Transforming Molecules into Medicines: Role of CDMOS in Phase-Appropriate Technology Transfers in Advancing Pharmaceutical Innovation ()
1. Introduction
Technology transfer is crucial for effectively sharing and disseminating knowledge, skills, and technologies across individuals, organizations, and countries. Technology transfer is vital in enabling innovation and accelerating the development of new products and processes, particularly in the rapidly evolving fields of science and technology [1] . By facilitating the transfer of knowledge and expertise, technology transfer enables organizations to build on the successes of others and avoid repeating past mistakes. This can lead to more efficient and cost-effective development processes and more significant overall progress in the field [2] . ICH Q10 guidelines state that the overarching objective of technology transfer activities is to facilitate the seamless transmission of knowledge about product and process information from the development stage to manufacturing and within or between manufacturing facilities to achieve product realization [3] . This critical knowledge is the foundation for the manufacturing process’s essential components, including control strategy, process validation approach, and continual improvement efforts (Figure 1). Each phase of drug product development requires specific criteria related to technology transfer activity to ensure that the transfer of knowledge, expertise, and technologies is effective and supports the overall success of the development process.
The technology transfer process is a two-way conduit between research and development and operations and between external pharmaceutical companies and contract development and manufacturing organizations (CDMOs). Technology transfer requires a seamless flow of information from the research and development phase to operations. CDMOs have always been into strategic limitations for any substantial changes to the existing process shared by the client and to the manufacturing infrastructure of CDMOs to accommodate each new cycle. This two-way approach increases awareness of design for manufacturability among development laboratories. Manufacturing teams should adapt to new technologies and integrate with development teams to transform from the conventional approach. The success of technology transfer hinges on creating a balanced partnership among research, development, and operations that fosters effective communication and mutual agreement between the sending and receiving units.
2. Regulatory Guidance about Technology Transfers for Drug Substances for NDAs and Preclinical Studies
The U.S. Food and Drug Administration (FDA) has published several guidance documents that provide recommendations on the tech transfer process for drug substances used in new drug applications (NDAs) and preclinical studies. These guidance documents are intended to help ensure that the tech transfer process is well-planned and executed and that the resulting drug substance is high quality and meets all regulatory requirements. Q7A Good Manufacturing Practice for Active Pharmaceutical Ingredients (APIs) guidance document provides recommendations for manufacturing APIs’ GMP requirements [4] . Q5C Quality by Design for Active Pharmaceutical Ingredients (APIs) guidance document provides quality by design (QbD) principles in developing and manufacturing APIs [5] . ICH Q9 Quality Risk Management guidance document recommends applying quality risk management (QRM) to pharmaceutical development and manufacturing [6] . ICH Q10 Pharmaceutical Quality System guidance document recommends implementing a pharmaceutical quality system. In addition to these guidance documents, the FDA also has several other resources available on its website that can be helpful for companies that are planning or executing a tech transfer for a drug substance. These resources include Companies planning or executing a tech transfer for a drug substance that should carefully review the FDA’s guidance documents and other resources to ensure they comply with all applicable regulations.
3. Overview of Technology Transfer between CDMOs & Innovator Biotechs
Technology transfers play a critical role in the life cycle of a molecule, occurring at various stages (Figure 1). When operating as a CDMO, initial technology transfer arises from a Process Development team from the innovator company to the CDMO. It is crucial to effectively communicate process information in a structured manner and collect detailed information; identifying gaps in the original development process provides insights to avoid unforeseen challenges during bench-scale confirmation or process scale-up. Standardized checklists, templates, and risk assessments are crucial for a successful technology transfer. This enables effective communication of critical process information between the innovator company and the CDMOs [7] , particularly during the transfer from Process Development to clinical operations across different sites. Before this transfer and scale-up, the work in the development laboratories of CDMOs is complete, which can vary from developing a new process to confirming a client’s process using appropriate scale-down models. At this juncture, the development laboratory transitions from the process move from Process Development to manufacturing for clinical production. Following clinical manufacturing, knowledge transfer can occur back to PD, typically for process characterization studies at the bench scale before process performance qualification (PPQ) batches and other process validation activities [8] .
The primary focus of the technology transfer approach revolves around final Manufacturing. This involves ensuring the product design is optimized for efficient and cost-effective manufacturing, maximizing its potential for commercial success. By embracing a design for manufacturability strategy, stakeholders can
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Figure 1. Overview of the technology transfer between CDMOs and Biotechs.
streamline the transfer process, identify potential roadblocks, and address them proactively. This, in turn, can significantly enhance the overall efficiency and effectiveness of the technology transfer process. The first step is to build a shared understanding of each manufacturing site’s capabilities, including equipment, raw materials, consumables, and expectations regarding buffer and media preparation. One should never assume that process developers have intimate knowledge of the equipment used in manufacturing if it is not made available, especially in cases where the manufacturing or research and development is newly integrated. This knowledge is critical because CDMOs cannot redesign a facility for every new molecule. Therefore, the development organization should have an intimate understanding of the receiving site’s capabilities, enabling the development of a seamless process that can scale up seamlessly and efficiently. As shown in Figure 2, the technology transfer process involves numerous back-and-forth exchanges between process development, process validation batches, and commercial manufacturing [9] .
Documentation is the utmost critical phase during the tech technology transfer. Each site has its documentation expectations, standard operating procedures (SOPs), and policies related to technology transfer. Although the transfer documents may seem similar, it is essential to have clarity regarding precise roles and responsibilities. This includes expectations for document approvals, in-process filter sizing responsibilities, and ownership of downstream process sizing. Limiting the number of new raw material introductions and buffer transfers can also streamline the process of technology transfer and new product introduction, ultimately saving valuable time and effort.
4. Types of Technology Transfers
Pharmaceutical organizations often seek technology transfer to CDMOs at various stages of drug development. Biotech companies rely on CDMOs to transform their assumptions and technology into reality by manufacturing the required materials. This process involves a one-sided technology transfer, whereby the technical expertise and knowledge of the biotech companies are transferred from their assumptions into reality. In drug development, biotech companies
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Figure 2. Technology transfer cycle from process development to commercial manufacturing.
with small-scale capabilities often develop the initial technology in-house and then transfer it to CDMOs to scale up and move to the next level. In some cases, technology transfer from one CDMO to another may be necessary due to limitations in technical capability, GMP preparedness, or other factors related to potency, finances, or timelines [10] .
In some instances, biotech companies may utilize CDMOs as alternate vendors or to increase their manufacturing capacity. This may also be driven by their company’s risk mitigation policies to sustain the molecule in the market. By engaging with CDMOs, biotech companies can access additional manufacturing capabilities and expertise, allowing them to scale up their production and ensure a reliable supply of the drug product. This can be particularly useful for molecules with high market demand or those needing rapid production to meet urgent patient needs. Moreover, utilizing CDMOs as alternate vendors can provide biotech companies with flexibility in their supply chain management. This can help mitigate production and supply disruptions risks, ultimately ensuring a more reliable drug product supply to patients (Figure 3).
4.1. Preclinical Stage Technology Transfer
Preclinical trials are conducted before testing new drugs or treatments in humans, typically using animals like mice or rats. These trials are crucial in identifying potential safety risks and gauging the efficacy of drugs. In vitro studies are conducted in laboratory settings with human cells or tissues, animal studies involve administering drugs to animals, and computational studies use computer models to predict a drug’s behavior. Preclinical trials help ensure the safety and effectiveness of the new drug. The technology transfer for the preclinical batch technically comes from Biotech’s technical expertise. Developing materials for preclinical batches is a complex and multi-step process requiring close collaboration between CDMOs and biotech companies. The process involves several key steps, including identifying the desired properties of the material, developing a manufacturing process, scaling up the process, and characterizing the material. Identifying the selected properties is the first step, and the manufacturing process is developed based on those properties. Scaling up the process requires careful control of the manufacturing parameters to ensure that the material meets the desired specifications. Characterization is the final step and involves
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Figure 3. Technology transfer cycle from preclinical to commercial stage.
various tests to confirm that the material meets the desired specifications and is safe for use in preclinical studies. Working together, CDMOs and biotech companies can develop high-quality materials essential for preclinical studies’ success [11] .
4.2. Preclinical to Phase-1 Technology Transfer
Once favorable preclinical results are obtained, Biotech companies move forward with Phase-1 material. Phase 1 studies are the initial step in testing new drugs in humans. Typically conducted on 20 to 80 healthy volunteers, these studies are designed to assess the drug’s safety. The primary objective of a Phase 1 study is to determine the drug’s maximum tolerated dose (MTD), which is the highest dose that can be safely administered to humans. To determine the MTD, researchers gradually increase the drug dose while closely monitoring the volunteers for side effects until they find a dose that causes unacceptable side effects in some of the volunteers. Aside from determining the MTD, Phase 1 studies also provide information on how the drug is absorbed, distributed, metabolized, and excreted by the body, which is crucial for designing future drug studies.
Additionally, they provide information on the drug’s side effects, which is essential in determining whether the drug is safe enough to continue testing in humans. Phase 1 studies are a critical step in the drug development process. They ensure that new drugs are safe enough to be tested in larger groups of people and provide crucial information on the drug’s safety and pharmacokinetics. By conducting these studies on healthy volunteers, researchers can ensure that potential patient risks are minimized when testing the drug in subsequent phases [12] .
The preclinical to phase 1 batch transfer is a crucial step in drug development that involves transferring drug manufacturing from a preclinical to a phase 1 clinical setting. Collaboration between CDMOs and biotech companies is essential for this process. The CDMO manufactures the drug in compliance with GMPs, while the biotech company provides the necessary resources and monitors progress. The process includes preparation, transfer, qualification, manufacturing, and drug release. However, challenges such as compliance with GMP regulations and resource allocation can arise. Despite these challenges, successful transfer ensures safe and effective drug manufacturing. CDMOs and biotech companies must work together to overcome challenges and achieve successful transfer.
4.3. Phase-1 to Phase 2 Technology Transfer
Phase 2 studies involve the administration of the drug to a larger group of patients, usually ranging from a few dozen to a few hundred, who have the disease or condition for which the drug is being developed. The primary objectives of these studies are to evaluate the drug’s effectiveness and further assess its safety. In Phase 2 studies, determining the optimal dose or doses of the drug candidate is a key focus. Researchers aim to establish the drug’s most effective and safe dose or dosing regimen to maximize its potential benefits while minimizing risks. By identifying the most suitable dose, researchers can confidently progress to the next stage of development and increase the probability of success in subsequent studies.
4.4. Phase-2 to Phase 3 Technology Transfer
During Phase 3 clinical trials, which are typically conducted for diseases affecting large patient populations, researchers typically enroll between 300 to 3000 participants from the intended patient population to evaluate the safety and efficacy of the drug candidate. The participants are divided into two groups, one receiving the medication being assessed and the other receiving either the current standard of care treatment or a placebo. The primary objective of Phase 3 studies is to demonstrate whether the drug offers a treatment benefit to the intended patient population, provide detailed safety data, and serve as the basis for product labeling. After completing one or more Phase 3 trials, researchers analyze the results to determine if the drug candidate is effective and safe in treating the disease. If the results are favorable, the company may submit a New Drug Application (NDA) to the applicable regulatory authority. The NDA must contain all the data and information gathered throughout the drug development process, including the Phase 3 clinical trial(s) results and other required information. Since the results of Phase 3 trials often provide the basis for approval, they are commonly referred to as pivotal trials.
4.5. Phase-3 to Commercial Stage
Once a pharmaceutical product is approved, manufacturers often turn to alternative CDMOs (contract development and manufacturing organizations) as a risk mitigation strategy. Technology transfer at the commercial phase is highly customized, as there is a brief history of the process controls and FDA review in place. If the same process needs to be transferred with some feasibility runs, the entire technology transfer program will be built to duplicate the existing technology. If the process requires minor adjustments, the proposal will thoroughly address them. Both parties will collaborate to determine the requirements and responsibilities for manufacturing on the CDMO side.
5. Initiating Tech Transfer Process
When transferring technology from Biotechs to CDMOs, it is essential to establish a detailed Tech Transfer process (Figure 4), which includes the transfer method, a comprehensive checklist, and technical discussions before drafting a request for proposal. The figure outlines the fundamental steps in the tech transfer process.
5.1. Initial Evaluation
Analysts actively examine various inputs in the initial evaluation stage of a
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Figure 4. Steps involved in technology transfer process.
potential production site to determine its feasibility. These inputs include assessing the regulatory position and timeline for changes in a regulatory filing and considering production volume, product characteristics, projected delivery schedules, process-specific equipment information, and EH&S information for products, intermediates, and raw materials. To ensure a smooth and efficient technology transfer process, all functional departments should develop checklists and comprehensively overview their roles and responsibilities (Figure 5). A general mechanism should be in place to initiate and continue the transfer process to the following stages, which can help identify potential risks and prevent duplication of effort. Effective communication and collaboration among all departments are essential for a successful technology transfer [13] .
In the world of manufacturing, selecting the appropriate production site is a critical step that can significantly impact the success of a project. This process involves evaluating the product characteristics, including whether the product is a controlled substance, its potency, and import/export capabilities. Furthermore, the process-specific equipment information must be assessed to ensure the use of appropriate glass damage prevention guidance when using glass-lined equipment. An internal evaluation report is then generated based on the request from the commercial or the client. This report assesses the potential production site(s) and is the foundation for selecting the location. The information includes an initial manufacturing concept that outlines the equipment, cycle time, batch size, waste streams, and economics involved in the manufacturing process.
Additionally, it may contain information regarding process-specific costs to projects and material handling and storage requirements. Once the evaluation
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Figure 5. Functional departments overview in technology transfer process.
report is completed, an internal manufacturing plan is developed, which details the projected manufacturing capacity, estimated timelines for costing projects, and delivery schedules. Nonetheless, defining the Scope of Work and Supply Agreement and identifying raw material suppliers must occur before proceeding.
In summary, the initial evaluation stage is a critical step in determining the feasibility of a potential production site. It involves a thorough analysis of various inputs, which are then used to generate an evaluation report and an internal manufacturing plan. These reports and plans are the foundation for selecting the appropriate production site and determining the projected manufacturing capacity, timelines, and delivery schedules [14] .
5.2. Establishing a Technology Transfer Team
The technology transfer process can be complex, requiring meticulous planning and execution. The next step after the evaluation is establishing project teams based on the evaluation report and the approved scope of work or supply agreement (Figure 6). This step ensures a smooth technology transition from the receiving site. The primary outputs include identifying the process designing and receiving sites, developing a team charter, conducting a project kickoff meeting, creating a project plan/schedule, organizing the project file structure, establishing a communication structure between process originating and receiving sites, determining the timeline for technical document review, initiating change control to comply with quality and supply chain requirements, and reviewing the Quality Agreement requirements (Figure 6). Once the manufacturing site has been selected, the process receiving team is assigned, consisting of all required functions from the manufacturing site necessary to transfer the technology and analytical methods and to implement the strategy into the plant. The project leader of the operation receiving site generates the team charter, initial project plan, project schedule, project file organization structure, and proposed communication structure. On the other hand, the composition of the originating site process team typically consists of chemists with in-depth development or production experience of the product to be transferred, analytical scientists,
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Figure 6. Key processes of technology transfer team.
personnel familiar with regulatory and compliance process needs, personnel with environmental, health, and safety background, and personnel with an engineering background.
Project Kickoff Meeting should be conducted between the process receiving and originating teams. The meeting is used to review and finalize the project schedule and develop working methods between the two groups, covering details such as communication and documentation review. The goal of this meeting is to ensure that both teams have a clear understanding of the project objectives, timelines, and expectations and to establish a collaborative working relationship between the two groups. Establishing a technology team is a critical stage in the technology transfer process, as it sets the foundation for successful collaboration between the process-originating and receiving groups. The project can progress smoothly and efficiently toward completion by establishing clear communication and documentation protocols, developing a comprehensive project plan, and identifying the key personnel responsible for the transfer.
5.3. Knowledge/Document Transfer
The next step of the technology transfer process is a critical stage in ensuring the successful transfer of technology from the originating site to the process receiving site. During this stage, the receiving site team will review the transferred documents and perform a gap analysis to identify missing information. A technical document review meeting may be held between the originating and receiving sites to ensure that the process-receiving team well understands the process. Once the review meeting is completed, the receiving site team will generate a technical transfer acceptance memo indicating that most of the requested information is available. The transfer can continue to the next stage. The receiving site team will refine the original manufacturing concept by identifying the manufacturing equipment, producing an updated process description and flow diagram, and determining the projected process batch time, cycle time (if applicable), and projected throughput. During the analytical method transfer, the receiving site team will transfer the analytical procedure to ensure the analytical techniques are available during the demonstration batches. The analytical method transfer protocols should be executed, and the data should be reviewed before moving to the next stage.
Process demonstration batches are then produced on a lab scale to familiarize the process-receiving team with the process. Samples from the demonstration batches are submitted for analysis to ensure that the process meets the proposed acceptance criteria and that the transferred analytical methods function as expected. The demonstration batches may also be used to perform a process deviation analysis to identify any potential product impact from processing deviations. Before continuing to the next step, a signed Quality Agreement should be in place (if applicable). The equivalency of stability packaging materials versus the bulk containers and the appropriateness of the proposed containers for their intended use must be evaluated, and stability studies must be conducted on the drug substance packaged in a container closure system that is the same as or simulates the packaging proposed for storage and distribution [15] .
5.4. Process Transfer
Process Transfer is the next step in the Technology Transfer process (Figure 7). To begin this step, the outputs from knowledge and document transfer must be available, along with the manufacturing equipment availability, production schedule, analytical method validation, and transfer reports. This step involves several deliverables from the EHS, Logistics, Facility Operations, and Operations groups. The EHS group is responsible for assessing all raw materials, intermediates, and final products for the upcoming manufacturing campaign. EHS ensure that all materials used or produced are handled and stored safely, and they characterize the process waste streams to identify any required permitting modifications. Additionally, the EHS group generates or updates emergency planning and response documents as needed. Logistics ensures the site can safely store the materials based on the EHS recommendations. They also identify any product or intermediate labeling requirements and shipping requirements. The group identifies all raw material suppliers and sets up supply agreements with critical raw material suppliers, where necessary, with input from the Operations group. Facility Operations confirms that any process-specific capital expenditure projects have been completed and qualified before the initial manufacturing campaign.
The Operations group performs a Process Hazard Analysis (PHA) to identify any necessary changes to the manufacturing concept before the first campaign at the receiving site. Following the PHA, the Operations group generates the Distributed Control System (DCS) (where applicable) and equipment setup documents. A Pre-Startup Safety Review (PSSR) ensures the equipment has been set up safely. The operations group also ensures that the necessary personnel has been trained.
Following the PSSR and training, process simulation batches may be performed (where applicable) to ensure the DCS recipe and overall process flow function as designed. During the generation and review of the master batch record, any required process validation protocols and cleaning batch records are also generated. Before moving to the following steps, the process validation protocols (if needed) and master batch records must be approved, and the change control must be supported for a startup.
5.5. Manufacturing Campaign
Before beginning the campaign, the necessary documents must be in place, such as the Master Batch Record, approved process validation protocols, approved analytical methods for raw materials, intermediates, and final products, and approved equipment cleaning methods. Once these documents are approved, the
initial manufacturing campaign can begin. During the initial manufacturing campaign, processing deviations and investigations should be thoroughly reviewed to identify any corrective and preventative actions required. The process validation summary reports should be generated to document the campaign results, and a campaign summary meeting should be held to review the results. The campaign summary report should contain a summary of the initial manufacturing campaign, processing deviations, investigations, corrective and preventative actions, and recommendations for continuous improvements. The campaign summary report should be used to identify any required modifications to the manufacturing documents before the next manufacturing campaign. These modifications may include updates to the Master Batch Record, Process Description, or other manufacturing documents. Continuous improvement recommendations should be implemented to improve the manufacturing process at the receiving site. The success of the initial manufacturing campaign will help determine the effectiveness of the technology transfer process and pave the way for future successful campaigns at the receiving site [15] .
5.6. Continuous Improvement
The inputs in a continuous improvement program include the campaign summary reports and the manufacturing data review. The goal of this step is to identify potential areas of improvement for future manufacturing campaigns. One of the outputs from this step could be equipment and process optimization, which can lead to cost reduction in manufacturing. The cost model should be regularly reviewed and updated as processes are optimized. Furthermore, alternate manufacturing processes can be developed, or the existing process can be modified to improve cost-effectiveness and increase efficiency. Ongoing process monitoring is essential to ensure the manufacturing process remains stable and produces the desired results. Any deviations or non-conformances should be documented and investigated to determine the root cause and implement corrective and preventative actions. Overall, step 6 is a continuous improvement process that involves analyzing data, identifying potential areas of improvement, and implementing changes to optimize the manufacturing process. The overall technology process is presented in Figure 8.
6. Factors Affecting Technology Transfer
Technology transfer involves transferring a process from the originator site to a receiving site, which can be complicated due to various factors (Figure 9). The complexity of a process may be inherent, and it may stem from a molecule’s fragile nature, tight specifications, or the complexity of the analytical package. Due to their high variability, analytical packages for complex molecules are particularly challenging to transfer. Moreover, changes during tech transfer require careful management from quality, regulatory, and technical perspectives. The product life-cycle stage is an essential factor that determines the complexity of a
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Figure 8. Technology transfer flow from evaluation to continuous improvement.
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Figure 9. Factors effecting technology transfer process.
tech transfer project. The farther a product moves through its clinical program, the higher the regulatory expectations during transfer, increasing project difficulty. On the other hand, more process knowledge is gained, making the transfer easier in theory. The maturity of the process technology is also linked to a project’s clinical phase, but the originator’s understanding of the process can differ significantly among projects. Assay qualification and validation are also far from standard across projects, and such factors interact with inherent process complexity. Transferring a complex process is even riskier than normal if it is somewhat underdeveloped for its clinical phase.
The receiving site’s maturity is another critical factor affecting tech transfer complexity. The site’s experience with similar transfers, the depth of its quality system, regulatory experience, and support functions (e.g., for development, production support, analytical, project management, and validation) should correspond with the transfer to be executed. A balance with the originator site should be maintained. Cultural differences between originators and receiving locations can also affect tech transfer complexity. Identifying cultural differences and comparing the cultures of both sites is crucial to ensure a successful transfer. Contractual arrangements can also influence tech transfer. A transfer project is typically contracted as a work package. Still, tight budgets and timelines can lead to undue stress on transfer teams and damage the long-term originator-recipient relationship. A quality agreement should be established early during the transfer to handle changes and deviations, and a joint approach must be defined. A longer-term manufacturing agreement should frame the success criteria of the transfer.
The inherent complexity, product life-cycle stage, process maturity, receiving site maturity, cultural differences, and contractual arrangements are critical factors that affect tech transfer complexity. A successful tech transfer requires a joint approach from the originator and receiving sites to ensure that the process is transferred efficiently and meets the required standards. The receiving site’s experience with similar transfers, the depth of its quality system, regulatory experience, and support functions should correspond with the transfer to be executed. Additionally, a quality agreement should be put in place early during the transfer to handle changes and deviations, and a longer-term manufacturing agreement should frame the success criteria of the transfer.
6.1. Analyzing Complexity to Improve Tech Transfer
To improve technology transfer, it is essential to understand and address the various sources of complexity that can arise during the process. These complexities can be related to the product’s life cycle, project changes, and cultural differences and can often be interdependent, resulting in greater complexity and increased risk. However, analyzing the transfer process from different complexity perspectives can be beneficial in several ways.
One advantage of examining complexity in technology transfer is that it can help develop clear criteria for selecting a recipient site or contract manufacturer. This selection process should focus on more than process fit and cost. Still, it should also consider factors such as the site’s ability to collaborate with the originator and its experience with similar transfers. Cultural fit is an essential factor that can significantly impact the success of a technology transfer project. While evaluating cultural fit may be challenging, it is an area that can be improved through active effort and effective communication. Identifying and addressing potential complexities and focusing on factors beyond process and cost alone can significantly improve the chances of a successful technology transfer.
Analyzing complexity can also help formulate a transfer project tailored to a specific case. Project elements will depend heavily on the transfer scope and technological complexity, the number of changes, the product’s life-cycle position, and the extent of information to be delivered. Risks inherent to a project will depend on these dimensions, as well as on the maturity of the originator and recipient sites and the cultural distance between them. By identifying essential transfer characteristics, complexity analysis allows for developing a well-defined project that can be customized to meet the unique needs of a particular case. The two main components of a transfer program are the information package and the experimental program before GMP manufacturing. Complexity criteria can help to shape both of these components. The information package should be designed to communicate the necessary information to the recipient site effectively. The experimental program should be tailored to the case to minimize risk and ensure success.
Globalization has brought various technical challenges that have significantly impacted the technology transfer process. However, transferring technology across borders has introduced new complexities and challenges, especially for biotechs and CDMOs involved in phase-appropriate technology transfer. These challenges include navigating the complexity of intellectual property rights and legal frameworks across different countries, dealing with language and cultural differences, and ensuring compliance with local regulations and standards. Moreover, the complexity of the technology transfer process requires biotech companies to have specialized expertise and resources, which can be challenging to obtain in-house. CDMOs can provide critical support to biotech companies by offering specialized expertise in process development, analytical testing, and quality assurance, which can accelerate the technology transfer process and ensure compliance with required international regulations and standards.
6.2. Managing Changes during Tech Transfer
Technology transfer often involves making changes, but it is essential to manage them carefully to ensure a successful transfer and comply with regulatory requirements. There are three changes during tech transfer: intentional, induced, and hidden. The transferring site makes intentional changes independently, such as optimizing a purification step. Induced changes are caused due to tech transfer, such as using a different method for primary separation. Hidden changes are small and may only be discovered through a detailed comparison of processes at both sites, such as differences in raw material properties. Both intentional and induced changes require regulatory notification and specific change-control actions, while hidden changes can usually be managed using a comprehensive approach. Identifying covert changes can be challenging, but risk identification and evaluation are recommended. Brainstorming, checklists, parameter lists, fishbone diagrams, and process walk-downs can be used to identify covert changes. Process walk-downs involve a team visualizing a process in detail and identifying differences between facilities. Once identified, risk-analysis tools can assess changes for possible impact, and appropriate actions can be taken. Scale-up is common, especially in early clinical phases, proper discussions of the affected factors can be challenging, and difficulties tend to arise in mass transfer, mixing, and sometimes shear. However, scale-up challenges can be approached through progressive scale increases, ending with an engineering run.
Dealing with changes of whatever type takes time and requires a joint team comprising members from both sites. Conducting thoughtful analyses and defining approaches can be a powerful means of team building between sites. A collaborative team also provides a forum for process information to surface and be shared. Consequences of changes are quite similar to those that accompany intrinsically complex processes: they require more elaborate programs, place a premium on experience and knowledge at both sites and require superior knowledge transfer. To ensure a smooth tech transfer process, all departments should collaborate and communicate effectively with the client regarding any changes [16] .
7. Technology Transfer and Product Life Cycle Management
Technology transfer is required throughout a product’s life cycle, from the first transfer from development into good manufacturing practice (GMP) production to end-of-life transitions into low-cost-base facilities. It is essential to understand that tech transfer always carries significant regulatory implications. Establishing comparability is critical to tech transfer and becomes exacting for commercial stages. Meeting specifications is usually insufficient to establish comparability; additional characterization and stability data are necessary. Analytical methods must yield equivalent results, and it is mandatory to demonstrate this during analytical method transfer.
Regulatory preferences can cause problems with new sites designed primarily for commercial manufacture, and optimal transfer transitions are essential. The life-cycle position strongly influences the nature and amount of information to transfer and transfer complexity. Work packages and documents to be produced as tech transfer deliverables differ significantly over a product’s life cycle.
Product life-cycle position strongly influences the nature and amount of information to transfer and transfer complexity. If knowledge can be efficiently and successfully communicated, then tech transfer should be facilitated and de-risked considerably. Addressing regulatory implications, product comparability, and analytical methods’ equivalency is critical to ensure a successful technology transfer.
8. Conclusion
Successful technology transfer is crucial for converting innovative molecules to commercial medicines efficiently and cost-effectively. To ensure a successful transfer, innovator companies need to work closely with CDMOs and establish clear expectations and quality agreements. Effective communication channels and regular updates should be maintained throughout the transfer process to promptly address any issues or concerns. Both parties should be aware of any regulatory requirements and changes that may arise during the transfer process. The CDMOs’ ability to convert molecules to medicines through successful technology transfers relies on their ability to develop and implement rigorous quality control measures and validate the transfer process thoroughly. By adhering to these principles and working closely with the innovator companies, CDMOs can successfully convert innovative molecules into commercially viable medicines.
Acknowledgements
I would like to thank the Veranova Leadership Team (VLT) for their invaluable support and insightful suggestions in preparing this article. I also wish to acknowledge the support and contributions of my colleagues from Business Development, Project Management, and functional heads, whose input was instrumental in developing this article. Lastly, I sincerely appreciate my Analytical Research & Development colleagues’ support and encouragement.