Tech Transfer in the New World of New Modalities

Emerging therapies and new modalities, such as cell and gene therapies (CGTs), have developed fast in the past decade. This ever-evolving development of not only new formulations but also new delivery methods has created an ever-complicated industry. Technology transfer is a critical step in drug manufacturing, specifically when contract manufacturers are involved.

According to Hewitt, et al. an efficient technology process ensures transferrable processes. “A well-defined and robust technology transfer process involves a systematic approach to transferring manufacturing processes, protocols, and knowledge from the research and development phase to the clinical and potentially commercial manufacturing setting” (1). “This process ensures the developed cell and/or gene therapy can be produced consistently, efficiently, and in compliance with regulatory requirements. The same requirements exist for transferring analytical methods to contract development and manufacturing organizations (CDMOs) or equivalent” (1).

“Tech transfer becomes more complex with emerging therapies and new modalities, particularly in method transfer, as these therapies are often derived from living cells, making consistency challenging to maintain,” says Satish Shetty, senior director, Product Development & Project Management, Halo Pharma (part of the Noramco Group). “Additionally, the manufacturing processes are highly intricate and rely on specific environmental and process conditions, which further complicates the transfer.”

Ahmed Youssef, senior manager USP, Process Development at Ascend, points to timing as being key for technology transfer with emerging therapies. “It takes an innovator around 12 to 24 months to make a product ready, tech transfer it, [and] complete the safety studies for it,” says Youssef. “But there could be other solutions that could be offered in the background that could make this more efficient, faster, and more attractive to product developers.”

Planning for technology transfer is essential, according to Hewitt et al. A smooth transfer requires careful evaluation, strategic decision making, and planning (1). Risk assessments are also crucial at this stage. “By proactively addressing these risks and implementing mitigation strategies during the initial assessment and planning stage, organizations can enhance the efficiency, reliability, and safety of the transfers” (1).

“A continuous feedback loop also encourages ongoing learning, incorporating insights from manufacturing teams into refining protocols. Regulatory alignment ensures compliance and adherence to guidelines. In essence, successful knowledge transfer ensures that the innovation harnessed in research is translated effectively, leading to consistent, high-quality outcomes in CGT manufacturing and accelerating the availability of transformative treatments to patients in need” (1).

Patient-centric therapies

Patient-centric therapies that might require small-batch manufacturing require flexible approaches to technology transfer, according to Andréa Simard, manager, Technical Services, Halo Pharma (part of the Noramco Group). This is particularly true for CDMOs that usually perform large-scale manufacturing. “Equipment train must be adjustable, and in-process control strategies should ensure process capability while meeting clinical or commercial needs,” Simard says. “Quality must be designed into the product through good knowledge of input materials and a robust manufacturing process, so that endpoint confirmation does not require extensive sampling and testing, which can greatly reduce the units available for the patients.”

However, Youssef remarks that tech transfer is a similar process no matter what batch size is involved. “Normally, when you tech transfer, you need to take risk-based approaches [and] appropriate measures to be able to tech transfer [a] process successfully and properly,” he says.

Brianna Kempfer, project manager at Sterling Pharma Solutions agrees. “The process of tech transfer is much the same, no matter the scale; a CDMO must evaluate the information provided: assessing any potential hazards, the scientific feasibility, and qualify the necessary synthetic and analytical methods. Through laboratory scale work, chemistry can be optimised and demonstrated to understand which parameters of the process are the most critical when scaling up and manufacturing.”

The smaller scale of patient-centric medicine production offers options for process development such as reagent and solvent choice, according to Kempfer. “Because of the smaller volumes of manufacturing, the costs of goods are usually higher, and so development of an efficient process that minimiszs potential losses in purification and isolation steps is crucial.”

One must understand technologies involved in formulation, as well, stresses Simard. “For example, formulation must consider patient-specific factors such as taste masking for bitter drugs or ease of administration for pediatric and geriatric populations,” she says. “Additionally, specialty packaging plays a crucial role in simplifying complex dosing regimens, making it easier for patients to adhere to treatment plans.”

End-to-end providers

Many bio/pharma outsourcing organizations have been moving to become full-service, end-to-end CDMOs. But does working with a contractor who offers services from every step of a drug’s lifecycle improve technology transfer. It depends, asserts Youssef. “If you mean by end to end, the whole process, from the start of plasmid manufacturing till commercial manufacturing of the batches and then the fill and finish and release, understand that the advantage would be that you're running all of that under one MSA [master supply agreement], one big MSA. But know that, not all CDMOs are expert and skilled in each unit operation when they offer the end-to-end process,” says Youssef.

Shetty points out that there are several reasons why tech transfer may be less complicated with an end-to-end service provider. “[A] unified sending unit (SU) and receiving unit (RU) enable seamless knowledge transfer. Tech transfers are often complicated by development knowledge getting lost through site transfers, and delays from having to set up project logistics at a new CDMO, so having both teams in the same organization is a solid advantage.”

End-to-end service providers often provide consistency in the equipment used between the different phases of development and manufacture, notes Shetty. There is also often the same project manager and core team involved, as well as the same excipient grades and reduced supply lead times. End-to-end providers also feature “fewer knowledge gaps and better identification of potential scale-up issues,” according to Shetty. “Consolidating R&D and supply chain expertise minimizes logistical delays and fosters smoother transitions, troubleshooting, and overall customer experience,” Shetty concludes.

“When scaling up between clinical phases and commercial launch, it is common for a process to move between sites, and potentially between countries, within an end-to-end provider, so this results in the need for a tech transfer. Whether this is an internal or external transfer, there is little difference in the process that needs to be undertaken,” says Kempfer.

Working together

When it comes to sponsors and contract organizations working together to ensure a secure tech transfer, Youssef specifies that the CDMO should shoulder the responsibility. “A good CDMO [should] have structured communication, because communication is key … when you're talking to your business partner. We always build that in a more collaborative environment,” says Youssef. “[A CDMO needs] to protect the IP [intellectual property] rights of their clients, their partners, as well as good documentation practices, in addition to a solid IT department. All of that gives the assurance to the security of the data and the security of the transfer information between the CDMO and their partner.”

Simard stresses that communication is key for secure tech transfer. “The first step is to define success criteria and core values, ensuring both parties have a mutual understanding of each other's capabilities, limitations, and the project's critical milestones. When issues arise, they should be treated with speed and transparency in an atmosphere fostering collaboration rather than finger-pointing, so that solutions and a path forward may be found as a team,” Simard says.

Expectations, milestones, goals, and needed processes should be communicated and understood, says Kempfer. “The more information that can be shared at the start will reduce the potential of unexpected problems; however, having a transparent relationship between parties, where communication is open will allow progress to be monitored, and any issues that do arise to be shared and understood as quickly as possible. Having a key point of contact within the CDMO who can liaise with all of the key members of the project team across multiple disciplines, allows a customer to gain direct access to progress and ensure that communication is as efficient as possible,” Kempfer states.

Trust and transparency should be established, confirms Shetty. Differences in facilities and excipients should be understood, and process documentation should be simplified. “[One should] ensure regular communication between subject matter experts, rather than relying solely on project managers,” Shetty summarizes. “[Sponsors and contractors should] proactively work as a team to identify and resolve potential issues [and] focus on a common goal that benefits both parties.”

Reference

1. Hewitt, M.; Bellot, L.; Anderson, C. Best Practice Tech Transfer Methods for CGTs. BioPharm International 2023 36 (11) pp. 30–33.