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Compulsory Licenses: A Tool to Improve Global Access to the HPV Vaccine?

Published online by Cambridge University Press:  06 January 2021

Peter Maybarduk  and
Sarah Rimmington
Peter Maybarduk
Affiliation:
University of California at Berkeley; Essential Action, Access to Medicines Project
Sarah Rimmington
Affiliation:
University of Windsor; Columbia University, School of International and Public Affairs (SIPA); Essential Action, Access to Medicines Project
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Abstract

Cervical cancer disproportionately affects women in lower- and middle-income countries. But the new vaccines developed to prevent infection with some strains of the human papillomavirus (HPV) that cause cervical cancer are priced beyond the reach of most women and health agencies in these regions, due in part to the monopoly pricing power of brand-name companies that hold the patents on the vaccines. Compulsory licenses, which authorize generic competition with patented products, could expand access to HPV vaccines under certain circumstances. If high-quality biogeneric HPV vaccines can be produced at low cost and be broadly and efficiently registered, and if Merck and GSK are unwilling to grant licenses on a voluntary basis, compulsory licensing could play a pivotal role in ensuring vaccinations against HPV are available to all, around the world, regardless of ability to pay.

Type
Article
Information
American Journal of Law & Medicine , Volume 35 , Issue 2-3 , June 2009 , pp. 323 - 350
Copyright
Copyright © American Society of Law, Medicine and Ethics and Boston University 2009

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References

1 World Health Organization (WHO), The Global Burden of Disease: 2004 Update 8, 13 tbl. 3 (2008) [hereinafter Global Burden 2008].

2 D. Maxwell Parkin & Freddie Bray, Chapter 2: The Burden of HPV-Related Cancers, 24 Vaccine (Supp. 3) S11, S11 (2006).

3 Leslie Mancuso, Cervical Cancer: An Overlooked Killer in Low-resource Countries, Pump Handle, Jan. 13, 2009, http://thepumphandle.wordpress.com/2009/01/13/cervicalcancer-an-overlooked-killer-in-low-resource-countries/.

4 Global Burden 2008, supra note 1.

5 See Emmanuela Gakidou et al., Coverage of Cervical Cancer Screening in 57 Countries: Low Average Levels and Large Inequalities, 5 PLos Medicine 863, 863 (2008).

6 The U.S. Food and Drug Administration (FDA) first approved Merck's Gardasil® [Human Papillomavirus Quadrivalent Vaccine (Types 6, 11, 16, and 18) Recombinant] in June 2006. Marc Kaufman, FDA Approves Vaccine that Should Prevent Most Cervical Cancers, Wash. Post, Jun. 9, 2006, http://www.washingtonpost.com/wpdyn/content/article/2006/06/08/AR2006060800865.html. The product is approved for the prevention of cervical, vulvar and vaginal cancers; genital warts; and precancerous or dysplastic lesions in girls and young women 9 through 26 years of age. Press Release, Merck, FDA Approves Merck's GARDASIL® to Protect Against Two Additional Cancers (Sept. 12, 2008), http://www.merck.com/newsroom/press_releases/product/2008_0925.html. GlaxoSmithKline's (GSK) product Cervarix® [Human Papillomavirus Vaccine (types 16, 18) Recombinant, Adjuvanted, Adsorbed] was first approved in Australia in March 2007 and the 27 member countries of the EU in September 2007. It is approved to prevent cervical, vulvar and vaginal cancers and precancerous or dysplastic lesions in girls and young women aged 15-25. Press Release, GlaxoSmithKline, Cervarix, GSK's Cervical Cancer Vaccine, Wins Tender for Dutch National Immunisation Programme (Nov. 20, 2008), http://www.gsk.com/media/pressreleases/2008/2008_pressrelease_10123.htm. HPV strains 16 and 18 are estimated to cause 70% of all cervical cancers. See e.g., Luisa L Villa et al., Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-like Particle Vaccine in Young Women: A Randomised Double-blind Placebo-controlled Multicentre Phase II Efficacy Trial, 6 Lancet Oncology 271, 271 (2005); F X Bosch et al., The Causal Relation Between Human Papillomavirus and Cervical Cancer, 55 J. Clinical Pathology 244, 248 (2002). Initial studies show that efficacy rates for both vaccines approach 100 percent if girls are inoculated prior to sexual debut. The duration of protection for both products is unknown. Diane M Harper et al., Sustained Efficacy Up to 4.5 Years of a Bivalent Li Virus-Like Particle Vaccine Against HPV Types 16 and 18: Follow Up from a Randomized Controlled Trial, 367 Lancet 1247, 1247 (2006).

7 Helen Saxenian, Program for Appropriate Technology Health (PATH), HPV Vaccine Adoption in Developing Countries: Cost and Financing Issues 8-11 (2007); Jan M. Agosti & Sue J. Goldie, Introducing HPV Vaccine in Developing Countries – Key Challenges and Issues, 356 New Eng. J. Med. 1908, 1909-10 (2007).

8 Ellen F.M. 't Hoen, The Global Politics of Pharmaceutical Monopoly Power 87 (2009).

9 For a basic overview of principles and international laws governing patents, see World Intellectual Property Organization (WIPO), What is Intellectual Property?, http://www.wipo.int/about-ip/en/ (last visited Apr. 9, 2009).

10 Patents cause high prices sources. 't Hoen, supra note 8.

11 Chee Yoke Ling, Third World Network, Malaysia's Experience in Increasing Access to Antiretroviral Drugs: Exercising the “Government Use” Option 5 (2006).

12 For example, see James Packard Love, Knowledge Ecology International, Recent Examples of Compulsory Licensing of Patents, James Packard Love 12 (2007), available at http://www.keionline.org/index.php?option=com_content&task=view&id=41&Itemid=1.

13 Id. at 16-17.

14 United States Congressional Budget Office (CBO), How Increased Competition from Generic Drugs Has Affected Prices and Returns in the Pharmaceutical Industry 32 (1998), available at http://www.cbo.gov/ftpdocs/6xx/doc655/pharm.pdf.

15 't Hoen, supra note 8, at 25.

16 The authors use the term “biogenerics” or “generic biologics” to include products that are determined to be “identical” and “therapeutically equivalent” by scientists, as well as products that are found to be “highly similar” and “comparable” (similar, comparable medicines are in the same product class and have the same therapeutic purpose, but the molecules cannot be scientifically characterized as identical and the product is not defined as therapeutically equivalent). Often a distinction is drawn between these two categories, with identical or equivalent products labeled “generics” or “biogenerics” and highly similar products called “biosimilars” or “follow-on biologics.” For the purposes of this paper and the sake of simplicity, the authors choose not to make a distinction between these two categories and to use the term biogenerics to refer to all of them. Technology and regulatory pathways for both categories of product are still developing, and the authors acknowledge no one has yet engineered or registered generic copies of any vaccine, and that it may be quite difficult to do. But it is possible the scientific know-how and the regulatory environment will evolve in coming years such that it will be possible to engineer and market generic HPV vaccines, which would in fact be called “biosimilar” or “biogeneric” products. The specific challenges related to engineering and registering generic versions of biologic products like the HPV vaccine will be discussed in greater detail in the text and footnotes of Section III.

17 At least one Indian vaccine-maker, Shantha Biotechnics, is currently attempting to engineer a low-cost second-generation HPV vaccine. Second-generation products are not generic imitations or copies of the original first-generation product (in the case of the HPV vaccine there are two first-generation products, Merck's Gardasil and GSK's Cervarix). Because second-generation products are not generics, but are new and different product albeit with the same therapeutic purpose, they have to undergo the full battery of safety and efficacy tests of the relevant regulatory authorities before being approved for sale. There is no guarantee that Shatha will be successful at developing this product, which some have estimated is not likely to be ready for marketing – if at all – until 2015 or beyond. Saxenian, supra note 7, at 6-7; Gunjan Pradhan Sinha, Byline, Shantha Developing $15 Cervical Cancer Vaccine, Econ. Times (India), October 16, 2007.

18 To learn more about other types of access initiatives see generally Colleen V. Chien, HIV/AIDS Drugs for Sub-Saharan Africa: How Do Brand and Generic Supply Compare? 3 PLoS ONE e278 (2007), P.J. Hammer, Differential Pricing of Essential AIDS Drugs: Markets, Politics and Public Health, 5 J. Int’l Econ. L. 2158 (2002), Kevin Outterson & Aaron S. Kesselheim, “Market-Based Licensing for HPV Vaccines in Developing Countries,” 27 Health Affairs 130 (2008); Press Release, Médecins san Frontières, Gilead's Tenofovir Access Program for Developing Countries: A Case of False Promises? (Feb. 7, 2006), http://www.msfaccess.org/media-room/press-releases/pressrelease-detail/?tx_ttnews%5Btt_news%5D=31&cHash=65d72b8994.

19 See, for example, Essential Action, Statement on Paragraph 6 Deal, Dec. 6, 2006, http://www.essentialaction.org/access/index.php?/archives/46-Statement-on-Paragraph-6-Deal.html.

20 See, for example, Essential Action, The WTO: Areas of Concern, and What We are Doing, http://www.essentialaction.org/access/index.php?/archives/49-The-WTO-Areasof-Concern,-and-What-We-Are-Doing.html.

21 Agreement on Trade-Related Aspects of Intellectual Property Rights, Marrakesh Agreement Establishing the World Trade Organization, Annex 1C, art. 9, Apr. 15, 1994, 33 I.L.M. 81, available at http://www.wto.org/english/docs_e/legal_e/27-trips.pdf [hereinafter TRIPS].

22 For a list of WTO member countries, see World Trade Organization, Understanding the WTO: The organization, http://www.wto.org/english/thewto_e/whatis_e/tif_e/org6_e.htm (last visited Apr. 10, 2009).

23 See, TRIPS supra note 21, art. 31.

24 't Hoen, supra note 8, at 35.

25 For example, in 1998, a coalition of pharmaceutical companies sued South Africa, alleging that its newly inaugurated Medicines Act, which permitted price-reducing, accesspromoting practices such as parallel importation and compulsory licensing, violated TRIPS. Public resistance and poor legal bases for these claims prompted the pharmaceutical manufacturers and United States to abandon this case. But this and other incidents underscored lingering conflicting understandings of TRIPS within the international community. See generally Robert Weissman, Aids Drugs for Africa: Grassroots Pressure Overcomes U.S.-Industry “Full Court Press” to Block South Africas Affordable Medicine Program, 20 Multinational Monitor 9 (1999), available at http://multinationalmonitor.org/mm1999/99sept/aids.html.

26 Declaration on the TRIPS Agreement and Public Health, WT/MIN(01)/DEC/2, para. 5b, 41 I.L.M. 755 (2002) [hereinafter Doha Declaration].

27 Paragraph 6 of the Doha Declaration recognized this burden on countries’ compulsory licensing rights, and instructed the TRIPS Council to “find an expeditious solution.” Doha Declaration, supra note 26, para. 6. On August 30, 2003, the WTO General Council responded with an implementing decision that indefinitely waives TRIPS article 31(f) for pharmaceutical patents, subject to certain limitations and labeling requirements. WTO, Implementation of Paragraph 6 of the Doha Declaration on the TRIPS Agreement and Public Health (Sept. 1, 2003), http://www.wto.org/English/tratop_e/trips_e/implem_para6_e.htm. WTO members have since agreed on a TRIPS amendment that will make this waiver permanent, and will enter into force upon ratification by two-thirds of the members. Press Release, World Trade Organization, Members OK amendment to make health flexibility permanent (December 6, 2005), http://www.wto.org/english/news_e/pres05_e/pr426_e.htm. Public health advocates argue that the “Paragraph 6 solution” is too procedurally onerous to be effective, and that a simpler solution should be put into place. Consumer Project on Technology, Joint NGO Statement on TRIPS and Public Health WTO Deal on Medicines: A “Gift Bound in Red Tape” (September 10, 2003), http://www.cptech.org/ip/wto/p6/ngos09102003.html.

28 Essential Action, Robert Weissman, Letter to the Editor submitted to the Bangkok Post by Robert Weissmman, Bangkok Post Letter: Commentator an Advisor to Law Firm that Represents Big Pharma, (May 11, 2007), http://www.essentialaction.org/access/index.php?/archives/96-Bangkok-Post-Letter-Commentator-an-advisor-to-law-firm-that-represents-Big-Pharma.html; Robert Weissman, Compulsory Licenses the Right Medicine for Prescriptions in Developing Countries, S. Fla. Sun-Sentinel, March 18, 2008; Robert Weissman, Ken Adelman's (New Lies), Huffington Post, May 7, 2007; Robert Weissman, Stronger Patent Protections Will Take Lives, Not Save Them, River Cities’ Reader (Iowa), March 19, 2008; Shaun Zeller, The Shadowy Drug Lobby that Has Thailand in Its Sights, CQ Wkly., May 14, 2007, http://www.essentialaction.org/access/index.php?/archives/105-The-Shadowy-Drug-Lobby-That-Has-Thailand-in-Its-Sites.html.

29 To read more about the opposition to the Thai compulsory licenses and related issues see, for example, Brook Baker, The Eight Deadly Lies of Big Pharma, Nation (Thail.), April 21, 2007; Professor Brook K Baker et al., Letter to the Editor, Article Misleads in Support of Big Pharma, Bangkok Post, April 26, 2007, available at http://www.essentialaction.org/access/index.php?/archives/58-Bangkok-Post-letter-Abbottslaw-firms-deceptions.html; Daniel Ten Kate, US-Thailand Dispute over Compulsory Licenses for AIDS Drugs, Asia Sentinel, May 9, 2007; Letter from Senator Joseph Lieberman et al. to United States Trade Representative (USTR) Susan Schwab (March 20, 2007), http://www.cptech.org/ip/health/c/thailand/.

30 For an example, see TRIPS, supra note 21, art. 31; WTO, TRIPS and Health: Frequently Asked Questions, Compulsory Licensing of Pharmaceuticals and TRIPS (September 2006), http://www.wto.org/english/tratop_e/TRIPs_e/public_health_faq_e.htm.

31 For a partial global list of compulsory licenses, see Love, supra note 12, at 2.

32 Id. at 5. The United States also threatened to issue a compulsory license on Tamiflu unless Roche produced it in the United States (Roche complied). Id. at 3. As early as 1952, the U.S. Supreme Court granted the “well-recognized remedy” of compulsory licenses in antitrust actions. United States v. Besser Mfg. Co., 343 U.S. 444, 447 (1952).

33 Patents in some of these countries are listed in the online databases referenced infra Section IV.

34 See note 57 for some information on projected expiration dates of the HPV vaccine patents.

35 See note 16 for the authors’ discussion of the term “biogeneric.”

36 The European Medicines Evaluation Agency (EMEA), located in London, authorizes marketing of conventional drugs and biologics throughout the European Union (EU) on the basis of a single application. In 2003, the EU passed legislation allowing for the sale of what it calls “biosimilars.” The legislation became effective in 2005. EMEA has approved five biogenerics (called “biosimilars” in their legislation) since 2004, including competitors with Johnson & Johnson's Eprex and Amgen's Neupogen. For more information, see European Medicines Evaluation Agency (EMEA), http://www.emea.europa.eu/ (last visited Apr. 13, 2009).

37 Press Release, Canadian Generic Pharmaceutical Association, First Subsequent Entry Biologic Approved in Canada (Apr. 23, 2009), http://www.canadiangenerics.ca/en/news/apr_23_09.asp, For information on the Canadian rules, see the Health Canada Biologics, Radiopharmaceuticals and Genetic Therapies webpage at http://www.hc-sc.gc.ca/dhp-mps/brgtherap/index-eng.php and Ogilvy Renault, Health Canada issues revised draft Guidance Document for Subsequent Entry Biologics, March 31, 2009, http://ogilvyrenault.com/en/resourceCentre_9170.htm.

38 The U.S. Congress is currently debating several proposals that would result in the introduction of a regulatory approval process for biogenerics. Many expect the legislation to pass by late 2009 or 2010. See John Carroll, Biosimilar Bill Offers 12 Years of Market Exclusivity, Fierce Biotech, Mar. 18, 2009, http://www.fiercebiotech.com/story/newbiosimilar-bill-offers-12-years-market-exclusivity/2009-03-18; Lewis Krauskopf, Teva Executive Upbeat on Biogenerics in 2009, Reuters, Dec. 23, 2008, http://www.reuters.com/article/ousiv/idUSTRE4BM4OA20081223; Lisa Richwine, U.S. Lawmakers Propose Generic Biotech Drug Plan, Reuters, Mar. 11, 2009, http://www.reuters.com/article/latestCrisis/idUSN11301138.

39 See for example, Bill Berkrot & Ransdell Pierson, Lilly Eyes Entry into Biogenerics Arena, Reuters, Dec. 11, 2008, http://www.reuters.com/article/rbssHealthcareNews/idUSN1138748320081211; John Carroll, Biotech Buyout Spree Ahead as Values Crumble, Fierce Biotech, Jan. 6, 2009, http://www.fiercebiotech.com/story/biotech-buyout-spree-ahead-values-crumble/2009-01-06; Ransdell Pierson, Merck CEO Says Biotechs a Buying Opportunity, Reuters, Oct. 22, 2008, http://www.reuters.com/article/euPrivateEquityNews/idUSTRE49L83L20081022; Barbara Martinez & Jacob Goldstein, Big Pharma Faces Grim Prognosis, Wall St. J., Dec. 6, 2007, available at http://online.wsj.com/public/article_print/SB119689933952615133.html; Lina Saigol & Andrew Jack, Financial Times, Pharma Spending Spree Could Swallow Biotechs, Gulf News, Jan. 6, 2009, http://www.gulfnews.com/BUSINESS/Business_Feature/10272938.html; Aaron Smith, CNNMoney.com, Big Pharma Blurring the Lines with Big Biotech (May 29, 2007), http://money.cnn.com/2007/05/25/news/companies/biotech/index.htm.

40 Sara E. Crager et al., University Contributions to HPV Vaccines and Implications for Access in Developing Countries: Potential Models for Improving Access to University Discovered Vaccines, 35 Am. J. L. & Med. 253 (2009).

41 The authors are also not certain if the Health Canada and EMEA guidelines would permit regulators the necessary discretion to vary the abbreviated approval procedures for determining the safety and efficacy of vaccines and other categories of biologics as scientific advancement occurs. A more thorough analysis of the guidelines would have to be conducted to draw any conclusion. EMEA, Human Medicines, http://www.emea.europa.eu/index/indexh1.htm (last visited Apr. 14, 2009).

42 See Eric S. Langer, Indian Biogenerics: An Evolving Industry, BioPharm Int’l February 1, 2008, http://biopharminternational.findpharma.com/biopharm/India+Today/Indian-Biogenerics-An-Evolving-Industry/ArticleStandard/Article/detail/490805.

43 India amended its patent rules to comply with TRIPS in 2006.

44 In some cases, the importing countries have had to issue licenses for domestic use, because the product was patented in their country. Remember, patent regimes are national. A product may be on patent in one country and not in another. WIPO, Frequently Asked Questions, http://www.wipo.int/patentscope/en/patents_faq.html#worldwide_patent (last visited Apr. 30, 2009).

45 See note 35 and accompanying text.

46 Doha Declaration, supra note 28, para. 6.

47 See note 29.

48 't Hoen, supra note 8, at 36.

49 't Hoen, supra note 8, at 35-38. Examples of countries that have implemented export legislation, and in some cases to see the text of the legislation, are available at Legislation to Allow for the Export of Pharmaceuticals Produced Under Compulsory License, http://www.cptech.org/ip/health/cl/cl-export-legislation.html (last visited Apr. 14, 2009).

50 Rwanda's notification to the TRIPS council can be downloaded at WTO, TRIPS: Trips Public Health ‘Paragraph 6’ System, Notifications by Exporting WTO Members, http://www.wto.org/english/tratop_e/trips_e/public_health_notif_export_e.htm (last visited Apr. 14, 2009).

51 Int’l Ctr. for Trade & Sustainable Dev., Canadian WTO Notification Clears Path for Rwanda to Import Generic HIV/AIDS Drug, Bridges Wkly. Trade News Dig., October 10, 2007, at 7-8, available at http://ictsd.net/i/news/bridgesweekly/6568/.

52 See Section III, supra.

53 See notes 58-59 and accompanying text.

54 Some countries may also have regulations making it difficult to register a follow-on drug if the original is not domestically registered. But Gardasil was already registered in 106 countries as of October 2008, with another 30 registrations pending; hence this should not be a significant barrier. See Press Release, Merck, FDA Approves Merck's GARDASIL® to Protect Against Two Additional Cancers (September 25, 2008), available at http://www.merck.com/newsroom/press_releases/product/2008_0925.html. As of September 25, 2008 Cervarix had been approved in more than 80 countries. Marketing applications have been submitted in more than 30 additional countries. GSK is still awaiting U.S. Food and Drug Administration (FDA) marketing approval for Cervarix™, which it applied for in March 2007. See Press Release, Glaxo Smith Kline, Cervarix, GSK's cervical cancer vaccine, Wins Tender for Dutch National Immunisation Programme (November 20, 2008), available at http://www.gsk.com/media/pressreleases/2008/2008_pressrelease_10123.htm.

55 Information about the World Health Organizations’ Prequalification Program is available at WHO, Prequalification Programme: A United Nations Programme Managed by WHO, http://healthtech.who.int/pq/ (last visited Apr. 14, 2009). Information about vaccine prequalification is available at WHO, A System for the Prequalification of Vaccines for UN Supply, http://www.who.int/immunization_standards/vaccine_quality/pq_system/en/index.html (last visited Apr. 14, 2009).

56 In countries with linkage rules (such as the United States), the drug regulatory authority will not approve a drug for sale if another party claims a patent on it. Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act) of 1984, Pub. L. No. 98- 417, 98 Stat. 1585 (codified at 15 U.S.C. §§ 68b-68c, 70b (1994); Federal Food, Drug, and Cosmetic Act, 21 U.S.C. §§ 301, 355, 360cc (1994); Creation of Remedy, 28 U.S.C. § 2201 (1994); Issue of Patents, 35 U.S.C. §§ 156, 271, 282 (1994)). In other words, under linkage, a drug generally must be off patent before generics can be sold. A compulsory license in a linkage system would allow the regulatory authority to approve a generic drug for sale in spite of a patent.

In countries without linkage, the drug regulatory authority gauges only safety and efficacy. If a drug works safely for its intended purpose, it may be sold on the national market. Drug companies enforce their patents through the courts or other dispute systems (in much of Latin America, patent holders file medidas cautelares), but not necessarily before a generic drug reaches market. In countries without linkage, generics may be found on the market even though a patent is claimed. Generics on the market may mean the drug is not patented, or that the patent holder has not filed suit to remove the generics, or that the claimed patent is actually weak or invalid. A compulsory license in a system without linkage would protect generics already on the market, and generics that might come on the market later, from enforcement actions brought by the patent holder.

A compulsory license provides generics companies, patients and government agencies security, ensuring a patent holder will not be able to force the generic off market after patients and agencies have come to rely on its low prices. This security may also act as an incentive to attract more generics firms to market. Drug registration, marketing and distribution are expensive for low-capitalized generics firms, and firms may prefer to avoid the risk if a drug is on patent, particularly in smaller countries where there is less potential profit to be made. Compulsory licenses assure generics firms their investment will be protected.

57 According to the Health Canada and European government patent databases, some HPV patents may expire as early as 2012, but others are slated for 2016. For a general search of Canadian and European patent databases, see Canada, Patent Register Search Page, http://www.patentregister.ca (last visited Apr. 30, 2009); European Patent Office, About Patent Information, http://www.epo.org/patents/patent-information/about.html (see infra text accompanying note 65) (last visited Apr. 30, 2009). There may be other patents set to expire later, and there remains the possibility of patent “evergreening,” filing new patents on the same products for relatively minor changes, which could extend the patents considerably longer. Absent licenses, Merck and GSK will be able to use patents to block competition until all patents covering technology necessary to produce HPV vaccines expire.

58 Practically, even absent linkage, most generic vaccine makers might not apply for FDA approval so long as the originator products are patented. See Michelle Meadow, Greater Access to Generic Drugs: New FDA Initiatives to Improve Drug Reviews and Reduce Legal Loopholes, FDA Consumer, Sept.-Oct. 2003, at 14. But if there were a pathway to generic vaccine approval and no linkage, FDA approval would at least be technically possible as a strategy to assist worldwide registration, even if the U.S. market would not be available for sales.

59 New products receive eight years of data exclusivity, after which follow-on companies may file “biosimilar” applications. Biosimilars will not be approved for sale until another two years have passed. See generally Janie Mackay, bioLOGIC Europe 2007, 10 IDrugs 543 (2007). If the innovator also receives approval for new uses of the original product, this can add one additional year of data exclusivity, for a total of eleven years available exclusivity (8+2+1) following marketing approval. European Generic Med. Ass’n, Data Exclusivity, http://www.egagenerics.com/gen-dataex.htm (last visited Apr. 30, 2009).

60 WHO, supra note 55.

61 Id. “The list of prequalified medicinal products used for HIV/AIDS, malaria, tuberculosis and for reproductive health produced by the Programme is used principally by United Nations agencies — including UNAIDS and UNICEF — to guide their procurement decisions. But, the list has become a vital tool for any agency or organization involved in bulk purchasing of medicines, be this at country level, or at international level, as demonstrated by the Global Fund to Fight AIDS, Tuberculosis and Malaria.” Id.

62 Gardasil® Applies for WHO Certification to Reinforce Global Access to the Vaccine – Approval Would Qualify Gardasil® for Procurement by United, Med. News Today, Jul. 18, 2007, http://www.medicalnewstoday.com/articles/77039.php (Merck); GSK Applies for WHO Prequalification of HPV Vaccine Cervarix, Med. News Today, Oct. 12, 2007, http://www.medicalnewstoday.com/articles/85302.php (GSK).

63 “The [National Regulatory Authority] of the producing country is found to meet all the critical indicators defined for prequalification purposes following a WHO independent assessment.” WHO, Procedures for Assessing the Acceptability of Vaccines for Purchase by United Nations Agencies 3 (2006), available at http://www.path.org/vaccineresources/files/Procedures_acceptability_purchase_by_UN.pdf.

64 The WHO prequalified vaccine list is available at WHO, WHO, List of Vaccines for Purchase by UN Agencies as of April 2009, http://www.who.int/immunization_standards/vaccine_quality/pq_suppliers/en/index.html (last visited Apr. 14, 2009).

65 Id.

66 The authority to license data is also implicit in the authority to issue compulsory licenses for patents, for what good would such licenses be if data exclusivity prevented registering generics in any event?

67 See Brook K. Baker, Presentation to Consumer Project on Technology - Next Steps and Strategies on Bilateral Free Trade Agreements, Using FTA Side Letters and Congressional Letters to Authorize Waiver of Data Exclusivity and Linkage, (Nov. 16, 2006), available at http://www.cptech.org/events/BrookBakerFTA.ppt.

68 There are, however, public databases listing patents for the wealthy countries.

69 The FDA's Orange Book is an example, though notably, it excludes the HPV patents. The Orange Book lists patents for drugs approved under the Food, Drug and Cosmetic Act; but Gardasil was approved under the Public Health Services Act, which regulates most biologic drugs and vaccines. The Electronic Orange Book, or Approved Drug Products with Therapeutic Equivalence Evaluations, is available at Food and Drug Administration, Electronic Orange Book, http://www.fda.gov/cder/ob/ (last visited Apr. 14, 2009) [hereinafter Electronic Orange Book].

70 In the United States, drug patent disclosure is a precondition of marketing approval. The Drug Price Competition and Patent Term Restoration Act of 1984 (more commonly known as the Hatch-Waxman Act) requires every person introducing a drug into commerce to file a new drug application (NDA) with the Food and Drug Administration (FDA). Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act) of 1984, Pub. L. No. 98- 417, 98 Stat. 1585 (codified at 15 U.S.C. §§ 68b-68c, 70b (1994); Federal Food, Drug, and Cosmetic Act, 21 U.S.C. §§ 301, 355, 360cc (1994); Creation of Remedy, 28 U.S.C. § 2201 (1994); Issue of Patents, 35 U.S.C. §§ 156, 271, 282 (1994)). The NDA must include patent information–specifically, the patent numbers and expiration dates of patents that might reasonably be asserted in an infringement action. Drugs cannot be marketed until the FDA approves this application. Id. The FDA's Orange Book includes the submitted patent information in its Addendum, making it a little easier for generics manufacturers or health agencies to research patents held on critical medicines. Electronic Orange Book, supra note 69.

71 Id.

72 For example, to access Great Britain's page, go to http://www.epo.org/patents/patent-information/about.html, click “Free databases,” follow “esp@cenet,” then “esp@cenet in your language,” then, http://gb.espacenet.com/search97cgi/s97_cgi.exe?Action=FormGen&Template=gb/EN/home. hts. Choose “Number Search,” and place the country abbreviation (in this case “CA” for Canada) before the numbers found on the Health Canada (or FDA, or other) website. Here, entering CA2215834 reveals a Merck patent; entering CA2113712 reveals a Frazer/Zhou patent.

73 It will be easy to look up patents if every time an application is filed, a priority number of US19950423387 19950425 (corresponding to the HIV/AIDS medicine Kaletra) is entered in precisely that format. If, however, country codes, spaces and dashes are treated differently with each application – such that the same patent listed above could read “1995042338719950425” – or if the number is entered incorrectly, or if the numbers are not always entered into the database, or if the number sequences entered are pulled from different sources each time, such a search could become unreliable (note that a search for only part of the number sequence – for example, 19950423387 – should turn up results so long as the number was entered correctly in some form). Id. In such a case, the patent officer might have to employ one further creative method: reading the international patents for unique keywords that are likely to be listed in the national patent (some patent offices use this method). For example, U.S. or European patents might include specific terms describing a drug's chemical makeup that are distinguishable from other drugs to an informed reader. These terms could be entered into a national database as a keyword search. It may be helpful if someone with a background in chemistry or pharmaceuticals is available to assist.

74 This does not necessarily mean the patents are valid, but assessment of the validity of the HPV patents is beyond the scope of this paper. For health policy planning purposes, the HPV patents sharing the aforementioned priority numbers have not been discredited.

Also recall some patents related to key medical products, such as those only covering the product when used in combination with a tangential product, may not create barriers to generic competition. That is, if a patent specifically protects only the combination of Medicine A and Medicine B, then it does not protect Medicine A used without Medicine B. Generics companies are free to market Medicine A unless a separate patent specifically protects Medicine A, its essential components, or exclusive manufacturing process. This point is relevant because patents held by little known companies sometimes surface in patent searches, claiming use of a variety of established medicines in combination with a separate, lesser known product. These patents cannot control use of the established products except as used in conjunction with their own. In other words, not every patent naming a medicine somewhere in its text actually prohibits competition with that medicine.

75 Regulations for compulsory licensing in Colombia are found in Superintendencia de Industria, Comercio y Turismo, Resolución No. 17585 (2001); Superintendencia de Industria, Comercio y Turismo, Decreto 4302 (2008).

76 The World Intellectual Property Organization's (WIPO) online portal is http://www.wipo.int/portal/index.html.en. Countries should generally consolidate their international obligations (TRIPS if already applicable, trade agreements, etc.) in the domestic law, but occasionally this might not happen. For example, Ecuador has its own Law on Intellectual Property (1998), with distinct terms, but also is a member of the Andean Community, which applies a Common Intellectual Property Regime (2000) for its members. Arguably, the two are not consistent (see, e.g., differences in the compulsory licensing chapters), but Ecuador has not amended its law to account for any differences. See Treaty Creating the Court of Justice of the Cartagena Agreement, art. 1, March 10, 1996 (discussing direct applicability of Andean Community decisions in member countries), available at http://www.comunidadandina.org/ingles/normativa/ande_trie2.htm. A non-official translation of Andean Community Decision 486: Common Intellectual Property Regime is available from the Andean Community at http://www.comunidadandina.org/ingles/normativa/D486e.htm. Ecuador's Law on Intellectual Property can be accessed through the World Intellectual Property Organization Collection of Laws for Electronic Access portal. World Intellectual Property Organization, Collection of Laws for Electronic Access (CLEA), http://www.wipo.int/clea/en/index.jsp (accessed on May 25, 2009).

77 In some cases, no clear procedures for issuing compulsory licenses are specified in the law. Government officers may be hesitant to initiate the licensing process without clear protocol guiding their decisions. For these reasons, it makes sense for governments to implement public health-friendly compulsory licensing regulations where they do not yet exist. The danger is implementing regulations that unnecessarily restrict government action. Regulations should ideally specify several possible clear paths to compulsory licenses, enabling anyone to request licenses and not limiting authority to grant them to any single government agency.

78 See WTO, TRIPS and Public Health, supra note 32. Note that while some countries may restrict the grounds for issuing compulsory licenses to situations of emergency or national security, most do not, and WTO rules leave the grounds entirely open. Id.

79 TRIPS, supra note 23, art. 31(b). Licenses issued to remedy anticompetitive practices are another exception. See id. at art. 31(k).

80 Id.

81 Id.

82 James Love, Health Economics and Drugs, TCM Series No. 18, Remuneration Guidelines for Non-Voluntary Use of a Patent on Medical Technologies, 6 (2005), available at http://www.who.int/medicines/areas/technical_cooperation/WHOTCM2005.1_OMS.pdf. For a more extended discussion, see id., at 45-49.