Edoardo Di Maggio LL.M. Candidate in Intellectual Property Law Queen Mary University of London Center for Commercial Law Studies

Table of contents

1.  TRIPS Agreement Article 39.3

2.  The United States of Biologics: Patient Protection and Affordable Care Act (PPACA)

3.  U.S.-Thai FTA

4.  E.U. Sources of Law

5.  The issue of Interchangeability

6.  TPP: What to expect?

TRIPS AgreementArticle 39.3

TRIPS Agreement•  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.

Art. 39.3 Brussels Draft  •  4  PARTIES,  when  requiring,  as  a  condi8on  of  approving  the  

marke8ng  of  new  pharmaceu8cal  products  or  of  a  new  agricultural  chemical  product,  the  submission  of  undisclosed  test  or  other  data,  the  origina8on  of  which  involves  a  considerable  effort,  shall  [protect  such  data  against  unfair  commercial  use.  Unless  the  person  submiEng  the  informa8on  agrees,  the  data  may  not  be  relyed  upon  for  the  approval  of  compe8ng  products  for  a  reasonable  8me,  generally  no  less  than  five  years,  commensurate  with  the  efforts  involved  in  the  origina8on  of  the  data,  their  nature,  and  the  expenditure  involved  in  their  prepara8on.  In  addi8on,  PARTIES  shall  protect  such  data  against  disclosure,  except  where  necessary  to  protect  the  public.]  

The United States of Biologics

U.S. •  Distinction between biologics and Small

Molecule Drugs.•  U.S. regulate biologics through the Public

Health and Safety Act (PHS Act), as amended by the Biologics Price and Competition Act (BPCA) as part of the Patient Protection and Affordable Care Act (PPACA).

•  Small molecule drugs are regulated by the Hatch-Waxman Act.

ObamaCare  

•  Introduces BPCA on 23 March 2010.•  Provides 12 years exclusivity for Biologics.

•  Draws a line between “mere” and interchengeable Biosimilars.

4  Years  Data    Exclusivity  

8  Years  Marke8ng  Exclusivity  

Interchangeability•  351 (k) (4) PHS Act: Safety standards for determining

interchangeability: Upon review of an application submitted under this subsection or any supplement to such application, the Secretary shall determine the biological product to be interchangeable with the reference product if the Secretary determines that the information submitted in the application (or a supplement to such application) is sufficient to show that:

•  (A) the biological product•  (i) is biosimilar to the reference product; and•  (ii) can be expected to produce the same clinical result as the reference

product in any given patient; and•  (B) for a biological product that is administered more than once to an

individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.

Justification of 12 years exclusivity

•  U.S. consider 12 years exclusivity necessary to recover the investments (Sen. Orrin Hatch). In fact:

1.  108 months of clinical trials and test data.2.  Average expense of 1.2 billion $.3.  6-10 months needed for FDA approval.•  Field studies: 14.3 years would be the

ideal period of protection.

Justification of 12 years exclusivity

•  Was it really necessary for Thailand to set a regime of data exclusivity?

•  Side letters do not take biologics into consideration.

•  As in other FTAs, it is a move to extend what was not reached with the Brussels draft of the TRIPS Agreement.

E.U. Sources of Law

•  Directive 2004/27/EC (EU Bio-similar)

•  Regulation 2004/726/EC (Exclusivity)

Directive 2004/27/EC(15) Biological medicinal products similar to a reference medicinal product do not usually meet all the conditions to be considered as a generic medicinal product mainly due to manufacturing process characteristics, raw materials used, molecular characteristics and therapeutic modes of action. When a biological medicinal product does not meet all the conditions to be considered as a generic medicinal product, the results of appropriate tests should be provided in order to fulfil the requirements related to safety (pre-clinical tests) or to efficacy (clinical tests) or to both.

Regulation 2004/726/ECArt. 14 (11): […] medicinal products for human use which have been authorised in accordance with the provisions of this Regulation shall benefit from an eight-year period of data protection and a ten-year period of marketing protection, in which connection the latter period shall be extended to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorisation holder obtains an authorisation for one or more new thera- peutic indications which, during the scientific evaluation prior to their authorisation, are held to bring a significant clinical benefit in comparison with existing therapies.

E.U.

2  Years  Mkt   1  Year  Mkt  

The issue of Interchangeability•  Unlike the United States, European Union lacks of

interchangeability provisions.•  According to the European Medicine Agency, the product

can only be comparable.•  EMEA Guidel ines (5): “the cl inical biosimilar

comparability exercise is normally a stepwise procedure that should begin with pharmacokinetic (PK) and, if feasible, pharmacodynamic (PD) studies followed by clinical efficacy and safety trial(s) or, in certain cases, confirmatory PK / PD studies for demonstrating clinical biosimilar comparability”.

•  O n l y s i n g l e E U M e m b e r s c a n i m p l e m e n t interchangeability within their Jurisdictions.

Article 18.52

•  First ever Article of an international Agreement that sets periods of exclusivity.

•  It is controversial to interpret.•  It refers to Article 18.50 (similar to

Brussels draft of Article 39.3 TRIPS).

18.52 NegotiationsExclusivity periods:

U.S. : 12 yearsJapan and Canada: 8 years

Rest of the countries: 5 – 0 years•  All 12 countries were concerned about the

switching of the exclusivity period.•  TPP is a trade agreement, hence, should it deal

with data exclusivity?•  U.S. “concerns”: Chilling effect on investment and

unchanged prices on biosimilars (Zarxio – Neupogen).

 

Creative ambiguities

•  Article 18.52: Biologics•  1. With regard to protecting new biologics, a Party shall either:•  (a) with respect to the first marketing approval in a Party of a new

pharmaceutical product that is or contains a biologic,[60],[61] provide effective market protection through the implementation of Article 18.50.1 (Protection of Undisclosed Test or Other Data) and Article 18.50.3, mutatis mutandis, for a period of at least eight years from the date of first marketing approval of that product in that Party; or, alternatively,

•  (b) with respect to the first marketing approval in a Party of a new pharmaceutical product that is or contains a biologic, provide effective market protection:

•  (i) through the implementation of Article 18.50.1 (Protection of Undisclosed Test or Other Data) and Article 18.50.3, mutatis mutandis, for a period of at least five years from the date of first marketing approval of that product in that Party.

•  (ii) through other measures, and•  (iii) recognising that market circumstances also contribute to effective

market protection.

Edoardo Di Maggio LL.M. Candidate in Intellectual Property Law Queen Mary University of London Center for Commercial Law Studies

 

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