Regulatory Consulting for Borderline and Drug-Device Combination Products

Drug-Device Combination and Borderline Devices

Adding a medicinal substance to a medical device can provide additional clinical benefits. Examples include drug-eluting stents and antimicrobial-coated catheters.  Some products contain several materials and substances which may have different modes of action. Examples include hemostats, wound dressings, and irrigation solutions. In many markets, medical devices and drugs are regulated differently and it is therefore important to determine whether your product is a medical device or a drug.

The borderline between medical devices and drugs is based on the primary mode of action of the product. Broadly speaking, products whose mode of action is primarily physical are regulated as medical devices. If the primary mode of action is medicinal (pharmacological, immunological, or metabolic), it will be regulated as a drug.

As an example, in Europe, if a product is determined to be a medical device but incorporates a medicinal substance with an ancillary action, it will be classified under Rule 14 of the Medical Device Regulation (MDR 2017/745).  MDCG 2022-5 provides more guidance on the borderline and definitions of pharmacological, immunological, or metabolic action as well as herbal medicines. Similar considerations are made for devices we work with for submissions in the US and Japan taking into consideration guidances and agency interactions.

Regulatory Compliance Strategy for Borderline and Drug-Device Products

If a product is classified under Rule 14 of the MDR, your Notified Body will consult with the European Medicines Agency or a national medicines agency.  In addition to the technical documentation on the device, you must prepare a consultation submission on the medicinal substance incorporated into the device. The format of this submission is based on the Common Technical Document (CTD) format used in pharmaceutical submissions. Your Notified Body will submit the consultation to the medicines agency for their review.

EU Notified Body Expertise on Staff

NAMSA has regulatory consultants with extensive experience with medical devices incorporating medicinal substances. Our team includes experts who have previously served as Notified Body reviewers of high-risk medical devices including device/drug combinations. Our expertise covers key product areas for these products such as wound care, cardiovascular, orthopedics, and organ transfusion. NAMSA can provide a comprehensive range of services including:

• Borderline and MDR Rule 14 classification assessments taking into account mode(s) of action, nature of the action – primary or ancillary and demarcation with Rule 21 where applicable
• Comprehensive reviews of the scientific literature supporting the mode or modes of action of device ingredients/formulations and preparation of documented rationales for submission to Notified Bodies and other regulators
• Preparation of medicinal substance consultation submissions to CTD format
• Experience with multiple medicines agencies (e.g. MEP, MEB, and ANSM) and multiple medicinal substance submissions
• Gap assessments of technical documentation, consultation, submissions, and associated key documents
• Review and gap assessment of  supplier documentation including ASMF (Active Substance Master Files)
• Clinical strategy and preparation of CERs including risk-benefit of the medicinal substance
• Support with Notified Body and medicines agency deficiencies