The technology transfer of a manufacturing process to a contract development and manufacturing organization (CDMO) is a key step on the road to developing and commercializing biopharmaceutical products. Successfully executing this step is critical to clearing regulatory expectations, avoiding production delays, and delivering drugs to the market. On the other hand, a failed process technology transfer can lead to problems such as:
- Delays in starting the first manufacturing batch, due to missing or incorrect process information or unclear roles and responsibilities of the sending team
- Unexpected results during execution of the first manufacturing campaign, which can delay product release due to the time required to troubleshoot the issue and (if needed) rework the process flow and manufacturing documentation
- Unexpected regulator feedback during review of the chemistry, manufacturing, and controls (CMC) section of regulatory filings, which can lead to delays in clinical trials or commercial launch
Premier Consulting has significant experience with process technology transfers, including those for unique product modalities and under tight timelines. In this post, we’ll identify and explain some of the key steps you can take to help ensure a successful process technology transfer to help drive clinical and commercial success.
Generate a process description document
First, we recommend that a “process description” document be generated and internally reviewed prior to the start of the process technology transfer. This document, which should be shared with a receiving CDMO after appropriate nondisclosure agreements have been signed, helps ensure that the CDMO has a clear understanding of the process as operated and designed by the sponsor. It should include information such as:
- A list of all raw materials used, along with the amounts needed and acceptable manufacturers
- A list of all consumables (e.g., single-use components) used in the process by the sponsor
- Detailed descriptions of all process steps, including all process input parameters (such as temperatures, pressures, pHs, mixing speeds, etc.) and historical output parameters/acceptance criteria—This should also include references to all analytical methods used by the sponsor in the process.
Depending on the phase of the development lifecycle, the items listed above may not be fully known. In those cases, documenting the current process description is still extremely valuable, as it can be changed as the sponsor’s understanding of the process matures. This method also allows a historical record of past processes to be created, which can be very helpful in generating eventual regulatory filing documentation.
Develop a change management plan
Second, we recommend that a sponsor develop and follow a documented plan to manage process changes during the process life cycle. Regulatory bodies generally expect sponsors to exercise strong technical oversight of the manufacturing processes for their products, regardless of whether the product is manufactured at sponsor-owned facilities or CDMOs. The development of a written and pre-approved change management plan is a critical part of exercising these sponsor-owned technical oversight responsibilities.
Minor process changes are almost always needed to fit an existing process to a new CDMO. Examples of typical changes include:
- Equipment size. Often one of the key goals of a process technology transfer is to achieve a larger process batch size, in order to create sufficient material supply for later phases. This typically drives the need for larger reaction vessels, larger solution preparation vessels, and the like. Of course, the use of larger equipment can raise technical questions around mixing, heat transfer, and (for biological processes) oxygen saturation that need to be assessed for process fit.
- Raw material suppliers. CDMOs will often have established business relationships with large raw material suppliers, and often they stock bulk quantities of commonly-used raw materials to support uninterrupted material production for their clients. Using these materials can potentially drive cost savings and lower time-to-market for sponsors. However, the suppliers used by the CDMOs may differ from those used by the sponsor. Even in cases where the CDMO’s material suppliers match those of the sponsor, the grade of the stocked materials may be different from those used or planned for use by the sponsor.
- Single-use consumable designs. As with raw materials, CDMOs often have standard platforms of single-use equipment designs to reduce inventory costs, risks of operational errors during manufacturing, and overall per-batch costs to their clients. However, these components are likely to differ – potentially significantly – from those used by a sponsor on prior campaigns.
The plan should list out the risk-based framework for managing changes and identify a sponsor’s various roles in assessing process changes (i.e., groups such as technical operations, regulatory affairs, and quality assurance). Finally, but most importantly, the document should explain how the change assessments will be documented and tracked across the process life cycle.
Prior to starting a process technology transfer, it is helpful to understand (as much as possible) the importance of each item in the process description as it concerns safety, potency, purity, and efficacy. This can be established by executing a risk assessment of the sponsor’s process, using a quality target product profile to establish the critical quality attributes and the sponsor’s level of understanding from past campaigns as a starting point. A robust comparability strategy may also be needed to justify the similarity of the new process-derived drug substance or product to the material used in nonclinical and previous clinical studies.
The criticality level established during the risk assessment can then be used to identify the level and types of supporting data needed to justify the process changes proposed by the CDMO. This can also help identify and address process risks prior to the execution of a small-scale manufacturing batch at the CDMO, which helps further reduce process and scheduling risks.
Acquire raw materials and components early
Finally, sponsors should prioritize identifying and procuring long-lead raw materials and components early in the process technology transfer process. Supply chain constraints are endemic for many goods in the post-COVID era, and this has impacted the pharmaceutical manufacturing industry as well. Delays in receiving even relatively common materials are not unusual and can easily lead to significant delays in manufacturing. Sponsors should never assume that “readily available” components can be easily obtained. Instead, early identification and procurement of long-lead materials can make a significant impact on the manufacturing start date for a development program.
Premier Consulting has significant experience in process technology transfer of both small molecule APIs and biotherapeutics, including both drug substance and drug product manufacturing. Contact us today to see if partnering with Premier Consulting is right for you!