Features

Navigating Complexities in Comparator Drug Procurement

Why a comprehensive sourcing strategy underpinned by clinical supply chain experience is critical.

By: Ed Lewis,

Carol Alexandre, Vice President, Clinical Trial Supplies, IQVIA

With outsourcing being an accepted and integral practice in clinical research, pharmaceutical and biotechnology companies look to contract research organizations (CROs) to help them achieve critical time and cost savings in the eternal race to get product to market quickly and without compromising quality. The needs of clinical trial sponsors can be complex and differ greatly but regardless of their size, location or therapeutic focuses, there is a universal need for qualified partners who can collaborate with flexibility and solve problems through experience and innovation.

One common problem revolves around sourcing comparators for use in clinical trials. Comparators are reference treatments used for comparison alongside investigational products. Comparator treatments are typically the gold standard against which an IP is measured and are increasingly being used in trials. According to a global market study published in May 2023, comparator sourcing is expected to increase from $974 million in 2022 to more than $1.3 billion by 2031.1

Comparators can be a critical part of a trial, but their use requires specific expertise to navigate supply nuances and potential pitfalls.

To properly evaluate the IP against treatment that may be the standard of care, a comprehensive supply strategy is needed. First, the sponsor needs to select the comparator or reference drug to use, and second, must source and provide it to every trial site without disruption while maintaining regulatory compliance. CROs typically assign a dedicated supply chain group to studies, which helps ensure that the end-to-end supply process is efficiently conducted without compromising data or quality or significantly adding to trial costs.

Given the multiple layers of operational considerations within the procurement process, close collaboration between trial sponsors and partners is integral to a procurement strategy with contingency scenarios to ensure trials are executed as planned. Because industry interest in comparator integration, notable components of a strong comparator procurement strategy are discussed below.

Why comparator sourcing?

In a highly competitive market, integrating comparator drugs into a trial can potentially help a sponsor demonstrate an IP’s superior safety and efficacy when treating certain diseases.

For therapeutic focuses like oncology and neurological disorders, as disease prevalence increases, the industry sees the need for additional treatment options for patients—creating space for comparator sourcing. The use of comparators can also help to determine drug pricing for IPs. 

For example, biologics used to treat varying conditions, like cancer, rheumatoid arthritis, and Crohn’s disease, are extremely targeted and can be effective. However, they can also be costly. Biosimilars are biological products that have proven to have no clinically meaningful differences from approved biologics or reference products. As seen in Figure 1, development of biosimilars is becoming more prevalent, with a global loss of exclusivity potential for biologics of up to half a trillion U.S. dollars by 2030.


Source: IQVIA data

Notable nuances in comparator procurement outsourcing

When outsourcing comparator procurement, sponsors typically have several objectives, including ensuring:

•  All trial participants receive the exact same treatment to make sure results are accurate and reliable.
•  Comparators meet quality standards per regulatory directives.
•  Supply oversight through audit checks and license reviews.
•  Alignment between comparator supply availability and documentation per country requirements regarding supply logs (e.g., Certificate of Analysis and Pedigree Statement).

While there are many complexities to comparator sourcing (e.g., logistics, regulatory adherence, and quality assurance), sponsors also need to think about the commercial considerations for supply. If not strategically managed, unit prices of comparators can be high and significantly impact trial components, including:

•  Trial feasibility: Making a trial economically unviable, especially for smaller organizations or academic institutions with limited funding.
•  Statistical accuracy: Smaller sample sizes due to costs can reduce the study’s statistical power and potentially make it difficult to detect meaningful differences between treatments.
•  Market access and reimbursement: If expensive and not covered by insurance, comparator costs may create barriers to trial participation and treatment for some patient populations.
•  Competitive landscape: Causing sponsors to steer development efforts toward indications with stronger return potential.
•  Trial design and endpoints: Influencing decisions about primary and secondary endpoints, choices of control arms and the duration of follow-up. Ethical concerns may arise if a comparator significantly exceeds the IP cost, which plays a role in design and patient recruitment decisions.

When considering these challenges, it is no surprise that outsourcing of comparators is a common strategy for sponsors, and one which is essential to get right.

Comparator procurement strategy: key components

Sponsors need to consider many factors when deciding whether to outsource comparator procurement, including trial size and complexity, their in-house capabilities and the expertise required. They should also conduct a thorough cost-benefit analysis, gauging whether outsourcing is cost-effective and identifying potential risks and costs associated with the approach. Poor planning and forecasting2 are primary factors in observing high levels of drug wastage and related costs for trial sponsors each year.

As comparator sourcing needs evolve, sponsors and CROs should be aware of the multiple layers that make up a strong end-to-end procurement outsourcing strategy. Early in strategy planning, it is important to account for the following and more:

•  Integrating essential expertise (e.g., supply chain managers, technology experts, packaging, and shipping partners, etc.) to work alongside the clinical team and operational leads.
•  Regulatory oversight for sourcing processes.
•  Labelling/packaging/blinding requirements and associated timelines, costs, and risks.
•  Access to data to gauge comparator use.
•  Technology solutions that help with end-to-end supply oversight and tracking in real-time.
• Determining whether sourcing will be from sites or centralized.
•  Forecasting requirements linked to patient recruitment and its connection to IP and Lab Kit requirements, including waste avoidance strategies to efficiently manage budgets.

Comparator drug sourcing

While outsourcing comparator procurement can yield expertise, resources, and cost savings, it also carries potential for added risks and costs that must be anticipated and managed.

For example, outsourcing without the appropriate oversight may cause a loss of control over the procurement process, leading to delays, quality and regulatory issues or supply chain disruptions.

Having a dedicated clinical trial supplies team with global supply chain management experts and operational leads is critical to successful sourcing.

Comparator selection optimization

To ensure consistency in comparator use across trial sites (e.g., same dose, formulation, and administration route), clarity in comparator selection processes is key. Working closely with CROs and trial teams to establish clear guidelines for comparator procurement can help achieve consistency. This may involve developing standardized procurement procedures, training site staff, and implementing quality control measures to make sure all comparators meet required specifications. Consistency across site supply can improve trial data reliability and reproducibility. Also, regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have specific requirements for comparator procurement and use in trials and failure to comply can result in regulatory action and delayed approval of an IP.

Typically, sponsors will determine what comparator is preferred and requires sourcing. These can often be the current gold standard of treatment. From there, CROs can create and execute a supply plan, taking into account approved supply routes inter- and intra-region as well as packaging, labelling and blinding requirements for the product as well as expiry date planning.

Careful evaluation of the procurement forecast can ensure appropriate amounts of overage are included in supply numbers. Getting the overage percentage right can be critical. CROs will rely on their experience running trials to determine an appropriate number. Advanced technology and available forecasting information will help model a percentage that balances minimizing waste (and budget) alongside ensuring treatment stock remains available. Getting this balance right is essential to avoid hefty costs and emphasizes why having a supply chain manager is paramount.

Data-driven predictive supply sourcing

As with many other aspects of trials, leveraging data sources to better predict and map out supply and demand is crucial to an effective procurement strategy. First, it is fundamental to develop a drug supply projection based on the protocol, including the number of patients per country and visits and potential for patient overage and trial drop-out/attrition rates.

Then, per those variables, supply chain experts can create forecasts for each region. To support related budgeting, the breadth of global sales and pricing data gathered from pharmacies, hospitals and wholesalers across numerous countries can help ensure data-driven projections are accurate.

Depending on where the comparator drug is used, clinical teams can gain granular insights on what products are used per country, an outlook as to where there may be potential drug shortages or increased demand and where the treatment price is lower. Based on cross-country analysis of these insights, the supply team can create evidence-based sourcing plans to be executed via external partnerships.

Trusted collaborations 

It is important for sponsors to recognize that clinical drug supply activities may be enhanced with close collaboration, especially considering todays innovative landscape of specialized care of cell and gene therapies and decentralized trial solution available to patients. Working with organizations that have solid relationships with multiple qualified external partners, including contract manufacturing organizations, can be key.

Depending on trial and individual site needs, options to effectively source comparators, include:

•  Open market sourcing: Because market volumes may shift over time and aren’t reliably predictable, quick accessibility to multiple qualified vendors to compare pricing and supply feasibility can be beneficial.
•  Direct-to-manufacturer: To procure large supplies of a comparator drug, it may be necessary to go straight to the manufacturer.

As with any treatment used in trials, the priority for all stakeholders must be patient safety. When using comparator drugs, managing the risk of counterfeit or substandard drugs that can compromise patient safety and trial efficacy and the potential for inaccurate or unreliable data is crucial. As noted earlier, working with qualified and trusted suppliers who have established track records of providing high-quality comparator drugs is critical to mitigating the risk of subpar product.

When outsourcing procurement, CROs should have established methodologies to qualify and regularly audit external partners. This helps ensure quality control measures, such as testing and inspection, are upheld, better ensuring comparators meet necessary specifications and are safe. For example, it is vital to qualify cold chain experts who will closely monitor and manage temperature-controlled medications and supplies. Being able to closely audit the trail of shipment allows for electronic accountability and integrity of maintaining quality contemporaneous temperature-controlled product movement, whether it is going to a depot, a site or being returned.

Drug supply management technologies

Given the intricacies of comparator drug integration in trials worldwide, clinical teams can rely on tech-enabled support to ensure supply is developed, packaged, shipped, and received as planned, with quality and patient safety in mind. CROs overseeing comparator procurement can manage supply in real-time with an interactive response technology that monitors progress every step of the way and avoids drug wastage due to sitting product and unforeseen roadblocks. Also, choosing an IRT provider that has effective algorithms for optimizing supply can result in mean significant cost savings realized by balancing site shipments verses reducing overage. An effective IRT can help reduce costs by as much as 70%3 depending on trial size, complexity, etc.

IRT solutions can also provide end-to-end visibility according to each team/expert’s responsibilities, including supply chain managers who need a bird’s-eye view of IP monitoring to address issues quickly. And, because supply management may require close collaboration with external partners, IRTs are intended to seamlessly and safely integrate with vendor systems and to patient data via data management platforms. 

Flexibility through evolving comparator sourcing

Within trial design, a comprehensive comparator procurement strategy can include a multitude of considerations, requiring intricate orchestration and deep expertise. When a comparator drug is not available for a particular site or patient or there are related challenges across a study, sponsors face delays and added costs as patients wait for viable treatments. Therefore, whether they are upholding evolving regulatory requirements or finding ways to mitigate known or avoidable supply chain disruptions, sponsors and CROs will need a thoughtful procurement strategy to ensure trials proceed as planned.

As more trials continue to incorporate comparators globally, sponsors and CROs will need to continuously explore new ways to adapt and stay flexible, particularly as sponsors aim to expand clinical pipelines.

References
1. https://growthmarketreports.com/report/comparator-drug-sourcing-market-global-industry-analysis.
2. https://www.mckinsey.com/industries/life-sciences/our-insights/clinical-supply-chains-how-to-boost-excellence-and-innovation?cid=eml-web.
3. IQVIA proprietary data.



With over 20 years of experience in the healthcare sector, Carol Alexandre leads the clinical trial supplies business within the IQVIA Research & Development organization and provides clinical supply chain services for global clinical trials. Carol is responsible for key relationships with suppliers and manages key global accounts. Developing services is an intrinsic part of her role, and she works closely with stakeholders in clinical and commercial supply chains, delivering customized services and commercial offerings across a range of markets.  

Ed Lewis has more than two decades of project management experience in the healthcare and clinical research industries. His diverse professional experience also includes roles in clinical manufacturing, formulation development, clinical packaging, operational team management and customer account management.

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