Test Data Protection Overview

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Test Data Protection Overview
BEIJING BRUSSELS CHICAGO DALLAS FRANKFURT
GENEVA HONG KONG LONDON LOS ANGELES NEW YORK
PALO ALTO SAN FRANCISCO SHANGHAI SINGAPORE
SYDNEY TOKYO WASHINGTON, D.C.

• Jeffrey P. Kushan, Washington, D.C.
• On behalf of the Biotechnology Industry
  Organization (BIO)

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What is Test Data?

• Data generated from testing of a regulated
  product to ensure the product may be safely used
  and is effective
• Test data is generated by rigorous, comprehensive
  and controlled scientific experiments
• Test data provides objective evidence about
  safety and effectiveness of the regulated product
  
• Test data helps protect the public health
• Regulated products may not be marketed without
  approval by government regulatory authority
• Test data is used by regulatory authorities to
  independently determine that a product is safe
  and effective before it is placed on the market
  and used by patients

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Examples of Regulated Products

• TRIPS identifies two categories of regulated
  products that are entitled to protection
• Pharmaceutical products
• Drugs small chemical molecules
• Biological products large chemical molecules
  such as proteins made by biotechnology, vaccines
• Agricultural chemical products
• Pesticides and Fertilizers chemical compounds
  used in agricultural applications

• Source TRIPS Agreement, Article 39.3.

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Generating Test Data is Risky, Expensive and
Time-Consuming

• New therapeutic agents
• On average, it costs US 1.2 to 1.3 billion and
  10-15 years to bring a pharmaceutical product
  having an active ingredient that has never been
  approved (i.e., a new chemical entity) to
  market
• Greater than 90 of products in development fail
  before getting to clinical trials, and only 30
  of those entering clinical trials are approved
• Clinical testing in humans is a significant
  contributor to cost and complexity of
  pharmaceutical development and clinical data
  generation, with scale of testing often thousands
  of patients over many years
• Agricultural chemical products
• New agricultural chemical entities typically cost
  more than US 200 million to bring to market

• Sources Dimasi et al., Manage. Decis. Econ. 28
  469479 (2007) www.croplife.org. These
  figures incorporate the costs of failed efforts
  to bring a new product to market.

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The Pharmaceutical Test Data Dossier

• A compilation of data and reports describing the
  pharmaceutical product, including
• Pre-clinical evidence, including from analysis of
  the components of the product (e.g., the active
  ingredient) by in vitro and animal testing
• Clinical evidence, including data from well
  controlled clinical investigations that evaluate
  effects of administering the product to
  individual human subjects, and summaries and
  analysis of such data
• Manufacturing information and data, including a
  description of the product, its components and
  properties, how the product is made,
  manufacturing batch records showing consistency
  and variations in the production of the product,
  etc.
• Other evidence, both from public literature and
  non-public sources, relevant to safety and
  effectiveness of the product

• Source 21 U.S.C. 355(b)(1)  505(b)(1) also,
  21 C.F.R.  314.50, which sets forth the specific
  requirements of a new drug application before the
  FDA.

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The Pharmaceutical Test Data Dossier

• Some information in the dossier cannot be
  publicly disclosed
• Personal privacy restrictions prohibit disclosure
  of information concerning the experiences of
  patients who participated in the studies
• Trade secret rights exist in various portions of
  the dossier, particularly manufacturing
  information
• Clinical data for biologics is linked to the
  particular method used to make the biological
  product
• During pendency of its review, the dossier as a
  whole is handled as confidential business
  information
• The regulatory authorities will base their
  decision to approve a new pharmaceutical product
  on the dossier considered as a whole, not on
  discrete or isolated elements of the dossier

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How is Test Data Protected from Unfair
Commercial Use?

• By providing a period of time during which a
  regulatory authority will not rely, directly or
  indirectly, on the innovators test data to
  support approval of a third party application
• Regulatory agencies rely on an innovators test
  data if they base their decision to approve a
  third party application on
• A review of the data in the innovators dossier
• An earlier approval by the same agency of the
  innovators application, or findings on the
  safety or effectiveness of the innovators
  product
• An earlier approval by another agency of the
  innovators product, or that agencys findings on
  safety or effectiveness, or
• Published summaries of the test data (e.g.,
  information in the approved prescribing
  instructions for the product)

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Market Dynamics Where Data Protection Is
Provided to Innovators

• During the data protection period, the
  innovators product competes with different
  products that can be used to treat the same
  disorder or disease
• Regulatory authority can approve other products
  supported by complete dossiers of independently
  generated clinical data
• Intense competition from different products in
  this period on average, new innovator products
  enter market within 2.5 years of market
  introduction of first innovative product
• After the data protection period ends, the
  innovators product competes with generic or
  biosimilar products
• Regulatory authorities can approve abbreviated
  applications that reference the innovator
  product, leading to less expensive versions
• Both forms of competition benefit public health

• Source Tufts Center for the Study of Drug
  Development, CSDD Impact Report, Marketing
  exclusivity for first-to-market drugs has
  shortened to 2.5 years, 11(5) (2009).

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Public Health Benefits of Test Data Protection

• Encourages companies to conduct initial clinical
  testing of new pharmaceutical products
• Provides regulatory authorities the objective
  scientific evidence needed to evaluate and
  justify approval of new pharmaceutical products
• Provides benefits to patients by encouraging
  clinical testing of new drugs, regardless of
  patent status, for use in treating unmet medical
  needs
• A new chemical entity is an active ingredient
  that has never been approved by the regulatory
  authority of the country for use in the same type
  of product

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Public Health Benefits of Test Data Protection

• Encourages additional clinical testing of an
  approved product to enable use in treating other
  diseases
• Many pharmaceutical products can treat multiple
  diseases, but each new use requires independent
  clinical proof of effectiveness and safety
• Experience shows that companies conduct extensive
  additional clinical research to support new uses
  of approved pharmaceutical products during the
  period of data protection
• Experiences with biologics approvals in the
  United States
• 47 of approved rDNA and monoclonal antibody
  products have been approved for at least one
  additional disease/disorder beyond the original
  indication
• One third of the new indications for these
  products were approved more than 7 years after
  the first approval

• Source Said et al., Continued Development of
  Approved Biological Products, Boston Consulting
  Group, White Paper (Dec. 2007)

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Public Health Benefits of Test Data Protection

• Enables lower cost, safe and effective generic
  and biosimilar products to be brought to market
• Products can be approved on the basis of an
  abbreviated application not having a complete
  dossier of clinical evidence
• A generic drug must have the identical active
  ingredient and exhibit the same behavior in the
  body
• A biosimilar product cannot be identical to the
  innovator product, and requires additional
  clinical evidence to support approval
• Generics and biosimilars are produced for a
  defined and existing market, have a far lower
  risk of failure of development, and a
  significantly reduced cost of development
  relative to innovator products

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Phases of a Pharmaceutical Product
AbbreviatedApproval Possible
Pre-Clinical
Clinical Development
Third Indication
Second Indication
First Indication
Data Protection Period
Start of Clinical Investigations
First Approval
Second Approval
ThirdApproval
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Two Different Obligations in TRIPS Article 39

• Article 39.2
• Requires laws/regulations that enable private
  parties to prevent unauthorized disclosure of
  their confidential business information (i.e.,
  trade secret protection) by any entity, including
  government agencies and employees
• Article 39.3
• Requires measures that prevent a regulatory
  authority from making unfair commercial use of
  undisclosed test or other data provided to the
  authority to support grant approval of the
  innovator product

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Article 39.3 Imposes Distinct Obligation Beyond
Non-Disclosure

• If Article 39.3 only imposed obligation to not
  disclose confidential information, it would be
  redundant with obligations of Article 39.2
• Separate and distinct provisions in an
  international agreement are presumed to impose
  distinct obligations
• Second sentence of Article 39.3 requires
  protection from unfair commercial use even if a
  Member requires disclosure of some of the
  protected test data for reasons necessary to
  protect public health
• Regulatory authorities often require a summary of
  the clinical trials to be included in the
  prescribing instructions for the product, and
  make other clinical trial information available
  online

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What is Unfair Commercial Use

• Something that provides an unfair commercial
  advantage to one entity at the expense of another
• A regulatory agencys conclusion that a generic
  or biosimilar product is safe and effective
  product is necessarily based on the test data
  dossier supporting approval of the referenced
  innovator product
• The regulatory authority thus uses the
  referenced innovators test data dossier to
  justify approval of an abbreviated application
  referencing an innovator product
• Allowing a generic or biosimilar product to enter
  the market too soon after the referenced
  innovator product has been launched constitutes
  an unfair commercial use of innovators test data

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The Unique Bifurcated U.S. System

• New and generic drugs regulated under the  505
  of the Federal Food Drug and Cosmetic Act
• Drugs generally have a small molecule active
  ingredient
• Abbreviated New Drug Application (ANDA) may not
  be filed for a period of 5 years from original
  approval of new drug, unless it contains a patent
  challenge, in which case it may be filed 4 years
  after approval
• If ANDA filed during fourth year, FDA may not
  approve the ANDA until 7.5 years after NDA
  approval
• ANDA approvals take on average 2 to 2.5 years
  from filing to be approved.
• Effectively, U.S. provides 7.5 years of data
  protection from the approval date of a new drug
  application

• Source 21 U.S.C.  355(b)(1) (new drug
  applications) 355(b)(2) (other applications
  referencing earlier approval) 355(j)
  (abbreviated new drug applications)

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The Unique Bifurcated U.S. System

• Biological products are regulated under  351 of
  the Public Health Service Act
• No current abbreviated pathway for approving
  biosimilar biological products
• Each application (BLA) must be supported by
  independently generated clinical data
• This means these products presently have an
  infinite period of data protection
• Pending legislation
• Biosimilar legislation that has passed the
  relevant House and Senate Committees would
  provide 12 years of data protection, plus an
  additional 6 months for pediatric studies

• Source 42 U.S.C.  262 H.R.

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European Practices

• Drugs and biological products are regulated under
  a single legal regime in the centralized approval
  procedure of the European Medicines Agency
• Single legal regime applies to both small
  molecule drugs and large molecule biological
  products
• Effective period of data protection for both
  types of products is 10 years, which may be
  extended to 11 if a new indication representing a
  significant clinical benefit in comparison with
  existing therapies is approved within 8 years of
  original approval

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Market Incentives Provided by Test Data
Protection

• Providing test data protection encourages
  innovator companies to enter and participate in
  markets, which increases the likelihood of
• Earlier launches of innovator products in the
  market, given the increased prospect for
  commercial success in that market
• Improved education among caregivers about the
  pharmaceutical product, its uses and its safety
  profile
• Entry of generic and biosimilar products once
  viable domestic market for the innovator product
  has been established
• Domestic clinical investigations to evaluate new
  applications of product or its therapeutic
  profile in the domestic population

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Data Protection vs. Patents

• Two distinct and independent mechanisms
• Patents protect technological inventions, and
• Are limited to a specific technological advance,
  and measured by novelty/inventiveness over public
  knowledge
• Enable owner to prevent unauthorized use of the
  invention
• Original patents often expire around time of
  product approval due to extended period of
  development and clinical testing
• May not be available for new products that
  contain a publicly known chemical compound, or
  for new uses discovered by additional clinical
  research
• Often do not provide adequate commercial
  protection in countries that do not have a
  long-established or robust patent systems

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Unique Features of Test Data Protection

• Test Data protection
• Is available even if the pharmaceutical product
  is not eligible to be patented, which ensures
  there is an incentive to conduct clinical testing
  needed to secure approval of new drugs and new
  uses of drugs
• Only prohibits regulatory agency from relying on
  innovators approval to approve another
  application any entity can secure marketing
  approval by supporting the application with a
  complete and independently generated clinical
  dossier
• Provides greater certainty than patents, both in
  developed and developing country markets, which
  functions to provide an incentive for innovator
  companies to undertake risky, expensive and
  difficult clinical testing of the product

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Conclusions

• Test data protection systems
• Provide all countries with many important public
  health benefits
• Support competition by both product innovation
  and on price
• Test data protection under TRIPS must extend
  beyond simply preventing public disclosure or
  theft of confidential data in the test data
  dossier
• The only viable way to provide effective test
  data protection is to defer the date on which a
  regulatory authority may rely on a prior approval
  of an innovator product to approve a generic or
  biosimilar application

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