The Complete 2026 Guide for Combination Products, Drug-Device Constituents, and Global Compliance
The line between a “drug” and a “medical device” has been blurring for years. Prefilled syringes, autoinjectors, insulin pens, inhalers, transdermal patches, drug-eluting stents, drug-coated catheters, on-body delivery systems, and digital therapeutics all combine pharmaceutical and device components into a single product the patient experiences as a single therapy. For regulators, that complexity raises a critical question. When a product is both a drug and a device, which identification system applies?
In the United States, the answer is the Unique Device Identifier (UDI) system. Established by the FDA’s UDI Final Rule in September 2013 (78 FR 58786), the UDI framework requires that every medical device sold in the country bear a unique, machine-readable identifier on its label and packaging, and that the device’s information be submitted to the Global Unique Device Identification Database (GUDID). For combination products with device constituent parts (such as a drug delivered through an autoinjector), the FDA’s June 2025 draft guidance “Unique Device Identifier (UDI) Requirements for Combination Products” clarified that UDI requirements apply to the device constituent in addition to any drug-side serialization obligations.
For pharmaceutical companies, contract manufacturers, packaging providers, and regulatory affairs teams, understanding unique device identifier UDI pharma requirements is now essential. This guide explains what UDI is, how it intersects with DSCSA pharmaceutical serialization, what the FDA’s 2025 combination products guidance changes, how GUDID submissions work, how the EU’s UDI framework under MDR aligns, and how to build a compliant UDI strategy in 2026 and beyond.
What Is a Unique Device Identifier (UDI)?
A Unique Device Identifier is a numeric or alphanumeric code created through an internationally accepted device identification and coding standard. Every UDI consists of two segments.
Device Identifier (DI). The mandatory, fixed portion of the UDI. The DI identifies the labeler (typically the manufacturer) and the specific version or model of the device. It is the searchable key that links a physical device to its public record in the GUDID database.
Production Identifier (PI). The conditional, variable portion of the UDI. When present, the PI includes one or more of the following: the lot or batch number, the serial number, the expiration date, the manufacturing date, or, for human cell, tissue, and cellular and tissue-based products (HCT/Ps) regulated as devices, a distinct identification code required under 21 CFR 1271.290(c).
Every UDI must appear in two forms on the device label and packaging. A human-readable plain-text version, and a machine-readable form using automatic identification and data capture (AIDC) technology, most commonly a GS1 DataMatrix or linear barcode, with RFID and other near-field communication technologies permitted as alternatives.
UDIs are issued through FDA-accredited issuing agencies. The three primary agencies are GS1 (the most widely used in pharma combination products), HIBCC (Health Industry Business Communications Council), and ICCBBA (which administers identifiers for blood and HCT/Ps). Device labelers must obtain their UDIs from one of these accredited issuing agencies.
Why UDI Matters in Pharma and Combination Products
The FDA designed the UDI system to deliver four interconnected outcomes that directly affect pharmaceutical manufacturers of drug-device combination products.
Patient safety. When a device is recalled or an adverse event reported, the UDI lets healthcare providers, patients, and regulators identify the exact device version, model, and lot involved in seconds rather than hours.
Faster, more targeted recalls. UDI-based recall identification dramatically reduces the scope, cost, and patient impact of removing defective products from the supply chain.
Postmarket surveillance. UDI integration into electronic health records and adverse event reports enables far more accurate signal detection in pharmacovigilance and medical device safety.
Supply chain efficiency. Standardized UDIs simplify inventory management, hospital procurement, distribution, and authentication across the healthcare ecosystem.
For pharmaceutical companies, the strategic implication is clear. If you sell a combination product with a device constituent (an autoinjector, prefilled syringe, inhaler, on-body injector, drug-coated implant, or similar), you have UDI obligations on top of, not instead of, your DSCSA drug-side serialization obligations.
UDI in Combination Products: The 2025 FDA Draft Guidance
In June 2025, the FDA published draft guidance titled “Unique Device Identifier (UDI) Requirements for Combination Products,” which was open for public comment until September 24, 2025. The draft was significant because it formally clarified an area that had created ambiguity for years.
A combination product, as defined in 21 CFR 3.2, is a therapeutic product comprising two or more different types of medical products, such as a drug combined with a device, a biologic combined with a device, a drug combined with a biologic, or all three. Each individual component (drug, device, or biologic) is referred to as a “constituent part” of the combination product.
The 2025 guidance reemphasizes a critical principle. If a combination product contains a device constituent part that would normally be subject to UDI requirements under 21 CFR Part 801 Subpart B, that device constituent part still requires a UDI when integrated into the combination product, unless an FDA-granted exception or alternative applies.
In practice, this means a prefilled syringe combination product needs the drug-side compliance (NDC, DSCSA serialization, EU FMD where applicable) and the device-side UDI on the syringe component label, plus GUDID submission for the device. The same logic applies to autoinjectors, inhalers, on-body injectors, transdermal delivery systems, and many other modern delivery platforms.
The FDA’s combination product UDI framework can be summarized as follows:
| Combination Product Type | UDI Required on Device Constituent? | Notes |
| Drug + Device (e.g., prefilled syringe) | Yes | UDI on device label, GUDID submission required |
| Biologic + Device (e.g., on-body injector) | Yes | UDI on device label, GUDID submission required |
| Drug + Biologic (no device part) | No | Drug-side identification only |
| Three-component combo with device part | Yes | UDI applies to the device constituent |
| Convenience kit containing a device | Yes | UDI applies to the device part inside the kit |
| Single-use device inside a convenience kit | Yes (with specific provisions) | Subject to device-level UDI rules |
The guidance also addresses labeling placement, formatting, and GUDID submission specifics for combination products, providing hypothetical examples that help sponsors understand exactly how to comply.
UDI vs. DSCSA Serialization: Two Systems, Two Purposes
This is the most common source of confusion in the pharma combination products space, and it is worth being precise about it.
DSCSA Serialization is a drug-side framework. It applies to prescription drugs in the United States and requires a unique identifier consisting of the NDC, a serial number, batch, and expiry, encoded in a 2D DataMatrix and exchanged via EPCIS through the supply chain.
UDI is a device-side framework. It applies to medical devices regulated under the FDA’s device authorities, requires a DI plus (where applicable) a PI, must be submitted to GUDID, and uses identifiers issued by accredited agencies (GS1, HIBCC, ICCBBA).
For a single combination product with both drug and device constituents, both regimes apply to their respective parts. The drug-side carton bears the DSCSA serialization barcode. The device constituent label bears the UDI. The same product can legally carry two identifiers without contradiction. In some cases, especially when GS1 is used for both, the same physical 2D DataMatrix code can encode the data needed by both regimes, but this requires careful regulatory and labeling design.
A clear understanding of this distinction is essential. Combination product manufacturers cannot rely on DSCSA serialization to satisfy UDI obligations, and vice versa.
The Global UDI Database (GUDID): What You Submit and Why
Every UDI device requires that the labeler submit information about the device to the FDA-administered Global Unique Device Identification Database (GUDID), which is publicly accessible through the AccessGUDID portal operated in partnership with the National Library of Medicine (NLM).
GUDID submissions include only the Device Identifier (DI) portion of the UDI, not the Production Identifier. Key data elements submitted include:
The DI itself, issued by an FDA-accredited issuing agency. The brand name, version or model number, and labeler name. The catalog number. The device’s premarket submission number (510(k), PMA, De Novo, or HDE). MR safety status (Magnetic Resonance Imaging compatibility). Whether the device is sterile, single-use, or contains latex. Storage and handling information. Clinical relevance flags (life-supporting, life-sustaining, implantable). GMDN (Global Medical Device Nomenclature) preferred term.
Labelers can submit information through two methods. Manual data entry via the GUDID web application, suitable for small portfolios. HL7 SPL XML submission via an electronic data exchange channel, used by labelers with large portfolios or automated submission workflows.
For combination products, the GUDID submission must accurately reflect the device constituent’s characteristics and clearly identify its association with the broader combination product where relevant.
UDI Compliance Dates and the End of Legacy Identifiers
The FDA implemented UDI in phases starting in 2013, with compliance dates staggered based on device class.
Class III devices (highest risk) had to comply earliest. Implantable, life-supporting, and life-sustaining (I/LS/LS) devices followed. Class II devices then came into scope. Class I and unclassified devices completed the rollout in the final phase. As of 2026, all non-sterile Class III, Class II, and I/LS/LS devices must bear UDI labeling, with specific compliance arrangements for sterile and certain other categories.
A critical milestone occurred on September 24, 2023. Before that date, the FDA permitted limited continued use of National Health Related Item Code (NHRIC) and National Drug Code (NDC) numbers on certain device labels as a transitional measure. Devices labeled on or after September 24, 2023, must comply with all applicable UDI requirements, including the prohibition on using legacy NDC or NHRIC numbers in place of a UDI.
For pharmaceutical companies whose combination products historically used NDC numbers for device-side labeling, this transition is now closed. Full UDI compliance is the only legal path.
Direct Marking Requirements
Some devices must be marked with the UDI directly on the device itself, not just on the label or packaging. This applies primarily to reusable devices that are reprocessed before each use, where the device is likely to become separated from its packaging during clinical use.
For combination products with a reusable device component (for example, a reusable autoinjector platform with disposable cartridges), the labeler should evaluate whether direct marking requirements apply and design accordingly. The FDA has issued some compliance policies for direct marking that may extend timelines for specific device categories, so consulting the latest FDA guidance is essential.
How UDI Aligns with the EU MDR and Global UDI Frameworks
The United States was the first major market to implement UDI at scale, but it is no longer alone. The European Union Medical Device Regulation (MDR) (EU 2017/745) and In Vitro Diagnostic Regulation (IVDR) (EU 2017/746) introduced their own UDI framework that parallels the FDA structure closely.
Under EU MDR, every medical device requires a UDI consisting of a UDI-DI (similar to the FDA’s DI) and a UDI-PI (similar to the FDA’s PI). UDI data must be submitted to EUDAMED, the European Database on Medical Devices, which is the EU counterpart to GUDID. The European UDI framework uses the same FDA-accredited issuing agencies (GS1, HIBCC, ICCBBA), enabling labelers to use a single UDI structure across both markets in most cases.
Other markets are following similar paths. Saudi Arabia, China NMPA, India CDSCO, Brazil ANVISA, Japan PMDA, and the United Kingdom MHRA have all introduced or are advancing UDI frameworks, generally aligned with the international consensus championed by the International Medical Device Regulators Forum (IMDRF).
For pharmaceutical companies selling combination products globally, a coordinated UDI strategy that satisfies the FDA, EU MDR, and emerging markets simultaneously is now the standard approach.
Practical UDI Implementation Steps for Pharma Combination Products
Successful UDI implementation for combination products typically follows a structured sequence.
Step 1: Confirm regulatory pathway. Determine whether your combination product is regulated as a drug, device, biologic, or some combination, and identify the device constituent parts subject to UDI.
Step 2: Engage an FDA-accredited issuing agency. Request your DI ranges from GS1, HIBCC, or ICCBBA depending on your product type and existing identification infrastructure.
Step 3: Design UDI labeling. Apply UDI in human-readable and AIDC form on the device constituent’s label and packaging. Common AIDC formats include GS1 DataMatrix and GS1-128 linear barcodes.
Step 4: Implement direct marking where required. For reusable device constituents likely to be separated from labeling, plan for direct marking using laser etching, ink printing, or similar permanent methods.
Step 5: Establish a GUDID submission process. Choose between web-based manual entry or HL7 SPL XML automated submission, and assign clear responsibility for data accuracy and updates.
Step 6: Coordinate with drug-side serialization. Ensure UDI labeling and DSCSA serialization work together without conflict, especially when both are encoded in 2D DataMatrix codes on the same packaging.
Step 7: Integrate with quality management and complaint handling. UDIs should flow through your complaint, recall, and adverse event reporting processes to maximize the patient safety benefits.
Step 8: Plan for EU UDI alignment. If you market in the EU, ensure your UDI strategy satisfies both FDA GUDID and EU EUDAMED submission requirements.
Step 9: Maintain and update. UDI data is not “submit once and forget.” Any change to the device version, model, labeler, packaging configuration, or critical attributes can require a new UDI or an updated GUDID record.
Common UDI Compliance Pitfalls
Assuming DSCSA serialization satisfies UDI. It does not. They are separate frameworks with separate obligations, and combination products often need both.
Missing the device constituent obligation. Many pharma companies focus on drug-side compliance and overlook the device constituent’s UDI labeling requirement.
Failing to update GUDID. A new model, version, or labeling change often triggers a new UDI requirement. Stale GUDID records are a frequent audit finding.
Improper AIDC implementation. Poorly printed barcodes that fail ISO/IEC 15415 grading rules render the UDI unreadable, defeating the purpose of the system.
Direct mark oversights. Reusable device constituents that should be directly marked but are not represent a frequent compliance gap.
Ignoring EU UDI alignment. Companies with global combination product portfolios that build separate FDA and EU labels duplicate cost and increase error risk.
Treating UDI as labeling work only. UDI touches quality systems, complaint handling, recall procedures, adverse event reporting, and supply chain. It is a cross-functional program, not a labeling task.
The Future of UDI in Pharma Combination Products
Three trends will shape UDI in the next three to five years.
Tighter convergence with DSCSA and EU FMD. Expect more dual-purpose GS1 DataMatrix implementations where the same physical code carries both drug-side and device-side data elements.
Expansion to digital therapeutics and connected devices. Connected drug delivery devices, smart inhalers, digital pills, and prescription digital therapeutics are bringing UDI into entirely new product categories. Expect FDA guidance to evolve accordingly.
Integration with Digital Product Passports and patient apps. The EU’s emerging Digital Product Passport framework and a growing number of patient-facing verification apps will increasingly leverage UDI data to deliver real-time device authenticity, recall, and clinical-use information directly to healthcare providers and patients.
For pharmaceutical companies developing or marketing combination products in 2026 and beyond, UDI is no longer a niche device-side concern. It is a core regulatory, quality, and supply chain capability that must operate alongside DSCSA, EU FMD, and other global pharmaceutical serialization frameworks.
Frequently Asked Questions
Q1. What is a Unique Device Identifier (UDI) and why does it matter for pharma? A UDI is a numeric or alphanumeric code that identifies a specific medical device, consisting of a Device Identifier (DI) and (where applicable) a Production Identifier (PI). It matters for pharma because combination products with device constituents (autoinjectors, prefilled syringes, inhalers, on-body injectors, etc.) must comply with UDI requirements on top of any drug-side DSCSA serialization obligations.
Q2. How is UDI different from DSCSA serialization? DSCSA serialization is a drug-side framework that applies to prescription drugs and uses an NDC plus serial number, batch, and expiry exchanged via EPCIS. UDI is a device-side framework that applies to medical devices and uses a DI plus PI submitted to the GUDID database. For combination products, both regimes can apply to their respective constituents.
Q3. Do all combination products require a UDI? Not all. The FDA evaluates the device constituent part of a combination product to determine UDI applicability. If the device constituent would normally be subject to UDI under 21 CFR Part 801 Subpart B, then UDI requirements apply unless an FDA-granted exception or alternative is in place.
Q4. What did the FDA’s June 2025 UDI combination products draft guidance change? The June 2025 draft guidance (Docket No. FDA-2025-D-0176) clarified how existing UDI requirements apply to combination products with device constituent parts. It reemphasized that each medical device constituent of a combination product requires a UDI on its label and packaging, and that the device labeler must submit information to GUDID, with specific examples covering drug-device, biologic-device, and three-component combinations.
Q5. What is GUDID and what gets submitted? GUDID is the Global Unique Device Identification Database administered by the FDA. Device labelers submit DI-level information about each device, including brand name, model, labeler details, premarket submission numbers, sterility status, MR safety, storage and handling, and clinical relevance flags. The Production Identifier (lot, serial, expiry) is not submitted to GUDID.
Q6. Who issues UDIs? UDIs are issued through FDA-accredited issuing agencies. The three primary agencies are GS1 (most widely used in pharma combination products), HIBCC (Health Industry Business Communications Council), and ICCBBA (which administers identifiers for blood and HCT/Ps).
Q7. Can I still use an NDC instead of a UDI on a device label? No, not for devices labeled on or after September 24, 2023. The FDA’s enforcement policy for legacy NDC and NHRIC numbers ended on that date. Devices labeled afterward must comply with all UDI requirements, including the prohibition on using legacy NDC or NHRIC numbers in place of a UDI.
Q8. What is direct marking and when is it required? Direct marking means applying the UDI permanently to the device itself, not just on its label or packaging. It is generally required for reusable devices intended to be reprocessed between uses, where the device is likely to become separated from its packaging. For combination products with reusable device platforms (such as a reusable autoinjector with disposable cartridges), direct marking may apply.
Q9. How does the EU MDR UDI framework compare to FDA UDI? The EU MDR UDI structure closely parallels the FDA system, using a UDI-DI (similar to FDA DI) and UDI-PI (similar to FDA PI), submitted to the European EUDAMED database. The EU framework uses the same FDA-accredited issuing agencies, enabling most labelers to design a single UDI strategy that satisfies both markets, with format-specific submissions to GUDID and EUDAMED.
Q10. Can a single 2D DataMatrix code carry both DSCSA serialization data and UDI data? Yes, in many cases. When both regimes use GS1 standards (which is common for combination products), a single GS1 DataMatrix code can encode the data elements required by both, including the device DI, lot, serial, expiry, and drug NDC where structured appropriately. This requires careful regulatory, labeling, and printing design but eliminates the need for two separate codes on the same package.
Q11. What happens when I make a labeling or design change to a combination product? Any change to the device version, model, labeler name, packaging configuration, sterility status, or other critical attributes may trigger the need for a new UDI and an updated GUDID record. Pharmaceutical companies should establish a change control process that automatically flags UDI implications for any combination product modification.Q12. What are the consequences of UDI non-compliance for a pharma combination product? Non-compliance can result in FDA warning letters, import alerts, product recalls, and refusal of admission for imported products. Combination products without a valid UDI on device constituents may also be rejected by hospitals, pharmacies, and group purchasing organizations that increasingly require UDI scanning for receiving and inventory management. Beyond regulatory risk, UDI gaps significantly slow recall response time and increase patient safety exposure.
