Positions + Comments

  • July 5, 2017 Khaudeja Bano, Chair of the CPC Postmarket Safety Working Group, Authors White Paper on Postmarket Safety Reporting for Combination Products

    With the assistance of the CPC Postmarket Safety Working Group, Khaudeja Bano (Chair of the Working Group) has prepared a white paper entitled “Industry Perspective of US Combination Product Rule: Postmarket Safety Reporting Challenges and Proposed Solutions.”

    Download the paper in PDF format.

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  • May 20, 2017 CPC Comments on FDA’s Draft Guidance Entitled “Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA”

    While the CPC agrees with many of the recommendations in the Draft Guidance, we strongly recommend that FDA revise the document to: (1) improve alignment between the Draft Guidance and existing human factors (“HF”) guidance provided by FDA and by recognized U.S. and international standards; (2) focus comparative analyses on risk, not use error rates; (3) describe HF studies as qualitative research (to assess the adequacy of the product user interface) rather than quantitative research (to assess the capabilities of the users); (4) promote innovation and improvements to the design of products to enhance safety and effectiveness; and (5) provide more information regarding topics not sufficiently addressed in the Draft Guidance.

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  • May 19, 2017 CPC Comments on FDA’s “Considerations in Demonstrating Interchangeability with a Reference Product: Draft Guidance for Industry”

    This comment letter closely mirrors the letter submitted by CPC in March 2017 with respect to the HF ANDA Draft Guidance, but contains additional comments specifically concerning interchangeability issues.

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  • October 14, 2016 CPC Requests 30-Day Extension to the Comment Period for the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (“Panel”) Meeting

    The CPC asks that FDA extend the comment period for the Panel Meeting docket for 30 days to allow stakeholders to fully assess information released by FDA shortly before the Meeting, further consider the comments made at the Meeting and prepare fulsome comments.

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  • August 5, 2016 CPC Submits Comments on MHRA’s “Human Factors and Usability Engineering – Guidance for Medical Devices Including Drug-Device Combination Products”

    The CPC believes that the MHRA draft guidance promotes harmonization with other existing guidelines (including guidance issued by FDA), but encourages further alignment on the details of those approaches.

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  • May 2, 2016 CPC Comments on FDA’s “Draft Guidance for Industry and Staff: Human Factors Studies and Related Clinical Study Considerations in Combination Product Design and Development”

    The CPC submitted comments on FDA’s Human Factors Studies and Related Clinical Study Considerations in Combination Product Design and Development Draft Guidance.  CPC’s comments included, among others, the following recommendations:

    • Resolve inconsistencies between the Draft Guidance and other FDA guidance documents
    • Better define the relationship between HF testing and clinical studies
    • Clarify expectations with respect to revalidation of post-HF validation changes
    • Clarify when HF testing is required for combination products and the scope of such testing

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  • April 20, 2016 CPC Submits Comments on FDA’s Combination Products Policy Council

    The Combination Products Coalition (“CPC”) congratulates the Food and Drug Administration on the creation of the Combination Products Policy Council.

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  • April 28, 2015 CPC Submits Comments on FDA’s Combination Product cGMP Draft Guidance

    The CPC submitted comments on FDA’s Current Good Manufacturing Practice Requirements for Combination Products Draft Guidance.  CPC’s comments included, among others, the following recommendations:

    • Revise the Draft Guidance’s language with respect to 21 C.F.R. Part 4 to:
      • Clarify that cGMP compliance with kitting activities when co-packaging constituent parts that are customarily sold in bulk as finished devices is sufficient to meet Part 4 requirements
      • Clarify that when combining a new constituent part with a cGMP-compliant kit, the manufacturer is only required to consider the combination of the kit with the new constituent part under Part 4
      • Emphasize that retrospective DHFs for combination products need only focus on combination issues
      • Provide specific examples of documentation sources that may be used to create a retrospective DHF
    • Clarify that Part 4 compliance is not assessed during the marketing application review process and that cGMP procedures generally should not be requested as part of such review

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  • April 2, 2015 CPC Submits to FDA Draft MAPPs and Review Checklists Related to IFU and Human Factors Review

    As part of its continued efforts to collaboration with FDA to improve coordination among FDA Centers, the CPC submitted draft MAPPs and checklists to Dr. Douglas Throckmorton, Deputy Center Director for Regulatory Programs, which propose a formal procedure for review of combination product instructions for use and human factors validation testing protocols.  The CPC is seeking feedback on the proposed procedures which would

    1. establish mandatory materials that must accompany each submission,
    2. ensure that sponsors receive substantive, consistent and timely feedback, and
    3. require input from all relevant FDA stakeholders, including DMEPA, Patient Labeling, and the CDRH Human Factors Group.

    The CPC intends to incorporate feedback from Dr. Throckmorton and his team before formally submitting the MAPPsdocuments to the FDA docket for formal consideration.

  • February 19, 2015 CPC Submits Comments to NIH on Clinical Trials Proposed Rule

    The CPC submitted comments to NIH’s Proposed Rule – Clinical Trials Registration and Results Submission, recommending that:

    • Applicable clinical trials involving combination products with a device PMOA should be considered “applicable device clinical trials” not “applicable drug clinical trials”
    • NIH should update the definitions of “FDA-regulated drug” and “FDA-regulated device” to include combination products with appropriate PMOAs
    • NIH should confirm that even if one constituent part of a combination product is approved, licensed or cleared independently, a combination product as a whole will be considered unapproved, unlicensed or uncleared by FDA so long as any constituent part remains unapproved, unlicensed or uncleared

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  • February 13, 2015 CPC Requests 30-Day Extension for cGMP Guidance Comment Period

    The CPC submitted a letter to the FDA docket requesting that the comment period for the Draft Guidance on Current Good Manufacturing Practice Requirements for Combination Products remain open for an additional thirty days in order to give stake holders to adequate time to analyze the complex issues and develop specific, actionable comments.

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  • February 2, 2015 CPC Submits Comments on FDA’s Draft LDT Framework

    The CPC submitted comments on FDA’s Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) Draft Guidance to recommend that FDA:

    • Couple development of the LDT Framework with
      • a “transitional” IVD approach giving more efficient access to tests developed by laboratories and traditional manufacturer
      • development of an Agency-wide guidance on companion diagnostics
    • Refrain from implementing enforcement discretion policies that restrict (1) the exchange of scientific ideas and interactions between laboratories and between laboratories and traditional manufacturers, and (2) access to the highest quality components for LDTs
    • Clarify the treatment of unmet medical need and rare disease under enforcement discretion, and the potential overlap of these categories with companion diagnostics
    • Develop, in consultation with CMS and other stakeholders, a document detailing the boundaries of the FDCA and CLIA requirements

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  • July 28, 2014 CPC Submits Letter to OMB Urging Release of Draft Guidance Outlining FDA’s Proposed Regulation of LDTs

    The CPC sent a letter to OMB urging release of draft guidance outlining FDA’s proposed regulation of LDTs. The letter emphasizes the importance of the draft guidance in advancing discussion about optimal regulation of LDTs and IVDs and, possibly, a combined regulatory system.

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  • June 4, 2014 CPC Submits Comments on FDA’s Policy to Be Proposed Regarding Premarket Notification Requirements for Modifications to Legally Marketed Devices

    The CPC submitted comments on FDA’s Report to Congress entitled Report on FDA’s Policy to be Proposed Regarding Premarket Notification Requirements for Modifications to Legally Marketed Devices, requesting that FDA take the following actions to clarify the application of any resulting guidance to combination products:

    • Expressly declare the applicability of the guidance to
      • combination products marketed pursuant to 510(k) clearance and
      • class II equivalent device constituent parts.
    • Include specific examples involving modifications to combination products to which the guidance applies.

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  • May 23, 2014 CPC Submits Paper on Improving Patient Care Through Better Combination Product Regulation

    The CPC submitted to FDA a white paper entitled Improving Patient Care Through Better Combination Product Regulation recommends the following improvements to the FDA combination product review process to enhance efficiency and consistency:

    1. Improve cross-Center coordination from the start of the review process to ensure consistent decision-making
    2. Improve communications with sponsors by coordinating guidance that conveys FDA requirements rather than more limited Center, Office, or Division standards
    3. Improve justifications for decisions while keeping an open mind to sponsors’ well-reasoned proposals

    The white paper also summarizes the results from CPC’s manufacturer survey on FDA’s review process and contains an appendix with recommendations for improvements specific to medical device usability testing.

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  • April 2, 2014 Letter to Commissioner Hamburg Requesting Release of Combination Product GMP Guidance

    The CPC’s letter urged Commissioner Hamburg to release pending combination product GMP guidance as soon as possible, making the following points:

    • The combination product GMP final rule contains many unresolved ambiguities, making full compliance difficult.
    • FDA has already taken enforcement action based on the GMP final rule, which is unfair because FDA has not yet provided clarification on critical compliance issues.

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  • October 3, 2013 CPC Submits Comments on FDA’s Draft Guidance on Medical Device Reporting for Manufacturers

    The CPC submitted comments on FDA’s Draft Guidance on Medical Device Reporting for Manufacturers addressing the following issues:

    • The immediate need for a final rule governing postmarketing safety reporting for combination products.
    • The reporting requirements in the Draft Guidance should align with those included in the combination products postmarketing safety reporting proposed rule.

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  • September 26, 2013 CPC Meets with Representatives from CDER, CBER, CDRH, OCP, and OSMP in Silver Springs

    The CPC met with representatives from CDER, CBER, CDRH, OCP, and OSMP in Silver Springs to discuss members’ top priorities related to combination product issues:

    • Clarification of the roles and responsibilities of each Center, as well as OCP
    • CDER and CBER expectations regarding human factors and usability studies
    • FDA requests for home-use/actual-use data
  • July 9, 2013 CPC Comments on FDA Guidance on Glass Syringes for Delivering Drug and Biological Products

    The CPC commented on FDA Guidance on Glass Syringes for Delivering Drug and Biological Products requesting:

    • Further clarity that the guidance applies only to products not yet cleared or approved, unless the products are undergoing significant changes requiring a new 510(k) or PMA.
    • Removal of recommendations not specific to the connectivity issue addressed in the guidance.
    • That the guidance address connectability issues due to luer access devices that do not meet the design specifications of ISO 594-1 and 594-2 Standards.

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  • July 1, 2013 CPC Comments on FDA’s Draft Guidance on Use of International Standard ISO-10993 “Biological Evaluation of Medical Devices Part 1: Evaluation and Testing”

    The CPC submitted comments for FDA Draft Guidance on the use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing, requesting that FDA provide additional guidance on the following issues:

    1. Considerations that manufacturers of combination products should analyze to determine the proper biocompatibility testing required to support a combination product marketing submission
    2. Whether the principles set forth in the Draft Guidance apply to all device constituent parts of combination products, regardless of a particular combination product’s primary mode of action

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  • June 30, 2013 CPC Submits Comments to FDA’s Draft Guidance on Rheumatoid Arthritis: Developing Drug Products for Treatment

    The CPC submitted comments to FDA’s Draft Guidance on Rheumatoid Arthritis: Developing Drug Products for Treatment, noting that that the general drug-device combination product guidance should not be included in RA-specific guidance.  Specifically, the comments requested:

    • That FDA delete general information on drug-device combination products and issue it in separate guidance and/or clarify how such information is specific to combination products intended for use in RA treatments.
    • That FDA require bench testing instead of additional clinical data for a bridging study for all modifications to the combination product not involving a change to the formulation of the drug constituent part or a change to the device constituent part that would result in a new route of administration.
    • Clarification on FDA’s requirement for a “real-life use study” when transitioning between a pre-filled syringe to an autoinjector.
    • That FDA reconsider its recommendation the human factors studies be conducted early in the development of a RA drug product.

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  • June 12, 2013 CPC Submits Comments on FDA Proposed Rule: Use of Certain Symbols in Labeling

    The CPC submitted comments on FDA proposed rule, Use of Certain Symbols in Labeling.  The CPC requested that FDA provide clarification on the following points:

    1. Application of the proposed rule to combination products;
    2. The meaning of “a standard FDA recognizes” in relation to symbols that labelers would be permitted to use;
    3. How the symbol glossary must “contemporaneously accompany” applicable product labeling.

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  • May 23, 2013 CPC Comments on FDA Draft Guidance on Distinguishing Medical Device Recalls from Product Enhancements; Reporting Requirements

    The CPC’s comments addressed three issues:

    • The need for better clarification between enhancements and recalls.
    • Whether FDA is expanding regulatory reporting requirements under 21 C.F.R. Part 806 through the guidance document.
    • Whether some of the guidance on enhancements addresses topics better reserved for new guidance FDA is developing on premarket notifications following product modifications.

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  • April 19, 2013 CPC Comments on FDA Draft Guidance on Submissions for Postapproval Modifications to a Combination Product Approved Under a BLA, NDA or PMA

    The CPC’s comments recommended changes to the guidance document that would address the following issues:

    • Whether the guidance only addresses the type of submission required if a manufacturer determines that a submission is necessary, or if it also addresses how manufacturers should evaluate whether a submission is required.
    • The types of submissions required when a change is made to a device constituent part that would be subject to 510(k) rules if it were a stand-alone device.
    • The need for new guidance on how to apply current regulations and guidance to determine whether a postmarket change to a constituent part requires a postmarket submission.

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  • April 7, 2013 CPC Labeling Q&A Matrix

    The CPC’s submitted to FDA a Q&A matrix that addressed the following topics:

    • The timing of the feedback provided to companies resulting from BLA/NDA reviews of instructions for use, product and secondary packaging labeling that accompany new pre-filled injectors.
    • FDA requests for changes to IFUs that have been validated in human factors studies conducted in accordance with Design Controls pursuant to 21 C.F.R. §820.30; Human Factors and Usability guidance issued by CDRH and widely accepted standards.
    • Information related to the “use” of an injector that should be provided in a Medication Guide Patient IFU versus specified sections in the Prescribing Information (PI) under the regulations in 21 C.F.R. § 201.
    • The development of abbreviated/reference IFUs or “quick start guides” or “reminder cards” for medical devices.
    • FDA expectations regarding validation of minor changes to a PIFU, either after human factors studies or after product approval.
    • The level of evidence/evidentiary standard required for drug delivery device-related labeling (including promotional) claims such as “ease of use”/”simplicity of use,” convenience, user preference, reduction of accidental needle-stick claims.
    • FDA’s current stance on use of internationally accepted symbols on primary and secondary package labels.

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  • March 12, 2013 CPC Comments to FDA Draft Guidance on Design Considerations for Devices Intended for Home Use

    The CPC’s comments addressed five issues:

    • Clarity is needed regarding the reviewing roles of the different Centers and Divisions, and how the various guidance documents addressing human factors will be applied.
    • Application of the Draft Guidance to home use combination products containing a drug constituent part should be clarified.
    • The guidance should clarify in what situations human factor testing may be subject to IDE requirements.
    • User checklists that include only the most critical steps necessary to ensure safe use of combination products should be implemented as part of the draft guidance.
    • FDA should clarify what it considers to be a “device design flaw” and recognize that labeling might mitigate some risks.

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  • February 11, 2013 CPC comments on FDA’s Draft Guidance on Safety Considerations for Product Design to Minimize Medication Errors

    The CPC’s comments addressed three issues related to three issues:

    • The failure of the draft guidance to spell out the roles and responsibilities of the various offices with jurisdictional oversight of combination products with respect to human factors issues.
    • The lack of clarity regarding whether existing human factors guidance documents would be relied on by DMEPA.
    • Whether DMEPA would defer to CDRH with respect to human factors as it relates to the device function of a drug-device combination product.

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  • February 6, 2013 CPC comments on the CDRH Proposed Guidance Development Agenda for Fiscal Year 2013

    The CPC proposed changes to CDRH’s guidance development agenda including that CDRH prioritize finalizing the following two draft guidance documents:

    • The Draft Guidance for Industry and Food and Drug Administration Staff – Applying Human Factors and Usability Engineering to Optimize Medical Device Design.
    • The Draft Guidance on Total Product Life Cycle: Infusion Pump – Premarket Notification [510(k)] Submissions.

     

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  • December 14, 2012 CPC Injector Systems Human Factors Topics Matrix

    This matrix, which was submitted to FDA’s Office of Combination Products, presents the CPC’s position on the following topics with respect to the application of Human Factors to injector systems:
    • The scope of intended users that should be included in human factors studies.
    • FDA requests for modifications to labeling that has been successfully validated in human factors studies
    • “Actual Use” Studies and the collection of usability information during clinical studies.
    • Actual Use versus Injection Pads during human factors validation studies.
    • Scope of formative versus summative study objectives.
    • When revalidation is required if a change is made to an injection system
    • The classification of human factors study results used to support a delivery device change in a BLA/NDA supplement with respect to PDUFA V review goals and fees.

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  • October 24, 2012 CPC Comments on Unique Device Identification System; Proposed Rule

    The CPC’s comments on the Agency’s Unique Device Identification System proposed rule recommended that:
    • The UDI system should not apply to cross-labeled combination products.
    • UDIs should not be required for combination products unless there are no UDI or NDC numbers associated with product constituents.
    • The exceptions to the UDI requirement (at 21 C.F.R. 801.30(11)) should be clarified.
    • FDA clarify whether exceptions to the UDI requirements (at 21 C.F.R. 801.30) apply if a device is a stand-alone product or a constituent of a combination product.
    • An exception to UDI requirements be added for device constituents being shipped for further processing as part of a combination product.
    • FDA publish guidance on the application of UDI regulations.
    • FDA harmonize regulations regarding combination products.

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  • October 19, 2012 CPC Points to Consider on Co-Development / Companion Diagnostics

    The CPC submitted this document to FDA in order to present its position on various issues FDA should consider when drafting Co-Development and Other Companion Diagnostic guidance including:

    • Companion diagnostics versus combination products.
    • De novo reclassification of companion diagnostics.
    • Evidence required for approval.
    • Labeling issues.

    Download pdf (123 KB)

  • June 21, 2012 CPC Injector System Working Group Questions

    The CPC Injector Systems Working Group’s outline of key questions and issues concerning the regulatory and technical considerations of injector systems that framed the discussions during the June 21, 2012 meeting with FDA.

    Key issues include:

    • Bridging strategies for presentation switches
    • Human factors studies
    • Coordination between centers
    • Submission requirements
    • Consistency between FDA’s technical guidance for injectors and ISO standards
    • Analytical release testing requirements for the combination product
    • Consistent application of FDA and ICH guidance

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  • June 21, 2012 CPC Companion Diagnostic Questions Final

    The Combination Products Coalition Personalized Medicine Working Group’s outline of key issues and questions regarding FDA’s Draft Companion Diagnostics Guidance that framed the discussions during the June 21, 2012 meeting with FDA.

    Questions concern:

    • FDA’s thinking on the distinctions between companion diagnostics and combination products.
    • The use of de novo petitions with companion diagnostics.
    • The evidence required supporting approval of companion diagnostics, with a focus on cases where companion diagnostics are not developed contemporaneously with therapeutics.
    • Labeling associated with companion diagnostics.
    • The timing of therapeutic and companion diagnostic approvals.
    • General issues regarding the regulatory process.

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  • June 8, 2012 CPC Citizen Petition Submission

    The CPC’s citizen’s petition requesting increased transparency related to the release of information about combination products by the FDA. The requests include:
    • Improve transparency in regards to combination products.
    • Ensure that more FDA records with respect to combination product regulation are available on the FDA’s website.
    • Improve processes and procedures for guidance document development.
    • Support transparency in both broad decision-making and individual adjudication.

    Download pdf (11.9 MB)

  • April 10, 2012 CPC One Page Issue Brief

    Issue brief detailing the concerns of the CPC regarding a lack of transparency in the methods in which FDA regulates combination products.

    Download pdf (28 KB)

  • February 27, 2012 Transparency 2012 Comment Letter

    The CPC’s comment letter to FDA requesting greater openness and transparency by the Agency in utilizing and incorporating public input in the following areas of concern:
    • The production of guidance documents to address combination product questions.
    • The release of information about combination products.
    • FDA’s response to industry comments and other input related to draft guidance documents published by the Agency.

    Download pdf (463 KB)

  • December 1, 2011 Transparency in Compliance and Enforcement Data Proposals Comments

    CPC’s comments to FDA recommending that FDA’s Transparency Initiative encompass combination products and recommending how combination product issues can be incorporated into the FDA’s Draft Proposals for Public Comment to Increase Transparency by Promoting Greater Access to the Agency’s Compliance and Enforcement Data.

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  • November 14, 2011 Pivotal Device Clinical Trial Guidance Comment

    Comment letter submitted by the CPC offering a response to the Draft Guidance for Industry, Clinical Investigators, and Food and Drug Administration Staff; Design Considerations for Pivotal Clinical Investigations for Medical Devices (“Draft Guidance”). CPC’s comments addressed:

    • The failure to including labeling for combination products in the guidance document.
    • The need for FDA to provide details regarding the applicability of drug or device regulatory principles to clinical trials involving combination products.
    • The need for clarification of jurisdictional issues relating to clinical trials

    Download pdf (165 KB)

  • September 15, 2011 Classification Guidance Final Comments

    The CPC’s comment letter in response to the Draft Guidance for Industry and FDA Staff – Classification of Products as Drugs and Devices and Additional Product Classification Issues wherein we requested the Agency ensure the consistent and appropriate regulation of similar products.

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  • September 15, 2011 Innovation Initiative Final Comments with Attachment

    The CPC’s comments to the Draft Guidance for Industry and Food and Drug Administration Staff: Classification of Products as Drugs and Devices and Additional Product Classification Issues highlighting the unique aspects of combination products that need to be addressed as the Agency considers accelerating the development and regulatory evaluation of innovative medical devices, including combination products.

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  • May 1, 2011 Comments on Cross-Labeled Combination Products

    The CPC’s comments detail major questions that were posed and discussed during the March 2, 2011 meeting with OCP relating to the regulation of cross-labeled combination products, including:

    • The necessity of a cross-labeling category;
    • Differences between cross-labeling and a mutually conforming labels;
    • The relabeling of combination products;
    • The overuse of the title “cross-labeling”;
    • How the European Union handles cross-labeling; and
    • Examples of cross-labeled products.

    The document also includes an appendix that addresses where cross labeling is important in the regulation of a product.

    Download pdf (199 KB)

  • October 14, 2010 CPC Medical Device User Fee Comments FINAL

    The CPC’s comment letter in response to the August 13, 2010 Federal Register notice regarding the reauthorization of the medical device user fee program, and specifically requesting that FDA:
    • Make guidance development a higher priority.
    • Use the published list of guidance documents under development as a tool for dialogue between the Agency and stakeholders on guidance development priorities.
    • Preserve informal communications and dialogue between the Agency and stakeholders.

    Download pdf (170 KB)

  • February 5, 2010 GMP Proposed Rule Comments FINAL

    The CPC’s comments in response to the Proposed Rule for Current Good Manufacturing Practice Requirements for Combination Products issued by the FDA concerning clarifications within the final rule to:
    • Ensure that the rule is flexible and efficient.
    • Demonstrate how the proposed rule will affect existing products and manufacturers.
    • Describe the type and amount of work required to develop an appropriate implementation plan.

    Download pdf (86 KB)

  • January 29, 2010 Adverse Event Final Proposed Rule Comments

    CPC’s comments in response to the Proposed Rule for Postmarketing Safety Reporting for Combination Products concerning:

    • The proposed rule existing as a “bridge” to a unified regulation.
    • The overall impact of the proposed rule on combination products.
    • Reporting events to the manufacturer of constituent part or to the FDA.
    • The definition of “Constituent Parts” as addressed in the proposed rule.
    • Submitting reports on combination products involving multiple applications.
    • Reconciling supplemental/overlapping-reporting requirements.
    • Reporting to the lead Center.
    • Implementation issues.

    Download pdf (83 KB)

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