The evolving geopolitical landscape and other challenges
Given the rapidly changing geopolitical landscape, (bio)pharmaceutical companies may be facing increasing challenges when conducting clinical trials in the US or EU with materials manufactured by Contract Development and Manufacturing Organisations (CDMOs) in Asia, and in particular China. Beyond geopolitical complexity, several other factors – such as time-zone differences, logistics and storage capabilities, cost-effectiveness, material reliability, and compliance with quality standards required by EU or US regulatory bodies, play a key role in selecting a manufacturing region.
Factors influencing the choice of manufacturing region
Time-zone differences can significantly impact communication and coordination. For a Japanese biotech client, the minimal time-zone gap was one of the key factors for shifting the manufacturing to China. Conversely, another client – where time-zone alignment was less critical – we are currently exploring a CDMO in Australia while planning clinical trials in the EU.
Logistics also plays a crucial role. Even within the EU, shipping clinical materials can take up to two days. The type of molecule, however, greatly influences decision-making. For more sensitive products, such as complex molecules or advanced therapy medicinal products (ATMPs), transportation becomes a critical and often costly consideration. In such cases, it may be more practical to partner with a CDMO within the same region or even produce materials on-site where they will be used.
When clinical trials are conducted in Asia, using a local CDMO is often significantly more cost-effective. However, if the product is intended for the US market, regulatory alignment becomes essential. In such scenarios, conducting at least part of the clinical development within the US can offer advantages. It is also worth noting that manufacturing costs within the US vary: the East Coast (e.g., California) is considerably more expensive than central regions like North Carolina or Colorado.
Regardless of geography, it is essential to ensure robust quality systems are in place. Materials must meet high standards, and the supply chain must be reliable. Lower-cost production – such as with certain Asian CDMOs – may require additional oversight and control mechanisms. While the intensity of quality assurance (QA) audits is generally consistent across regions, the focus may vary. For example, in Asia or certain parts of the US, particular attention should be paid to the water supply, due to a higher risk of contamination. In contrast, water quality in the EU tends to be more consistent. A single instance of contamination can result in an entire batch being discarded, forcing the CDMO to restart production—potentially leading to delays of several months and considerable costs.
Reliability is key
Among manufacturing regions, the US is widely recognised for its strong regulatory oversight and quality assurance. Selecting a CDMO in Asia, often necessitates a more thorough evaluation process. This includes assessing whether the facility has on-site water purification systems, stringent quality controls, and meets the compliance standards required for international markets. Conducting a QA audit as early as possible in the selection process is highly recommended.
CDMOs in the EU and US are routinely inspected by their respective regulatory authorities, making them a more reliable choice for many clients. These facilities often have established quality systems in place, allowing sponsors to engage later in the process with greater confidence.
In Asia, CDMOs that have been inspected by the FDA are generally considered to be more reliable but are often more expensive. The FDA typically inspects sites only if they are named in a regulatory filing for a product intended for the US market. As a result, some facilities may be fully FDA-ready but have never been audited simply because no product has been submitted from that site.
CDMOs serving Big Pharma clients also tend to maintain higher reliability standards, having undergone thorough audits and quality reviews – but again, this comes at a premium. Big Pharma companies typically maintain one or two backup CDMOs to ensure supply chain continuity. Reliability is paramount: if a CDMO encounters a stockout, it can delay clinical trials and regulatory submissions to the FDA or EMA, potentially damaging the sponsor’s reputation and impacting overall timelines.
It is a balancing act
Choosing the right CDMO involves balancing cost, reliability, logistics, and regulatory requirements. While lower-cost regions like Asia offer advantages, they may require closer oversight. Ultimately, ensuring quality and supply chain reliability is key to avoiding delays and maintaining clinical and regulatory timelines.
Erik Gout, Venn’s Director of Chemistry, Manufacturing, and Controls(CMC). With 40 years of experience in the pharmaceutical industry, Erik worked as an analytical and pharmaceutical development scientist, CMC lead, and QA engineer. His CMC expertise spans drug development, technology transfers, GMP audits, and regulatory, making him a trusted and expert partner in due diligence and compliance. With a deep understanding of industry standards and best practices, Erik plays a crucial role at Venn to ensure the successful development and regulatory approval of pharmaceutical products.
Azra Gholami, Venn’s CMC Consultant, has over 11 years of experience in the pharmaceutical industry. With a PhD in Molecular Biology from Ghent University and a background as a pharmacist, she specialises in Quality-by-Design-based analytical method development and validation for both small and large molecules. Since joining Venn in 2022, she has focused on using her experience in process optimisation, technology transfers, and CMC documentation to ensure compliance and efficiency in drug development.
Biopharmaceutical companies often seek support in selecting a Contract Development & Manufacturing Organisation (CDMO) when they need to scale up drug product production – going from small sites to larger facilities – and do not have the capabilities in-house. Erik Gout, Director of Chemistry, Manufacturing, and Controls (CMC), and Azra Gholami, CMC Consultant, at Venn Life Sciences (“Venn”) share their expertise in helping a Japanese biotech company select a new CDMO partner.
Erik highlights the crucial role Venn has played in providing drug development consultancy, specifically CMC, from pre-Phase I to late-stage trials, and across multiple projects for a Japanese biotech client. “Over the many years we have worked with them, the scope of services we provided has expanded, to not only include CDMO selection and management, but also other CMC aspects and additionally non-clinical and clinical consultancy, making us the preferred provider.”
Venn’s collaboration with this client began when they were seeking a new CDMO partner to deliver larger quantities of their medicinal product for a clinical trial, underway in the US. “The client’s EU-based CDMO at the time had scale limitations and rising costs – a common challenge when scaling up from early-phase to clinical trials – and it was at this point that they sought Venn's expertise in CDMO selection.”
Erik explains, “We needed to ensure the new CDMO had the appropriate equipment for large-scale production, and this could be done cost-effectively while meeting the quality standards for the US and European markets.” Azra adds, “Adhering to the strict timelines for on-time delivery and avoiding any material shortages during a clinical trial is also crucial. A CDMO not only has to meet technical and quality requirements but also ensure smooth progression of clinical trials and overall project success.”
Venn used its expertise to assess and shortlist CDMOs. Erik elaborates, “After evaluating a long list of potential CDMOs by assessing the key inclusion criteria, we identified eight CDMOs – located in Europe, the US, India, and China – that aligned with the client’s project requirements. Those based in Europe were the most expensive whilst communication with the India-based company proved too challenging, leading to the elimination of four candidates. This left us with three CDMOs, two based in China and one in the US.”
The next step in the selection process involved the three companies responding to technical questions, provided to them by Venn prior to any meetings. During the individual meeting they introduced themselves and answered the queries. “We created a comprehensive checklist, based on the client’s requirements, categorising various topics as important, moderately important, and less so. This checklist was filled out by the client, me and Azra to ensure thorough evaluation. Our Japanese client strongly favoured moving manufacturing to China due to two main reasons; significant cost savings – provided that end supplies and filings would be approved in the US – and the small-time-zone difference between them and China compared with the US. Although it was thought that communication would be an issue, both Chinese CDMOs had management teams either based in or originated from the US, and they had awareness of Western standards for medicines and regulatory requirements. In this case, one CDMO was chosen, and the other was kept as a backup for risk management reasons.”
Seamless technology transfer from the CDMO in Europe to China required careful technical coordination of both the manufacturing and analytical methods. To ensure smooth transfer, Erik and Azra travelled with the client in 2022 to visit the two CDMOs in China and organised technical meetings. Erik explains, “We asked both CDMOs how they would manage the upscaling process, what type of equipment they planned to use, whether they had an escalation process in place for addressing serious issues, and if they had an established quality system.”
With his expertise in both CMC and quality assurance (QA), Erik also conducted a comprehensive QA audit of the preferred CDMO site to ensure the chosen CDMO met both technical and quality standards, laying a solid foundation for a successful partnership. Additionally, Venn’s regulatory team was heavily involved as the jurisdiction change meant that the project had to be documented to include China in the filing.
One of the most significant risks is the CDMO’s ability to meet the quality standards required for the US and European markets. “It’s no surprise that a CDMO may show you a high-quality facility, but the actual manufacturing takes place in an older, less-equipped facility without your knowledge. Whenever I visit a facility in a non-Western country, I carefully inspect the type of buildings nearby; if older buildings are on-site, there is potentially a higher risk, and activities should be closely monitored and managed.”
Azra emphasises that during the selection of the CDMO for this project, she carefully considered the significant challenges associated with the analytical work. “One of the reasons for traveling to China was to familiarise the CDMO with the methods that were being developed and used at the European CDMO. I met with the employees in person and trained them on analytical testing, troubleshooting, and processing specifically for this project. As the work progressed, it quickly became apparent that the trained employees had been reassigned to other projects. Working with new employees and encountering communication issues due to the point of contact not speaking English led us to initially escalate the matter to the client, who then escalated the issue to higher management at the CDMO. Our involvement and experience in effectively overcoming such communication breakdowns, by immediate recognising and escalating the issue, provided the client with the necessary information so they could request a reinstatement of the originally trained employees, and thereby resolving the issue to their satisfaction.”
Despite these unforeseen challenges, the CDMO filing was approved by the US FDA and the materials produced are now being supplied for the clinical trial in the US. There have since been no issues with the CDMO operations and Venn continues to manage them smoothly.
Venn Life Sciences successfully guided a Japanese biotech company for CDMO selection and technology transfer – from Europe to China – and continue to support them manage the chosen CDMO while offering guidance on the ever-changing regulatory landscape. This demonstrates Venn’s expertise not only in CMC but also on a broader drug consultancy level with the ability to tailor the strategy on a case-by-case basis, depending on the development stages and product lifecycle, to enhance the overall value delivered to clients.
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Erik brings over 35 years of experience in the pharmaceutical industry as an analytical and pharmaceutical development scientist, CMC lead, and QA engineer. His CMC expertise spans drug development, technology transfers, GMP audits, and regulatory, making him a trusted and expert partner in due diligence and compliance. With a deep understanding of industry standards and best practices, Erik plays a crucial role at Venn to ensure the successful development and regulatory approval of pharmaceutical products.
Azra has over 11 years of experience in the pharmaceutical industry. With a PhD in Molecular Biology from Ghent University and a background as a pharmacist, she specialises in Quality-by-Design-based analytical method development and validation for both small and large molecules. Since joining Venn in 2022, she has focused on using her experience in process optimisation, technology transfers and CMC documentation to ensure compliance and efficiency in drug development.
An article by Clinical & Translational Science on the American Society for Clinical Pharmacology & Therapeutics.
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