Combination Products

Combination products represent one of the fastest-growing and most complex categories in the life sciences industry, merging drugs, biologics, and medical devices into a single therapeutic solution.

As new therapies increasingly rely on advanced delivery mechanisms, digital health integration, and personalized medicine, regulatory authorities have tightened expectations for how these products are designed, manufactured, validated, labeled, and monitored throughout their lifecycle. This training provides a structured foundation for understanding the regulatory and compliance requirements that govern combination products, particularly within U.S. FDA and EU frameworks.

The course begins with fundamental definitions and distinctions. Participants learn how combination products are classified based on the integration of at least two regulated components-drug, device, or biologic-with a focus on how a product's Primary Mode of Action (PMOA) determines its regulatory pathway. PMOA is a critical concept because it dictates whether a product will be regulated primarily as a drug, device, or biologic, and therefore which regulatory requirements take precedence. The session also clarifies how combination products differ from co-packaged items or products that require cross-labeling-areas where companies often struggle to interpret regulatory expectations.

After establishing foundational concepts, participants explore common industry examples, such as insulin pens, prefilled syringes, autoinjectors, inhalers, drug-eluting stents, vaccine prefilled devices, and cell-therapy delivery systems. These examples illustrate the variety of product types and highlight how evolving technology-especially wearable or "smart" drug delivery devices-creates new compliance obligations related to software, cybersecurity, usability, and patient interaction.

A significant portion of the training focuses on the U.S. regulatory landscape, led by the FDA and the Office of Combination Products (OCP). Participants gain an understanding of key governing regulations, such as 21 CFR Part 3, Part 4, and applicable portions of Parts 210, 211, and 820. The content explains how combination products must often comply with both device Quality System (QS) regulations and pharmaceutical Current Good Manufacturing Practice (CGMP) requirements. This dual compliance framework demands a harmonized quality management approach, especially in areas of design controls, sterility assurance, supplier management, production validation, documentation, and risk management.

The training also addresses European Union requirements under EU MDR 2017/745, IVDR, and pharmaceutical GMP legislation. Differences between FDA and EU regulatory strategies are highlighted, including device conformity assessments by Notified Bodies and CE marking when a medicinal product contains a device component. Additional considerations related to Brexit and UKCA are briefly discussed for manufacturers distributing within the UK market.

Participants then examine critical lifecycle controls, including risk management, human factors engineering, and post-market vigilance. Human factors and usability engineering play a crucial role in combination product safety, especially for self-administered therapy. Regulatory expectations increasingly mandate usability studies to prevent use-related hazards, especially in drug delivery devices used by patients without clinical supervision.

Finally, the program provides guidance on documentation and submission requirements, highlighting common pitfalls in regulatory submissions such as poor traceability across quality systems, insufficient risk documentation, and inadequate human factors data. Post-market expectations-including adverse event reporting, complaints, recalls, and integration of MAUDE and FAERS-are emphasized to reinforce the importance of lifecycle vigilance.

Overall, this training prepares professionals to navigate the intricate regulatory environment surrounding combination products, helping organizations build more compliant, safe, and effective solutions for patient care.

Why you should Attend:
Professionals should attend this training because combination products are rapidly transforming the medical landscape, and the regulatory expectations surrounding them are stricter and more complex than traditional drug or device requirements. Organizations that develop or work with drug-delivery technologies, prefilled systems, biologic–device integrations, or advanced digital health therapies must understand how to design, manufacture, validate, and control these products under multiple regulatory frameworks at the same time. Failure to do so often results in slowed approvals, post-market findings, costly remediation, or patient safety risks that damage an organization's credibility and competitiveness.

This training equips participants with practical knowledge they can apply immediately within research, development, quality assurance, regulatory affairs, manufacturing, engineering, or post-market compliance roles. Attendees will gain a clearer understanding of how FDA and EU regulators interpret quality expectations for combination products, how PMOA determines the regulatory pathway, and how to integrate CGMP and QMS requirements without duplication, gaps, or compliance conflicts. The course delivers clear insights into risk management, human factors engineering, documentation pitfalls, and regulatory submission expectations that often cause product approval delays or inspection observations.

By attending, participants enhance their ability to prevent errors, strengthen regulatory submissions, support cross-functional decision-making, and build a compliant product lifecycle strategy-skills now essential in a rapidly evolving, technology-driven therapeutic market.

Areas Covered in the Session:

• Welcome, Overview & Learning Objectives (5 minutes)
• What are combination products?
• Why regulations differ from traditional products
• Goals:
• Define major types of combination products
• Understand regulatory pathways and governing agencies (FDA, EMA, etc.)
• Explain CGMP & lifecycle expectations
• Identify key compliance risks & documentation impacts
• Combination Product Fundamentals (10 minutes)
• FDA & EMA definitions of combination products
• Primary Mode of Action (PMOA) as a regulatory driver
• Key elements of combination products:
• Device + Drug
• Device + Biologic
• Drug + Biologic
• Device/Drug/Biologic + Accessories
• Distinction from "co-packaged" or "cross-labeled" products
• Common misconceptions and borderline definitions
• Types & Examples of Combination Products (10 minutes)
• Drug-Device Examples
• Insulin pens, prefilled syringes, autoinjectors, inhalers
• Device-Biologic
• Prefilled vaccines, bone graft/implant biologic scaffolds
• Drug-Biologic
• Cell therapy delivery systems
• Cross-Labeled Products
• Drug product required to be used with a device per labeling
• Industry Trends
• Wearable drug delivery, advanced personalized treatments, digital health integrations
• FDA Regulatory Framework (15 minutes)
• 21 CFR Parts 3, 4, 210, 211, 820
• Office of Combination Products (OCP)
• Role in assignment, regulation, compliance
• Primary Mode of Action (PMOA)
• Definition & regulatory classification
• Design & Development
• Human factors requirements for drug delivery devices
• Software considerations (SaMD & cybersecurity)
• Quality System Requirements
• QS Regulation (Device) + Drug CGMP + Biologics requirements
• 21 CFR Part 4 Quality requirements
• EMA / EU Requirements (10 minutes)
• Definition under EU MDR & EU pharmaceutical law
• Applicable regulatory frameworks:
• EU MDR (2017/745)
• EU IVDR when applicable
• EU GMP Directive for medicinal products
• Conformity assessments with Notified Bodies
• Unique Labeling & CE Marking considerations
• Impact of Brexit on Combination Product registration (UKCA)
• CGMP Requirements & Quality System Integration (15 minutes)
• 21 CFR Part 4: Key Quality Requirements
• Design controls (820.30)
• Sterility assurance and aseptic processing
• Supplier controls & material traceability
• Validation & qualification (PQ, IQ/OQ)
• Pharmaceutical CGMP Expectations
• Data integrity & documentation
• Stability studies for integrated products
• Container closure system and extractables/leachables
• Biologics Considerations
• Chain of identity & custody
• Viral safety & contamination risks
• Risk Management & Human Factors (10 minutes)
• ISO 14971 Risk Management
• Safety-risk-benefit analysis across drug/device interface
• Human Factors Engineering
• Use-related risk analysis (URRA)
• Usability for patient self-administration
• Labeling, IFUs, training materials
• ISO 11608 (Needle-Based Systems)
• "Smart" combination products & digital interfaces (cybersecurity risk)
• Documentation & Regulatory Submissions (10 minutes)
• IND/NDA/BLA submissions containing devices
• 510(k), PMA + Drug application interactions
• Combination product technical files & Design History Files (DHF)
• Common submission pitfalls:
• Incomplete risk documentation
• Lack of cross-QMS traceability
• Inadequate human factors studies
• Post-market vigilance integration (MAUDE + FAERS)
• Post-Market Safety, Reporting & Vigilance (5 minutes)
• MDR reporting for devices
• AE reporting for drug & biologics
• Complaint handling & trend analysis
• Recalls and field safety corrective actions (FSCAs)
• Unique Device Identification (UDI) within drug packaging
• Summary, Key Takeaways, Q&A (5 minutes)
• Key messages on classification, compliance, and lifecycle risk
• Importance of early regulatory engagement
• Building an integrated QMS approach
• Questions & discussion

• Quality Assurance
• Quality Control
• Regulatory Affairs
• Manufacturing
• Operations
• Engineering
• Validation / Qualification
• Research & Development
• Supply Chain
• Procurement
• Technical Services
• Document Control
• Materials Management
• Information Technology (IT / CSV)
• Project Management
• Executive Leadership / Quality Governance