From IV to subcutaneous to oral: is this the natural evolution of a medicine?

An attractive hypothesis

A customer recently offered a thought-provoking view of drug development: a medicine may begin as an intravenous infusion, progress to subcutaneous injection and ultimately reach the “holy grail” of an oral tablet.

The attraction is obvious. Each step appears to move treatment away from the clinic and further into the patient’s own hands:

IV infusion → subcutaneous injection → oral medicine

As a broad model of increasing convenience, it has real value. As a prediction of what happens to every medicine, however, it needs qualification. The pathway depends on the molecule, dose, disease, patient population and the biological barriers associated with each route of administration.

Why some medicines begin with IV administration

Intravenous administration offers benefits during the development and early commercial life of some medicines, particularly biologics. It provides complete systemic availability, permits controlled administration and can accommodate volumes that would be difficult to deliver into subcutaneous tissue. Patients can also be observed during treatment, which may be important while the safety profile and administration process are still being established.

The disadvantages are equally clear. IV therapy may require travel to a hospital or infusion centre, trained staff, clinical infrastructure and a significant amount of the patient’s time. Those demands recur with every administration and become especially important for long-term treatment.

This makes an IV-to-subcutaneous programme more than a formulation exercise. It can be a lifecycle strategy that changes where treatment happens, who administers it and how healthcare resources are used.

The move to subcutaneous delivery

A successful subcutaneous presentation can shorten administration and may enable treatment in a community or home setting. Depending on the product and user, it might be delivered using a prefilled syringe, autoinjector or wearable injector. The European Medicines Agency’s public information for subcutaneous infliximab, for example, notes comparable effectiveness to infusion in relevant studies and the convenience of home treatment.

But this is not simply the same medicine placed in a different container. Developers may need to address:

• the volume that can be delivered comfortably;
• the concentration and viscosity of the formulation;
• stability throughout manufacture, storage and use;
• absorption and pharmacokinetic variability;
• injection-site reactions and tolerability;
• the forces, time and energy needed to complete delivery;
• compatibility between the formulation, primary container and delivery device; and
• whether patients or caregivers can use the complete system safely and reliably.

The drug, device, user interface, packaging, instructions, training and support arrangements therefore become one therapeutic system. A technically successful injection is not enough if the intended user cannot prepare, initiate and complete it confidently.

Is a tablet always the ultimate destination?

For many people, taking a tablet is more familiar and acceptable than receiving an injection. Oral medicines are portable and usually need little equipment or training. That does not mean that every injectable medicine can—or should—be converted into one.

For proteins, peptides and antibodies, oral delivery presents formidable barriers. The medicine may be degraded by stomach acid and digestive enzymes. Even if it survives, a large molecule may cross the intestinal wall poorly. Food, water, gastric emptying and other gastrointestinal factors may further affect exposure.

This is why “oral dosage form” is more accurate than “solid form”. Making an injectable product physically solid does not solve the absorption problem. An injectable product can itself be freeze-dried or provided as an implant or depot, while an oral medicine need not be a tablet.

Oral semaglutide demonstrates both what is possible and why the challenge should not be underestimated. Its formulation uses an absorption enhancer; current FDA labelling reports much lower absolute bioavailability after oral administration than after subcutaneous injection. This is a success for specialised formulation science, not evidence that conventional tablet conversion is available to biologics generally.

Subcutaneous delivery may be the destination

If an oral form would require an impractical dose, produce unacceptable variability or introduce new safety and usability concerns, subcutaneous delivery may offer the better overall balance. It can preserve reliable systemic delivery while removing much of the burden associated with an infusion clinic.

This reframes subcutaneous administration. It need not be viewed as an imperfect stage on the way to a pill. For some therapies, a well-designed injection system may be the mature, patient-centred presentation.

The relevant development question is therefore not simply, “Can we eliminate the needle?” It is, “Which treatment system provides reliable delivery with the lowest reasonable burden for this medicine and these patients?”

Digital health changes the progression

When treatment moves from the clinic into the home, it loses some of the surrounding clinical support. In the clinic, a healthcare professional guides the process, observes administration and creates a record. At home, the patient or caregiver assumes more of that responsibility.

A connected injection system can potentially help close part of this gap by providing:

• treatment schedules, reminders and preparation guidance;
• feedback during administration;
• confirmation that the delivery sequence was completed;
• a reliable time and dose history;
• adherence support based on actual treatment behaviour;
• selected information for caregivers or clinical teams; and
• links between treatment use, symptoms and patient-reported outcomes.

This can create value beyond convenience. Prescription and dispensing records show that a medicine was supplied, but they do not necessarily show whether a dose was prepared correctly or completed. Device-generated information, interpreted within its limitations, can help distinguish a treatment problem from an administration or adherence problem.

It can also support service improvement and more informed conversations between patients and healthcare professionals. The purpose should be to help the patient and care team—not to create surveillance for its own sake.

Connectivity must earn its place

Adding an app, sensor or cloud service does not automatically make a therapy better. Digital functionality introduces its own usability, privacy, cybersecurity, interoperability, maintenance and lifecycle responsibilities. It may also exclude people who lack a compatible phone, reliable connectivity, confidence with technology or the desire to share treatment data.

A connected treatment should therefore have a defined clinical or user benefit. Its essential therapy functions must remain safe when a phone is unavailable, a network connection fails or a supporting service is temporarily inaccessible. Developers must decide what the connected system is intended to claim, which decisions may rely upon its data and how long the complete ecosystem will be supported.

Digital health works best when it is designed as part of the therapy from the outset: aligned with the intended use, risk management, human factors, data strategy and post-market plan. Added late, it can become an expensive accessory looking for a purpose.

Perhaps the progression is no longer linear

The original hypothesis remains a useful way to stimulate discussion, but its most important insight may not be the sequence of dosage forms. It is the movement of treatment towards greater patient independence.

The future pathway may therefore be better expressed as:

Clinic-administered therapy → patient-administered therapy → digitally supported and increasingly personalised treatment

For some medicines, that journey will lead to an oral product. For others, a connected autoinjector, wearable injector or another home-use delivery system may provide the best combination of biological feasibility, reliable administration and patient confidence.

The goal is not necessarily to eliminate the injection. It is to make treatment fit safely, reliably and naturally into the patient’s life.

What do you think? Is subcutaneous delivery principally a stepping stone to oral medication—or, for many biologics, the destination that digital health can make substantially better?

Selected sources

• European Medicines Agency: Remsima product overview—including the evidence and home-treatment rationale for subcutaneous infliximab.
• US FDA prescribing information for oral semaglutide tablets—including the role of SNAC and reported oral bioavailability.