Combination Products: Jurisdictional Issues

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Combination Products  Jurisdictional Issues

• MassMEDIC Presentation
• March 28, 2006
• Janice Hogan, Esq.
• Partner
• Hogan Hartson, LLP
• jmhogan_at_hhlaw.com

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Determining Jurisdiction over Combination Products

• FDA procedure for determining which center within
  FDA shall have primary jurisdiction for the
  premarket review of combination products (21
  C.F.R. 3.1)
• FDA determines the appropriate center based on
  the primary mode of action of the combination
  product (21 C.F.R. 3.4)
• Designation of center does not preclude
  consultation with another center, or requiring
  separate applications

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Two Alternative Approaches

• Combination Products covered by an Intercenter
  Agreement
• Request for Designation for combination products
  not covered by an Intercenter Agreement or for
  which the center designation is in dispute or
  otherwise unclear

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Intercenter Agreements

• Set forth the allocation of responsibility for
  certain categories of products or specific
  products (21 C.F.R. 3.5(a)(1))
• Intercenter Agreements provide non-binding
  determinations as guidance to the public (21
  C.F.R. 3.5(a)(2))
• The sponsor of a premarket application or
  required investigational filing for a combination
  product covered by an Intercenter Agreement
  should contact the designated center before
  submitting an application to confirm coverage and
  to discuss the application process (21 C.F.R.
  3.5(a)(3))

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Intercenter Agreements

• Apply to all 3 centers
• Use examples, but not all inclusive
• Intercenter Agreements now written so long ago
  that they are not up to date and are undergoing
  review for possible revision

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Request for Designation

• Formal determination by FDA on assignment of the
  lead agency center for the products premarket
  review and regulation
• Should be filed whenever
• intercenter agreements do not cover a combination
  product
• product jurisdiction is unclear or in dispute
• When to File Before manufacturer files an
  application for premarket review (either
  marketing or investigational)

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Request for Designation

• RFD is a 15 page or less summary document that
  includes
• identity of sponsor
• description of the product
• sponsors recommendation as to which component
  should have primary jurisdiction and statement of
  reasons

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Request for Designation

• Primary mode of action - Key elements in an RFD
  argument for regulation under the device or drug
  authorities include
• Relevant legal definitions (drug, device,
  biologic, combination product)
• Scientific description/analysis
• Relevant precedents (cite or distinguish)
• Policy arguments (re center expertise, FDA
  convenience)

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Request for Designation Timing

• Review Timing
• Each Request for Designation will be reviewed for
  completeness within 5 days of receipt
• Within 60 days of receiving a complete request,
  the FDA will issue a letter of designation
  specifying the FDA component having primary
  jurisdiction
• If a letter of designation is not issued within
  60 days, the sponsors recommendation becomes
  binding

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Request for Designation Appeal

• Sponsor may request reconsideration of FDAs
  decision within 15 days of receiving letter of
  designation
• No new information may be submitted
• FDA must act on request for reconsideration
  within 15 days
• FDA may change designation (a) with the written
  consent of the sponsor or (b) without such
  consent to protect the public health or for other
  compelling purposes (21 C.F.R. 3.9(b))

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Request for Designation

• Decisions are not public
• Lack of transparency leads to industry perception
  that process is unclear and often seemingly
  inconsistent
• FDA may change designated lead Center with or
  without written consent of the sponsor to protect
  the public health or for other compelling
  reasons
• Sponsor gets 30 days notice and opportunity to
  object

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Why does it matter which center within FDA has
jurisdiction?

• Drugs, Biologics, and Medical Devices are all
  subject to unique sets of statutes, regulations,
  and guidance documents
• The separate centers within FDA have different
  organizational structures, sets of nomenclature,
  and regulatory cultures

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Regulatory Review and Approval Timeframes

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Office of Combination Products (OCP)

• OCP was established on Dec. 24, 2002, as required
  by the Medical Device User Fee and Modernization
  Act of 2002
• Responsibilities include
• assigning an FDA Center to have primary
  jurisdiction for review of a combination product
• ensuring timely and effective premarket review of
  combination products by overseeing reviews
  involving more than one agency center

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Office of Combination Products (OCP)

• Responsibilities of OCP (continued)
• ensuring consistency and appropriateness of
  postmarket regulation of combination products
• resolving disputes regarding the timeliness of
  premarket review of combination products
• updating agreements, guidance documents or
  practices specific to the assignment of
  combination products

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Jurisdictional Determinations

• To improve the transparency of the jurisdiction
  process, FDA now posts a summary list of
  jurisdictional determinations
• Capsular descriptions of selected
  jurisdictional decisions
• Limited to products that have been publicly
  disclosed by the sponsor
• Describe prior FDA RFD decisions
• Not policy statements

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Jurisdictional Determinations

• Combination Products with Drug Primary Mode of
  Action
• Cytotoxic agent and biologic for targeted cancer
  treatment
• Photosynthesizing drug and light source for
  cancer treatment
• Drug and transdermal iontophoretic delivery
  system
• Drug with implantable delivery device
• Drug and radiation emitting device for cancer
  treatment

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Jurisdictional Determinations

• Combination Products with Biologic Primary Mode
  of Action
• Biologic product with implantable delivery device
• Interferon and injector for treatment of
  hepatitis C
• Injectable protein with delivery device for
  orthopedic use
• Drug/Biologic embolization agent
• Radiolabeled antibody with detector device

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Jurisdictional Determinations

• Combination Products with Device Primary Mode of
  Action
• Laser and photosynthesizing agent for
  antimicrobial use
• Dialysate with drug component
• Drug-eluting cardiovascular stent
• Vascular graft with antibiotic
• Physical/chemical embolization product
• Cardiovascular stent and injectable drug
• Orthopedic prosthesis coated with growth factor

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FDA Guidance

• Guidance for Industry and FDA Staff Application
  User Fees for Combination Products (April 2005),
  at http//www.fda.gov/oc/combination/userfees.html
  
• Guidance for Industry and FDA Staff Submission
  and Resolution of Formal Disputes Regarding the
  Timeliness of Premarket Review of a Combination
  Product (March 2005), at http//www.fda.gov/cber/g
  dlns/comboprod.pdf
• Draft Guidance for Industry and FDA Current Good
  Manufacturing Practice for Combination Products
  (Sept. 2004), at http//www.fda.gov/oc/combination
  /OCLove1dft.html
• Intercenter Consultative/Collaborative Review
  Process (June 2004), at http//www.fda.gov/oc/ombu
  dsman/intercentersop.pdf