Combination
Products

Leaders in Drug-Device Regulatory Strategy

Why Combination Products Are Different

Two Sets of Rules, One Product, No Room for Guesswork.

A drug-device or biologic-device combination sits astride two entire regulatory frameworks at once, and one early decision governs everything downstream: the primary mode of action determines which FDA center leads your review, which application you file, and which quality system you build. Get the classification or jurisdiction wrong and you rework years of development. We help sponsors settle the determination early, engage the Office of Combination Products with a defensible position, and build a program that satisfies drug, biologic, and device expectations without doing everything twice.

Not sure which FDA center owns your product? That answer changes everything. Let's settle it.

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Capabilities

Every Constituent Part. One Integrated Strategy.

A combination product only works when its drug, biologic, and device pieces are developed against one coordinated plan. We cover the decisions that bridge them, from classification through postmarket.

Classification & PMOA

Determining the primary mode of action that decides your lead center, your application, and your quality system.
Jurisdiction & RFD Strategy

Pre-RFD and Request for Designation strategy to lock in lead-center jurisdiction with the Office of Combination Products.
Submission Pathway Strategy

Single or cross-labeled IND/IDE, NDA, BLA, 510(k), De Novo, and PMA strategy for combined constituent parts.
Human Factors & Design Controls

Use-related risk analysis, formative and validation usability studies, and design control expectations for the device constituent.
cGMP & 21 CFR Part 4

Streamlined versus full dual compliance, and the quality system that satisfies both drug cGMP and device QSR.
Global Combination Strategy

EU MDR Article 117, notified body consultation, and UKCA marking, aligned with your US pathway.
Classification & Primary Mode of Action

One Determination Sets the Entire Program in Motion.

The primary mode of action is the single constituent — drug, biologic, or device — that provides the most important therapeutic action of your product. It decides whether CDER, CBER, or CDRH leads your review, which application you file, and which quality system you build. When the PMOA is genuinely ambiguous, the argument you make for it is a strategic choice, not a formality. We build the classification analysis, weigh the consequences of each plausible determination, and position the one that gives your program the cleanest path.

What We Assess

  • Combination product classification (single-entity, co-packaged, cross-labeled)
  • Primary mode of action (PMOA) analysis and argumentation
  • Consequences of each plausible PMOA determination
  • Lead-center jurisdiction (CDER, CBER, CDRH) implications
  • Constituent-part definition and boundary issues
  • Early strategy for genuinely ambiguous products
  • Precedent analysis from comparable combination products
Jurisdiction & Request for Designation

Get the Agency to Agree Before You Build Around the Answer.

The Office of Combination Products assigns your lead center, and you do not have to guess what it will decide. A pre-RFD gives you non-binding early feedback; a formal Request for Designation gives you a binding assignment you can build a multi-year program on. We prepare both, framed to support the jurisdiction that fits your development plan, and open the early, candid dialogue with OCP that keeps a classification surprise from surfacing late.

Included Capabilities

  • Pre-RFD strategy and submission preparation
  • Request for Designation (RFD) authoring and defense
  • Office of Combination Products (OCP) engagement strategy
  • Lead-center assignment positioning
  • Inter-center consult planning and management
  • Jurisdictional dispute and reconsideration strategy
  • Early agency meetings to confirm the pathway
Submission Pathway Strategy

One Product Can Mean One Application, or Several.

Most combination products move through a single marketing application aligned to the lead center — an NDA, BLA, or PMA that carries the full constituent story. Some require cross-labeled or separate applications, and the investigational stage may call for a single IND or IDE spanning both parts. We design the submission architecture, build the eCTD or device structure that consolidates drug and device information, and make sure the device constituent's evidence lands where reviewers expect it.

Submission Types Covered

  • Single, cross-labeled, and separate application strategy
  • Combined IND / IDE investigational submissions
  • NDA, BLA, 510(k), De Novo, and PMA pathways
  • Device constituent evidence within a drug or biologic filing
  • eCTD and device submission structure and consolidation
  • Bridging and reference strategy across constituent parts
  • Lifecycle supplements and change submissions

Building the quality system for a combination product? Get the Part 4 approach right the first time.

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Human Factors & Design Controls

The Device Constituent Has Its Own Burden of Proof.

Even when a drug provides the primary mode of action, the device constituent still has to prove it is safe and usable in real hands. FDA expects use-related risk analysis, formative studies during development, and a validation usability study for products where use error carries clinical consequence — think autoinjectors, prefilled syringes, and on-body delivery systems. We build the human factors program and the design control documentation that reviewers now scrutinize as closely as the clinical data.

Included Capabilities

  • Use-related risk analysis and use-error assessment
  • Formative and validation (summative) usability studies
  • Human factors engineering (HFE) protocol and report authoring
  • Design control and design history file (DHF) strategy
  • Essential performance requirements and verification planning
  • Delivery device selection and platform strategy
  • Instructions for use and labeling comprehension testing
cGMP & 21 CFR Part 4

Two Quality Systems, or One Built the Smart Way.

Under 21 CFR Part 4 you can comply two ways: run drug cGMP and device Quality System Regulation fully and independently, or build one streamlined system on whichever base fits your product and add the specific provisions from the other. The streamlined route saves enormous duplication, but only if you choose the right base and cover the right elements — design controls, purchasing, CAPA, complaint handling. We design the quality system, map the applicable provisions, and get you inspection-ready against both frameworks.

Included Capabilities

  • Streamlined vs. full dual compliance analysis
  • 21 CFR Part 4 quality system design and gap assessment
  • Design controls and CAPA integration for combination products
  • Supplier, purchasing, and constituent-part controls
  • Complaint handling and nonconformance systems
  • Inspection readiness across drug and device expectations
  • Remediation of legacy or acquired quality systems
Global Combination Strategy

Europe Treats Your Combination Product Differently. Plan for It.

Outside the US, the same product can be regulated as a medicinal product with a device part, and EU MDR Article 117 now requires a notified body opinion on the device constituent inside a marketing authorization application. Add UKCA marking after Brexit and regional quality expectations, and a US-only plan leaves gaps. We align your global strategy so one development program supports FDA, EU, and UK requirements together instead of in sequence.

Included Capabilities

  • EU MDR Article 117 notified body opinion strategy
  • Integral vs. non-integral device constituent classification
  • EU medicinal product with device part pathway planning
  • UKCA marking and post-Brexit route strategy
  • Notified body selection and consultation management
  • Global quality system harmonization
  • US-EU-UK evidence reuse and submission sequencing
Beyond Approval

The Combination Doesn't End at Launch.

Two areas trip up combination product sponsors after the science is settled: the postmarket safety reporting rule that spans both constituents, and the diligence and remediation that acquired or legacy products demand.

Postmarket Safety & Lifecycle

Two Reporting Regimes, One Combination Product.

The combination product postmarket safety reporting rule pulls together drug adverse event reporting and device MDR obligations, with combined timelines and five-day and malfunction reports that catch drug-first companies off guard. We build the postmarket surveillance and reporting system that satisfies both, and manage the change control and supplements that keep a marketed combination product compliant as the device evolves.

Included Capabilities

  • Combination Product Postmarket Safety Reporting (PMSR) systems
  • Integrated adverse event and MDR reporting workflows
  • Five-day, malfunction, and correction/removal reporting
  • Post-approval change control and supplement strategy
  • Device change assessment against the drug application
  • Field action and recall strategy for combination products
Diligence & Remediation

The Product You Acquired May Not Be as Clean as the Deal Deck.

Combination products change hands constantly, and legacy ones often carry undocumented PMOA rationales, thin human factors files, or a quality system built for only one constituent. We run regulatory diligence for licensing and acquisition, surface the gaps that matter before they become inspection findings, and lead the remediation that brings a combination product back into defensible shape.

Included Capabilities

  • Regulatory due diligence for licensing and M&A
  • Combination product gap assessments
  • Human factors and design control remediation
  • Quality system remediation across constituent parts
  • Legacy PMOA and jurisdiction reconstruction
  • Integration planning for acquired combination products
Who You're Working With

People Fluent in Both Halves of Your Product.

Combination products fail when a drug team treats the device as an afterthought, or a device team underestimates the drug. Our practitioners have led both drug and device programs, sat across all three FDA centers, and built the quality systems that carry a combination product through inspection. You get someone who speaks both languages.

Former FDA, Across Centers

Consultants with experience spanning CDER, CBER, and CDRH, who understand how the Office of Combination Products actually assigns and coordinates review.

Drug and Device Fluency

Leaders who have run both pharmaceutical and medical device programs, so neither constituent gets treated as a bolt-on to the other.

Quality Systems That Pass Inspection

Practitioners who have built and remediated 21 CFR Part 4 quality systems, not just advised on them, and stood in the room during inspections.

Modality and Therapeutic Breadth

Prefilled syringes, autoinjectors, on-body delivery, drug-eluting devices, and combination diagnostics across oncology, immunology, rare disease, and beyond.

Work With Us

Settle the Classification. Then Build With Confidence.

Tell us about your product, its constituents, and where you are in development. We'll pressure-test your PMOA and pathway and match you with a senior combination product lead, with a response within one business day. All inquiries are strictly confidential.

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Insights & News

Thought Leadership on Combination Products.

Our team's perspectives on PMOA strategy, 21 CFR Part 4 compliance, and drug-device development: coming soon. In the meantime, reach out directly with a question you'd like to see addressed.

Coming Soon

When Your PMOA Is Genuinely Ambiguous

How to argue primary mode of action when the answer isn't obvious.

Coming Soon

Streamlined vs. Full Part 4 Compliance

Choosing the quality-system base that saves the most duplication.

Coming Soon

EU MDR Article 117 for US Sponsors

What the notified body opinion means for your global filing timeline.