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.

Three vaccines currently in circulation are showing high rates of effectiveness in preventing COVID-19. Pfizer-BioNTech Moderna University of Oxford/AstraZeneca Pfizer-BioNTech and Moderna are developing vaccines in late-stage clinical trials that are showing over 94 and 95% effectiveness. The University of Oxford, while in earlier clinical trial stages, is showing strong immune responses already in adults over 60. Pfizer-BioNTech Pfizer and German mRNA biotech partner BioNTech released information regarding their experimental pandemic vaccine, with the results looking positive. In its phase III clinical trial, Pfizer and BioNTech’s vaccine candidate named BNT162b2 has demonstrated over 94% effectiveness in preventing COVID-19 in subjects without prior SARS-CoV-2 infection. Pfizer has warned that as more results come in as clinical trials for this vaccine continue, the results could change, increasing or decreasing its effectiveness percentage. Pfizer and BioNTech found 94 confirmed COVID-19 cases among the 43,538 participants that took part in the trial of BNT162b2. Moderna US company Moderna has released similar results, revealing that their vaccine has shown 95% effectiveness in protecting against COVID-19. The trial in the US included 30,000 participants; half of which were given two doses of the vaccine four weeks apart, the rest were given dummy vaccines. Out of the target group of 95, only five of those given the real vaccine developed the coronavirus, while 90 of the cases were given the dummy vaccine. Moderna hopes to make the vaccine available worldwide in 2021; with the UK announcing that it will have five million doses of the Moderna vaccine, enough for 2.5 million people, in spring. University of Oxford/AstraZeneca The University of Oxford vaccine, while in earlier clinical trial stages than Pfizer-BioNTech and Moderna, is showing strong results as it moves into the phase III trial in the coming weeks. In adults in their 60s and 70s, the Oxford vaccine shows a strong immune response; increasing hopes that it can protect older adults most at risk from the virus. The Oxford vaccine is manufactured by AstraZeneca and has been ordered by the UK government in larger doses than any other vaccine. The government has ordered 100 million doses of the Oxford vaccine compared to 40 million doses of Pfizer-BioNTech and five million of Moderna. When will the COVID-19 vaccines be rolled out and who is first in line? How countries plan to roll out the vaccines has not been disclosed, but it has been suggested that Italy, Spain and other EU member states would benefit from small numbers of doses ready in December, with most ready in 2021. What is the impact of COVID-19 vaccine trials on clinical trials? COVID-19 vaccine trials have dominated clinical trial resources. Some of the most recent largest clinical trials to take place with experimental agents puts this into context. In accordance with the number of phase III trials registered in clinicaltrials.gov, COVID-19 vaccine trials account for five of the 10 most expansive in terms of participants. This is because vaccine trials require expansive programmes to identify low-frequency safety risks that might occur in the wider population. Another reason is to ensure there are enough participants involved in the study to be able to gather significant statistics in events that are rare. As such, we have seen a significant concentration of resources into vaccine research. In addition, asthma medication and COVID related medication experience very high demand and potential shortages. At CSI, we have mapped the entire global market and can successfully supply COVID related medication for your trials.

Successful clinical trials need effective supply chain management procedures to make sure risks are identified and managed in a timely manner so the required medication is available at the site when needed. Taking a holistic approach to assessing and managing risks makes sure you can prevent things that will impact the trial and the data generated. There needs to be a robust methodology in place for identifying, evaluating, and proactively managing the risks involved in clinical trials. So, what are the risks involved in clinical trial supplies and how can you manage these risks to ensure a successful clinical trial? Phases of clinical supply complexity Looking at the different phases of the study and the complexities each one encompasses is a great way to identify where risks may arise. Phase 1 is characterised by a small group of subjects, short-duration and limited distribution. Within this phase, the amount of investigational medicinal product (IMP) can vary depending on the dosing scheme, with a possible increase of up to two or three times more than the original by adding just another subject for example. The product shelf life is still up for review and data will confirm this as it becomes available throughout the study. Costs and duration tend to be lower in this phase than the others due to limited scope and therefore limited resources are required to manage clinical supplies. Phase 2 is made up of hundreds of subjects and studies can last over months or years. The study can expand into a number of regions and sites which introduces treatment arms that bring with them their own challenges. In this phase, an Interactive Response Technologies (IRT) platform is used to look after randomising and dispensing. Packaging campaigns are also needed to account for country-specific labels in the local language. At a trial in this phase, risk management must be prioritised to ensure costs and timelines are aligned. Phase 3 involves hundreds and even thousands of subjects with a study duration lasting up to four years. Trials are held at clinical sites across the world spanning multiple regions and countries. The phase 2 challenges still stand in phase 3 but are exaggerated because of the scale of the study. With global studies, differences in how the trials are conducted and managed require more thought. Particularly into the required documentation that differs from countries and continents. At CSI, we run studies with 35+ different medications in many countries. To ensure successful delivery, we spend significant time planning and evaluating supplies. Managing risk in clinical trial supplies The risk management process can be carried out in six clear steps from identification to reporting. While there may be some additional actions taken within the process such as time and resources, the benefit of having detailed risk management ensures your costs and data can be protected. Identify Risks Knowing which risks to identify before conducting clinical trials is the first step in risk management. Specific characteristics of the trial design and drugs can lead to different risks that make the process complex. This requires critical thinking from team members to understand where risks can occur, the severity of the risks and the controls involved. Specific comparators are studied in terms of availability, shelf life, handling conditions, distribution requirements and paperwork. Evaluate risks The risks should be evaluated to ensure they’re prioritised effectively. Look at how likely the risk is to occur in this specific trial and what level of risk it poses to the success of the trial. The risks that are likely to occur and would have a moderate or high impact on trial success should be acted on first and foremost. Using a risk impact matrix is a useful tool to achieve this. Place the risks on a likelihood scale from rare to almost certain, with consequences ranging from insignificant to catastrophic. You could categorise them as low, medium or high risk to decide which risks must be controlled as a matter of priority. At CSI we always develop contingency plans and critically evaluate comparator sourcing related risks. Control risks Putting control procedures in place will ensure the trial risks don’t turn into issues. Risks must be controlled to prevent them from occurring and having consequences on the trial itself. How you decide to control the risks involved depends on the design of the trial and the drugs used. Think about if you will be using an IRT, if the study is blinded, what resupplies will be needed, is there enough internal resource available at each trial stage? These are the types of questions that should be addressed to put actions into place at the right stages of the trial. Communicate risks An aligned team is essential to ensure trial risks can be identified, monitored and managed effectively. Communicating internally will make sure everyone understands the elements of the trial, the risks involved and the controls that are in place to prevent them. Communicating externally is essential too; sponsors, vendors and stakeholders must have the relevant risk information to track the progress and conduct of the study. We appreciate that nobody likes surprises that can impact study timelines. When medicines are unavailable, we scan the entire global market to provide timely solutions. Review risks The risk management plan should be updated in line with the trial to track changes to the known risks and if any new risks arise during conduct. Look closely at whether the control measures put in place are working effectively and if the risks that had a high likelihood of occurring are being prevented. If they’re not, what else can be done to make sure they don’t occur? This requires resources on hand to document the mitigation’s during the conduct of the trial to make sure critical thinking isn’t overlooked. Report risks The final stage is reporting on the trial and its process. What were the objectives of the study, what was the design of the trial, who was involved internally and externally? Based on these factors, what were the risks that had a likelihood of occurring and what was the consequence of the trial if they happened? If the risks weren’t mitigated by the control measures and the issues occurred, what impact did it have on the trial and data validity? The key to effective risk management is being proactive. Using critical thinking to identify risks involved in clinical trial supplies and evaluating the impact they could have on the trial if not controlled. Managing risks ensures they don’t become expensive problems and that high quality, valid data can be gathered throughout the trial. Reviewing and reporting on the conduct of the trial and the risk management process ensures you’re best positioned to achieve your trial outcomes. Contact CSI to discuss how we can deliver a detailed, zero-tolerance risk management approach for your clinical trial supplies.

How can you be sure that your comparator sourcing partner will provide you with the best available solution? How do you know that the company has a truly global reach? How do you know whether your partner could save you hundreds of thousands of pounds, or not? Vanessa Dekou, CEO at Clinical Services International, identifies the key element that can help you make the right choice for your clinical trial supplier. You’re only as strong as your data Data collection is vital to serving our clients well, and behind every two-line confirmation email saying “Yes, we can help” is an army of researchers working away to find the most comprehensive solution to each of our clients’ comparator sourcing problems. One of the challenges of global comparator sourcing is ensuring that our understanding remains up to date. Last quarter’s preferred supplier for a particular drug in a given country may not be offering the best deal this quarter. It takes time, energy and a commitment to research to ensure that data remains useful; if it is inaccurate or misleading, it can waste valuable time or, worst of all, fail to help us secure the very best solution for our clients. And that is something we simply cannot accept. “Behind every two-line confirmation email is an army of researchers working away to find the most comprehensive solution to our client’s comparator sourcing problem.” Data in, data out Solving a client’s problem requires a thorough understanding of what we are dealing with; as the old adage goes, ‘garbage in, garbage out.’ Without knowing the scope of a clinical trial and nailing down the details – comparators, timelines, quantities, etc. – it’s almost impossible to develop a comprehensive solution, even with an excellent global network of suppliers and manufacturers. We’re also keen to fully understand a client’s key concerns, so that we can offer alternative packages to suit their needs. For example, a more expensive product may be available within a shorter time frame than a cheaper alternative, and our client can make the final call as to whether time or money is the priority. Map the market Before responding to a client’s request, we need to ‘map the market’ and undertake extensive research to understand global comparator availability, quantity, cost, import and export regulations, and logistics – there’s an awful lot to consider! For example, it might be that a supplier in a small market such as Greece or Bulgaria can offer the lowest price, but simply cannot offer the quantity required for a large clinical trial. In addition, it’s important to have a handle on the product usage per country to forecast potential disruptions in comparator supply. “The goal is to turn data into information, and information into insight.” Carly Fiorina, former CEO at Hewlett-Packard Data drives a better deal In everyday life, we are used to shopping around for a better deal rather than going with the first item we find, and we don’t expect a product’s price to increase for no discernible reason. Knowledge is power, and the same holds for comparator sourcing. Keeping track of price hikes and reductions, and alternative suppliers often enables us to negotiate a better deal for our clients, or walk away from an offer that on reflection is not as promising as it first seems. Reliable data enables us to determine what a ‘good deal’ really looks like. Data delivers better service to all clients, big and small At CSI, we’re proud to stand by our belief that all our clients deserve the very best service, whether they are sourcing comparators worth thousands, or hundreds of thousands, of pounds. Delivering this kind of service is made much easier when we can draw on an extensive database, and offer an overview of drug pricing, quantities, suppliers, etc. across the world. Rather than starting from scratch each time, we can simply build on our existing knowledge and connections, with each new project refining and contributing to our overall understanding of the global market and supply chains. Data-driven solutions that you can rely on Since our founding, CSI has recognised the value of data in delivering excellent service and value for money. Our ongoing research and methodical approach to capturing and organising data allows us to truly evaluate and identify the ideal comparator sourcing package for our clients. So, when it comes to choosing your next partner, why not ask the following simple question: “How do you know that you are offering us the best solution?” If the answer doesn’t mention extensive data collection, management and ongoing research, then it’s time to contact CSI and discover for yourself how comprehensive our service is.

How CSI has saved a leading global pharmaceutical company €1 million by sourcing pembrolizumab from the market at the best possible price Pembrolizumab is a type of immunotherapy indicated by the European Medicines Agency (MHA) for the treatment of a wide variety of cancers, including non-small cell lung cancer, melanoma and classical Hodgkin lymphoma. Challenge Pembrolizumab is one of the most sought-after medicines for use as a comparator in clinical trials. Because of this, the manufacturer makes sourcing the product challenging, commanding a very high premium for its use in clinical trials compared to the wholesale price of the product in most European markets. Our client, a leading global pharmaceutical company, required considerable volumes of the product for their clients’ trials and came to CSI for a cost-effective sourcing solution. Solution CSI identified reliable suppliers that could offer the product in significant volumes with all the relevant documents available and no trial disclosure required, and all at a price significantly lower than that offered to our client by the manufacturer: a 30% reduction when all supporting documentation was required, and 40% when Certificates of Analysis (CoA) were not mandatory. Result CSI has been delivering pembrolizumab (sourced at 30–40% lower than the manufacturer’s price) consistently to our pharmaceutical company client for the past couple of years, fulfilling seven purchase orders on time and, in the process, delivering a saving in the region of €1 million.

15th – 16th march, nh milano congress centre, italy We are attending Clinical Trial Supply Europe 2023 at the NH Milano Congress Centre, Italy on the 15th and 16th of March 2023. If you would like to arrange a meeting to discuss your clinical trial requirements with our Managing Director, Vanessa Dekou. Our team of experts will also be available at Booth 13 to answer any questions you may have. You can find out more about the upcoming event by clicking here. Join CSI’s discussions at CTS Milan Day one - Vanessa Dekou, Managing Director, CSI Vanessa Dekou will be chairing on the 15th of March, and will be presenting and moderating the following discussions: 8:20 – Chairperson Vanessa Dekou’s opening remarks 15:00 – [Stream A] Presenting: “Holistic approach to effective clinical trial supply strategies: beyond comparator sourcing” 15:30 – [Stream A] Moderating the panel discussion on: “Running your clinical trial internationally: overcoming logistical challenges to maximise supply chain efficiency panel discussion" 17:30 – Chairperson Vanessa Dekou’s closing remarks Day two - Andrea Giochetta, Director of Strategy and Business Development, CSI Andrea Giochetta, our Director of Strategy and Business Development, will be chairing the event on 16th March and moderating a discussion: 8:50 – Chairperson Andrea Giochetta’s opening remarks 11:30 – [Stream A] Moderating the panel discussion on: Operational agility: the importance of maintaining flexibility in your clinical supply chain 16:00 – Chairperson Andrea Giochetta’s closing remarks Register today If you’ve not yet booked your ticket to CTS Europe, you can do so by clicking here.