6 Steps to 21 CFR Part 4 Compliance for Your Combination Product

Combination products, made up of two or more components, have skyrocketed in the healthcare industry in recent years; however, complying with evolving legislation can be a nightmare for manufacturers.

When two or more products are packaged separately, it must state clearly on the label that each component can be used together. In addition, the Food and Drug Administration (FDA) stipulates how combination product makers adhere to current good manufacturing practices (cGMP).

Companies will need to comply with 21 CFR Part 4 — part of the FDA’s Code of Federal Regulations — before they launch a product to ensure there is no delay in the rollout process. Legacy products will also need to be checked. Here’s what you need to do:

1. Survey Your Existing Products

You will need to ensure legacy products are FDA-compliant in respect to 21 CFR Part 4. Before you engage in this effort, you will need a clear idea regarding the scope of products involved. Determine which of your products are actually combination products (e.g. single entity, co-packaged, or cross-labeled.

2. Determine What Type and Combination the Combination Product Is

21 CFR Part 4 only applies to combination products, not conventional drugs or devices. Product types include “single entity”, when a product is comprised of two or more regulated components, “cross-labeled”, when two or more separate products are packaged together in a single package or as a unit, or “cross-labeled”, when a drug, device, or biological product is packaged separately that according to its proposed labeling is for use only with another individually specified drug, device, or biologic. Product combinations include drug/device, biologic/device, drug/biologic, or drug/device/biologic. To define the scope of the project at hand, a list should be put together to define all types and combination. Each part of a combination product will still need to be manufactured in accordance with the relevant cGMP requirements, specifically design controls.

3. Define What Needs to Happen

Complying with the FDA is imperative. Not ensuring your products are aligned with 21 CFR Part 4 could put your company at risk for regulatory noncompliance. Your role is to determine what specific current good manufacturing practice requirements apply, implement the appropriate quality system requirements, and conduct an audit to ensure compliance.

4. Perform a Gap Assessment

Perform gap analysis to evaluate whether your current design and development documents comply with 21 CFR Part 820 Subpart C – Design Controls (Sec. 820.30). If they do not, take fast action to determine how gaps may be remediated.

5. Remediate the Gaps

Be specific about how you are going to bridge the gap between the design and development documents you currently have in place and the objectives you need to meet to become fully compliant. For example, you might identify the changes you need to make to your risk management activities, design verification, or design validation records. Set up a remediation team to help you make changes. Immediately escalate any gaps that cannot be easily resolved and refer them to your company’s corrective and preventative action progeam

6. Review Your Changes

Finally, perform a design review of the assessment of all documents and any corresponding changes you have made. Check that the entire design control process, from design and development planning to current complaint data, is fully compliant with 21 CFR Part 4.

Ensuring your combination products are fully compliant with 21 CFR Part 4 can sound like a challenge; however, breaking down the compliance process into manageable chunks can help you share the burden with your team. Start by analyzing your product, perform gap analysis, and then carry out a final review.

Don’t worry if you get stuck. Calling in an expert could be worth the investment and will guarantee your manufacturing facility is not at risk of noncompliance. Quality Solutions Now (QSN) specializes in combination products and can provide you with the support you need when getting up to speed with 21 CFR Part 4.