Timely and Effective Premarket Review
OCP is to ensure the timely and effective premarket review of combination products by overseeing the timeliness of reviews and coordinating reviews involving more than one Center. On July 31, 2002, FDA issued an internal document to provide 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. The objectives of this internal document were to improve intercenter communication as well as timeliness and administrative consistency in the conduct of intercenter consultative and collaborative reviews. This internal document was formally incorporated into the FDA Staff Manual Guide, Agency Program Procedures, Volume IV in July 2005, and is available on the OCP Web site at: Intercenter Consultative/Collaborative Review Process.
OCP FY 2008 activities and impacts related to premarket review are as follows:
- Facilitated the premarket review processes for a variety of combination products presenting complex regulatory issues. OCP fostered early interactions between industry and FDA to develop clearly delineated regulatory schemes for the development and expeditious review of marketing submissions for combination products. Responding to requests from both industry and FDA review staff, OCP consulted and provided guidance on the unique regulatory issues presented by combination products. OCP also facilitated and led or participated in meetings and discussions to ensure continued and consistent communication between sponsors and FDA review staff.
- Responded to 359 contacts from Centers and sponsors relating to premarket review issues. Sixty-six percent (237 of 359) of the contacts were from external stakeholders, and 34 percent (122 of 359) of the contacts were from internal stakeholders. These activities included a number of specific issues that contributed to ensuring the timely and effective review of combination products. Examples included: clinical study design, clinical study monitoring approaches, co-packaged products, pre-filled products, cross labeling, indications for use/intended use, labeling, cGMPs, master files, content and format of marketing applications, number of marketing applications, over-the-counter monograph drugs, product design, regulatory pathways, review processes, separately approved products, test methods, registration and listing, and user fees. OCP facilitations addressed needs in areas, such as, dentistry, drug delivery, in-vitro diagnostics, iontophoresis, lock-flush products, medical imaging, pharmacogenomics, photodynamic therapy, and wound healing products.
- Publication of Draft Guidance to Industry: New Contrast Imaging Indication Considerations for Devices and Approved Drug and Biological Products, September 2008. As part of MDUFA II, FDA agreed to develop guidance for medical imaging devices for use with imaging drug or biological products, for example, various contrast agents or radiopharmaceuticals. Before publication, OCP requested stakeholder comments on areas of interest for guidance development. OCP also convened an intercenter working group to consider the principles. The guidance clarifies the approaches for product development and submission of applications by device and drug developers and is available at: Combination Products Guidance Documents.
- Continued development of possible regulatory pathways for new products intended to be used with another sponsor’s already approved product. Subsequent to an OCP public workshop held in FY 2005 entitled, “Combination Products and Mutually Conforming Labeling,” in cooperation with the Drug Information Association, OCP continued to develop clarifications on numerous public health and legal issues that were discussed at the meeting and in written comments submitted to OCP. OCP frequently worked with the Centers and the Office of Chief Counsel on a product-specific basis to develop approaches to resolve the difficult and complex legal and public health issues associated with determining when cross labeling is necessary when another sponsor’s already approved product is involved. OCP will continue to develop information for stakeholder comment on the regulatory approaches for cross-labeling to ensure safety and effectiveness of differently regulated products. In the interim, some aspects of cross-labeling considerations were included in the OCP draft guidance “New Contrast Imaging Indication Considerations for Devices and Approved Drug and Biological Products” (see paragraph above).
- Continued development of guidance on the scientific and regulatory pathway issues for injectors. Various types of injector devices are increasingly being developed to enhance the delivery of drugs or biological products. The working group completed a draft guidance to address the scientific and regulatory pathway issues for injectors. At the close of FY 2008 (September 30, 2008), this draft guidance was pending.
- Participated in numerous intercenter working groups clarifying issues related to combination products and product jurisdiction. The working groups are developing policies and guidances for the development, jurisdiction and assignment, and/or regulatory review of a variety of new technologies and types of combination products. Topics covered by specific working groups in FY 2008 included: artificial pancreas, nanotechnology, premarket issues, product labeling, biologics and tissues, and wound care products. Also, OCP participation on the stent working group contributed to the FDA guidance documents published March 2008 entitled, “Guidance for Industry: Coronary Drug-Eluting Stents-Nonclinical and Clinical Studies” and its companion document.
- Continued to promote activities for pharmacogenomic drug-diagnostic device regulatory pathways. Personalized medicine is a rapidly expanding therapeutic area and was one of the Department of Health and Human Services (HHS) FY 2007 Departmental Objectives. Pharmacogenomics is a form of personalized medicine that utilizes specific testing technologies to guide and inform the use of certain drugs, biological products, and devices. OCP is facilitating development of the regulatory principles for in vitro diagnostics that are important to the use of a therapeutic product.
- Served as a resource for FDA staff on the appropriate use and interpretation of the combination product categorization algorithm and associated categories. The categories for combination products are based on the types of regulatory issues the products present, for example, a prefilled drug or biologic delivery system; a device physically combined with a drug or biologic; a co-packaged product or kit; or separate products with mutually conforming labeling. All premarket applications in CBER, CDER, and CDRH are categorized as to whether they concern a combination product, and if so, what type.
- Analyzed monthly reports from CBER, CDER, and CDRH capturing data on the categorization of combination products. Data on new product applications in CBER, CDER, and CDRH are reviewed by OCP to ensure that combination product categories are being accurately assigned. Questionable categorizations are reported to the Centers for clarification and possible correction to ensure the accuracy of the data reported annually to Congress on the numbers and types of combination products under review. These data are also used by OCP to monitor the progress of premarket applications for combination products under review by FDA.
Consultative/Collaborative Review Process
OCP FY 2008 activities and impacts related to the consultative/collaborative review process are as follows:
- Actively monitored the intercenter consultation process on combination products under review to ensure the requesting Center received timely and constructive feedback. OCP tracked, monitored, and followed up on a total of 371 intercenter consult requests in FY 2008. Consult requests by Center are presented in the next section of this report.
- Provided support to FDA review staff to facilitate the intercenter consultation process for intercenter consults. Many of the consults required extensive OCP involvement in areas that included clarifying internal operating procedures, roles, and responsibilities; identifying consulting divisions and contacts; clarifying due dates and completion status; and facilitating access to electronic review documents. Other areas of extensive OCP involvement included clarifying specific review requirements under the Prescription Drug User Fee Act (PDUFA) and MDUFA II; identifying resolution of barriers to timely completion of consultation requests; and ensuring timely receipt of review documents by the consulting Centers. Approximately 70 intercenter consults required significant OCP support or facilitation to complete the consult request in a timely fashion.
- Facilitated intercenter communication and procedures for the consult review process and issues relating to specific product areas. OCP facilitations assisted in the review of a wide range of products. Significant consultations requiring multiple meetings and interactions were undertaken in a variety of areas, such as, diagnostic tests for personalized use of drug/biologic products; injector delivery systems; medical imaging drugs and devices; and wound care. Significant issues relating to the consult review process were facilitated in a variety of areas, including the coordination of premarket cGMP inspections; certificates to foreign governments; electronic submissions; facilitation for groups that are new to the consult process; and intercenter compliance consultations. Other significant areas requiring OCP facilitation included posting of combination product information on the National Library of Medicine Web page; registration and listing; the regulatory approach for devices that enhance the safety of drug/biological products; and risk determination assessments.
- Initiated and conducting a test of an automated system for tracking and managing intercenter consult requests. Testing of the system is to determine if the system will be used FDA-wide. Information gained from the initial test is being used to revise the system with changes being incorporated into an updated system scheduled to undergo testing in FY 2009.