For clinical trial sponsors across the world, sourcing comparators can present a number of logistical and regulatory issues. How to source, transport and deliver comparators for a clinical study are all part of a complex process involving a myriad of stakeholders.
In this Industry Viewpoint, CTA Editor Henry Kerali speaks to Ian Hoban, Julian Wolfe and Kevin Wolfe of Pilatus Clinical Services, as they explain the keys to effective comparator sourcing.
Henry Kerali: What are some the key considerations sponsors need to factor in when sourcing comparators for a clinical trial?
Ian Hoban: With respect to comparator sourcing, sponsors need to understand what they’re trying to achieve and where they’re trying to achieve it. From there, it’s important to assess how that relates to the availability of the comparator by asking of themselves the following questions:
- What quality documentation is required and is it freely available?
- What markets are comparators being sourced from – are they large enough to sustain the required demand, and should I consider having back-up alternatives planned in?
- What countries and markets are the trial site contained within?
- What customs documentation/tariffs are required for both the previous two points and what back-up plans are required for unforeseen circumstances, such as customs hold-ups, to ensure product integrity is maintained?
- Do I want to share trial details with the comparator manufacturer, and if not, am I fully aware of and happy with the limitations this may result in?
- What commercial market intelligence do I have, and is it current and detailed enough to avoid potential supply disruptions?
- Have I selected the right comparator sourcing partner and do they challenge my thought process sufficiently to keep me one step ahead of the game?
HK: What length of time is required when planning to source a comparator?
Ian Hoban: The starting point should be determining the worst case scenario, namely, a severe delay to the trial start date. That delay will subsequently have a knock-on effect on the study end date, and can ultimately affect the sponsor obtaining a timely marketing authorization. This could well have an impact the market analyst’s value of a sponsor organization, which can be catastrophic. So, in effect, planning for the worst case scenario can set you on the right course when sourcing a comparator.
Julian Wolfe: Quite often, comparators are thought of a little too late. Therefore, it’s essential sponsors set out a plan for sourcing comparators by a certain date and by a certain time, and working back from there. Furthermore, establishing a plan that’s robust with a Plan B and a Plan C allows the sponsor to act in unforeseen circumstances. Ultimately, it’s difficult to place a set timeframe on a comparator, which is why it’s important to understand the market dynamics and the usage of that comparator as each product is different.
HK: What information are sponsors expected to supply before and when purchasing their comparator product?
Ian Hoban: In clinical trials, there needs to be a hard endpoint when the stock is required. Sponsors therefore need to consider when to have a conversation about comparator sourcing – a few months beforehand simply isn’t sufficient enough lead time. Questions surrounding what a reasonable batch size is and how many batches you want are important factors to consider. By sourcing larger quantities, sponsors can carry out packaging and labelling for study purposes as a one-off cost, rather than in multiples. However, this is where expiry date availability becomes a factor. Typically, products have their own profile on what’s available in the market and what’s available from the manufacturer’s likely lead times. This can guide sponsors on the correct course of action to take.
Kevin Wolfe: Furthermore, it’s key to consider what presentation do sponsors need to do the trial again. If you’re trying to source a vial, and the comparator is only available as a pen, how can you get around that? Is the dosage in the right format in the volumes required? We’ve had studies in Asia-Pacific where a sponsor used one strength by virtue of the patient population and the disease, whereas in Europe and the U.S. a different strength was used. And yet, they were trying to source a product from the bigger markets in a presentation that isn’t freely available because they’ve put the wrong dosage form in their submitted protocols. Therefore, it’s essential to plan ahead, and this is where Pilatus can offer guidance and advice.
Julian Wolfe: Another consideration that many sponsors fall foul of and where comparator experts come into play is what the destination points for that product are. Sponsors must know what product documentation is needed, what the tax and customs regulations are, and the lead times needed when applying for certification. This is key in enabling freer movement from market to market.
Kevin Wolfe: What’s more, providing a forecast schedule for the lifetime of the product will greatly help when working with the manufacturer. Here at Pilatus, we engage with manufacturers on a regular basis to ensure the volume requirements for the study are met further down the line. We see a lot of requests come through for a specific amount at a specific point in time. While that may be achievable, when scaling up that might not be feasible. So, it’s important to engage with the manufacturer earlier in the process to guard against hiccups in the future.
HK: From a comparator purchasing point of view, what do sponsors need to consider when submitting protocols for a global study?
Ian Hoban: It’s important to have a number of sourcing options built into the protocol. If Plan A fails, Plan B can be enacted, meaning the sponsor won’t have to reapprove the trial by inserting things that could have been done upfront. Many sponsors don’t engage with their comparator partners early enough to ensure a contingency plan is put in place. We believe it’s an important function of a comparator sourcing specialist like Pilatus to challenge our clients and make them plan for the worst case scenario.
HK: What are your views on Brexit in relation to comparator sourcing?
Ian Hoban: There are three factors to bear in mind when it comes to the impact of Brexit: the regulatory impact on the pharmaceutical industry, the movement of goods, and the differentials in currency exchange rates.
If you think about the regulatory impact, at the start of March for the first time, we got real clarity from the U.K. government when Theresa May proposed an affiliate membership of the European Medicines Agency. The remaining issues thereafter would surround the extent to which the U.K. will pay to be an affiliated member, as well as what rights and privileges they have in proposing new regulations.
As for the movement of goods, Brexit has engendered a fair amount of concern. The reality is if there’s a very soft Brexit, not a whole lot will change. If there’s a hard Brexit, in the worst case scenario there will be tariffs to move goods around. That said, working with a comparator sourcing specialist, such as Pilatus, is beneficial as they will constantly monitor the regulations, customs requirements, lead times, and all the speed barriers hampering the movement of goods around the EU.
Lastly, with currency fluctuations, it’s important to have a foot in both camps – a presence in the U.K. and the EU. Sponsors must switch their strategy accordingly and minimize the risk incurred when currencies change. Overall, I think there’s a little bit of clarity emerging with regards to Brexit.
But what Brexit does emphasize is the fact that change is ongoing. However, there are always a few key drivers generating the demand for comparator sourcing in clinical trials. It’s incumbent upon everyone operating in this space to evolve ahead of the game – look at what’s happening in the future, and plan for it, rather than react to it, and that differentiates those who succeed from those who fail.
Sales and Marketing Director
Pilatus Clinical Services – global comparator and biosimilar sourcing for clinical trials
Our vision is simple – “to establish proven and trustworthy solutions in the complex and demanding arena of comparator sourcing for clinical trials”