Navigating the evolving, complex sea of regulations for Combination Products can be confusing and leave you with uncertainties. Strategic product development, coupled with an effective regulatory submission framework, increases the likelihood of a successful and timely launch of Combination Products.


Regulatory Compliance Associates® Inc.’s has developed an eight-step strategic regulatory plan for Combination Products:


  1. Define the Combination Product / Constituent Parts / Primary Mode of Action (PMOA)
  2. Prepare a Preliminary Regulatory Strategy
  3. Submit a Pre-Request for Designation (Pre-RFD)
  4. Update the Regulatory Strategy based on FDA’s Preliminary Informal, Non-Binding Designation
  5. Submit a Request for Designation (RFD)
  6. Update the Regulatory Strategy based on FDA’s Formal, Binding Designation Letter
  7. Early Collaboration Meeting with Lead Agency Center / Pre-Submission (PreSub) Meeting
  8. Submit Marketing Application(s) to Lead Agency Center


Support for your Combination Products

We have the expertise to see you through the entire lifecycle of your Combination Products. Count on us to support you with:


  • Development and Design Validation
  • Product Assessment and Request for Designation (RFD Submissions)
  • Global Regulatory Strategies
  • Agency Briefing Packages and Meeting Execution
  • Chemistry, Manufacturing, and Controls (CMC) and Clinical Data Support
  • Quality Systems Development and Support
  • Product Submissions (NDA, IND, ANDA, BLA, IND, 510(k), and PMA)
  • Electronic Common Technical Document (eCTD) Publishing and Electronic Submission
  • Inspectional Readiness
  • Training for Modified Quality Systems
  • Life Cycle Management and Post Approval Support
  • Due Diligence Audits / Mergers and Acquisitions


Understanding the Rules for Combination Products

The rules for Current Good Manufacturing Practice (cGMP) Requirements for Combination Products were issued by the FDA in 2013. Existing Quality Systems can stay in place, but new requirements are necessary for the components not already addressed.


When adding a Device to Existing Drug or Biologic Product:

  • Design controls apply when a device constituent part is used in a combination product
  • Corrective and Preventive Actions (CAPA) process required
  • Management responsibility must be clearly identified


When adding a Drug or Biologic to a Device Product:

  • Need incoming materials and Release Testing
  • Expiration Dating and Stability Testing are required
  • Calculation of Yield must be included
  • Component, container-closure, and tamper-evident requirements are added


Assessing Risk in Combination Products

Molecule manufacturers may be less familiar with medical device constituent parts, and even less familiar with the evolving FDA rules. As the guidance is better understood by inspectors, it’s important for manufacturers to keep up and understand the rules or the risk becomes greater.


We can help you understand:


  • How to best assure compliance of products and effectiveness of the cGMP controls in light of the evolving regulatory landscape
  • Obtaining objective evidence for the Design History File (DHF) that the drug / biologic is appropriate for use with the device and vice versa (“Drug-Device Interactions”)
  • How to incorporate Risk Management throughout the product life cycle
  • How to effectively merge CAPA and Non-Conforming Materials processes
  • The current enforcement climate and changes in Agency enforcement focus


About RCA

combination product consultantsRegulatory Compliance Associates® (RCA) provides healthcare consulting services to the following industries for resolution of compliance and regulatory challenges:



We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA and globally-regulated companies.


As your partners, we can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.


  • Founded in 2000
  • Headquartered in Wisconsin (USA)
  • Expertise backed by over 500 industry subject matter experts
  • Acquired by Sotera Health in 2021


To begin the RCA® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

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