Pharma Workshop 4 Data exclusivity provision and availability around the world

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2 Pharma Workshop 4 Data exclusivity provision and availability around the world AIPPI Forum & ExCo Helsinki 6 September 2013 Panel: David Rosenberg, Vice President, Corporate IP Policy, GlaxoSmithKline Yoichi Okumura, General Manager, IP Department, Takeda Pharmaceutical Company Limited Gabriel Di Blasi, Partner, Di Blasi Parente & Associados (in absentia) Moderator: Sarah Matheson, Deputy Reporter General, AIPPI 2

3 Pharma Workshop 4 Data exclusivity provision and availability around the world AIPPI Forum & ExCo Helsinki 6 September 2103 David Rosenberg Vice-President, Corporate IP Policy GlaxoSmithKline

4 A brief introduction The need for R&D incentives for pharmaceuticals What is data exclusivity A brief history The interface between patents and data exclusivity National and international legal framework

5 Developing new medicines for patients

6 The need for incentives For every 5-10,000 compounds tested, 1 reaches the market Average time to market years (eating into patent term) Most pharmaceuticals easy and cheap to manufacture once safety and efficacy of innovator have been proved GSK spent 3.5 billion on R&D in 2012

7 Patents and Data Exclusivity Patents protect the invention and entitle the patent holder to protect its product by excluding potential competitors from reproducing the patented product/process Data Exclusivity (DE) is a form of IP right which protects the value of the extensive pre-clinical and clinical data that establish a drug s safety and efficacy and identifies appropriate clinical indications and uses. Without such data, regulatory agencies cannot grant a marketing authorization. Not dependent on factors affecting patent validity e.g. novelty, inventive step Basis of right is the effort expended to produce the data

8 The ideal DE law Requires States (through regulatory agencies) to protect proprietary pharmaceutical registration data generated by the originator of a new medicine against unauthorized disclosure to or reference by a third party for a fixed period of time During the DE period, other companies and regulatory authorities are not allowed to rely, directly or indirectly, on the registration data in their applications to register generic versions of the originator drug. Regulatory agencies do not grant generic manufacturers marketing approvals during the DE period unless they have produced and submitted their own safety and efficacy test data. After the DE period expires, generic applicants can rely on originator s data to obtain a marketing approval for their versions of the originator drug. They only need to prove the bioequivalence of their version of the originator drug and show that their manufacturing process complies with good manufacturing practices

9 The origins of DE 1984 US Hatch-Waxman Act previous unlimited DE limited to 5 years for new chemical entity, 3 years for new indication and 6 months for paediatric indication 1987 EU Directive 87/21 6 or 10 years for NCE 1994 USA, Canada, Mexico (NAFTA) no less than 5 years 1995 TRIPs Art 39.3 Members, when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products, which utilize new chemical entities, 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.

10 DE and patents - separate but complementary protections Patents run from date of filing - term of effective exclusivity depends on development time and is usually much less than 20 years, even with patent term restoration fact of exclusivity (i.e. commercial value) depends on validity and de facto enforceability DE provides fixed duration of protection against generic products enforced by the state independent of technical patent validity issues DE does not prevent innovative products coming to market DE rarely extends period of exclusivity on the market beyond patent term

11 IP and the development process (EU example) Patent + SPC protection = 13 years + 6 months paediatric Data excl 8 yrs + 2 yrs +1yr Years Patent Filing Date First MA in EEA Patent Expiry SPC Expiry SPC Extension Expiry

12 The significance of DE DE rarely extends period of exclusivity on the market beyond patent term Commercial significance most likely where: Development time is unusually long Biological products are involved. Compound/product patent protection relatively rare and process patents may not give adequate exclusivity There are validity/infringement issues which might prevent enforcement of patent against generic competitors DE may provide more effective protection for new indications than patents Patent enforcement system is weak

13 The exclusivity regimes of USA, EU and Japan (non-patent) USA EU Japan** New chemical entity 5 years 12 years for biologics 10 years (8 years before application + 2 years before marketing) 8 years New indication(s) 3 years 1 year for compound if significant clinical benefit compared to existing therapies 6 years Paediatric indication 0.5 years 0.5 years* Orphan drug*** 7 years (<) 10 years 10 years Off-patent drug 8+2 years for paediatric use Notes: * EU paediatric exclusivity is an extension of the SPC but rewards the generation of data, irrespective of patentability. ** DE in Japan is known as reexamination period after approval of new medicines production. *** Orphan drug incentives may not be strictly DE regimes

14 Japan Pharmaceutical Manufacturers & Association Drug Re-Examination/Data Exclusivity in JAPAN and Neighboring Countries AIPPI Forum & ExCo Workshop Pharma IV September 6, 2013 at Helsinki Yoichi OKUMURA Takeda Pharmaceutical Company, Ltd.

15 What is the Re-examination Term? Re-examination term Term for carrying out post-marketing examination to ensure efficacy and safety of the drug No marketing application for generic drugs during this term Substantial Regulatory Data Exclusivity! 15

16 Re-examination System in Japan Patent term Date of 1 st marketing approval Maximum 25 years + β Date of 2nd marketing approval Expiration of Exclusivity Filing date Issue date Re-examination term New active ingredient 8 years + α Generic Drug Entry Orphan or Pediatric* 10 years + α Additional indication 4 years + α α : Term between generic drug application and its approval/price listing β : Term between generic drug approval and its price listing Pediatric*: Pediatric an be extendable to original term up to 10 years 16

17 Grounds for 8th Year Re-examination (1/2) Safety Measures Peak for modification/revision of important drug info is the 7th year. Most of such modifications are made five to eight years after approval of the new active ingredient, the peak being the seventh year 70% of the modifications/revisions are revised within 8 years. About 70% of all drug package inserts are revised within 8 years after approval of the new active ingredient. Dealt with by revision of implementing rules, not laws Re-examination on the 8th year

18 Grounds for 8th Year Re-examination (2/2) Period from Marketing Approval of Drugs to Revision of Cautions during Use of Drug Revision of Cautions during Use (Number of Ingredients) New active ingredient (6th year reexamination) New active ingredient (10th year ) New administration route (6th year ) Accumulated Percentage Note 1) Those added changes to cautions during use dictated by a directive of the manager of the safety policy department from July 2003 to July 2006 are counted. Source: Pharmaceutical and Medical Safety Bureau, Ministry of Health, Labour and Welfare Note 2) Drugs containing new active ingredients which have been approved since 1989 are counted.

19 Introduction of Twice-a-Year Generic Drug Price Listing System Twice-a-Year Generic Drug Price Listing Promotion of Generic Drugs In the past Expiration of approval Expiration of approval Next Jul. Price listing Price listing This Jul. March This July Next March Next July Period between approval and price listing: 4 ~16 months After 2007 Expiration of approval Expiration of approval This Jun. This Dec. Next June February This June August This December Period between approval and price listing: 4 ~10 months

20 Korean DE

21 Korean Effective PMS: 4 6 years Items to be re examined six (6) years : New Drugs. Ethical Drugs different from already licensed drugs in terms of active ingredients or mixture ratios. Ethical Drugs different from already licensed ones in the route of administration, while containing the same active ingredients. Items to be re examined four (4) years: Ethical drugs which are identical to already licensed drugs in terms of active ingredients and route of administration but distinctively different in added indications. Other drugs whose re examination is deemed necessary by the Commissioner of the Korean FDA. During PMS period, third parties cannot obtain approval for generic versions of the same product unless they can submit data which are: a) different from the data submitted for the first approval; and b) equivalent to or exceeds the scope of data submitted for the first approval. The re examination (PMS) period in effect works as data exclusivity in Korea.

22 DE in Korea US Free Trade Agreement The Korean Patent Act currently provides six (6) or four (4) years of data exclusivity under the drug re examination system. As part of the FTA, Korea agreed to provide five (5) or three (3) years of data exclusivity for information relating to the safety and efficacy submitted in support of the marketing approval of pharmaceutical product. South Korea US Free Trade Agreement agreements/free trade agreements/korus fta/final text Five (5) years' data exclusivity applies, from the date of marketing approval, to all safety and efficacy information submitted in the process of a marketing approval if the origination of this information involves a considerable effort (Article , FTA). Three (3) years' data exclusivity applies, from the date of marketing approval, to new clinical information that is submitted in the process of obtaining marketing approval for product containing a chemical entity (Article , FTA).

23 Incrementally Modified Drug Three categories of drug approval 1. New Drug Approval 2. Drug approval with minimum required Data so called as " Incrementally Modified Drug", which is similar to the U.S. 505(b)(2) 3. Generic drug Approval Korean Incrementally Modified Drug (IMD) Approval IMD modification can encompass modification of the structure, formulation, or indication of existing drugs. IMD is generally recognized as an improved version of the original drug in terms of safety, efficacy or convenience. Hanmi's Incrementally Modified Drug, Esomezol, Enters US market recently. This is the first Korean case of overcoming the Hatch Waxman patent barrier of the US. Pharmaceutical Companies can reduce astronomical budget required to develop a new drug. Be careful about Green List of Patent Linkage

24 Chinese DE

25 Data Exclusivity: 6 years Regulations for Implementation of the Drug Administration Law of the People s Republic of China (Decree of the State Council No. 360) Article 35 The State protects undisclosed data of drug study and others which are independently acquired and submitted by drug manufacturers or sellers to obtain production or marketing approval of the drugs in question which contain new chemical entities. No one may make unfair commercial use of the said data. Within six years from the date a drug manufacturer or seller obtains the approval documents for producing or marketing a drug containing new chemical entities, if any other applicant uses the data mentioned in the preceding paragraph to apply for approval for production or marketing of the drug in question without permission of the original applicant who has obtained the approval, no approval may be given to any other applicant by the drug regulatory department except that the data submitted are acquired independently. No drug regulatory department may disclose the data set forth in the first paragraph of this Article except (1) for the need of public interests; or (2) where steps are taken to ensure that the data are protected against unfair commercial use.

26 Possible Problem on Data Exclusivity? It is still unclear how this DE would apply to import drugs, which are manufactured abroad to be marketed within China. The last portion of the article sets out exception when the State may disclose clinical trial data. Therefore it does not support the construction that the state will not give marketing approval to a generic company following the establishment of the national standards of the new drug Special 301 Report pointed that there is evidence that generic manufacturers have, in fact, been granted marketing approvals by the State Food and Drug Administration (SFDA) prior to the expiration of this period, and in some cases, even before the originator s product has been approved.

27 2013 Special 301 report China IPR Protection for Pharmaceutical Products The United States is very concerned about barriers in China to IPR protection for pharmaceutical products. In the patent area, China s revised implementation of Article 26.3 of its patent law has led the State Intellectual Property Office (SIPO) to refuse to consider post filing supplementary test data supporting previously filed patent applications, contrary to the practice of the major patent offices around the world. This has led Chinese authorities not only to reject pending patent applications but also retroactively to revoke previously granted patents. These revisions make obtaining protection of patents of a reasonable scope very difficult in China when compared to other major markets. In addition, the United States continues to encourage China to provide an effective system for expeditiously addressing patent issues in connection with applications to market pharmaceutical products. In addition, the United States continues to have concerns about the extent to which China provides effective protection against unfair commercial use, as well as unauthorized disclosure, of undisclosed test or other data generated to obtain marketing approval for pharmaceutical products. China s law and its WTO accession commitments require China to ensure that no subsequent applicant may rely on the undisclosed test or other data submitted in support of an application for marketing approval of new pharmaceutical products for a period of at least six years from the date of marketing approval in China. However, there is evidence that generic manufacturers have, in fact, been granted marketing approvals by the State Food and Drug Administration (SFDA) prior to the expiration of this period, and in some cases, even before the originator s product has been approved. The United States was encouraged by China s 2012 JCCT commitment to define new chemical entity, a term that is central to the marketing approval process, in a manner consistent with international research and development practice. The United States looks forward to China s implementation of this commitment without undue delay.

28 New Drug Observation Period? Provisions for Drug Registration(SFDA Order No. 28) Section 3 New Drug Observation Period Article 66 In order to protect the public health, the State Food and Drug Administration may set an observation period for any new drug approved for production. The observation period of a new drug shall be no longer than five years from the date the drug is approved for production. During the observation period of a new drug, the State Food and Drug Administration shall not approve other manufacturers to produce, change dosage form of or import the drug. => It is still unclear how this Observation Period would apply to import drugs. Applications for clinical trials submitted by Chinese local company will be acceptable. Article 71 Starting from the date a new drug enters the observation period, other registration applications for the same drug shall no longer be accepted. The other applicants applications for the same drug already accepted but not yet approved for clinical trials shall be returned; upon the expiration of the observation period of the drug, the registration of a generic or import drug may be applied for. => Such Period is applied to the drug of a non originator, a local company. Due to that, even an IND request of the drug originator cannot be accepted.

29 Provisions and Availability Around the World Workshop Pharma 4 Data Exclusivity Gabriel Di Blasi

30 DATA EXCLUSIVITY IN BRAZIL DRUGS FOR HUMAN BEINGS Law No. 9,279/96 (art. 195, XI, XII and XIV) No specific period of time for data protection Criminal sanctions under Unfair Competition Disclosure by government entities possible when necessary to protect the public health/based on public interest No prohibition to use data for request of authorization for the commercialization of the drug No administrative procedure to prevent the disclosure of data

31 DATA EXCLUSIVITY FOR VETERINARY AND AGROCHEMICAL USE Law No. 10,603, December 17 TH, 2002 Originated by the Provisional Act 69/02 Provides for protection for non-disclosed information for veterinary and agrochemical products only Up to 10 years protection Does not apply for data for medicines for human beings

32 DATA EXCLUSIVITY BRAZILIAN MARKET OVERVIEW The generic market represents 25% of the global pharmaceutical market Brazilian pharma companies provide 88% of the generics in the market

33 GENERIC SALES IN BRAZIL 1. Brazil 88% 2. Switzerland 5,1% 3. India 3,6% 4. Germany 1,8% 5. USA 1,1% 6. Canada 0,3%

34 DATA EXCLUSIVITY IN BRAZIL COMPARATIVE ANALYSIS Lundbeck AS and Lundbeck Brasil Ltda./. ANVISA Brazilian Superior Court STJ SLS nº 1425/DF The STJ reversed the decision suspending the marketing approval provided by the ANVISA based on public interest. The maintainance of the suspension decision would weaken the National policy of the acess to generic drugs and would worsen the public health economy. Also, this decision strengthens the Brazilian Generic Market. Eli Lilly and Company and Eli Lilly do Brasil LTDA./. ANVISA Case No The application of the 10 years protection term, as encompassed for pharmaceutical products for veterinary use, fertilizing and agrochemical, cannot be extended to pharmaceutical products destined for human use.

35 Possible issues for debate Are there ways of satisfying TRIPs 39.3 requirements without classic DE? Would payment of a reasonable royalty protect against unfair commercial use? What is a new chemical entity? Patentable? Marketed for the first time in the country concerned? Marketed for the first time anywhere in the world? What is the minimum time required for DE by TRIPs? When should DE run from? First authorisation anywhere or in the country concerned? (The permanent exclusivity issue) Should DE be extended beyond NCEs? Is there a tension between increasing pressure (e.g. in Europe) for transparency of clinical trial data and DE? Is DE just a way for big pharma to extend its monopoly position? Does DE prevent access to medicines? What is the likely role of DE in emerging markets? How might it benefit emerging market economies? 35

36 TRIPS Article 39(3) Members, when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products which utilize new chemical entities, 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. 36

37 Thank you ありがとう Obrigado Kiitos 37