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.
