Your Next Tech Transfer Should Include These Modern Tools

By Sagi Nahum, MsC, Ph.D., senior director, analytical sciences and CMC, Cell and Gene Therapies, Orgenesis

Technology transfer is a crucial process in the pharmaceutical industry, involving the exchange of knowledge, expertise, manufacturing, and analytical capabilities from one stage to another or from one site to another to ensure the smooth transition of medicinal product manufacturing and testing. Tech transfer is essential for maintaining product quality, safety, and efficacy and is a key pillar of pharmaceutical manufacturing.

However, the technology transfer of cell and gene therapy products differs significantly from traditional methods because of the unique nature of these products and their complex manufacturing processes. This article discusses the relatively new technological tools for technology transfer between sponsors and decentralized manufacturing sites or CDMOs, including electronic batch records (EBRs), laboratory information management systems (LIMS), automated monitoring, analytics, and process optimization tools.

The complexity of cell and gene therapy product manufacturing starts with the variability of the main starting materials (such as cells and tissues) and reagents. For all other reagents and materials, sponsors and receiving units, including centralized and decentralized manufacturing organizations, must source GMP-grade or pharmacopeial-grade products from reliable suppliers for the technology transfer process to be successful.

Additionally, all products should be manufactured and tested according to applicable standards, with compliance to USP Section <1043> typically required for manufacturers and developers of cell, gene, and tissue-engineered products to meet regulatory requirements and obtain approvals for their products.

Analytical method validation and comparability studies are also essential for technology transfer, as variability in analytical methods can arise from multiple sources, including differences in sample matrix composition, performance and calibration of instrumentation, quality and performance of reagents, analyst performance, method parameters, and reference standards. These differences in analytical methods can impact the comparability and consistency of results, especially for critical quality attribute measurements. Therefore, it is crucial to conduct robust analytical method validation and comparability studies to ensure that the methods used by both parties are aligned and reliable. In addition, quality by design can help reduce final product variability and support efficient technology transfer processes within and between sites. Validation of analytical procedures can also support efficient technology transfer by guiding standardization of analytical procedures, robustness testing, development of method transfer protocols, demonstration of equivalency, and ensuring regulatory compliance.

Tech Transfer Is A Herculean Document-Sharing Effort

Traditional approaches to technology transfer process for cell and gene therapy can be complex and time-consuming, requiring various documents to be completed and transferred between the two parties. The transfer of technology from one organization to receiving units involves extensive documentation to ensure compliance with regulatory requirements, such as:

• standard operating procedures
• batch records
• process development reports
• analytical methods
• specifications
• sampling plans
• material transfer agreements
• regulatory documentation
• training records
• change control
• deviation reports

On the other hand, to ensure the quality and safety of the product and to evaluate the success of the tech transfer process, the manufacturer must provide critical documentation and information back to the sponsor. This documentation may include:

• deviation reports
• process performance data
• process improvement suggestions
• documentation updates
• training records

Once the receiving unit has received the technology transfer documents, they typically study them thoroughly to ensure they have a complete understanding of the manufacturing process and associated quality control procedures. The receiving unit typically uses these documents to conduct a gap analysis to identify any potential differences between their existing processes and those documented in the transfer documents and will then develop a plan to address any gaps identified. Fixing the gaps may include modifications to existing procedures, staff training, or new equipment or materials.

Batch Records Play An Outsize Role In Standardizing Processes

Dynamic documents such as batch records are essential in manufacturing processes as they encompass vital data that affect the entire production journey. Analytical method worksheets and working instructions can generate substantial amounts of data for functional/potency assays, which involve multiple stages like cell culture, cell counting, flow cytometry, and cytokine secretion.

These live documents are instrumental in recording critical information throughout the manufacturing process, ensuring accurate and comprehensive documentation of each stage. Many companies have implemented a variety of data collection, documentation, and data tracking/trending technologies to efficiently control and manage the vast amount of information and inherent variability associated with their products. These technologies include EBRs and LIMS, which ensure data integrity and compliance by providing secure, traceable, and auditable records. They also enable real-time data tracking and reduce the risk of errors.

Moreover, EBRs and LIMS facilitate standardization and automation of processes, leading to improved efficiency and reduced variability. They also enhance collaboration and communication among stakeholders involved in technology transfer. Other companies have taken it to the next level, combining AI systems, sensors, and machine learning that can significantly aid in the tech transfer of cell and gene therapy products.

Case Study: Careful Planning Leads To A Seamless Tech Transfer

A case study that illustrates this process is the technology transfer of a CAR T cell therapy product between a research institution and a hospital-based manufacturing facility. In this case, the manufacturing facility received technology transfer documents from the sponsor company, including process development reports, analytical methods, and batch records.

The receiving unit conducted a thorough review of the documents upon receiving them to identify any gaps between their existing processes and those documented in the transfer documents. They identified several areas for improvement, including modifications to existing procedures to ensure consistency with the transfer documents. The transfer unit specified a flow cytometry analysis that must be performed on some in-process samples. The test results had to be received in the manufacturing suite in less than one hour so the team could proceed to the next step in the process.

To make the recommended improvements and meet the tight time requirements, the manufacturer changed several local procedures, added staff and more training on new equipment and analytical methods. The receiving unit developed a comprehensive plan to address these gaps, which includes developing new SOPs and providing extensive training to staff on new equipment and analytical methods. The plan was then implemented, and the manufacturing process was successfully transferred to the receiving unit. Throughout the process, close communication and collaboration between the sending and receiving units were essential to ensure a successful technology transfer. Additionally, the regulatory requirements for the product were carefully considered and followed to ensure that the transfer was compliant with all applicable regulations.

Here's How Artificial Intelligence Already Streamlines Some Tech Transfer Processes

Real-time monitoring and process control through sensors and AI algorithms can ensure consistent and accurate execution of transferred processes. Machine learning, predictive analytics, and process optimization can identify patterns and optimize process parameters for improved efficiency and product quality. Some AI/ML tools are already implemented in cutting-edge technologies for cell and gene manufacturing units and bioreactors.¹ Quality control and defect detection can be enhanced through AI systems, reducing the risk of product failures or rejections. Data integration and knowledge management using AI can streamline the transfer process and accelerate learning at the receiving site. Risk assessment and decision support through AI can minimize risks and ensure compliance with regulatory requirements during tech transfer.

Automated devices, such as automated flow cytometry, in-process cell counting, and other automated measurements, such as pH and dissolved oxygen sensors, glucose, and lactate analyzers, can significantly contribute to better cell and gene therapy tech transfer. These devices help reduce analyst-to-analyst variation by providing standardized and consistent measurements, eliminating subjective interpretations, and reducing human error. This ensures that the data generated during tech transfer is reliable and reproducible, allowing for better comparability of results between different sites. Additionally, automated devices are often user-friendly, with intuitive interfaces and easy-to-follow protocols, which shortens training time for operators. This makes training new personnel easier during tech transfer, ensuring consistent operation and reducing variability due to different operator skills.

Tech Transfer Is More Than Information and Equipment —It’s People, Too

In addition, sponsors and receiving units must ensure that the transfer is done promptly, with the receiving site equipped with the necessary resources and personnel to replicate the process successfully. Timely technology transfer is essential to ensure the product reaches the market on time and complies with regulatory requirements.² Furthermore, it is important to consider the economic aspects of technology transfer, as the costs associated with transferring technology from one site to another can be significant. Sponsors and receiving units should carefully evaluate the costs and benefits of technology transfer and ensure the process is done cost-effectively and efficiently.

The transfer of technology also involves personnel.³ It is important to ensure that the personnel involved have the necessary skills and expertise to transfer the technology successfully. This includes training personnel on the new processes and systems, providing them with the necessary tools and resources, and ensuring they are properly trained on the transferred technology. Moreover, personnel must be aware of the risks associated with technology transfer and take the necessary steps to mitigate these risks.

Finally, sponsors and receiving units should ensure that the transferring and receiving sites comply with the regulatory requirements. This includes ensuring that the transferring site complies with GMP and other applicable regulations and that the receiving site has the necessary documentation and personnel to implement the new processes and systems. Furthermore, sponsors and receiving units should ensure that any changes to the process or systems are documented, with the changes and their impact on the product quality, safety, and efficacy assessed.⁴

Conclusion

Overall, technology transfer is a critical process in the biopharmaceutical industry that plays a pivotal role in the successful development and commercialization of novel therapies. New and best practices for technology transfer between sponsors and receiving units include using dynamic documents such as batch records, data collection technologies like EBRs and LIMS systems, and integrating AI systems, sensors, and machine learning. Furthermore, sponsors and receiving units need to ensure that the transfer is done in a timely, cost-effective, and compliant manner, with personnel properly trained on the technology being transferred. Following these best practices can ensure that technology transfer is successful and can help to ensure product quality, safety, and efficacy.

Integrating AI systems, sensors, and machine learning can significantly aid in the tech transfer of cell and gene therapy products, enabling real-time monitoring, predictive analytics, process optimization, and decision support. Automated devices also enhance the comparability of results and reduce variability, thus contributing to the successful transfer of cell and gene therapy processes from one site to another.⁵

The biopharmaceutical industry must embrace innovative technologies to streamline and optimize the technology transfer, ensuring product quality, safety, and efficacy.

References

1. Moutsatsou, P., Ochs, J., Schmitt, R.H. et al. Automation in cell and gene therapy manufacturing: from past to future. Biotechnol Lett 41, 1245–1253 (2019). https://doi.org/10.1007/s10529-019-02732-z
2. Unites States Pharmacopeia (USP) Section <1043> Ancillary Materials for Cell, Gene, and Tissue-Engineered Products,
3. Silverman, L.I., Flanagan, F., Rodriguez-Granrose, D. et al. Identifying and Managing Sources of Variability in Cell Therapy Manufacturing and Clinical Trials. Regen. Eng. Transl. Med. 5, 354–361 (2019). https://doi.org/10.1007/s40883-019-00129-y
4. ICH Q2(1): Validation of Analytical Procedures. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use: Geneva, Switzerland, 1994
5. USP <1224> Transfer of Analytical Procedures. USP–NF. US Pharmacopeial Convention: Rockville, MD

About the Author:

Sagi Nahum holds a Ph.D. in medical science focused on genetics and immunology from the Faculty of Medicine at the Technion Institute in Israel. With over a decade of experience in the biotechnology industry, Nahum is an expert in developing innovative cell and gene therapy products. He currently leads global analytical sciences and CMC activities at Orgenesis in Maryland, where he focuses on innovative manufacturing and analytical solutions for cell and gene therapies in a point-of-care setting, as well as decentralized manufacturing of cutting-edge cell and gene therapy products. Before joining Orgenesis, he led the Innovation Lab at Cognate Bioservices, where he developed and validated high-throughput capable assays. He is a member of the ISO Technical Committee 276 Biotechnology and has authored and collaborated on several articles in the fields of plant and human genetics, as well as biological assay development and transfer.