More than half of the TOP20 drug products on the market include at least one device constituent part and are therefore considered Drug-device combination products. Drug-Device combination products are specifically regulated in the US. However, there is also an increasing oversight by regulatory authorities in the EU. Compliant development and life-cycle management are, therefore, essential for obtaining and maintain a marketing authorization for such products.
What is a Combination Product?
“Combination Product”, as per 21 CFR Part 3.2(e), is a term defined by the FDA to cover products which consist of two or more components (i.e., drug, biologic, device) regulated under different regulations. The FDA differentiates between three basic types of combination products:
- Single-entity combination products,
- Co-packaged combination products,
- Cross-labeled combination products.
Beyond these basic types also combinations of those basic types are possible.
During the past years, FDA established regulations and guidances for Combination Products, which further clarify what Combination Products are and which rules apply to such combinations.
21 CFR Part 4, along with the final guidance “Current Good Manufacturing Practice (cGMP) Requirements for Combination Products”, provides guidance on applicable quality requirements for combination products.
One essential requirement is to apply Design Controls as defined in 21 CFR Part 820.30 to the combination product as a whole. Design Controls are a set of quality practices and procedures to control the design process to assure that the combination product meets the user needs, intended uses and specified requirements. Design Controls support a systematic design and development process and ensure that the product fulfils those requirements which have been defined at the beginning of the project and that the final product fulfils the purpose. Design Controls are described in ISO 13485 (applicable for Medical Devices), in ISO 15378 (applicable to primary packaging materials) and even in the general standard for quality management system ISO 9001.
In the EU, so far, there has been no equivalent term to “Combination Product”, a product is either considered a Medical Device or a Medicinal Product. Medical devices have to comply currently with the Medical Device Directive and shortly with the EU Medical Device Regulation (MDR). Even though the term Combination Product does not exist, also in EU, the Design Controls apply to the so-called single-integral products, which are similar to single-entity combination products as defined in the US.
Also shared in EU and US is the requirement to apply Risk Management to those products. The respective standard ISO 14971 has been revised in 2019. The course will consider the recent changes and provides guidance on how to apply Risk Management to drug-device combination products.
And lastly, also Usability Engineering, also known as Human Factors Engineering, needs to be considered in the Design and Development of combination products. The recent increase in attention to this topic has brought many manufacturers into difficulties as they aim to prove high levels of intuitive use, use safety and efficacy of the drug delivery system as a whole - for a Combination Product it is no longer just about the drug. Again, regulation, directives, guidance, standards and review expectations continue to evolve in this area.
This course focuses on design controls as applicable to various combinations of drugs and biologics with devices. The course intends to set a solid basic understanding of the application on Design Controls as well as on the topics of Risk Management and Usability Engineering. Beyond the basic understanding, the course also aims to offer some practical experiences with the different elements to be considered.