The IV-to-Subcutaneous Shift: How On-Body Delivery Systems Are Reshaping Biologic Drug Administration and Regulatory Strategy in 2026

At a Glance: The IV-to-Subcutaneous Paradigm Shift

The pharmaceutical industry is in the midst of a fundamental transformation in how biologic therapies are delivered to patients. Intravenous (IV) infusion — long the standard of care for monoclonal antibodies, enzyme replacement therapies, and other complex biologics — is being systematically replaced by subcutaneous (SC) administration through wearable on-body delivery systems (OBDS). This shift is being driven by patient demand for home-based care, pharma economics favoring self-administration, and regulatory frameworks that increasingly support drug-device combination products.

The scale of the transformation is substantial. The intravenous-to-subcutaneous drug repositioning market was valued at $35.87 billion in 2025 and is projected to reach $68.71 billion by 2034, growing at a CAGR of 7.53%. In 2024 alone, 40% of the antibodies approved by the FDA were administered subcutaneously.

What Are On-Body Delivery Systems?

Definition and Technology

On-body delivery systems (OBDS), also called wearable injectors or patch pumps, are medical devices designed to be worn on the patient's body (typically the abdomen) during drug administration. Unlike traditional autoinjectors that deliver a rapid injection over seconds, OBDS deliver larger volumes of medication subcutaneously over minutes to hours through a small, often hidden needle or cannula.

Key technical characteristics of modern OBDS platforms:

Why OBDS Exist: The Volume Problem

The fundamental driver for OBDS is volume. Traditional autoinjectors and prefilled syringes are limited to approximately 1–2.5 mL of drug delivery. However, many biologic therapies — particularly monoclonal antibodies — require much larger volumes when reformulated for subcutaneous delivery:

• Pegcetacoplan (EMPAVELI/Aspaveli): 20 mL per dose, delivered via enFuse
• Pembrolizumab (Keytruda): Previously 30-minute IV infusion, now approved for subcutaneous injection
• Darzalex Faspro (daratumumab): Subcutaneous formulation approved for multiple myeloma
• Sarclisa (isatuximab): CHMP recommended SC formulation via on-body injector in Europe

Higher drug concentrations and novel formulation approaches (such as Halozyme's ENHANZE technology using recombinant human hyaluronidase) are enabling more drugs to be delivered subcutaneously, but many still require volumes that exceed what conventional devices can handle. This is where OBDS fill the gap.

The Enable Injections enFuse Platform: A Case Study

Company Background

Enable Injections, headquartered in Cincinnati, Ohio, has developed the enFuse platform as one of the leading OBDS technologies. The company was founded by Michael D. Hooven, a medical device industry veteran, and has attracted significant investment:

• 2018: $50 million Series B led by Sanofi
• 2022: $215 million Series C led by Magnetar Capital, including Sanofi and other institutional investors
• 2026: $30 million investment from Sanofi to accelerate manufacturing buildout

The company is building a 90,000-square-foot Manufacturing Center of Excellence in Springdale, Ohio, and has over 100 patents related to its technology.

Regulatory Milestones

The enFuse platform has achieved a series of regulatory milestones across multiple jurisdictions:

The Apellis Partnership: EMPAVELI Injector

The first commercial application of enFuse technology is the EMPAVELI Injector, a combination product developed in partnership with Apellis Pharmaceuticals for the subcutaneous delivery of pegcetacoplan (EMPAVELI) to adults with paroxysmal nocturnal hemoglobinuria (PNH). This was the first FDA-approved combination product based on enFuse technology, approved in September 2023.

Pegcetacoplan is a targeted C3 therapy that regulates excessive activation of the complement cascade. Prior to the EMPAVELI Injector, patients self-administered the drug via traditional infusion pump — a more complex and time-consuming process. The enFuse-based system delivers 20 mL of medication through a compact, wearable device with a hidden needle, push-button activation, and hands-free delivery.

The Sobi Partnership: Aspaveli in Europe

In September 2024, Enable Injections announced a strategic partnership with Swedish Orphan Biovitrum AB (Sobi) to develop and distribute Aspaveli (the ex-US trade name for pegcetacoplan) in combination with enFuse technology across Sobi's territories. The May 2026 expanded CE certification enables European patients with PNH, C3 glomerulopathy (C3G), and primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) to receive their medication via the enFuse on-body injector.

The Sanofi Manufacturing Investment

In early 2026, Sanofi invested $30 million specifically to accelerate Enable Injections' manufacturing buildout. This investment reflects Sanofi's strategic interest in the enFuse platform as an enabler for its own biologic pipeline — potentially including Sarclisa (isatuximab), for which a CHMP recommendation was issued for a subcutaneous formulation delivered via on-body injector.

Additional Partnerships

Enable Injections is working with multiple pharmaceutical partners beyond Apellis, Sobi, and Sanofi, including Roche and Incyte, for clinical trials and commercial launch planning. The company also partnered with Aptar Digital Health for a companion digital solution for the enFuse platform, adding connected health capabilities.

The Competitive OBDS Landscape

BD Libertas Wearable Injector

Becton, Dickinson and Company (BD) is developing the Libertas wearable injector, designed for subcutaneous administration of high-dose biologics. Key features:

• Configurations for 2–5 mL and 5–10 mL delivery volumes
• Supports biologics with viscosities up to 50 centipoise
• In July 2025, BD announced the first pharma-sponsored clinical trial using Libertas for subcutaneous delivery of complex biologics
• Device component of a combination product, not subject to independent FDA 510(k) clearance or EU CE mark certification

BD framed the opportunity around converting therapies that require hospital or clinic visits into more flexible care settings, including home self-injection.

West Pharmaceutical Services SmartDose

West Pharma's SmartDose platform was the first OBDS to achieve FDA approval in combination with an approved drug — Amgen's Neulasta (pegfilgrastim) delivered via the Neulasta Onpro injector. The platform has since been used with Amgen's Repatha (evolocumab) Pushtronex system.

The SmartDose platform demonstrates the regulatory precedent for OBDS as combination products: the device is evaluated as part of the drug's Biologics License Application (BLA) or New Drug Application (NDA), rather than receiving independent device clearance.

Ypsomed and Other Platforms

Ypsomed, a Swiss company, offers the SmartPilot platform for large-volume wearable injection. SHL Medical develops reconstitution autoinjectors for lyophilized drugs. Multiple other companies are developing OBDS platforms, reflecting the broad industry recognition that on-body delivery is becoming a primary lever of competitive advantage in biologic drug commercialization.

Regulatory Pathway for OBDS Combination Products

FDA Framework

On-body delivery systems used with specific drugs are regulated as drug-device combination products. The FDA's Office of Combination Products (OCP) assigns a lead center based on the primary mode of action:

• CBER: For biologic-device combinations (e.g., enFuse with EMPAVELI/pegcetacoplan)
• CDER: For drug-device combinations
• CDRH: When the device has independent device functionality

For most OBDS combination products, CBER or CDER takes the lead, and the device is evaluated as part of the drug's marketing application (BLA, NDA, or ANDA supplement). This means the OBDS does not receive independent 510(k) clearance — instead, its safety and efficacy are assessed in the context of the specific drug it delivers.

Key Regulatory Requirements

1. Human Factors Engineering (HFE): FDA expects comprehensive human factors testing for OBDS, given that patients self-administer in uncontrolled home environments. This includes:

   • Use-related risk analysis
   • Formative usability testing during development
   • Summative (validation) usability testing with representative users
   • Evaluation of all critical tasks: device application, drug loading, activation, wear, removal, and error recovery

2. Essential Drug Delivery Outputs (EDDOs): FDA's guidance on "Essential Drug Delivery Outputs for Devices Intended to Deliver Drug and Biological Products" requires applicants to identify and control the critical performance parameters of the delivery system, such as deliverable volume and injection forces.

3. Combination Product Quality: The final rule effective February 2, 2026, incorporates ISO 13485 by reference into 21 CFR Part 820, harmonizing the quality system requirements for device components of combination products with international standards.

EU MDR Requirements

Under the EU Medical Device Regulation, OBDS are classified based on their characteristics:

• If the device is integral to the drug (pre-filled, pre-assembled), it is regulated as part of the drug product under the human medicines framework
• If the device is supplied separately (as enFuse is — the device and drug are not pre-integrated), the device must independently comply with MDR requirements, including CE marking through a Notified Body

Enable Injections received EU MDR CE Mark for the enFuse syringe transfer system in March 2025, a separate device authorization that allows the platform to be supplied independently to healthcare facilities.

Human Factors: The Critical Differentiator

As West Pharma noted in its 2026 regulatory guidance for OBDS: "OBDS devices aren't just drug containers. They're wearable systems that patients must apply, wear, monitor, and eventually remove. This introduces unique usability risks not typically present in autoinjectors, prefilled syringes, or inhalers."

Key human factors considerations specific to OBDS include:

• Application: Correct positioning on the body, securing the adhesive
• Drug loading: Transfer from vial or syringe to the device (error-prone step)
• Activation: Starting the delivery, confirming correct operation
• Monitoring: Recognizing normal vs. abnormal delivery, handling alarms
• Removal: Proper disposal of the used device and drug container
• Error recovery: What to do if the device malfunctions mid-delivery

Market Drivers: Why the IV-to-SC Shift Is Accelerating

Patient Demand for Home-Based Care

The COVID-19 pandemic permanently accelerated the shift toward home-based healthcare. Patients with chronic conditions who previously traveled to infusion centers every 2–4 weeks for IV therapy increasingly prefer — and expect — self-administration options. OBDS enable this transition for biologics that require volumes beyond what autoinjectors can deliver.

Pharma Economics

The economic case for IV-to-SC conversion is compelling for pharmaceutical companies:

• Reduced COGS: Eliminating infusion center administration reduces per-dose delivery costs
• Competitive differentiation: A self-administered formulation can capture market share from IV-only competitors
• Lifecycle management: Converting an IV biologic to SC extends the product's commercial life, particularly valuable as biosimilar competition intensifies
• Expanded addressable market: Home administration removes access barriers for patients in rural or underserved areas

Clinical Equivalence

A growing body of evidence supports pharmacokinetic comparability between IV and SC formulations. The key regulatory requirement is demonstrating that the SC formulation achieves equivalent drug exposure (AUC) to the IV formulation, even if the absorption profile differs. Halozyme's ENHANZE technology, which uses recombinant human hyaluronidase to temporarily increase SC tissue permeability, has been instrumental in enabling high-volume SC delivery.

Key Market Approvals

Several recent high-profile approvals illustrate the accelerating trend:

The ADC Frontier: Antibody-Drug Conjugates Move to SC

A particularly significant emerging application for OBDS technology is the IV-to-SC conversion of antibody-drug conjugates (ADCs). The ADC market is projected to grow from approximately $15 billion in 2025 to $71 billion by 2031 (CAGR ~29%), with more than 15 ADCs already FDA-approved and over 400 in clinical development. As these complex molecules are reformulated for SC delivery, their dosing volumes and viscosity requirements will demand advanced OBDS platforms capable of reliable large-volume delivery. The IRAKLIA Phase III study demonstrated the feasibility of isatuximab SC delivery via on-body injector, setting a regulatory precedent that other ADC developers are expected to follow.

Market Size by Segment

Implications for Industry Stakeholders

For Pharmaceutical Companies

The OBDS ecosystem is becoming a primary commercial consideration in biologic drug development. Companies developing high-volume biologics should:

1. Evaluate SC formulation feasibility early in the development process
2. Select OBDS platform partners during Phase 2 to enable concurrent device-drug development
3. Invest in human factors studies specific to the chosen delivery platform
4. Plan regulatory submissions as combination products, with integrated device and drug data packages

For Medical Device Manufacturers

The OBDS market is still early in its growth trajectory. Device companies should consider:

1. Platform scalability: Designing devices that accommodate a range of drug viscosities, volumes, and delivery profiles
2. Digital integration: Adding connected health capabilities (Bluetooth, companion apps, dose tracking) that differentiate from basic mechanical systems
3. Regulatory strategy: Building EU MDR CE Mark and FDA combination product experience as competitive moats
4. Manufacturing capacity: The $30M Sanofi investment in Enable Injections' manufacturing signals that pharma partners are willing to co-invest in capacity

For Regulatory Professionals

The OBDS space requires fluency in both drug and device regulatory frameworks. Key areas of expertise include:

1. Combination product designation and lead center determination
2. Human factors engineering for home-use medical devices
3. Essential drug delivery output characterization
4. ISO 13485 quality management for device components of combination products
5. Post-market surveillance for combination products (drug and device vigilance requirements)

For Patients and Healthcare Systems

The IV-to-SC shift has profound implications:

• Reduced infusion center burden: Every patient converted to home self-administration frees infusion center capacity for patients who must receive IV therapy
• Improved adherence: Self-administration with simple, wearable devices improves treatment persistence
• Geographic access: Patients in rural or underserved areas gain access to therapies previously available only at infusion centers
• Quality of life: Fewer clinic visits, shorter administration times, and greater scheduling flexibility

Key Takeaways

1. Structural shift: The IV-to-subcutaneous transition is not a trend — it is a structural transformation in biologic drug delivery, with a $68.7 billion market by 2034
2. OBDS as enabler: On-body delivery systems are the key enabling technology, solving the volume problem that prevents many biologics from being reformulated for SC administration
3. Regulatory complexity: OBDS are regulated as drug-device combination products, requiring integrated development strategies and expertise in both drug and device regulatory frameworks
4. Platform competition: Enable Injections enFuse, BD Libertas, and West SmartDose are the leading platforms, each with distinct technology, partnership models, and regulatory positioning
5. Human factors critical: FDA and EU regulators are scrutinizing OBDS usability closely, given the unique risks of wearable self-administration devices
6. Investment signal: Sanofi's $30M manufacturing investment in Enable Injections reflects pharma's willingness to co-invest in OBDS infrastructure, validating the commercial model
7. Patient impact: The shift from IV to SC fundamentally reorganizes where and how care is delivered, moving biologic therapy from infusion centers into patients' homes