Devices 101

Knowledge, itself, is power, and understanding is the path to success.

In an effort to ensure the right questions are asked and the right information guides your progress, we have created a short-list of key topics that arise when pharmaceutical companies embark on new combination product ventures. The following are defined and explained below – feel free to click and jump or scroll through at your leisure.

Definition of Combination Products

Combination Products can be cross-labeled (constituent parts sold separately), co-packaged (constituent parts packaged and sold together), or single-entry (chemically or physically combined constituent parts).

FDA Combination Product Definition

European Medicines Agency Definition of Combination Product

Examples of Combination Products with a Device Constituent Part

• Empty syringes packaged with a drug product
• Empty injection systems packaged with a drug product
• Transfer sets
• Lyophilized drug product vials packaged with reconstitution components.
• Surgical kits containing both a drug and a device to be used with it

• Prefilled syringes
• Prefilled auto-injectors
• Metered-dose inhalers
• Dry powder inhalers
• Nasal-spray
• Prefilled pumps
• Transdermal patch systems
• Prefilled iontophoresis system Microneedle “patch”
• Drug pills embedded with sensors
• Contact lens coated with a drug
• Drug-eluting stents
• Drug-eluting leads
• Condoms with spermicide
• Dental floss with fluoride
• Antimicrobial coated catheters/sutures
• Bone cements with antibiotics
• Live cells seeded on/in a device scaffold
• Extracorporeal column with column-bound protein

• Light-activated drugs/biological products labeled for use with a specific light source device

Device Requirements

Human Factors & Usability Engineering

Primary Mode of Action (PMOA)

The PMOA is the main therapeutic component that defines the combination product’s intended use.   For drug delivery devices, that primary intended use will be attributed to either the drug part or the device constituent part of the combination product. For example, in a drug-eluting stent for opening diseased arteries, the PMOA is the device’s ability to open the artery. The drug provides a secondary PMOA as an “aid.” This designation as “primary” vs. “aid” helps determine through what regulatory body the combination product will be submitted. In the United States, a Combination Product with a PMOA related to the drug will be submitted to the Center for Drug Evaluation and Research (CDER); one related to the device will go to the Center for Devices and Radiological Health (CDRH).

Regulatory Submission Pathway

Consultants at Suttons Creek can guide you through both the development process and the submissions pathway. Governing bodies also supply guidance for your regulatory compliance.

FDA Guidance Documents

European Commission Guidance Documents

Device Platform

Governing Agencies

Combination Products are regulated by various governing agencies, depending on where you plan to market them. Each will have its own set of complex rules and requirements. In this global marketplace, remaining compliant in an efficient and effective manner can be a very complicated puzzle to piece together.

For the United States of America, the US Food & Drug Administration (FDA) is the governing force. To serve as a focal point for all issues related to combination products, in 2002, the FDA created the Office of Combination Products (OCP). This office maintains compliance to all combination product related regulations and enforces the regulations outlined in the Current Good Manufacturing Practices (cGMP), which ensures that they are manufactured in a quality controlled environment.

For the European Union, the European Commission (EC) is the governing agency for combination products. Like the FDA’s OCP, the EC establishes and enforces combination product regulations for the safety of their constituents.

MDR and IVDR:

The European Parliament created and enforced the new Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) in April 2017, replacing the Medical Device Directives (MDD) and the EU’s current Directive on in vitro diagnostic medical devices, in an effort to keep pace with the tremendous advancements and innovations in science and technology, to better protect patient safety, and to enhance transparency. It provides medical device manufacturers with a three-year window to implement compliance efforts before the May 2020 date of application (DOA) of the MDR and May 2022 DOA of the IVDR. Any medical device that is to be newly placed on the EU market after this date must comply with these new regulations.

• There is a broadening of the number and types of devices that are covered by the MDR. Cosmetic devices, as well as devices that have an ancillary use (e.g. devices that sterilize medical equipment), contact lenses and equipment for liposuction are now regulated under the MDR. Specifically, the MDR now officially defines a “medical device” as any “instrument, apparatus, appliance, software, implant, reagent, material, or other article intended by the manufacturer to be used, alone or in combination, for human being for one or more of the following specific medical purposes:
  1. Diagnosis, prevention, monitoring, predication, prognosis, treatment or alleviation of disease.
  2. Diagnosis, monitoring, treatment, alleviation of, or compensation for, and injury or disability.
  3. Investigation, replacement, or modification of an anatomical, physiological, or pathological process or state.
  4. Providing information by means of in-vitro examination of specimens derived from a human body, including organ, blood and tissue donations.
• With changes to the device classification rules, some devices are being reclassified to a higher risk class, such as surgical meshes and spinal implants, requiring more stringent and longer reviews as well as an increased need for clinical data. In fact, most software that was previously classified as a Class I medical device and self-certified will require Notified Body review under the MDR.
• The inclusion of a Unique Device Identification (UDI) mandate is another big change under the MDR. This will help make devices identifiable throughout the supply chain and sales region. Two identifiers are required, a device identifier that indicates the manufacturer and device, and a production identifier that indicates the production series/product batch.
• Notified Bodies must be assessed and designated to new higher standards under the Medical Device Regulation before they can conduct audits of manufacturers and reviews of medical devices. As a result, there will be fewer Notified Bodies available to review submissions and certify products, as well as more stringent oversight of their activities.
• Regulations concerning vigilance and post-market surveillance lead to the establishment of an EU database on Medical Devices, to correlate information from manufacturer, authorized representative, and importer. Information such as device registration, accredited Notified Bodies, Safety and Clinical Performance Reports, Serious Incidents, UDI, and Clinical Investigation Data will be captured.
• Stakeholders – suppliers, manufacturers, assemblers, subcontractors, distributors, importers, and EU Authorized Representatives – will assume larger, more defined responsibilities, as the new legislation Articles outline who is responsible for what obligations to conform to regulations. The Articles also newly require a qualified and experienced medical device expert available in the company and designated responsible for regulatory compliance.