Impact of Article 39.3 in India: A Practical Perspective, 30 (2006); cf. http://www.fda.gov/cder/about/smallbiz/exclusivity.htm.
(7) Judit Rius Sanjuan, James Love & Robert Weissman, A cost sharing model to protect investments in pharmaceutical test data, CPTech Policy Brief No. 1 (Revised: 18 May 2006).
(8) I-MAK, supra note 6, has listed the following questions and concerns:
• How royalty standards are set. This would include identifying and explicitly setting out the costs that would be subject to compensation. For example, guidelines should be provided that clarify whether costs relating to failed trials form part of an assessment for compensation.
• What mechanisms would be utilised for government verification of originator claims, possibly including the creation of a specific authority set up under the Ministry of Health and/or Drug Controller General in India.
• How to catalyse access to undisclosed information relating to the cost of clinical trials and market-share data.
• What laws exist relating to the discovery of costs of clinical trials and market share data.
• How to devise mechanisms that will monitor effectively the amount of compensation the originator will receive, and whether the amount exceeds the original investment.
• What cap should be set on compensation and the percentage of original investment that can be recouped by originator, e.g. 80% as suggested by Fellmeth. Effectiveness and Procedural Aspects of Arbitration/Litigation
• How to ensure that production of medicines is permitted during arbitration and litigation so that extended administrative procedures do not become a bar to competition.
• Whether a specialist arbitration panel composed of public health experts is needed for such arbitration.
• How to prevent delay by expediting arbitration and litigation in compensation cases.
• How and whether appeals can be made from arbitration decisions.
• What the relative bargaining position of different market players is likely to be at the commencement of arbitration, and how this will affect competition.
• How to prevent “gaming” of a market share system—for example, where an originator refrains from selling a drug after obtaining marketing approval, the generic company pays 100% of the costs of the data for that drug.
• What the impact of artificial barriers will be to market entry on economic growth.
• Whether Indian industry is able to share in the costs of original investment, given that clinical trials will often have been conducted in the United States or Europe where costs are much greater, and whether the expense for Indian manufacturers would be prohibitive.
• How market share will be measured, and when will it be measured, because if assessments are not predictable, Indian manufacturers will not be able to assess risks or costs/benefits and make informed business decisions.
• Which Ministry will be responsible for monitoring implementation of the cost-sharing model, and other significant administrative aspects of this model, and how cumbersome these burdens will be to implement in practice.
To this list one could add questions about whether market share will be based on dollar volume of sales or pill volume of sales and how India would acknowledge or assess market share of later entrants?
(9) See Donald W. Light & Joel Lexchin, Foreign Free Riders and the High Prices of U.S. Patented Drugs, 331 British Med. J, 958-60 (2005).
(10) One of the primary rationales for data exclusivity from the U.S. perspective is that it allows a guaranteed period of market exclusivity and monopoly pricing even if a patent was never filed or if a granted patent has expired.
