How CSI supplied large quantities of ruxolitinib to a biotech’s ongoing Phase 3 oncology study involving 14 countries, nine depots and 67 site shipments Challenge CSI was approached by a biotech conducting a full global Phase 3 oncology study spanning 14 countries. We were asked to purchase and supply a significant quantity of ruxolitinib within a tight timeframe: with the contract signed in December 2022, the client aimed to have the first sites supplied by March 2023. The client also required three annual resupplies of the oncology medicine to be factored into the request. Solution Within eight weeks, the entire study setup had been meticulously organised, ensuring the smooth and timely execution of the clinical trial supply chain. CSI’s strong relationships with manufacturers around the world and outstanding access to oncology products allowed for the procurement of a substantial volume of ruxolitinib within a short timeframe. CSI’s global depot network facilitated the efficient delivery of the oncology medication without delay – just in time for the client’s tight deadline. Result CSI’s scientific expertise ensured a seamless and smart study setup, with all aspects of the trial addressed meticulously in the supply planning phase. Despite the challenge of working to a tight deadline and the logistical complexities involved in coordinating product supply across 14 countries, nine depots and 67 individual site shipments, CSI successfully delivered a large quantity of the required oncology medicine in line with the client’s needs and expectations. This, in turn, allowed for Site Initiation Visits (SIVs), which had already been scheduled, to take place as planned, keeping the client’s study on track.

How CSI’s regulatory guidance and robust sourcing solutions ensured the success of a global flu vaccine trial that could not afford to run behind schedule Challenge CSI was approached to support a quadrivalent influenza vaccine study running in multiple countries in the Northern Hemisphere. The sponsor wanted to use the same product across all participating countries in the trial. Due to the seasonal nature of this vaccine, there is only one production run per year, which takes place each summer: manufacturers look at predictions from the World Health Organization (WHO) for what the dominant flu strain will be the following winter and produce vaccines accordingly. The vaccine doses are typically booked well in advance by customers – around January – and there is very little oversupply. Solution When our client was ready to run the study, several manufacturers in the United States were already overbooked versus their production and would not have been able to support the requirements of the trial in all regions. CSI was able to leverage its longstanding relationship with a major European manufacturer that could supply the product in the quantity required for the whole trial. Working with this manufacturer, CSI demonstrated the equivalence of the EU and USA products. The trial also ran in some South East Asian countries; in order to bypass tricky import requirements, CSI sourced the product locally in these countries. Result With a flu vaccine trial, getting the sourcing wrong can be very costly. Failure to secure supplies would postpone the trial by a full calendar year since the Southern Hemisphere is a poor option when it comes to running a flu vaccine trial, having fewer countries and a circulation of poorly defined flu strains. CSI provided sound scientific and regulatory guidance alongside a robust sourcing option that ultimately safeguarded the entire study. Without this strategy, the trial would have been delayed by one year at great expense to the sponsor.

How CSI leveraged relationships with multiple manufacturers to urgently supply large quantities of a generic drug to a global Phase 3 trial Challenge CSI received an urgent request to supply a large quantity of a generic drug for an ongoing Phase 3 trial. These products were initially overlooked by the client as it was assumed the trial sites would supply them. When this was discovered to be unfeasible, the trial initiation date was already close, so the timescale to deliver the products – and keep the trial on track – was extremely tight. Solution We carried out extensive research to determine what drugs were licensed in the countries participating in the trial, which spanned three continents. All major generic manufacturers were approached to ensure coverage across all regions. Working closely with these manufacturers, CSI executed a literature review and obtained equivalency statements for the products required. Approaching a wide range of manufacturers allowed CSI to present the client with a sourcing option that would cover all countries in the trial. The equivalency statements provided proof of clinical equivalency across products, which allowed the trial to proceed. Result 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 prudent as one manufacturer could no longer support the required quantity at the time of order due to changes in production. Securing a second manufacturer who was able to support the requested volume meant the study ran to schedule. Engaging CSI at the protocol design stage allowed the sponsor flexibility in sourcing strategy and provided a safety net in the form of a back-up option. The scientific expertise that CSI has was crucial to allowing the trial to follow a central sourcing model, minimising the risk of shortages in supply by only sourcing from one market.

How CSI delivered mission impossible: sourcing specific tested batches of an expensive oncology product from several European markets Challenge A client approached CSI with a very specific request: to test samples of an expensive oncology product before purchasing the same batches that had passed the testing stage. This was a challenging assignment as it required visibility of batches currently on the market before purchasing, which is only possible in certain markets where product availability is moderate. Due to the nature of the trial, the client was not willing to disclose trial details and required documentation (Certificate of Analysis and Pedigree documents). Solution Without the possibility of disclosure, we had to source the product from the open market. This was challenging because we had to fulfil four requirements: Batch testing Advance visibility of batches Product from specific batch available Documentation The most effective solution was to work with our audited suppliers to devise a ‘hit list’ of batches that had had a positive result in testing. This required close cooperation with suppliers in those markets where batch visibility and documentation were possible, to keep an up-to-date list of batches on the market at any given time, and whether they had had a positive or negative test. Result At CSI, we pride ourselves on implementing effective sourcing strategies for even the most complex trials. In this case, our high level of market knowledge resulted in the successful delivery of the required product and ensured the client’s trial never ran dry. This type of sourcing strategy is dependent on very close communication between CSI, the client, and our suppliers. As suitable markets usually have limited availability, the product had to be collected over time before being delivered to the client in bulk. Guaranteeing a stable supply chain to the client, and ultimately the patient, was paramount at all times. CSI also leveraged its strong relationships with suppliers to keep stock on hold, with the promise to purchase if the batch testing was successful. This solution is only possible when mutual trust exists between all parties, there is a deep understanding of the specific trial requirements, and you have a united team with the determination to deliver for the benefit of the patient.

How CSI used its scientific expertise at the protocol stage to provide flexibility in sourcing strategy and ensure high volumes of a single product were supplied on time to multiple countries Challenge CSI was asked to support a client’s clinical trial by supplying grass pollen allergen tests to many different countries. There were two main concerns: 1. No product was licensed in all countries where the trial was running 2. The same product had to be used for all patients to ensure consistency in trial results and the sponsor was concerned about sourcing the considerable quantities required within the timeline necessary to support the trial Solution CSI carried out an extensive review of the available literature, gathering evidence on products that were considered equivalent, having largely the same composition to the original product. The licensing aspect was further clarified as 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 identified as a central model direct from a manufacturer, rather than relying on local sourcing from many different countries. CSI decided the most suitable option was to approach two independent manufacturers to protect the supply. Result 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 prudent as one manufacturer could no longer support the required quantity at the time of order due to changes in production. Securing a second manufacturer who was able to support the requested volume meant the study ran to schedule. Engaging CSI at the protocol design stage allowed the sponsor flexibility in sourcing strategy and provided a safety net in the form of a back-up option. The scientific expertise that CSI has was crucial to allowing the trial to follow a central sourcing model, minimising the risk of shortages in supply by only sourcing from one market.

How CSI’s scientific insight delivered an agile sourcing model and substantial cost savings for a listed biotechnology company’s global trial Challenge One of our clients, a leading T Cell Receptor (TCR) biotechnology company, has several biological therapy products in development for a range of oncology and autoimmune indications. They also conduct first-in-class research into new treatments for infectious diseases utilising their pioneering immunotherapies. The client approached CSI while running clinical trials in many different countries for an investigational product that is administered in conjunction with saline and human serum albumin (HSA). CSI was approached to evaluate and provide evidence so that our client could move from a central model to a local sourcing model for these ancillary products. There are a wide variety of saline and HSA products available in the trial countries, each with different bag or container materials. Since there was limited stability data regarding the equivalency of local products, the client initially had to source all saline and HSA centrally. This had a significant impact on costs and logistical complexity. While saline and HSA bags or containers are inexpensive, they are bulky and heavy products, so a central sourcing model increases overhead costs and adds complications and potential delays to the supply chain. In this case, the saline and HSA had to be relabelled to reflect the language of each trial country, which added yet more expense and complexity to the undertaking. Solution CSI provided scientific insight regarding the different types of bag or container materials that are marketed and used to carry saline and HSA, as well as the different strengths of HSA available across the large number of countries in the trial, including: Australia Canada France Germany New Zealand Russia Ukraine United Kingdom United States The range of products was diverse and included rigid containers and flexible bags made from a variety of materials, including polyethylene (PE), polypropylene (PP), PE/PP copolymers and blends, and polyvinylchloride (PVC). CSI sourced quantities of these products in different pack sizes and from different countries, covering the full range of materials used. Our client then carried out analytical testing to confirm the compatibility of their investigational product with each type of container material and the different strengths of HSA. Result After confirming the compatibility of their investigational product with the different saline and HSA bag or container products, our client migrated to a local site sourcing model for the saline and HSA used in their trial. This averted the need to centrally source and distribute these heavy items, creating a much simpler, more efficient, agile and cost-effective supply chain. In addition, the core product became easier to use and more attractive since no specific ancillaries were required for its administration. This resulted in very significant savings for the duration of the study. "It has been very beneficial working with the CSI team. They have excellent scientific expertise, clearly understood the challenge, and provided outstanding solutions. Their global reach allowed us to tap into many markets. They are customer-focused, result-driven, and we enjoyed working with them. Well done, Team!" – Director of Drug Product, Formulation & Stability at a leading gene therapy Biotechnology company

Here is a success story that demonstrates how CSI can support your clinical trial supplies. CSI managed to compress six months of deliveries from a drug manufacturer into less than three weeks for a large pharmaceutical client. Some might call this "Mission Impossible" – like packing a small suitcase for a long trip. How did we do it? Follow our journey below and speak to our team to understand how CSI can support your clinical trial supply requirements.

27–28 November, Zurich Switzerland Email us at info@csint.com to book a meeting with our experts! Read more about the Clinical Operations in Oncology Trials conference.

CSI is attending Outsourcing in Clinical Trials and Clinical Trial Supply Nordics 2021 conference on 26–27 October at Scandic, Copenhagen, Denmark. Email us at info@csint.com or contact us via the website to book a meeting with our experts! Find out more about the upcoming event here.

November is Lung Cancer Awareness Month 2020 in the UK. According to the NHS, lung cancer is the most common cancer in the world, with around 44,000 new cases diagnosed in the UK each year. These staggering statistics show the importance of cancer research and awareness. Reducing the risk of developing lung cancer and improving treatment is crucial to support the lives of patients. A person’s risk of developing lung cancer depends on factors including lifestyle, age, genetics exposure to chemicals and air pollution. Older age is one of the main risk factors for developing lung cancer. More than 4 out of 10 people diagnosed with lung cancer in the UK are aged 75 and older. This is because as people get older, the respiratory system undergoes changes due to the ageing process. The major causes of lung cancer There are many preventable risk factors that lead to lung cancer. Smoking plays a big part in the cause of lung cancer with 72% of lung cancer cases linked to exposure to tobacco smoke. People who smoke tobacco directly and those who inhale environmental tobacco smoke are at a high risk of lung cancer. The duration and amount of smoking contribute to the cause of the disease, with duration having the most effect on risk. Smoking is more strongly linked with the risk of developing small cell lung cancer and squamous cell carcinoma (SCC) than other types of lung cancer. A person’s occupation can cause risk of lung cancer. 13% of lung cancer cases are caused by workplace exposures. Asbestos, silica, diesel engine exhaust and other occupational exposures, while are not significant causes of lung cancer themselves, can increase the risk of the disease when combined with other risk factors. Approximately 8% of lung cancer cases are caused by air pollution. Research shows that the risk of death caused by lung cancer is greater in people living near major roads. This is closely linked to the occupational risk caused by those who are highly exposed to diesel exhaust emissions. Indoor air pollution is linked to people who use coal at home for cooking or heating. Treatments for lung cancer Treatments of lung cancer are mostly used in combination with one another and can change through the patient’s lifecycle depending on how well the cancer is responding to the treatment. Radiotherapy - Radiotherapy is the most common and effective treatment for non-small cell lung cancers (NSCLC). X rays destroy cancer cells while avoiding non-cancerous cells. It can also be used for small cell lung cancer when chemotherapy is unsuitable. Chemotherapy - Chemotherapy is the main treatment for small cell lung cancer (SCLC)and is also used for non-small cell lung cancer. It uses drugs to target cancer cells before the need for surgery or radiotherapy. It can also remove cells after surgery or to prevent a recurrence. Surgery - Surgery is most suitable for removing early lung cancer. The two ways to do this are using open surgery or via video-assisted thoracoscopic surgery. Clinical trials into the effectiveness of both surgeries are currently being conducted. Targeted cancer drugs/Immunotherapy - Targeted drugs work by seeking out and destroying cancer cells. Immunotherapy drugs help the immune system to destroy cancer. Targeted drugs can be used for more advanced cancers and in conjunction with other types of cancer treatment.Common drugs used to treat lung cancer include either 2 or 3 drugs given together, or 1 drug given by itself. Some common drugs include: Carboplatin or cisplatin (both are available as generic drugs) Docetaxel Gemcitabine Nab-paclitaxel Paclitaxel Pemetrexed Vinorelbine Immunotherapy Immunotherapy, is designed to boost the body`s natural defences to fight the cancer. For example, the PD-1 pathway may be very important in the immune system’s ability to control cancer growth. Blocking this pathway with PD-1 and PD-L1 antibodies has stopped or slowed the growth of NSCLC for some patients. The following immunotherapy drugs block this pathway: Atezolizumab Durvalumab Nivolumab Pembrolizumab Importance of lung cancer clinical trial participation Clinical trials are an essential part of lung cancer research. People living with lung cancer can volunteer to participate in clinical trials to help progress research into the disease. Clinical trials are not limited to researching treatments for lung cancer. Clinical trials also conduct research into causes of lung cancer, early diagnosis and screening, and living with lung cancer. How CSI can advance your Lung Cancer Clinical Trials At CSI, we have worked on many oncology studies. We have sourced thousands of vials of the medicines mentioned above and successfully distributed them all over the world. We have well-established relationships with all leading manufacturers and as such we can provide cost-efficient and timely solutions and design a robust supply chain to advance your trial.

We are pleased to annonce that we will be attending the Jefferies Virtual London Healthcare Conference! We want to use this opportunity to catch up with you virtually. If you would like to arrange a call with our team, please contact us.

Webinar: How to identify and manage risks in clinical trial supplies and comparator sourcing CSI hosted a webinar with Xtalks on Monday 16 November 2020 on how to identify and manage risks in clinical trial supplies and comparator sourcing. If you joined us on the day, we hope you had a great experience and took away some interesting learnings from our discussion. The webinar, hosted by Vanessa Dekou and Kotaro Yoshizawa, centred on discussing the risks involved in clinical trial supplies and comparator sourcing, and how you can manage these to ensure a successful clinical trial on a global scale. The webinar covered: How comparators are used in different clinical trial phases The risks associated with the supply chain in each trial phase The steps to take to identify the risks How to proactively address and manage risks Why and how a partnership with CSI's global reach can mitigate risks If you missed the webinar or would like to watch it again, please follow this link.