Office of Combination Products: Programs and Priorities

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Office of Combination ProductsPrograms and
Priorities
MassMEDIC Innovation at the Crossroads February
28, 2003

• Mark D. Kramer
• Director, Office of Combination Products

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Overview

• Introduction to the Office of Combination
  Products
• OCPs Role in the Assignment and Review of
  Combination Products
• FDA Initiatives for Combination Products

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Combination Product

• Combination Product (21 CFR 3.2(e))
• a product comprised of two or more regulated
  components that are physically, chemically or
  otherwise combined or mixed as a single entity
• two or more separate products packaged together
  (e.g., drug and device products) or
• provided separately but intended for use together
  where both are required to achieve the intended
  use, indication, or effect and where mutually
  conforming labeling is needed.
• NOT drug-drug, device-device, or
  biologic-biologic combinations

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Regulation of Combination Products

• Assigned to lead Center based on primary mode
  of action
• Intercenter consultation
• Premarket regulatory authorities
• One application vs. two
• Postmarket regulatory authorities

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Employee and Industry Views

• Information Gathering
• learn more about combination products issues
• areas needing policy development or revision
• suggestions for improvement
• identify best practices

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Employee Perspectives

• See other Centers as black box
• Intercenter interactions strained by lack of
  familiarity with organizations, statutes,
  regulations, policies, timeframes, and cultures
  of other Centers
• Timeframes not always met
• Awareness of frontline staff to jurisdiction and
  combination product issues
• Degree of managerial oversight
• Mail system inadequate

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Industry Perspectives

• Need more
• clarity
• predictability
• transparency
• consistency
• communication
• speed
• legislation

• Need less
• conflict
• turf battles

Public Meeting November 25, 2002
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Office of Combination Products (Established
December 24, 2002)

• Assignment of combination products
• Timely and effective premarket review
• Facilitation and coordination
• Centers responsible to Office for timeliness
• Consistent and appropriate postmarket regulation
• Dispute resolution
• Review/update guidance, agreements, practices
• Reports to Congress

P. L. 107-250 -- enacted 10-26-02
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Assignment of Combination Products

• Role of Ombudsmans Office
• Classification under Section 563 of the Act
• Role of Office of Combination Products
• Determine primary mode of action
• Assign lead Center
• Role of Centers

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Assignment of Combination Products

• Initiatives
• Primary Mode of Action
• Selection of regulatory authorities (premarket
  and postmarket)
• 1 application vs. 2
• RFD Process
• RFD Precedent Documentation
• Intercenter Agreements

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Review of Combination Products

• Initiatives
• Monitoring, Tracking and Reporting
• Consults vs. other applications
• Intercenter Consultation/Collaboration Process
• Reviewer tools and training
• Submission Format and Content
• Mail System

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Review Management

• SOP on Intercenter Consultative/Collaborative
  Review Process
• Effective July 31, 2002
• Revised February 2003

• Provides the policies and procedures for FDA
  staff to follow when requesting, receiving,
  handling, processing, and tracking formal
  consultative and collaborative reviews of
  combination products, devices, drugs and
  biologics.

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SOP -- Objectives/Scope

• To improve intercenter communication on
  combination products.
• To improve the timeliness and consistency of
  intercenter consultative and collaborative
  reviews.
• Does not establish standards for when a
  consultative or collaborative review is needed.

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SOP -- Consultation

• Consultation -- a review activity in which a
  reviewer in one Center requests advice from a
  reviewer in another Center on a specific question
  or issue raised in the review of a submission.
  The consultative review will be used to assist
  the requesting reviewer in making appropriate
  regulatory/scientific decisions.

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SOP -- Collaboration

• Collaboration -- a review activity in which
  reviewers in two or more Centers have primary
  review responsibilities, generally for a defined
  portion of a submission. Regulatory and
  scientific decisions will be made by the
  management of each Center for that portion of the
  review assigned to it, including the decision to
  approve or disapprove the product.

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SOP -- Policy Highlights

• Consults Count
• Agencys work
• Consulted Centers are accountable for
• quality
• timeliness
• Consulted reviewers receive credit

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Requesting Center Responsibilities

• Identify need for consultation ASAP.
• Identify specific questions/areas of concern.
• Send it to the right place/make sure it gets
  there.
• Agreement on/accountability for timeframes.
• Frequent communication with consulted Center.
• Track review progress.
• Keep OCP informed.
• Keep sponsors informed.

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Consulted Center Responsibilities

• Notify requester ASAP if review will be delayed.
• Negotiate new due date or reassign and meet
  previously established date.
• Perform complete review of issues identified by
  requester. If the assigned reviewer does not
  have expertise, reassign as appropriate.
• Prepare review memorandum with
• brief summary of information reviewed
• recommendations for action
• letter-ready comments/requests for information
• Keep OCP informed.

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Testing -- General Considerations

• Elucidate primary mode of action (jurisdiction)
• Consider regulatory pathway and questions that
  need to be addressed for that pathway
• Consider the additive effect of the new
  component
• effect of drug or biologic on device/vice versa
• consider safety, effectiveness and
  toxicology/biocompatibility
• Review guidance documents that may address
  related issues
• Consult with FDA

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Submission Content, Format and Process

• Discuss with review staff of lead Center
• Ask for advice from consulting Center
• Example would a stand-alone section for
  consulting Center be helpful?
• Communication, communication, communication

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Contact Us Agency Jurisdictional Experts

• Suzanne OShea
• FDA Product Jurisdiction Officer
• [phone]
• CBER Sherry Lard [phone]
• CDER Warren Rumble [phone]
• CDRH Gene Berk [phone]

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Contact Us Office of Combination Products

• Mark D. Kramer
• Director, Office of Combination Products
• 5600 Fishers Lane (HF-7)
• Rockville, MD 20857
• [phone]
• combination_at_fda.gov
• http//www.fda.gov/oc/ombudsman/combination.html