Did you know that Office of Combination Products (OCP) at FDA was established in 2002 as required by Sec. 204 of the Medical Device User Fee and Modernization Act of 2002 (MDUFMA) 1) to serve as a focal point for combination product issues and for medical product classification and assignment issues for agency staff and industry, 2) to develop guidance and regulations to clarify the regulation of combination products, 3) to classify medical products as drugs, devices, biological products or combination products and assign them to an FDA center for premarket review and regulation, where their classification or assignment is unclear or in dispute, 4) to ensure timely and effective premarket review of combination products by overseeing the timeliness, alignment of coordination of reviews involving more than one agency center, including through monitoring and management of the inter-center consult process, 5) to ensure consistent and appropriate post-market regulation of combination products, and 6) to resolve disputes (guidance document) regarding the timeliness of premarket review of combination products.
Note: OCP does not provide review/assessment or approval of combination products.
The traditional approach to filing CBER, CDER, or CDRH applications are
Biologic (CBER)
BLA (Biologic License Application)
IND (Investigational New Drug)
Drug (CDER)
• NDA (New Drug Application)
• IND
Device (CDRH)
• PMA (Premarket Approval)
• 510K
• IDE (Investigational Device Exemption)
With combination products, one investigational application is sufficient based on PMOA (primary mode of action) such that
• IND is submitted if combo product has a drug or biologic PMOA
• IDE is submitted if a combo product has a device as PMOA
But a sponsor may also submit separate marketing applications for different constituent parts (i.e. cross labeling of separate products). See eCTD Technical Conformance Guide (Contains Nonbinding Recommendations) to submit application.
Note: the FDA has tried to lower the regulatory burden by allowing a streamline approach type of inspection (see Inspections of CDER-led or CDRH-led Combination Products) where
CDER or drug-led PMOA with device follow 21 CFR 211 and provisions from the device QS regulation in accordance with 21 CFR 4.4(b)(1) (drug CGMP-based streamlined approach):
• 21 CFR 820.20 Management responsibility
• 21 CFR 820.30 Design controls
• 21 CFR 820.50 Purchasing controls
• 21 CFR 820.100 Corrective and preventive action
• 21 CFR 820.170 Installation
• 21 CFR 820.200 Servicing
CDRH or device-led PMOA with drug follow 21 CFR 820 and the following called-out provisions from the drug CGMPs in accordance with 21 CFR 4.4(b)(2) (device QS regulation-based streamlined approach):
• 21 CFR 211.84 - Testing and approval or rejection of components, drug product containers, and closures
• 21 CFR 211.103 - Calculation of yield
• 21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products
• 21 CFR 211.137 - Expiration dating
• 21 CFR 211.165 - Testing and release for distribution
• 21 CFR 211.166 - Stability testing
• 21 CFR 211.167 - Special testing requirements
• 21 CFR 211.170 - Reserve samples
CBER or biologics-led PMOA with device in addition to applicable parts of 21 CFR 211 and 21 CFR 820 also follow
• All applicable CGMP requirements for biological products (including standards) that are found within 21 CFR Parts 600 through 680 (21 CFR 4.3(c)).
• For a combination product that includes any HCT/P, the manufacturer must demonstrate compliance with all applicable regulations in 21 CFR Part 1271.
If you're unclear which pathway your combination product belongs to, please contact OCP directly.
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