FDA Issues Final Guidance Covering CGMP Requirements for Combination Products

FDA Final Guidance on CGMP Requirements for Combination Products

The U.S. Food and Drug Administration (FDA) issued its final guidance covering good manufacturing practice (CGMP) requirements for combination products.

We've summarized the key takeaways from the 59-page document below.

The Definition of a Combination Product

The guidance offers a concrete definition of a combination product, under 21 CFR Part 3, as a product composed of two or more different types of medical products such as a combined drug, device and/or biological product.

The guidance goes on to explain combination products in greater detail under 21 CFR 3.2(e), including the following characteristics:

• "A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity (a “single entity” combination product, such as a prefilled syringe or drug-eluting stent);

• Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products (a “co-packaged” combination product, such as a surgical or first-aid kit);

• A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling 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 and where upon approval of the proposed product the labeling of the approved product would need to be changed (e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose) (a “cross-labeled” combination product, as might be the case for a light-emitting device and a light activated drug); or

• Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect (another type of crosslabeled combination product)."

An Overview of FDA's Rule for CGMP Requirements of Combination Products

The final guidance also includes the CGMP requirements for combination projects first released in 2013 and codified in 21 CFR Part 4.

In particular, the final guidance covers the purpose and content of the CGMP requirements included in the final ruling.

Roles and Compliance Responsibilities

Throughout the document, FDA gives detailed descriptions of various associated roles such as that of the lead center and other parties directly involved in CGMP matters. It also addresses items to consider for CGMP compliance of combination products, including possible scenarios illustrating the appropriate actions manufacturers should take to comply with certain CGMP requirements.

The final guidance offers more detailed discussion around how CGMP requirements apply and which compliance approaches are acceptable for manufacturers and sponsors to take.

Regulators encourage those with specific questions regarding combination product compliance to contact the lead Center or the Office of Combination Products.

Postmarket Safety of Combination Products

The final guidance follows last month's finalized ruling on postmarket safety for combination products.

The newly passed 21st Century Cures Act also includes provisions for regulating combination products, requiring regulators meet with manufacturers early on in the development process to ensure standards for approval can be met, and clarifying dispute resolution between various FDA centers.

[Read Also:] How the 21st Century Cures Act Will Accelerate Medical Device Approvals

This comes in response to concerns expressed by industry groups around consistency and communication related to combination product review.

Click here to access the full guidance document or grab one of our free white papers summarizing FDA trends and new developments in 2016.

Read: FDA Trends & Developments in the Pharmaceutical Industry: 2016

Read: FDA Trends & Developments in the Medical Device Industry: 2016 

Topics: News, Regulations, Good Manufacturing Processes