Tag Archives: Study

Case Study – Sourcing Flu Vaccines for a Global Study

CSI was approached to support a quadrivalent flu vaccine study running in multiple countries in the Northern Hemisphere. The sponsor also wanted to use the same product in the trial across all participating countries.

Due to the seasonal nature of this vaccine, there is only one production run per year (in the Summer), manufacturers look at predictions from the WHO of what the dominant flu strain will be in the Winter and then produce vaccines accordingly. The vaccine doses are typically booked well in advance (approximately in January) by customers and there is very little oversupply.

CSI Approach
When our client was ready to run the study, several USA manufacturers were already overbooked versus their production and would not have been able to support the requirements of the trial in all regions alongside their current orders.

CSI was able to leverage its relationship with a EU manufacturer that could supply the product in the quantity required for the whole trial. Working with this manufacturer CSI demonstrated the equivalency between the EU an USA products. The trial also ran in some South East Asian countries, to bypass tricky import requirements CSI sourced the product locally in these countries.

Challenges and Results
With a flu vaccine trial, the cost of getting the sourcing wrong is very significant. Failure to secure supplies would postpone the trial by a full calendar year as the Southern Hemisphere is a poor option to run a flu vaccine trial (less countries, and poorly defined flu strains circulating).

CSI provided sound scientific and regulatory guidance alongside a robust sourcing option that ultimately safeguarded the study.

Case Study – Delivering Comparators for an Allergy Study

CSI was asked to support a client trial for sourcing of grass pollen allergen tests. There were 2 main concerns:

1. No product was licensed in all countries where the trial was running
2. Quantities required were considerable and the Sponsor was worried about the availability of the required quantity in the timelines to support the trial The client wished to utilise the same product for all patients enrolled to ensure consistency in trial results.

The client wished to utilise the same product for all patients enrolled to ensure consistency in trial results.

CSI Approach
The Licensing aspect was clarified as the products are considered equivalent in literature, the composition was largely the same across products and the use of unlicensed products was common in many markets.

Due to the request for a large quantity of the same product the optimal sourcing strategy was a central model direct from a manufacturer. CSI decided the most pertinent option was to approach two independent manufacturers to protect the supply.

Challenges and Results
Using the evidence gathered by CSI on equivalency across products and the use of unlicensed medication the sponsor submitted with the two products to country regulators successfully.

Approaching two manufacturers was a prudent choice as when it came time to order the first choice could no longer support the quantity due to changes in production. The second-choice manufacturer was able to support the requested volume and the study ran to schedule.

Engaging CSI at the protocol design stage allowed the sponsor flexibility in sourcing strategy and provided a safety net with a backup option. The scientific expertise that CSI has was crucial in allowing the trial to follow a central sourcing model – minimizing risk of shortages in supply by only sourcing in one market.

Case Study – Overcome Shortages by leveraging Relationship with Manufacturer

CSI had an urgent request to supply a large quantity of a generic drug for an ongoing Phase 3 trial. These products were initially overlooked as it was assumed the sites would supply. When this turned out to not be feasible it was close to trial initiation date, so timelines were extremely tight to deliver and keep the trial on track.

CSI Approach
CSI carried out extensive research to determine what drugs were licensed in the participating countries that spanned three continents. All major generic manufacturers where approached to ensure coverage over all regions, working closely with these manufacturers CSI executed a literature review and procured equivalency statements for the products required.

Approaching a range of manufacturers allowed CSI to present an option that could cover all countries in the trial, the equivalency statements provided the appropriate justification to prove clinical equivalency across products that allowed the trial to go ahead.

Challenges and Results
Liaising with multiple manufacturers and the client to ensure not only the supply of medication but also to prove equivalency between products was a very challenging task. It required a high level of scientific expertise and knowledge of clinical trial regulatory requirements.

Ultimately the strategy was a success and allowed the trial to begin without delay. This experience highlights the importance of appropriately planning the sourcing of comparator and co-medication at an early stage in the clinical trial process. Leaving it to the last minute, as was done here, not only increases the risk of delaying trial initiation but can massively increase the costs associated with sourcing these materials.

Case Study – Delivering Enormous Cost Savings by Providing Sourcing Options for Oncology Products.

A client approached us with a request for a large quantity of an expensive oncology product, documentation such as Certificate of Analysis (CoA) was required for import into several of the countries involved in the trial.

CSI Approach
Due to the high value of the product and the importance of choosing a suitable strategy for the trial and sponsor CSI decided to investigate a range of options with different advantages and disadvantages so that the client could decide what best suited their trial. The solutions presented to the customer where;

1. Directly contact the marketing authorization holder (MAH) of the branded product.
Advantages: Guaranteed supply, single batch, full documentation, midlength lead time.
Disadvantages: Highest price of the options.

2. Source from authorized wholesalers in the open market.
Advantages: Cheaper than option 1.
Disadvantages: Susceptible to market changes – supply is less secure, longest lead time, CoA only available form some (small) markets – increases risk to supply chain.

3. Source a Biosimilar product registered in the USA and Europe directly from the biosimilar manufacturer.

Advantages: Cheapest price, guaranteed supply from manufacturer, quickest lead time
Disadvantages: Using a biosimilar in a trial can introduce pressure from regulators to prove equivalent clinical effect as the branded product.

CSI worked closely with the manufacturer of the biosimilar and was able to provide an extensive metaanalysis alongside equivalency statements to prove that the biosimilar was equivalent to its branded counterpart.

Challenges and Results
Using the meta-analysis and equivalency statements provided by CSI the sponsor was able to justify the use of the biosimilar option for the trial. This option allowed timely sourcing with full documentation at a massive cost saving, over the course of the study the sponsor saved in excess of €7 million compared to the branded option.

This was a remarkable achievement for CSI and our client. We demonstrated our scientific knowledge, expertise, and ability to deliver novel solutions.

Case Study – Delivering Devices to Sites in Russia, Ukraine, Belarus and Georgia

CSI was contacted by a client that urgently required medical devices to be delivered to Russia, Ukraine, Belarus, and Georgia for a large oncology trial.

These devices/markers were required during the patient screening visit. These devices are only applied to a very limited number of patients under a standard of care; however, due to the increased level of follow up required in the environment of the clinical trial, the devices were being applied to all patients. The client thought initially that the sites would be able to source themselves, but the quantities required were higher than UK and German joint monthly consumption, and deliveries had to be arranged on demand to 100 sites.

CSI Approach
The quantities were so large compared to normal demand that they placed strain on the manufacturer’s own production and supply chain capability.

CSI worked closely with the client’s medical team to identify options for products with the same characteristics as a secondary solution. Using a combination of primary and secondary solutions CSI presented an option that had feasible sourcing timelines. Working closely with local partners in each country CSI developed a distribution strategy at the site level in a just in time model.

Challenges and Results
A just in time distribution model is dependent on robust and dependable sourcing, adding a secondary solution to the trial relieved pressure from the manufacturer of the primary solution – this meant that there was always a solution available when a site required resupply of devices. Liaising with the manufacturers of the devices, the client, and importantly couriers was a logistically challenging task but one that had to run smoothly to safeguard the continuation of the trial.

The model developed by CSI was successful in ensuring sites never ran out of stock of these devices, using a primary and secondary solution was a novel approach that operated efficiently. CSI provided that all required documentation for smooth import and distribution, forecasted demand, and developed a safety net stock level to respond to variable patient recruitment levels – avoiding delays to patient recruitment.

Whitepaper – Oncology Trials Comparator Sourcing

Comparator Sourcing for Oncology Trials – Current Trends and How to Safeguard Trial Progress

This is an exciting time for oncology trials, year on year record numbers of therapeutics are launched and the indications for many drugs on the market are increasing rapidly. Immunotherapies and next generation biotherapeutics are being approved for more tumour types and a growing percentage of the late stage oncology pipeline are targeted biologics.

However, with growth comes increased risk. Trials are more complex than ever, with more locations in new geographies and adaptive trials becoming more common. This complexity is affecting trial success rates which are routinely lower than other therapy areas. Post-trial oncology products also experience difficulty entering the market. Immunotherapies and next generation biotherapeutics may be the future of oncology but they are significantly more expensive than older non-specific therapies on the market.

Positive results from health technology assessments, used to inform purchasing decisions, are becoming less and less common in oncology as costs of therapies skyrocket and specificity

increases. For a clinical trial to demonstrate the added value of the IMP it is now essential that it is compared to the standard of care rather than a placebo.

This increases costs and therefore risks of a trial but is a necessary component for a novel therapies’ success. It is therefore imperative that a clinical trial is well managed and efficient with resources to minimise risks and ensure that the IMP goes to market positively.

There are some encouraging trends, biomarkers and selecting patients from prescreened pools have increased productivity of trials and lowered costs. Streamlining comparator sourcing is another strategy that can dramatically affect the efficacy of an oncology clinical trial.

Comparator selection is a vital component of a sourcing strategy. Using biosimilars or generics where available can decrease the cost of comparators in a trial by as much as 50%. However, this can be a complicated solution, licensing on biosimilars is dependent on proven pharmaceutical similarity to the reference drug, this can be different between markets potentially affecting the sourcing strategy.

Different sourcing strategies have positives and negatives, local sourcing can be an effective strategy for a small phase I trial in a handful of countries but can be very challenging in a global phase III trial spanning many countries and regulatory bodies. Regulatory complexity is compounded by logistical complexity, working with stakeholders across the globe to deliver products in a timely manner can be especially challenging. There is not a one fits all solution in comparator sourcing, it is therefore important that extensive research is undertaken to find a range of options. With CSI as a partner you will be receiving gold standard service to de-risk comparator supply in your clinical trial.