An estimated two-thirds of clinical trials involve a comparator drug or co-therapy. For most sponsors, the operational complexity of sourcing that product is not visible at the point in the development process when it would be most useful.
By the time it becomes apparent, the window for good decision-making has closed. The choices that determine whether supply will be available, compliant, and on time have already been made, often by default.
The gap between protocol supply and reality
A comparator is defined in a clinical trial protocol and specifies which product, at what dose, and for what duration. The sourcing effort that sits behind that definition is rarely visible in protocol language and seldom factored into trial timelines with the precision it requires. An Akesa survey of 25 Australian biotechnology companies, CROs, and clinical trial sponsors in 2024 found that availability, guarantee of supply, speed of sourcing, and lead time ranked as the top challenges in clinical trial supply. These are not procurement preferences. They are operational risk factors.
The comparator sourcing market reflects how critical this challenge has become. Independent market analysis commissioned by Akesa estimates the total addressable market (excluding U.S.-only trials) at between A$7.4โ9.3 billion. The analysis indicates continued market expansion through 2030 as clinical trial activity increases, biologics become more prevalent as comparators, and multi-regional studies continue to grow. The result is a steadily increasing investment by sponsors in securing reliable comparator supply for clinical trials.
The regulatory dimension
Every jurisdiction in which a trial operates imposes its own requirements on the comparator. In Australia, the TGA’s Clinical Trial Handbook is explicit: if a sponsor determines that a comparator constitutes an unapproved therapeutic good, a CTN or CTA must be in place before the product can be supplied, including products already listed on the ARTG but altered for trial purposes.
That is one jurisdiction. A Phase III trial running across Australia, Japan, South Korea, and one or more European markets will encounter a different regulatory framework at each site. Documentation requirements vary.
Labelling specifications differ. Import approval processes have their own timelines and conditions. A product procured in one country may not be acceptable in another.
The EU Clinical Trials Regulation (CTR 536/2014), now fully operational through the Clinical Trials Information System following a mandatory transition completed in January 2025, introduced standardised documentation requirements for comparator drugs in EU trials. Non-compliance carries the risk of regulatory rejection or trial suspension. For sponsors managing multi-regional studies, each jurisdiction must be treated as a distinct sourcing pipeline, not a variation of the same process.
The consequence of treating regulatory compliance as a late-stage consideration is delay. Not a minor delay. The kind that compounds into protocol amendments, site activation gaps, and budget overruns that were not anticipated at study design.
The documentation chain
Obtaining a comparator drug is not the same as obtaining the documentation that makes it usable in a trial. Certificates of Analysis, Certificates of Conformity, GMP certificates, and import/export permits must all be in place before supply can proceed. Many of these documents require direct engagement with the Marketing Authorisation Holder (MAH); Intermediaries cannot provide them.
The inability to obtain pedigree and product documentation is one of the most common sources of operational, regulatory, and financial setbacks for trial sponsors.
The timeline for assembling this documentation is not fixed. It depends on the product, the manufacturer’s processes, and the jurisdictions involved. For some comparators, particularly patented or limited-distribution products, the MAH may require a formal approval process before releasing documentation for trial use. This process can take weeks. When it is not initiated early, it becomes the critical path item that determines whether a trial starts on schedule.
Direct manufacturer relationships are the most reliable mechanism for managing this risk. A sourcing partner with established MAH relationships can initiate documentation requests earlier, negotiate access to the required certificates, and maintain visibility over timelines in a way that open-market procurement cannot.
The availability problem
The global shortage of pharmaceutical products has worsened steadily. According to the FDA’s Drug Shortages Database, active drug shortages in the United States remained elevated throughout 2024, with sterile injectables, oncology agents, and biologics consistently among the most affected categories. The ASHP recorded over 320 active shortages in early 2024, a level sustained across the year despite modest improvement by year-end. The European Medicines Agency formally launched the European Shortages Monitoring Platform in November 2024 to centralise shortage reporting across member states; a structural response to a supply problem regulators had acknowledged as increasingly acute.
What is particularly significant for clinical trial supply is the growing competition between commercial drug demand and trial demand for the same molecules. As biosimilar development accelerates, sponsors require innovator biologics as comparators in increasing volumes, against a supply base that is simultaneously serving commercial markets. Comparator sourcing has become the fastest-growing category of clinical trial supply services, driven specifically by the growth of head-to-head comparisons in oncology, immunology, and rare disease.
For sponsors, this means that availability assumptions made at protocol design may not hold by the time sourcing begins in earnest. Products that appeared available are allocated. Prices have moved. Lead times have extended. A sourcing strategy that relies on open-market access alone carries more risk than it did five years ago.
The APAC dimension
Australia and the broader APAC region present particular sourcing considerations. Trial activity across APAC has grown substantially, but supply chain infrastructure has not kept pace. Over-reliance on European supply sources is a documented vulnerability. Speaking at the OCT/CTS Korea 2025 conference, Akesa co-CEO George Vlachos made a point that reflects the companyโs operating philosophy: APAC-based trials require a deliberate multi-sourcing strategy built around local and regional access points, not European pipelines that were never designed to serve this region at current volumes. It is a principle Akesa has built into its sourcing model from the ground up.
APAC regulators must also be engaged early on in labelling, packaging, documentation, and acceptance pathways. These are not administrative details. In Japan, South Korea, Australia, and Singapore, the requirements differ in ways that affect whether a comparator sourced from a European market is usable at an APAC trial site at all. Discovering that incompatibility at the point of import is a far more expensive lesson than addressing it during feasibility.
Australia’s position within this picture is distinctive. The CTN pathway allows investigational products to be imported, labelled, and prepared before final trial approval. That flexibility is an operational asset, but it does not reduce the documentation or regulatory burden on the comparator itself. Those requirements remain.
A case for early engagement
The most consistent finding across Akesa’s experience, and across the sourcing challenges documented in the 2024 Australian industry survey, is that the problems which derail comparator supply are not inherently unsolvable. They are the predictable consequences of late engagement.
When sourcing is initiated during protocol design and feasibility, rather than after regulatory approvals are secured, the documentation timeline runs in parallel with study start-up rather than after it. Market availability can be assessed before the trial, depending on a specific product. Manufacturer relationships can be established before urgency drives the negotiation. Regulatory requirements in each jurisdiction can inform sourcing decisions rather than constrain them.
For Akesa, this is not a positioning statement. It is how the business operates. With wholesale licences across Australia, New Zealand, Japan, and Singapore, and established manufacturer relationships built across more than a decade of APAC clinical trial supply, the company is structured to engage at feasibility rather than at crisis. The clinical trial supply capability developed over years of operating in APAC reflects the view that comparator sourcing is a strategic activity, not a procurement task. The distinction matters most when the product is constrained, the timeline is fixed, and the trial cannot proceed without it.ย
Akesaโs infrastructure, including its just-in-time ordering platform for standard-of-care and comparator products, was built specifically to reduce the lead time gap that catches sponsors off guard. The tools exist. The supplier network exists. What determines outcomes is whether they are engaged before the problem exists or after it has already become one.
The complexity behind a single IMP line item does not change.
What changes is when it is addressed.
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