The Legal Conundrums and Solutions of Polypharmacy. Professor Amir Attaran Canada Research Chair Faculty of Law and Faculty of Medicine

Transcription

1 The Legal Conundrums and Solutions of Polypharmacy Professor Amir Attaran Canada Research Chair Faculty of Law and Faculty of Medicine

2 WHO Essential Medicines: patent situation (2003) There are 319 WHO Essential Medicines, of which only 17 are patentable: Antiparasitics: Lariam, Coartem Antifungals: Diflucan Antibacterials: Cipro; Zithromax Antiretrovirals: AZT, 3TC, ddi, d4t, ABC, IND, EFV, NEV, RTV, SQV, NFV, LPV+RTV Data relationships (sample of 291 meds in 65 countries): Patent coverage overall is 1.4%. Where patentability existed, inventors used it 31% of the time, but passed on it 69% of the time. Patents are found more often in large than small countries, and middle income than low income countries (p < 0.05). The more people or money your country has, the more likely inventors will look for profit and patent there. These are descriptive statistics of a general nature. Note specific countries and specific medicines can have much higher patent burdens. Source: Amir Attaran, Health Affairs (2004)

3 Fixed-dose combinations: more challenging Simplified therapies are a public health necessity for AIDS treatment. Nonadherence can increase death risk by 250%. Stavudine (BMS) - very few patents Lamivudine (GSK) - many patents Nevirapine (Boehringer Ingelheim) - many patents + + or d4t + 3TC + NVP (patented in 46 or 65 countries) In the USA, one-pill options are still very limited, worse than Africa All GSK: abacavir + zidovudine + lamivudine (Trizivir) All Gilead: tenofovir + emtricitabine + elvitegravir + cobicistat (Stribild) Gilead and BMS and Merck: tenofovir + emtricitabine + efavirenz (Atripla)

4 Polycap s ingredients are not patented These patents are expired: Aspirin -- but challenges remain Simvastatin (Atorvastatin in the process of expiring) Atenolol Ramipril Hydrochlorothiazide However, there are patents on coformulations, delivery technologies and manufacturing processes too. What to do about that?

5 Option One: Avoid

6

7 Option Two: Infringe

8

9

10

11

12 Option Three: Develop Oneself

13 Sanz 2011; DOI: /s

14 Tiered pricing in the vaccine market

15 We believe that out-licensing, to improve access to medicines, should be pursued systematically. Companies should consider taking a few, experimental steps to offer outlicenses on the WHO Essential Medicines, and possibly others. [This would] answer the concern that patents impede treatment access Source: Michael Friedman, Henk den Besten and Amir Attaran, Lancet 361: (2003).

16 Inventor Company Master Out-license (IP) Service agreement (tech) Pro-poor IP custodian + QA/QC partner Sub-licenses (low royalty) Tech services, & QA/QC Generic mfg #1 Generic mfg #2 Generic mfg #3 Developing Country A Developing Country B Developing Country C Developing Country D Developing Country E

17

18 Option Four: Partner in the Pool

19 Mutually-beneficial patent pooling This problem is rather like HIV/AIDS, except a little simpler because most APIs are totally off-patent Pooling has only worked where a lucrative market is nonexistent or remote: Neglected tropical diseases (no market) Alzheimer s disease (no useful candidates: stuck at phase 2) Epigenetics research (screening tools only) Pooling is legally risky because of antitrust law concerns. A third party matchmaker is helpful.

20 Philanthropists or Aid Donors Fund R&D Bulk Out-License IP Funding IP holders (pharma) PPP for trials and R&D Humanitarian invention Market rights in developing world Profitable invention Market rights in rich world NEWLY PATENTED POLYPILL WITH RETURNS TO SUPPORTERS

21 History of the WHO Model List of Essential Drugs 1977 First Model list published, ± 200 active substances List is revised every two years by WHO Expert Committee 2002 Revised procedures approved by WHO March 2011 list contains 358 active substances See Comparative analysis Next revision 2013 Department of Essential Medicines & Pharmaceutical Policies TBS 2011 (21)

22 How prequalification is organized? (I) Role of WHO: Managing and organizing the project on behalf of the United Nations. provides technical and scientific support and guarantee that international norms and standards are applied all through the process including assessment, inspection (GMP, GCP, GLP) and quality control Partners: UNICEF, UN Population Fund (UNFPA), UNAIDS and with the support of the World Bank (IPC group); WHO disease oriented programs WHO Prequalification Programme June 2007

23 Steps of prequalification 1. Expression of interest (EOI) from a prospective supplier interested in a voluntary participation in the program. 2. Receipt of the dossier at UNICEF in Copenhagen and the Site Master File in WHO Geneva. Explicative notes and guidelines are published on the WEB in order to explain how to bring together a product dossier meeting the requirements for prequalification. 3. Screening of the dossier, "Quality" part, "Clinical" part and samples. possible inspection 4. Assessment of the dossier and writing of the assessment report and assessment letter. 5. Outcome of the evaluation communicated to supplier Health Technologies and Pharmaceuticals 23 WHO - PSM

24 Steps of prequalification cont 6.Inspection of the site (s) of manufacturing and follow-up inspection when necessary GMP compliant list of manufacturers 7.Inspection of the Research Laboratory or Contract Research Laboratory (CRO) where the bioequivalence study has been performed GCP compliant list of CROs 8.Conclusion and listing of the product in the prequalification list 9.Publication of the Public Assessment (WHOPAR) and Inspection (WHOPIR) Reports 10.Assessment of the variation when submitted, market survey, de-listing if necessary 11.Re-qualification after 3 years Health Technologies and Pharmaceuticals 24 WHO - PSM

25 Law exists to facilitate, not to obstruct. First build the partnerships and develop the products. Act uninhibitedly. (And frankly, if the lawyers complain, quote Shakespeare.) The law can always be made to fit.

26

27 Example of legal analysis: prescribing 1. Does the prescribing law allow lay HCWs to prescribe? If no i. Is there a statutory discretion: i. For lay persons to prescribe in limited circumstances? ii. To re-designate a medicinal product as not a prescription medicine? iii. For research purposes? 2. Can physicians lawfully? i. Pre-write blank prescriptions? ii. Delegate general prescribing authority based on a protocol? iii. Prescribe by SMS - text message? iv. Dispense to lower HCWs for onward distribution?

28 How I think of international health policy: What we can affect in international public health is usually determined by three separate but overlapping questions: 1. Who has the resources? (money, knowledge, trained people) 2. What are the rules? (human rights, intellectual property rights, regulations, sovereignty) 3. Who sets the priorities? (ethics, expectations, epidemiology, economics, equity) THE REALM OF POLICY SUCCESS: 3. Concurrence on strategies & programs 2. Access to interventions & patients 1. Sufficient money & knowledge

29 There are five priorities for intervention Deontology ---- Utilitarianism People cite basically 5 reasons to intervene (or not): Economics: Doing X is more cost effective than doing Y. Epidemiology: Doing X will help avoid more health problems to come. Equity: Doing X will contribute to poverty reduction. Expectations: Doing X is what the community supports. Ethics: all of the above, depending on who you are! Recently 2 new justifications have joined the discourse: Macroeconomic: Doing X will lead to economic growth and wealth. Security: Doing X will stop a demographic or political cataclysm. Source: Amir Attaran (forthcoming).

30 There are only three ways to persuade Logos Or logic. Emphasis on evidence. Clinical trial evidence Critical pathway & barrier analysis Ethos Or character. Emphasis on authority. Scientists, doctors, key opinion leaders Celebrities Pathos Or sentiment. Emphasis on emotion. Health advocates & NGOs Feature journalism

31

32 WWF on banning DDT totally DDT can and should be phased out by no later than WWF believes that concerns [about malaria] can be addressed while maintaining a deadline of 2007 for outlawing DDT. We have called for a phase-out of the use of DDT by 2007 and that remains our position [as of 1999] - Resolving the DDT Dilemma, Rolling Back Malaria and Eliminating DDT, (17-26 may 1999) - Clif Curtis (WWF press release August 31, 1999)

33 Malaria eradication: results By 1961, 650 m persons protected, at a cost of per capita India: 75 m cases/y, down to 100,000 1 m deaths/y, down to 1000 Sri Lanka (Ceylon): 2.8 m cases/y, down to 17 cases and ZERO deaths Then USA cut off funding rebounded to nearly 1 m cases by 1970

34 Malaria Cases and Deaths - South Africa DEATHS CASES DDT withdrawn Deaths Cases Years 0

35 BMJ (Dec 2000)

36 Nature Med (July 2000)

37 DDT-malaria open letter doctors, scientists & development specialists, including Nobel laureates, from 63 countries

38

39

40

41

42

43 And what if we don t?

44 Botswana: up to 80% of adults dead in MEN WOMEN With AIDS in Without AIDS in 2020 Age in years Population (thousands) Source: US Census Bureau, World Population Profile 2000

45 This girl does not know when global health policies are right or wrong. We do. She cannot invent the health technologies she needs. We can. That is our blessing and our responsibility both. More questions? Please write: