Preparing an Internationally Developed Therapy for Late-stage U.S. Trials

Bringing an internationally developed drug product into a new site and market requires aligning local manufacturing, regulatory filings, and clinical data, with U.S. standards. Key processes involve Chemistry, Manufacturing, and Controls (CMC), scale-up, and addressing supply chain logistics.

Onconic Therapeutics, a Korea-based biopharmaceutical company, recently selected Bora Pharmaceuticals as its manufacturing partner to support the U.S. clinical development of JAQBO, an oral P-CAB treatment for GERD (chronic acid reflux) that’s approved and marketed in Korea. 

Under the agreement, Bora’s newest OSD facility in Maple Grove, MN, will also support quality control, stability testing, and the preparation of related chemistry, manufacturing, and controls documentation for Onconic’s planned U.S. Phase 3 clinical trial of JAQBO.

Helen Clark, Global Head of MSAT at Bora Pharmaceuticals, shares insight on processes for regulatory alignment and compliance, the capabilities needed for tech transfer and scale-up, and managing quality and analytical validation to support late-stage trials in the U.S.

Contract Pharma: What is your process for regulatory alignment and compliance?

Helen Clark: When bringing an internationally developed product into a new site and market, the first step is understanding what has already been established and how that aligns with the requirements of the target market. We work closely with the client to understand the existing filing, manufacturing process, product specifications, and supporting data, then identify any gaps that need to be addressed as the program transfers to the new site.

From there, regulatory, quality, and manufacturing teams need to stay closely connected throughout the transfer. Compliance is not something that is addressed at the end of the process. It must be built into how the product is manufactured, tested, and documented from the beginning. Bora is taking this approach with JAQBO as Onconic prepares the product for planned U.S. Phase 3 development after being commercially available in Korea. For a late-stage program, that also means making sure the manufacturing and analytical work generates the appropriate CMC and stability information needed to support the next phase of clinical development. 

Contract Pharma: What capabilities are needed for tech transfer and process scale-up?

Helen Clark: Successful tech transfer starts with process knowledge. Before moving a product into a new facility, the receiving team needs to understand how the process was developed, which parameters are critical to product quality, and where variability could affect the finished product. From there, process engineering teams can conduct a gap assessment to determine how the existing process translates to the new site and what may need to be adapted. This also includes a failure modes assessment to proactively look at potential issues with the transfer.

Scale-up expertise is equally important because a process that performs well at one scale does not automatically behave the same way at another. The equipment must be appropriate for the product and capable of achieving the same critical quality attributes at the intended scale. For an oral solid dose product, that may involve capabilities across granulation, blending, compression, coating, and packaging. Analytics can also help the team to evaluate the product throughout the transfer. 

The goal is not just to reproduce the process on different equipment, but to understand the science behind the process well enough to transfer and scale it while maintaining consistent product quality.

Contract Pharma: How do you manage quality and analytical validation?

Helen Clark: One of the first questions is whether the analytical methods arriving at the receiving site have already been validated and are suitable for transfer, or whether additional method development or validation is required. With a new market involved, is there any additional market specific testing needed for raw materials or the finished product.  If validation is needed, the analytical team evaluates parameters such as specificity, accuracy, precision, linearity, range, detection and quantitation limits, and robustness to demonstrate that the method performs reliably for its intended use.

That analytical work also must connect back to the broader quality strategy for the product and the CQAs. Everything must remain aligned as the program moves between sites and into late-stage development. The objective is to establish confidence that both the manufacturing process and the methods used to evaluate the product can consistently generate reliable data. 

Contract Pharma: How are supply chain logistics handled?

Helen Clark: For an internationally developed therapy, the CDMO and sponsor need a clear understanding of where raw materials and components are coming from, expected lead times, inventory requirements, and any import/export requirements that could affect the program. In addition, is there an opportunity to change any of the raw materials to a locally sourced alternative. 

That requires strong forecasting and inventory management. Connecting with qualified suppliers and reliable logistics partners help with end-to-end traceability. Depending on the product, it can also include cold-chain requirements. Other considerations include clinical packaging and labeling, as well as contingency planning for materials or transportation routes that could become constrained. Depending on the potential volume of the product, dual sourcing of key raw materials or components is considered.

Communication across this entire network is critical. The sponsor, CDMO, suppliers, and logistics partners need to agree early on responsibilities and timelines. By late-stage development, relatively small disruptions can have significant consequences for manufacturing schedules or clinical supply, so the objective is to identify these risks early to prevent them from impacting the trial.