From The Editor | August 26, 2016

Tips For Efficient Comparator Sourcing In Biosimilar Clinical Trials

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By Anna Rose Welch, Editorial & Community Director, Advancing RNA

A few months ago, I sat in on a webinar that offered a glimpse into the challenges behind comparator sourcing strategies. Not only do biosimilars face aggressive clinical timelines, there is also pressure for companies to accelerate the clinical development of a biosimilar to make it to market before it becomes overcrowded. One challenge facing companies is comparator sourcing for their Phase 1 and Phase 3 trials.

There are two strategies biosimilar companies might choose when sourcing a biologic comparator. There is direct sourcing, which is when a company approaches the innovator company for its biologic. Then, there is open market sourcing, in which companies approach wholesalers for the product. Open market sourcing can be carried out in a number of ways, including sourcing and distributing the biologic to a number of different trial sites in different countries. For instance, a company might choose to purchase a biologic in Germany and ship it to treat patients in Romania, Bulgaria, and Sweden. Or the company might buy the biologic in one country, for instance Korea, and only treat patients in Korea — a process also referred to as local sourcing.

What Are The Benefits Of These Sourcing Strategies?

As Khaled El-Gendy, associate director, comparator sourcing, Fisher Clinical Services, explained in the webinar, each strategy comes with its own advantages and disadvantages. One benefit of the open market strategy is that biosimilar makers can keep their clinical trial data private. Unlike an innovator company, a wholesaler will not request access to your clinical trial data, enabling a company to maintain confidentiality. In addition, a company could find there will be shorter lead times in obtaining the biologic, as wholesalers usually already have the stock on hand or at a nearby manufacturing site.

For direct sourcing, the fact there is no middleman is a big benefit. As the industry continues to grow, so does the complexity of the supply chain. (In fact, I once heard companies’ long supply chains likened to the Family Circus cartoons with the kids walking around.) In an effort to optimize the supply chain and cut down on the threat of counterfeit drugs slipping into the supply, direct sourcing can keep the number of parties involved in each transaction to a manageable minimum. A biosimilar company will also be privy to a number of documents only the innovator can provide, including batch, packaging, and equivalency certificates. In some cases, a company can even discuss the possibility of receiving a placebo from the innovator to use in the trial, as well.  

What Are The Biggest Biosimilar Sourcing Concerns And Challenges?

According to a poll taken in the midst of the webinar, attendees had three primary concerns about comparator sourcing for Phase 3 trials. In first place, garnering 28 percent of attendee votes, was gaining access to documentation. This was followed by concerns about overage and waste (26 percent) and integrating clinical supply services (20 percent). Other choices included quality concerns (15 percent) and disclosing clinical trial data to innovators (11 percent).

Similarly, as more companies launch global studies, there are often questions about how to get a drug shipped from point A to point B. Each market has its own import and export procedures, which can change quickly. As such, there is a growing need for companies to have connections in other markets or market intelligence teams within their organizations that have a grasp on the dynamics in different countries.

Monitoring the market is also key to tackling one of the biggest challenges of comparator sourcing. A biosimilar company needs samples from multiple batches of the comparator. These samples must also have different expiration dates. As El-Gendy explains, “This is challenging because the number of batches and expiry dates will be limited because the amount of batches released onto the market are also limited.” The larger, key markets are important sources here, as they usually are first to get access to the newest batches, and they often obtain more than one batch in a delivery.

Which Sourcing Strategy Is Best For Phase 1 And 3?

Generally, a Phase 1 clinical trial only runs on one or two sites and requires a limited quantity (or bags) of the treatment. A Phase 3, on the other hand, requires large quantities, since many sites are involved globally. Similarly, because a Phase 3 runs longer than a Phase 1, a biosimilar maker will need to secure a reliable supply of the reference biologic.

Given the differences between the two phases, El-Gendy suggests pursuing open market sourcing for Phase 1 and direct sourcing for Phase 3. Turning to the open market for Phase 1 can cut off certain challenges before they occur. For instance, as El-Gendy describes, a biosimilar maker could find it more difficult to source Phase 1 supplies through the manufacturer because of the size of the order. “Many manufacturers do not want to work on a small scale,” he said. There will also be more competitive pricing on the open market because a company can look into purchasing from several different wholesalers, ensuring they get the best possible price. (This is also recommended for companies developing biosimilars for orphan drugs. Given the small size of both Phase 1 and Phase 3 trials for orphan drugs, however, El-Gendy suggested looking into wholesalers that specialize in supplying pharmacies. The manufacturer might be reluctant to supply a minimum order, though this is also worth a shot, given the small population receiving the drug in the first place.)

For Phase 3, however, working with the manufacturer directly can ensure a long-term, consistent supply — both from quantity and cost standpoints. Not only does this strategy grant access to the documentation about the origins of the product, but a company will also be protected from open market pricing dynamics. For instance, El-Gendy warns that companies should be wary of wholesalers that promise an uninterrupted supply at a fixed cost for the entire duration of the trial. He said, “This cannot be true. The open market is all about supply and demand, and, as such, the prices and availability of the stock will differ from day to day.” When working directly with the manufacturer, however, it will be easier to plan how much the comparator will cost throughout the life of a trial. “Usually when you source the drug directly from the manufacturer, the price is the same for today’s delivery and the subsequent deliveries over the coming quarters” El-Gendy described.

Overall, because these comparators are expensive biologics, there will always be questions coming from a company’s finance team about how not to exceed the trial’s budget. However, pushing for a low cost on the comparator will not be the only way to lower the cost of biosimilar development. Biosimilar clinical trials are complex, and, as such, the strategic approach for biosimilar trials will be quite different than the strategies cooked up for small molecule trials.

“This comprehensive approach will include all companies, as well as planning, procurement, production, and distribution because we are facing high costs,” El-Gendy said. “We are facing the risk of wastage, and, in turn, lost resources. But with good control over the clinical supply chain, you can achieve cost reduction or 20 percent — upwards of $10 million.”