Despite a surge in the number of comparative effectiveness trials now taking place, sourcing the necessary comparator drugs is far from straightforward – especially when trials are conducted on an international scale. We talk to GlaxoSmithKline’s Ron Raby about some of the logistical and regulatory hurdles facing pharmaceutical companies.

main

In recent years, drug developers have found themselves under increasing amounts of pressure to evince the relative benefits of their products during the clinical trial process.

Yet, in spite of the mounted interest in comparative effectiveness, the process of sourcing the necessary comparator drugs – an investigational or marketed drug deployed as a reference during a clinical trial – remains a challenging and unpredictable undertaking.

Ongoing snags for trial sponsors include difficulties in obtaining product documentation for the respective comparator, poor supply chain visibility, and the anathema posed by counterfeit drugs.

In order to yield better results, companies are encouraged to implement more transparent, efficient and cost-effective strategies not only in the way drugs are procured, but also the means by which they are delivered to trial sites. The more direct the supply chain, the better.

However, in line with the increasingly globalised nature of the clinical trials sector – marked by more trials held across disparate geographical regions – a constant spate of mutable local and general-trade regulations makes this a particularly taxing task. Consequently, supply and logistics personnel require deep-rooted regulatory expertise, specific to each country where comparator drugs are sourced.

"The changing regulations at a local level are the main driver at the moment," says Ron Raby, global head of comparator strategy and planning, investigational material supply at GlaxoSmithKline. "So, whether it be a source from a wholesaler, or a distributor in their local market, the requests around the clinical trials you are running, as well as the protocol for the information – and then pulling that information together – make it difficult to source products."

Central or local?

According to Raby, sponsors have two main options when it comes to comparator sourcing in what is essentially a federal marketplace. They can either adopt a centralised purchase model, or use local operating companies; both carry their own sets of pros and cons, he says.

"Companies need to strike the right cost balance," he says. "You can purchase centrally, but you might have multiple import-export duties, and there is also documentation that’s required. An easier way might be to source the drug locally, but, then again, you may have requirements from the pharmaceutical companies around information on the studies that they are running. There’s also potentially a much higher cost locally."

Sponsors also need to know who they are working with, in order to mitigate potential risks. For instance, comparator drug vendors should be vetted before a partnership commences. This is particularly burdensome given the common time constraints associated with clinical trials.

Consequently, GlaxoSmithKline (GSK) is one group to have a designated comparator strategy team, charged with enabling drug procurement in the simplest, safest way.

"This department works hand in hand with our local operating companies that have processes and vendors set up locally to source products," says Raby. "But when they find that they are having issues in the market in actually sourcing products – whether it be due to a shortage, or the product just isn’t available for some other reason – they connect with us centrally to see if we can help them source."

Most companies also tend to source products for clinical trials directly from other tried-and-tested pharmaceutical companies – sometimes even competitors – by way of a supply agreement. This is done with the aim of offsetting the possibility of stock shortage in lower-cost markets, while also driving down the threat of counterfeiting.

"Our first intention is always to go directly to another pharmaceutical company, because it allows us to have a secure supply."

"Counterfeiting is a risk that is always there and that we are always trying to cut out," says Raby. "It’s another reason why we have gone down the route of setting up these strategic vendors that we use to source products. They have vetted and qualified their product suppliers.

"But our first intention is always to go directly to another pharmaceutical company, because it allows us to have a secure supply. It also reduces your overages, just in case something happens and you are not able to import a product into a particular country."

Best practice

In spite of the array of challenges associated with comparator sourcing, there is much to intimate that the industry has done its upmost to tackle them head on over the last decade or so.

The 2004 EU Clinical Trials Directive was the first legislation to highlight the importance of sourcing comparators on the Continent. Thereof, the industry first acknowledged that it could not source comparators in one country and ship them all over the world, but instead was required to source the drugs in the region where the trial was being conducted.

In 2012, the International Society for Pharmaceutical Engineering (ISPE) created the ‘ISPE Good Practice Guide: Comparator Management’, the industry’s first resource of strategic and tactical considerations for the sourcing and procuring of comparator drugs for use in a clinical trial.

As well as outlining the risks inherent in poor sourcing methods for comparators, the ISPE guidelines provide clear strategies for avoiding the costs, delays and potential case study inaccuracies that can come about through poor comparator management.

And, last year, the TransCelerate BioPharma industry group – a US-based, non-profit consortium, comprising the world’s ten foremost biopharmaceutical companies – introduced its own comparator network, as a way of removing open market risks and allowing members to source drugs through the secure boundaries of a trusted system.

Communicate, collaborate

It is hoped that information shared between sponsors and manufacturers will decrease the risk of vendors entering a region and buying a surfeit of drugs, and subsequently creating a shortage for other companies.

"As the members receive the forecasts from the other members who need their products, this will better enable the member companies’ commercial units to develop supply chain forecasts, which will decrease the incidences of supply chain disruption," said Terry Walsh, chairman of the network, at the time of its launch.

GSK has already benefitted from its membership, says Raby.

"It’s so important to be clear and very open with collaborators and partners – as well as other pharmaceutical companies," he explains. "This is one of the reasons why we are one of the leaders behind TransCelerate. Through the network, we’ve been able to drive collaborative efforts in getting these products for clinical trials."

While initiatives such as TransCelerate clearly carry benefits, the aforementioned regulatory hurdles, which make comparator sourcing such a trying art are not set to disappear anytime soon. To tackle these, Raby believes the industry would do well to put up a stronger front in approaching the necessary authorities.

"I think we need to go to these regulatory authorities – whether it be the FDA or EMA – and really talk to them as a unit," he says. "We are all trying to get products into these countries, and work with them, but, unfortunately, this doesn’t always happen.

"So, it’s about going to them and talking to them in a conversation, as opposed to issuing caveats – it is about speaking with one voice. I think we are starting to get there with some of the collaborative efforts that are going on in the industry, but we really need to continue to do that."

Ultimately, the chief objective of comparator sourcing is to get the right drug to the right site in the fastest time possible. While there are obvious commercial advantages on offer to the companies that are able to succeed in doing this, Raby is acutely aware that the definitive stakeholder in the entire process should always be the patient.

"There’s a patient at the end of every supply chain," he says. "That’s the mantra we live by. We want to make this a positive experience for patients and ensure that we are bringing the right product in, doing the right trials, and advancing medicine in whichever region we are present."