Design Reviews for Drug-Device Combination Products: What Should Be Reviewed?
24 Sep 2026
A drug-device combination product can contain a well-developed drug and a well-developed device and still create problems when the two are brought together. The interaction between the drug, device, container, user and manufacturing process can introduce risks that may not be visible when each constituent part is considered separately.
This is why design reviews are important. They provide formal checkpoints during development where the team can ask whether the design is still meeting its intended purpose, whether risks are controlled, and whether sufficient evidence exists to proceed.
For combination products, the review should go beyond asking whether the device works. The more important question is: does the complete combination product work as intended, for the intended user, under the intended conditions?
FDA identifies design controls as important development controls for applicable medical devices, while its combination-product requirements recognize the need to address the combined use of constituent parts. (U.S. Food and Drug Administration)
What Is a Design Review?
A design review is a formal evaluation of the design and the development activities at an appropriate stage of development.
It should not simply be another project meeting. A project meeting may focus on timelines and tasks, whereas a design review should examine whether the design is adequately defined, risks are understood, requirements are being addressed and the project is ready to move to the next stage.
For a combination product, the review should consider both the individual constituent parts and, importantly, the interfaces between them.
What Should Be Reviewed?
1. User Needs and Intended Use
The review should first confirm that the design continues to address the intended users, patients, use environment and intended purpose.
For example, an autoinjector may successfully deliver the required dose during laboratory testing. But can the intended patient remove the cap, position the device and activate it correctly?
Human factors, foreseeable use errors and the actual use environment should therefore remain part of the design review.
2. Design Inputs
Design inputs establish what the product is required to achieve. They should be clear, sufficiently detailed and capable of being verified.
For a drug-device combination product, inputs may include:
- dose accuracy;
- delivery volume;
- injection force;
- activation force;
- delivery time;
- material requirements;
- compatibility requirements;
- usability requirements;
- shelf-life requirements; and
- packaging and transportation requirements.
The review should determine whether the inputs remain complete and whether important user, regulatory and risk requirements have been incorporated.
A weak design input can create problems much later because verification may then be performed against an incomplete requirement.
3. Risk Management
Risk management should be actively considered during design reviews rather than being treated as a separate documentation exercise. The team should examine whether new hazards have appeared, whether existing risk controls remain effective and whether design changes have introduced new risks.
For example, reducing the activation force of an autoinjector may improve usability, but could also increase the possibility of unintended activation.
The important question is therefore not simply “Has the risk assessment been completed?” but “Does the current design still reflect the conclusions of the risk assessment?”
4. Drug-Device Interface
This is one of the most important areas for combination-product design reviews. The drug and device may each meet their individual specifications but behave differently when used together.
Consider injection force. A change in formulation viscosity may affect the force required to deliver the dose. Similarly, materials used in a syringe, cartridge, needle or container closure may require compatibility evaluation with the drug formulation.
FDA’s combination-product guidance recognizes that design controls need to address the combined use of constituent parts, particularly where an existing component is modified or its use within the combination creates new design considerations. (U.S. Food and Drug Administration)
The review should therefore explicitly identify important drug-device interfaces rather than assuming that existing constituent-part data are automatically sufficient.
5. Design Outputs
The review should confirm that design outputs adequately define the product that will eventually be manufactured and tested.
Depending on the product, this may include drawings, specifications, material requirements, software requirements, packaging specifications, assembly instructions and other controlled outputs.
The key question is:
Do the outputs adequately address the approved design inputs?
Traceability is particularly useful here because it allows the team to identify whether important requirements have been translated into actual design features and specifications.
6. Verification and Validation
A design review should examine whether the verification and validation strategy is appropriate for the stage of development.
Verification should establish whether design outputs meet specified requirements, while validation should address whether the resulting product meets user needs and intended use.
For a combination product, the evidence may include dose-delivery testing, functional testing, usability evaluation, compatibility studies, stability-related assessments, packaging testing and other product-specific activities.
FDA also identifies drug-delivery performance as an important area for products that deliver drugs or biological products, including evaluation of the design attributes and manufacturing processes that affect delivery. (U.S. Food and Drug Administration)
The review should also ask whether acceptance criteria are clearly defined. Test results are much more meaningful when the organization already knows what constitutes acceptable performance.
7. Manufacturing and Design Transfer
A prototype that performs well in an engineering laboratory is not necessarily ready for commercial manufacturing.
The design review should therefore consider manufacturing readiness, including critical specifications, suppliers, assembly methods, manufacturing controls and process-validation requirements.
For example, an engineering build may rely on manual assembly that cannot be consistently reproduced during commercial production.
Has the design been developed with manufacturing reality in mind?
Design reviews provide an opportunity to identify these problems before design transfer rather than after production difficulties appear.
8. Design Changes and Open Actions
Finally, the review should examine what has changed since the previous review and whether those changes have been appropriately assessed. A change to a material, needle, spring, container, software parameter or assembly process may affect risk, verification, validation or regulatory documentation.
Every significant action identified during the review should have a responsible owner and a defined follow-up. A review that identifies problems but does not control their resolution provides limited value.
Who Should Participate?
Design reviews should involve the functions relevant to the development stage.
Depending on the product, this may include:
- engineering;
- quality;
- regulatory affairs;
- pharmaceutical development;
- manufacturing;
- human factors;
- clinical functions; and
- project management.
Cross-functional participation is particularly important for combination products because the critical issue may exist at the boundary between disciplines.
An engineering team may understand the device mechanism very well, for example, while a pharmaceutical team understands the formulation. The design review creates a controlled opportunity to examine where those two areas interact.
What Should the Review Record Contain?
The design review should leave objective evidence behind.
The record should normally identify:
- the date and development stage;
- participants;
- documents and data reviewed;
- decisions and conclusions;
- identified problems;
- assigned actions; and
- required follow-up.
The records should remain controlled and traceable within the design documentation.
For a combination product, this evidence becomes particularly useful when the organization needs to demonstrate how decisions concerning the drug-device interface, risks, design changes and verification activities were made.
Conclusion
A design review should not be treated as a meeting held simply because the development procedure requires one.
For drug-device combination products, it is an opportunity to challenge the design before problems become expensive.
The most effective reviews examine user needs, design inputs, risk management, drug-device interfaces, design outputs, verification and validation, manufacturing readiness and design changes.
When these elements remain connected throughout development, the design review becomes much more than a compliance activity. It becomes a practical development control that helps the organization identify problems earlier, maintain traceability and build stronger evidence for regulatory submission and commercialization.
How TS Quality & Engineering Can Help
TS Quality & Engineering supports drug-device combination product development through practical expertise in design controls, design inputs and reviews, risk management, verification and validation, human factors, design transfer and technical documentation. For organizations developing a new combination product or strengthening an existing design-control system, TSQE can help establish a structured and traceable development approach.
References
U.S. Food and Drug Administration (FDA) (n.d.) Combination Product Definition Combination Product Types. Available at: FDA Combination Products (Accessed: 20 September 2026). (U.S. Food and Drug Administration)
U.S. Food and Drug Administration (FDA) (n.d.) Current Good Manufacturing Practice Requirements for Combination Products. Available at: FDA Combination Product CGMP Guidance (Accessed: 20 September 2026). (U.S. Food and Drug Administration
