What You Need to Know About
Developing Combination Products

With our extensive experience guiding combination products through development,
we can help you through a smooth and efficient development cycle.

Table of Contents

  • What is a combination product?
  • Who at FDA regulates combination products?
  • What are human factor studies? Do you need to conduct them?
  • What information is required during development?
  • Where does combination product information go in the IND and BLA?
  • How can HW assist you with the development of your combination product?

What is a combination product?

A combination product is a product composed of two or more types of medical products that are physically, chemically, or otherwise combined and produced as a single entity.

Some biological products are associated with a device or drug to form a therapeutic product, for example:

  • prefilled syringes
  • autoinjectors
  • patches, etc.

A combination product can also be made up of two or more separate products packaged together, like drug and device products, device and biological products, or biological and drug products.

A combination product can also be a drug, device, or biological product packaged separately that is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect. This is also called a “cross-labeled combination product.”

These products are often very complex and require a collaboration of scientist and FDA reviewers from different backgrounds to assure that they are safe and effective. As technology advances allow merging new product types, components that would normally be regulated and reviewed by different FDA centers are being used together in combination products. This raises regulatory and management challenges.

Differences in the regulatory pathways and timelines of each component of your combination product impact the regulatory processes from product development to post-approval modifications.

Who at FDA regulates combination products?

The FDA Office of Combination Products (OCP) develops guidance to clarify the regulation of combination products, and the office acts as a focal point for combination product issues.

The OCP will issue the classification (type of product) and the jurisdiction of the combination product which will determine which FDA lead center (CDER, CBER, CDRH) the product will fall under (Figure 1). Once the lead center is determined, you’ll have meetings and communicate with the FDA through the lead center.

As product types are being merged, the separation between centers is being less and less emphasized. Reviewers from the different centers often collaborate to evaluate combination products and organize inspections. The OCP will ensure that your premarket review timelines are respected.

We have extensive experience with multiple centers and can walk you through submitting your documents to them.

FDA Guidance Combination Products With Different Centers

What are human factor studies? Do you need to conduct them?

You may need to conduct human factor studies with a representative population of users to evaluate how well your combination product works for the targeted population and to eliminate or mitigate any use-related hazards.

When one part of your combination product is a device, human factor studies and usability engineering are very important to establish whether it will be safe and effective for use by the intended users and in appropriate environments.

These studies are conducted to evaluate the user interface of a product and to make sure that the user is able to carry out critical tasks and to understand the information provided in your product’s packaging and labeling.

There are different types of human factor studies, including:

  • Human factor formative studies to evaluate early combination product prototypes
  • Human factor validation studies to demonstrate that your final product will be used safely and effectively by the intended users (can be simulated-use or actual-use validations studies)

Generally, simulated-use validations studies are sufficient to demonstrate the adequacy of the user interface design.

Finally, remember that you may have to carry out human factor knowledge task studies as part of formative or validation studies. These studies are necessary when it is critical for the user to understand your product labeling to use your product safely and effectively. We can draft a plan for your studies to submit to the FDA, and help you incorporate their suggestions and feedback.

What information is required during development?

Should you have to carry out human factors studies, you are strongly encouraged to share with the FDA the summaries and plans that you are planning on conducting prior to the start of the studies. This allows the FDA to offer their feedback on the appropriateness of your proposed studies. By submitting information ahead of time, you will save time and cost. Let us prepare and submit your plans to the FDA for you.

Where does combination product information go in the IND and BLA?

In your IND, you should submit your combination product specific use-related risk analysis.

In general, the information regarding combination products is located in the same eCTD sections that would provide similar information for the drug or biological product alone.

In a BLA, you can submit a reviewer’s guide which will be useful to guide the reviewer to the appropriate sections about the combination product.

In a BLA, you should identify on the Form FDA 356h all the facilities involved in the manufacture and testing of the combination product. You should also include all the manufacturer information regarding the combination product in the appropriate Module 3 sections.

In all submissions made in the eCTD format, your human factor submissions should be located in Module 5.3.5.4 Other Study Reports and related information.

If you need help with these documents, don’t hesitate to contact us. With our familiarity with the complex paperwork involved, you can trust us to draft your documents correctly.

How can HW assist you with the development of your combination product?

Due to the complexity of combination products, you can encounter several issues during product development. We have helped numerous biologics and biosimilar manufacturers using delivery devices to administer their product, and have also helped drug manufacturers using devices for delivery. Our intense knowledge of the regulatory requirements and our strong understanding of FDA’s expectations will strongly benefit you during product development.

We can assist you with early development and strategical planning, preparing for meetings, and understanding and interpreting FDA centers’ opinions obtained from meetings with the agency.

We have extensive experience with combination products, including prefilled syringes and autoinjectors. At HW, we can assist you with the regulatory strategy and project management throughout the whole combination product development, allowing your company to save time, save cost, and reach patients faster.

Let us help you draft and format your documents, and prepare and submit your eCTD submission for combination products, all according to FDA’s expectations.

Are you in the process of developing a combination product?

Do you need help in preparing your IND or BLA? We can help. Contact us today to learn more about how we can help you gain approval from the FDA.