The growth in the biosimilar market since 2006 has been significant. Biosimilars have no meaningful clinical differences between the originator medicine in terms of safety and efficacy and are typically less expensive than the originator. These factors lead to the popularity of biosimilars to help bring safe and effective drugs to market at an affordable price What are biosimilars and biological medicines? A biosimilar medicine is a type of biological medicine that is developed to be highly similar and clinically equivalent to the existing biological medicine. A biosimilar contains a version of an active substance of an already approved biological medicine, which is referred to as the ‘reference medicine’ or ‘originator medicine’. It is similar to reference medicine in terms of quality, structure and biological activity. To understand the key features of biosimilars, you should first understand the class of medicines that they are part of – biological medicines. Biological medicines, or biologicals, contain active substances that are derived from a biological source, for example from living cells or organisms. Biologicals are used in clinical trials and crucial in the treatment of many serious conditions such as cancers, diabetes and autoimmune disease. Did you know 8 of the top 10 selling pharmaceuticals were biologicals? Many of the biologicals licensed are proteins that can vary greatly in size and structure from simple proteins such as insulin to complex antibodies. Biosimilar medicines are those that have a high degree of similarity to another biological medicine already licensed. Biosimilar companies can gain market approval for their biosimilars when market protection of the original biological has finished. The approval of the biosimilar is supported by evidence proven in clinical trials demonstrating no meaningful clinical difference between the biosimilar and the originator medicine. What is batch variability and why does it occur? The manufacturing of complex biologicals is significantly more intricate than chemically-derived molecules. Most of them are manufactured by sophisticated biotechnology processes such as cell systems or recombinant DNA technology. The complex nature of these molecules and the manufacturing process means there is a degree of variability called ‘microheterogeneity’. This means that there are subtle differences in the structure of the active substance within and between batches. To ensure efficacy and patient safety with this variability in mind, the microheterogeneity must be within an acceptable range. This can be achieved by adjusting manufacturing processes to guarantee consistency among batches. However, there may be a small variability within or between batches of the same biological medicine. This can occur during manufacturing if the process is modified during the commercial life of the medicine, for example when increasing the scale of production. Manufacturers apply strict measures and regulations to make sure that, despite variability, there is consistency between batches, and that any differences present in the batches do not affect the safety or efficacy of the medicine. Typically when using the same manufacturing process, variability within a batch or between batches batch-to-batch is very low. What are the key regulatory considerations of biosimilar development? To ensure consistency and quality of all biological medicines, including biosimilars, the EU legislation upholds strict requirements for the manufacture of all medicines: Manufacturers in the EU must hold a manufacturer’s license and are legally obliged to comply with Good Manufacturing Practice (GMP), the agreed standards to obtain a medicine with proven quality. National regulatory authorities in the EU regularly inspect manufacturing sites for compliance with GMP requirements. If some manufacturing steps take place outside the EU, then non-EU manufacturers, importers and wholesale distributors are obliged to follow the same strict requirements and are also regularly inspected. For biological medicines, some of the GMP requirements have been adapted to take into account their specific nature (e.g. use of appropriate aseptic techniques, refrigeration and other storage conditions, stability, transport etc.). What does this mean for biosimilars in clinical trials? Clinical trials are carried out to prove that the active substance is highly similar to the reference medicine, this is known as biosimilarity. Clinical trials aim to demonstrate high biosimilarity so that the biosimilar can rely on the efficacy and safety experience of the reference biological medicine, therefore avoiding the repetition of clinical trials. Clinical trials for biosimilars do not need to include all of the studies that are needed for the reference medicine in order to prove safety and efficacy for patients. It is important to note that biosimilars are not considered generics of biologicals. This is because of the natural variability caused by the complex manufacturing of biologicals as discussed above. CSI has experience in sourcing biosimilars for clinical trials CSI has extensive experience in sourcing products for biosimilar studies even in countries where strict government regulations exist. Want to find out more about sourcing biosimilars for your clinical trial? Get in touch with us to discuss your requirements. Summary A biosimilar medicine is a type of biological medicine that is developed to be highly similar and clinically equivalent to the existing biological medicine. A biosimilar contains a version of an active substance of an already approved biological medicine, which is referred to as the ‘reference medicine’ or ‘originator medicine’. It is similar to reference medicine in terms of quality, structure and biological activity.

Globalised clinical trials face a number of challenges when it comes to sourcing, supplying packaging and labelling and distributing clinical trial supplies and comparator products Supply chains are facing disruptions when importing and exporting medicines, maintaining regulatory compliance across countries, and controlling temperature conditions. These supply chain inefficiencies can prove very expensive and more importantly, put patient safety at risk. The comparator sourcing supply chain requires expert planning and management to ensure successful delivery. Successfully managing the clinical trial supply chain helps to improve efficiencies, minimise risk and maximise cost savings. Here are 5 reasons why clinical trial supply management is crucial in today’s clinical trial climate: Improve efficiencies In a complex clinical supply chain, it only takes one element to fall out of place for the whole process to be negatively impacted. These inefficiencies most often include manufacturing delays, quality control, temperature deviation, changed import and export regulations, and site storage conditions. Proactive management identifies opportunities where the supply chain can be optimised and puts processes in place to improve efficiencies and anticipate challenges. This ensures consistent quality assurance processes, storage and distribution solutions and temperature controls are implemented; remaining compliant with regulatory requirements at every stage. Minimise risks Successful clinical trials need effective supply chain management procedures. This ensures risks are identified and managed in a timely manner, and the required medication is available at the site when needed. Taking a holistic approach to assessing and managing risks prevents issues that impact the trial and the data generated. Looking at the different phases of the study and the complexities each one encompasses is a great way to identify where risks may arise. Employing a 6 step risk management process - identify, evaluate, control, communicate, review and report - ensures costs and trial data can be protected. Maximise cost savings Delays and inefficiencies can equate to significant financial loss. For example, if product acquisition is delayed, the window to package, label and distribute is shortened and there might be no medication available at the site for patients. Calculating shipping times and costs at the protocol design level enables supply chain managers to forecast the feasibility of the study and iron out design flaws before implementing them. Knowing all of the study information, such as the countries the products are being sourced from and distributed to, can ensure the most efficient and cost-effective transport route, therefore saving money along the way. Reduce product waste Accurate supply chain planning reduces unnecessarily high levels of stock and avoids oversupply. Having full visibility of the number of trial participants, the dosages required and the clinical distribution sites ensures the right product reaches the right site at the right time. By using flexible solutions, such as just in time deliveries and packaging and labelling products on an as-needed basis, companies can reduce product waste, reduce costs and prevent a negative impact on the conduct of the trial. Maintain regulatory compliance Collaborating with suppliers and manufacturers across the world ensures companies can leverage regulatory and country-specific expertise. Regulations are ever-changing and can differ greatly from country to country. This puts companies at risk of having their products blocked from entering the trial country or recalled entirely. Comparator sourcing partners apply global regulatory knowledge when acquiring documentation, understanding import and export regulations, and overcoming language barriers to ensure companies remain compliant throughout the trial process. Partnering with CSI at the protocol design stage optimises your supply chain, implements effective processes and technology. There is no one size fits all approach - we devise a bespoke supply chain management strategy that caters to your trial requirements. With more than 1000 trials successfully supplied with medicines all over the world, we have the experience, expertise and knowledge to deliver value to your studies.

Clinical trials are designed in different ways depending on primary and secondary endpoints and the product being investigated Clinical trial designs determine the way the trial is structured and the impact it has on the participants. The trial design significantly affects how the investigational products, comparators and concomitant medication must be sourced and supplied. This includes where the product is sourced from, how quickly it can be supplied, how it is packaged, stored and distributed. Understanding the different types of clinical trials and designs is crucial to creating a sourcing strategy that effectively supplies the most suitable products for your study. There are 5 main types of clinical trial design: randomised trials, single-blind trials, add-on trials, open-label trials and double-blind trials. Randomised clinical trials A randomised clinical trial refers to randomly allocating trial participants to one or multiple treatments under the study. This is done to compare the outcomes of the different treatments or one treatment compared to a placebo. Randomised clinical trials are the most common trial design as they produce unbiased results. When it comes to sourcing products for randomised trials, it is crucial for clinical trial suppliers to have all of the relevant information. This includes the number of participants in each arm of the study, the dosages required, the quantity of the medication, and the clinical distribution sites. This allows the supplier to locally or centrally source the products and supply them at the right time and place. Single-blind clinical trials Single blinding refers to the participants involved in the clinical trial being unaware of the medication they are taking. Only the investigator is aware of the product and cannot disclose any of the product information to the participants. If a study is blinded, the clinical trial supplier must make a number of considerations. As well as blinding the active comparator drugs, the product documentation must be blinded, which can cause difficulties when it comes to importing and exporting products. Double-blind clinical trials In double-blinded clinical trials, neither the participants nor the investigators know which participants are receiving the treatment being investigated, and which are receiving the placebo or comparator. This is done to remove any bias and produce objective results. Double-blinded studies can cause further challenges for suppliers because the study personnel must be unaware of the investigative product. This means the way products are shipped and stored must be considered. If the storage and shipping conditions are different for each product, blinding must be maintained to ensure the study staff cannot identify the products used. Open-label clinical trials In open-label clinical trials, both the participants and the investigators know the medication that is being studied. For this type of study, clinical trial suppliers do not have to take blinding requirements into consideration. Suppliers can locally source products without the need to repackage them as they are already in the local language. There is also less regulatory pressure surrounding import and export, as the product is commercially available in the country of the trial and documentation can be obtained. Local wholesalers can often supply the comparator at a lower cost with shorter lead times than the manufacturer. Add-on clinical trials In add-on clinical studies, all of the participants receive the commercially available treatment, but some also receive an additional experimental product. The rest of the participants either do not receive the additional treatment or are given a placebo. The purpose of add-on trials is to test a mechanism in the additional treatment that has a different action from that of the established treatment. When supplying products to add-on trials, great consideration must be applied at the protocol design level to ensure that the right products reach the right participants at the correct stage of the trial. Especially if the products are blinded, it is crucial to review the treatments to ensure they do not have adverse effects on the patients when combined. Partnering with CSI, a world-leading comparator sourcing partner and clinical trial supplier, at the protocol design stage ensures that your trial runs efficiently and successfully. There is no one size fits all approach to comparator sourcing. We devise a bespoke sourcing strategy that caters to the type of trial and its design to find the most effective solution. Contact us to discuss how we source comparators globally to ensure the successful supply of your clinical trials.

Distribution is a crucial part of the clinical trial supply chain Following the globalisation of clinical trials, ensuring investigational medicinal products (IMPs) requires overcoming challenges including import, export, regulatory requirements, and transport logistics. Establishing an effective clinical trial distribution strategy ensures the right IMPs reach the trial site, distribution agency or patient at the right time while maintaining product quality. Partnering with an experienced distribution partner is the most effective solution. As distribution experts, we use our experience to forecast the supply chain and minimise risks that may arise during the process. This ensures we overcome challenges, stick to budget and timeframes. Here are three key reasons why an effective clinical trial distribution strategy is crucial 1. Maintain compliance with regulatory requirements Regulations can differ from country to country. When clinical trials are conducted in multiple countries and regions, it is vital to be aware of the different regulations and how to comply with them. This may include import, export, data protection, packaging and ethics. Having strong relationships with distribution partners, suppliers and manufacturers with the relevant global expertise ensures you can understand and maintain compliance with country-specific regulations. Leveraging access to real-time data and knowledge across the globe provides a solution to the challenges companies face when distributing IMPs worldwide. 2. Ensure the quality and safety of IMPs It is vital to maintain the quality and therefore safety of the IMP as required by the standards set out by the Medicines and Healthcare Products Regulatory Agency (MHRA). A distribution strategy considers the relevant quality standards and maintains a robust quality assurance process throughout the clinical trial supply chain. At CSI, we have expertly controlled storage facilities, are licensed by the MHRA and have a quality management system that ensures full compliance with distribution requirements. Our storage and distribution service is fully integrated and monitored at every step of the supply chain, including: Good Distribution Practice (GDP) Good Storage Practice (GSP) Temperature-controlled cold (2–8°C) Ambient storage (15-25°C) Stock batch traceability, products recall in place Vaulted storage for controlled medications (Schedules CII–V) Secondary labelling and assembly if required Highly secure environment 3. Ensures a cost-effective supply chain A well defined clinical trial distribution strategy will maximise cost savings throughout the supply chain. By forecasting the supply chain, you can identify risks and mitigate them prior to conducting the trial. This will help to prevent making changes during trial conduct which can incur significant costs. With a well-forecasted clinical supply chain, you can include detailed consideration of trial design, or study-specific lead times, kit designs, country-specific challenges, and logistics associated with manufacturing, packaging, and distribution of supplies, particularly where product blinding is involved. CSI is an experienced distribution partner CSI has extensive expertise in supply chain management and distribution. We understand where your supply chain can be optimised and implement effective processes and technology that improve your operations. We efficiently and cost-effectively distribute IMPs to packaging agents, trial sites, patients, or warehouses to ensure your products are ready for use. Our supply management and distribution solution ensures pharmaceuticals, CROs and CMOs can operate efficiently. This helps to save time, money and resources across the entire clinical trial supply chain.

Pharmaceutical companies and CROs must have robust comparator sourcing strategies in place to ensure that comparator drugs are supplied to all clinical trial sites without disruption Working with a comparator sourcing partner like Clinical Services International (CSI) will streamline your clinical trial supply chain and ensure high-quality comparator drugs are sourced in a timely and cost-effective manner. Partnering with CSI at the protocol design stage ensures that your trial runs efficiently and successfully. There is no one size fits all approach to comparator sourcing. We devise a bespoke sourcing strategy that caters to your trial requirements. With 25 years of experience in comparator sourcing, we have gained expert insight into how to develop the most effective comparator sourcing strategies. Here are our top 3 contributing factors: 1. Global reach Clinical trials are not often isolated to one location. Most clinical trials span a number of regions and countries which requires comparator sourcing partners to have a global reach. It is essential to leverage country-specific expertise and source comparator drugs across the world while maintaining regulatory compliance. A global reach allows CSI to identify opportunities for cost savings by using the most appropriate strategy, be it local, central, market, manufacturer or hybrid sourcing. This means your company can save resources by sourcing from the market that the trial is conducted in, or sourcing products in one country and shipping for use in other countries. 2. Excellent supplier and manufacturer relationships Not being able to source the comparator in the desired quantity within the trial timeline can prevent your trial from proceeding. Excellent relationships with audited suppliers, originators and dedicated wholesalers allows CSI to overcome product shortages and unavailability on the open market. Direct relationships also help to minimise disruption to the supply chain and improve efficiencies. Working closely with suppliers and manufacturers helps to understand where there are challenges in the supply chain, such as logistics, quantity or expiry, and devise solutions to optimise them. CSI has outstanding relationships and direct account with all big pharmaceuticals and as such we also have intelligence about product changes well before they happen. 3. Compliance and regulatory expertise Clinical trials are subject to strict regulations surrounding product import, export, distribution, logistics, data and ethics. All of these factors can be human capital intensive for your company and cause difficulties when it comes to maintaining compliance without the relevant regulatory expertise. CSI understands the dynamic clinical trial approval processes, regulatory requirements, language barriers and has access to experienced clinical research staff to ensure you remain compliant throughout the trial process. Working with regularly audited suppliers and manufacturers ensures you adhere to quality and patient safety standards required in the supply chain at every stage of the clinical trial. CSI is a leading global comparator sourcing partner We improve trial success rates by securely sourcing comparator drugs in short supply with the longest expiry, ensuring comparators are available for trial participants at the right place and time. We leverage our global network of over 95 manufacturers to source high-quality comparator drugs and ensure the efficient, effective delivery of your studies. While our headquarters are in London, we operate in the UK, Germany, Denmark, Japan and the USA and have an extensive network of depots all over the world. Our excellent relationships with suppliers and manufacturers across the world help us source medications from Europe, the USA, Latin America and Asia Pacific (APAC). By partnering with CSI, your sourcing strategy takes the most appropriate route to improve the speed and agility of your clinical trial. Contact us to discuss how we source comparators globally to ensure the successful supply of your clinical trials.

There are many drivers that affect the cost of clinical trials including the cost of supplies and equipment, increased regulations, transportation and logistics, patient recruitment and complex procedures Streamlining the supply chain and ironing out risks can help to reduce costs and save resources. As a world-leading comparator sourcing partner, CSI delivers the best solutions to ensure your clinical trial runs smoothly, within the most stringent budgets and timelines. Our supply chain management expertise ensures the successful delivery of your clinical trial. Here are 5 ways CSI achieves a cost-effective clinical trial supply chain: 1. Early incorporation of trial supply management Incorporating supply chain management in the protocol design stage ensures that your clinical trial is efficient and cost-effective. By forecasting the supply chain, you can identify risks and mitigate them prior to conducting the trial. This will help to prevent making changes during trial conduct which can incur significant costs and increase timelines. With a well-forecasted clinical supply chain, you can include detailed consideration of trial design, or study-specific lead times, kit designs, country-specific challenges, and logistics associated with manufacturing, packaging, and distribution of supplies, particularly where product blinding is involved. 2. As-needed supplies and just in time deliveries A significant cost driver in clinical trials is product wastage. Without sufficient trial details including the number of participants, trial timeframes, product dosage and product expiry dates, it’s impossible to ensure the correct supply arrives at the trial sites at the right time. Packaging and labelling products on an as-needed basis and using a just in time delivery solution helps to reduce unnecessarily high levels of stock, avoid oversupply, and prevent having to make costly changes in the middle of trial conduct. 3. Implement a robust risk management process Risk management is an essential part of clinical trials to ensure you can generate a clear return on investment without disruptions. Each clinical trial has its own complexities based on the comparator, data, stock shortages which can delay timelines and increase costs. Mistakes can prove very expensive and more importantly, put patient safety at risk. 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. 4. Bespoke sourcing strategies CSI will work closely with you to devise the most appropriate and cost effective strategy depending on the study design. i.e single country, multi-sites or multiple countries multi-sites, open label or double blind. Locally sourcing products in the same country as the trial helps to reduce costs associated with importing and exporting products out of the country, packaging and labelling. However it might not be the most appropriate for global studies. We have multiple options available to ensure the sourcing strategy is best suited to your study protocol. 5. Direct-to-patient distribution Delays and inefficiencies can equate to significant financial loss. If product acquisition is delayed, the window to package, label and distribute is shortened and there might be no medication available at the site for patients. Direct to patient distribution improves the cost-effectiveness of the comparator supply chain by increasing patient retention and compliance. Just in time deliveries enable immediate distribution in direct to patient trials, allowing for more deliveries, tighter deadlines, and fewer errors. Calculating shipping times and costs at the protocol design level enables supply chain managers to forecast the feasibility of the study and iron out design flaws before implementing them. Working with an expert comparator sourcing and clinical trial supplier like CSI ensures the most efficient and cost-effective supply chain helping you save money along the way and deliver your study on time and budget with minimum wastage.

In today’s global market, clinical trials are rarely isolated to one location Most clinical trials span many countries and regions, which requires comparator sourcing partners to have a global reach. Country-specific expertise and strong relationships with suppliers and manufacturers enable partners, like Clinical Services International (CSI), to source comparator drugs globally while maintaining regulatory compliance and maximising cost savings. Here are four reasons why having a global comparator sourcing network is beneficial: Identify opportunities for cost savings As a comparator sourcing partner, we use knowledge of global markets to choose the most appropriate sourcing strategy, whether it is local, central, market or manufacturing sourcing. By weighing up the appropriate strategies, we can identify where your company can save resources. For example, sourcing from the market that the trial is conducted in or sourcing products in one country and shipping for use in other countries. Typically, oncology drugs are less expensive to source in regions such as Asia and Latin America than in the United States or Europe. This is caused by the differential costs of local sourcing. On the other hand, exporting and importing comparators from emerging regions may bring with it higher distribution and logistical costs. Rather than sourcing comparators in established markets, we can source products from emerging regions and create cost-saving opportunities for your business. Remain compliant with regulatory requirements Regulations and legislation can differ greatly from country to country. When clinical trials are conducted in multiple countries, we need to be aware of the governing bodies and regulatory differences that may impact the conduct of the trial. This can include factors such as import, export, data, ethics and logistics. A global reach enables us to understand dynamic clinical trial approval processes, regulatory requirements and language barriers. We can obtain the right documentation, such as certificates of analysis, and translate it into the appropriate language that will successfully demonstrate the chain of custody from the source to the final destination. This avoids misinterpretation and ensures we maintain compliance throughout the trial process regardless of the participating countries. Substantial comparator availability Availability of comparator drugs in the United States or Europe can often be scarce. This is typically due to high demand and obstacles with the manufacturer limiting supply to the open market to keep product exclusivity. If this occurs, we often turn to other global markets to source the comparator product, where demand may be less and there is sufficient availability of the drug required for trial. Excellent relationships with audited suppliers, manufacturers and wholesalers across the world help us source products that would otherwise be unavailable in established markets. Our country-specific knowledge of regulations then enables us to identify whether the products can be exported and imported successfully, all while considering the trial design and logistics, such as product blinding. Delivery within the required timeframe When sourcing comparators from emerging regions, there is a risk that the product may not reach the trial site for use in the study within the product expiration date. This can be due to complications such as Brexit when gaining approval to import and export comparators into other countries. Using our global expertise, we can forecast the supply chain, communicate with local suppliers and manufacturers to overcome challenges, choose the appropriate strategy and deliver the product within the required timeframe. CSI is a world-leading comparator sourcing partner Working with a comparator sourcing partner like CSI will streamline your clinical trial supply chain and ensure high-quality comparator drugs are sourced in a timely and cost-effective manner. While our headquarters are in London, we operate in the UK, Germany, Japan and the USA. We leverage our global network and country-specific expertise to source comparator drugs from audited suppliers, originators and dedicated wholesalers in Europe, the USA, Latin America and the Asia Pacific (APAC) while maintaining regulatory compliance. Contact us to discuss how we source comparators globally to ensure the successful supply of your clinical trials.

An effective comparator sourcing strategy requires the development of a robust supply chain, forecasting operations, distribution and logistics A comparator sourcing strategy has many moving parts. Ensuring all these parts work together requires comparator sourcing expertise to maintain product quality, safety and security standards. Clinical Services International (CSI) has over 25 years of experience in developing effective comparator sourcing strategies. We use our expertise to successfully plan and manage the comparator sourcing supply chain, to help shorten the supply chain process, minimise risk and maximise cost savings. Here are four steps to develop an effective comparator sourcing strategy. 1. Understand the trial protocol It’s important to take a step back and look at the bigger picture, to gather all the relevant information during the clinical trial supply planning process. We consider a list of initial questions when beginning a project to understand the comparator requirements. These questions include: Which comparator drug is required? What quantity of the comparator is required? Which countries are participating in the trial? Which documents are required for import and export? What is the delivery timeframe for the duration of the study? Is there a generic form of the comparator product available? After the answers to these questions have been considered, we can then choose the most suitable sourcing strategy, whether it’s using a local, central, market, manufacturer or hybrid approach. Choosing the most appropriate sourcing strategy ensures we stay within stringent budgets and timelines so the product and trial can be delivered successfully. 2. Forecast the supply chain to overcome risks Forecasting the supply chain helps to improve efficiencies, minimise risk and maximise cost savings. We forecast the supply chain based on the trial protocol to identify where risks may occur and the impact they have on the supply chain. This helps us put measures in place to prevent risks from occurring, ensuring they don’t affect the comparator, trial and data generated. We look at the different phases of the study and the complexities that arise in each stage. We then employ a 6 step risk management process - identify, evaluate, control, communicate, review and report – to ensure the supply chain is thoroughly considered and costs and trial data can be protected. 3. Leverage global network and supplier relationships Being unable to source the comparator product in the desired quantity within the trial timeline can prevent the trial from proceeding. Leveraging excellent relationships with audited suppliers, originators and dedicated wholesalers around the world allows us to overcome product shortages and unavailability on the open market. Working closely with suppliers and manufacturers helps us understand where there are challenges in the supply chain, such as logistics, quantity or expiry, and devise solutions to optimise them. Developing strong relationships ensures we gain intelligence about product changes well before they happen so we can always remain ahead of the market. 4. Choose the right comparator sourcing partner Developing an effective comparator sourcing strategy is challenging without the right team in place. By partnering with CSI, your comparator sourcing strategy will take the most appropriate route to improve the speed and agility of your clinical trial. We leverage our global network of over 95 manufacturers to source high-quality comparator drugs and ensure the efficient, effective delivery of your studies. We improve trial success rates by securely sourcing comparator drugs in short supply with the longest expiry, ensuring comparators are available for trial participants at the right place and time. Contact us to discuss how we source comparators globally to ensure the successful supply of your clinical trials.

Here are three ways CSI helps you overcome challenges to ensure successful delivery of your clinical trial supplies Managing clinical trial supplies continues to be a challenge for companies in the healthcare and pharmaceutical industries. Amongst dealing with unpredictable lead times, restrictions on availability and trial delays, sponsors must consider the most appropriate strategies, to overcome challenges, save resources, and ensure trial success. CSI has over 25 years of experience in developing effective comparator sourcing strategies. We use our expertise to successfully plan and manage the comparator sourcing supply chain, to help shorten the supply chain process, minimise risk and maximise cost savings. There are many prominent challenges sponsors have experienced over the last few years, including expiry dates, COVID-imposed restrictions on comparator availability, stock wastage, and acquisition cost. Here are 3 ways CSI helps you overcome these challenges to ensure the successful delivery of your clinical trial supplies: 1. Balancing the risk of supply shortages against wastage The pharmaceutical industry continues to struggle with ongoing shortages of comparator drugs and investigational medicinal products (IMPs). Companies are increasingly pooling clinical trial supplies in fear of another nationwide lockdown or shipment delays caused by the pandemic and Brexit. With decentralised trials also increasing, companies are ensuring they have product overages to account for patients running out of medication. Pooled supplies and product overages can lead to wastage, which is a significant strain on financial resources. To avoid wastage, companies are accounting for a lower percentage of overage than they might usually. Minimising overage to only what is necessary, can reduce the number of products that go unused, therefore reducing product wastage. 2. Balancing comparator acquisition price against reliability The cost to acquire comparator products and IMPs is often high due to a competitive market, premium manufacturers' command for clinical trials, shipment delays and supply shortages. When choosing a comparator supplier, it’s important to consider the cost of the product while ensuring the reliability of the supply isn’t compromised. When comparator products are in limited supply, sponsors are often forced to pay retail prices compared to wholesale or local prices to secure sufficient supply, which can be very costly. Choosing a comparator sourcing partner that uses the best strategy for your trial design and comparator product will ensure you can maximise cost-effectiveness. A comparator sourcing partner will use local, market or manufacturer sourcing strategies based on the location of your clinical trial and available supply, to save you time and resources throughout the clinical trial supply chain. 3. Use trial forecasting to source products within expiry With lengthy lead times and delays in the clinical trial supply process, it’s common for comparator products and clinical trial supplies to surpass their expiration date before reaching the end of the study. When sponsors pool comparator products, have large overages or experience significant delays in the clinical trial supply chain, often the products can expire prior to being used in the trial. This can cause disruption to patient activities and result in relabelling activities at trial sites and distribution depots to extend the expiry dates on product supply. Sourcing partners must forecast the supply chain and understand the trial design to source and distribute products to the right place at the right time. This helps to reduce wastage, use products within the expiry dates, and save resources. Choose the right comparator sourcing partner By partnering with CSI, your clinical trial supplies and comparator sourcing strategy will take the most appropriate route to overcome challenges and improve the speed and agility of your trial. We leverage our global network of over 95 manufacturers to source high-quality comparator drugs and ensure the efficient, effective delivery of your studies. We improve trial success rates by securely sourcing comparator drugs in short supply with the longest expiry, ensuring comparators are available for trial participants. Contact us to discuss how we source comparators globally to ensure the successful supply of your clinical trials.

The clinical supply chain is a complex process involving not only logistics, but crucially compliance. How can this be maintained? The clinical supply chain is a complex process involving logistics and compliance. A clinical supply company must optimise their management processes to ensure compliance with local, national and international regulations. Maintaining compliance with the various regulations throughout the clinical trial supply chain is vital to the overall trial supply process. Clinical Services International (CSI) has extensive experience in clinical trials worldwide, which has led to expert knowledge of compliance in the clinical trial supply chain. These six tips will help you remain compliant with your supply chain. 1. Identify and manage risk Risk management protocols are essential for ensuring a smooth supply chain for clinical trials. You must address every compliance risk individually because each trial is unique. For example, each product must be kept within its specific storage conditions to remain effective and not present a health risk. It is critical to consider risks, even if they seem obvious. Due to the complexity of clinical trials, it is possible that regulations are not followed if proper risk management is not implemented. 2. Be aware of the complexity of regulatory requirements Imports, exports, data protection, and other regulations are different from country to country. Therefore, you need to carefully research the countries where the products are being transported to. When you have researched the regulations in each location, your clinical supply management strategy has nothing to hide if regulators inspect your processes. 3. Implement regulatory advice We have seen first-hand the challenges of complying with regulatory standards. Seeking advice from CSI can help you be compliant in the clinical trial supply chain. We offer: Certificates of Analysis (CofAs) Batch Release Certificates (BRCs) Statements of Authenticity (SoFaS) QP consultation CSI stays up to date on the latest regulatory developments and have built relationships with all major pharmaceutical manufacturers. Our trusted network of suppliers is fully audited and is fully compliant with regulations, such as the Falsified Medicines Directive (FMD). 4. Maintain excellent quality control The clinical supply chain must implement excellent quality control to maintain compliance since regulators can easily see discrepancies in the supply chain. Effective clinical supply management system that ensures appropriate systems are in place will reduce the risk of quality control falling below the required standard. For example, products must always be transported correctly. The FMD requires that there be a unique identifier code on the packaging to be scanned throughout the clinical supply chain. 5. Role of customs agents Exports and imports of clinical trial supplies must pass through customs and meet the regulations of each country. Therefore, in addition to doing your research, you may benefit from using local and international customs agents who can represent you at customs and process your declaration for you. The effectiveness of a customs agent in the clinical trial supply chain depends on the complexity and the volume of products that need to be transported - but they tend to be used with high volume, highly complicated supply chains. So, due to the nature of clinical trial supplies, using a customs agent can enable the products to be delivered in a timely manner. This will enable the clinical trials to run on time. CSI has extensive experience acting as an Importer of Record and working with local agents to facilitate all requirements and ensure smooth sailing. 6. Plan effectively The key to maintaining compliance in the clinical trial supply chain is to plan the entire process, as time and money can be saved with suitable organisation and having a reliable strategy. Aside from an effective plan being able to identify risks - as highlighted earlier, it also minimises the risk of not being compliant and having products held at customs, confiscated, or rendered ineffective. Overall, effective planning will help maintain compliance in the clinical trial supply chain. For further information, see our blog highlighting five reasons why clinical trial supply management is crucial. CSI implements strict operating procedures to maintain an excellent supply chain that ensures that all clinical trial supplies remain compliant. Contact us to see how we can help your clinical supply company meet regulatory standards in the clinical trial supply chain.

Direct to patient trials have surged in popularity in the wake of the coronavirus pandemic, offering several benefits to patients and clinical trials sponsors. Vanessa Dekou, Managing Director at Clinical Services International, reflects on the opportunities and challenges this creates for comparator sourcing partners. There’s little doubt that COVID-19 has disrupted the clinical trials industry, with many pharmaceutical companies reconsidering the best ways to reach patients, and so it’s no surprise that one outcome of the pandemic is the drive towards direct-to-patient (DtP) trials where possible. Many sponsors recognise the benefits of increased patient diversity, improved patient recruitment and retention, and reduced site visits, particularly for vulnerable patients with compromised immune systems. Logistics companies are keen to benefit from the increased demand – writing a lot of online articles extolling the virtues of DtP trials! – but what does this potential shift mean for comparator sourcing companies? How can they prepare themselves for a possible change in the landscape of clinical trials? From centralised bases to multiple depots In most instances, clinical trials are conducted through test centres – often hospitals – in various countries around the world, with one or more centralised bases supplying the centres. In such a model, the logistics of comparator sourcing and delivery are orientated around these supply hubs. In contrast, DtP trials rely on timely supply to multiple depots where an authorised distributor takes over the supply chain. This multiplication of delivery sites introduces a significant degree of logistical complexity and introduces a further ‘node’ in the cold chain. “Simplicity does not precede complexity but follows it.” Alan Perlis, computer scientist ‘Just-in-time’ deliveries Hospital sites or test centres often have the storage facilities to handle all the necessary drugs for the duration of an entire clinical trial, so may only need to receive two to three deliveries, simplifying the comparator sourcing supply chain. In contrast, authorised distributors in DtP trials are unlikely to have the capacity to store clinical trial supplies on-site to then be distributed over an extended period. Instead, DtP trials rely on multiple ‘just-in-time’ deliveries to depots, for near immediate distribution to patients. A comparator sourcing solution needs to allow for an increase in the volume of deliveries with much tighter deadlines and less margin for error. At CSI, this is nothing new; we have a wealth of experience in running oncology trials that can include over 30 different medicines, all requiring just in time delivery. These are generally open-label trials, and patients often self-administer the drug, so the products are sourced locally. Although this adds considerable complexity, we have all the necessary tools to manage supplies with an excellent success rate. Local versus international This move towards patient administration and in-country sourcing has eliminated the need to relabel the medicine or comparator. Yet this potential advantage is not without its downsides. Locally sourcing comparators poses challenges, such as limited supply and a non-competitive market, making it harder to meet a sponsor’s competing desires for convenience and reduced cost. However, at CSI we put patient safety first and, to do that, we work either directly with manufacturers or authorised country distributors to ensure continuity of medication. Efficiency is the primary driver Cost, however you spin it, is still a primary concern for any clinical trial sponsor, and we understand that. Local sourcing and DtP distribution can carry significant cost implications, although these may be offset by certain advantages such as increased patient retention and compliance. Working with an experienced comparator sourcing partner with an extensive database and well-established relationships with manufacturers and suppliers will be even more crucial than ever in helping to develop the most effective and efficient comparator sourcing solution.

Here are four ways CSI maintains quality assurance in clinical trial supply Maintaining quality throughout a clinical trial is an ongoing process that requires consistency and management. Having a robust quality assurance process ensures the relevant quality standards, regulations and guidelines are met in each clinical trial. What is quality assurance? Quality assurance is a systematic process of checks and analysis that determines whether the clinical trial supply is up to standard and meets specific requirements. Three of the most common regulations and codes of conduct that clinical trials must adhere to are the Falsified Medicines Directive (FMD), Good Distribution Practice (GDP) and Good Storage Practice (GSP). What is the clinical trial quality assurance process? The clinical trial quality assurance process involves all trial-related activities and documentation. Using the trial design, protocol and system of checks, the process examines whether the trial is conducted correctly, the data produced is reliable and accurate, and whether regulations including the FDA, GDP and GSP are adhered to. There are many challenges that can disrupt the clinical supply chain and the effectiveness of your study. To ensure the clinical trial isn’t deemed below standard, it’s important to forecast risks and identify solutions throughout the duration of the study. This ongoing, dynamic process requires your team to be aware of the challenges and how to mitigate them and maintain communication with vendors and partners so that the quality of the study isn’t compromised at any point in the supply chain. The quality assurance process is in-depth and covers a breadth of areas from trial design to delivery. These activities can include examining trial sites, auditing suppliers and vendors, ensuring correct packaging and labelling, and maintaining suitable storage and distribution conditions. This plan will also consider the study design, site and data management, and the final clinical study report (CSR). Auditing this documentation examines whether the data represented is accurate and reliable, and ensures the study is compliant with GDP, GSP and FDA regulations. How does CSI maintain quality assurance? You should engage with a partner that understands the complexities of regulatory processes and timelines. We pride ourselves on our robust quality assurance processes that ensure the quality of every product and trial we help to deliver. 1. Dedicated quality department Our dedicated quality department’s sole function is to ensure that you receive the highest quality of clinical trial supplies so your study can run as smoothly and successfully as possible. To ensure your clinical trial supplies are thoroughly quality checked and assured, we provide: • Certificates of Analysis (CofAs) • Batch Release Certificates (BRCs) • Statements of Authenticity (SofAs) • Global market knowledge • Ethically sourced products 2. Qualification processes for suppliers and vendors We visit 90% of our suppliers, especially those based outside Europe. We manage the risks of outsourcing clinical trial supply partners by ensuring stringent processes that prevent issues including supply and delivery. 3. Global network Our global network of audited suppliers and manufacturers ensures we are compliant with regulations across the world. Our partners have local and regional market knowledge, regulatory knowledge, and are commonly part of the regulatory bodies themselves. Our partnerships ensure we know which processes to follow and how to best adhere to them. 4. Qualified Person (QP) services Our QP is a qualified pharmacist with 40 years of experience in compliance and quality control. We offer many services covering supply chain auditing including: Auditing to GMP/GLP/PICS Production of QP 3rd party declarations Batch certification of investigational medicinal products (IMPs) QP GMP certification of IMP or commercial packaging undertaken IMPD support (simplified, full, compliance review) Regulatory advice and support Consultation with a QP We also hold the IMP/MIA license, ensuring our quality management system is vigorous and robust. CSI is a world-leading partner in clinical trial supplies and comparator sourcing Working with an external clinical trial supplies partner can help to support your quality assurance process. Using our scientific ability and decades of experience in clinical trial and supply chain management, we implement robust quality assurance processes that ensure the integrity and accuracy of your study. By using our global network and strong relationships with audited suppliers, manufacturers, authorised distributors, and pharmaceutical wholesalers, we ensure your trial is compliant with differing regulations across the world.