by Michael Firgens
Technology transfers are frequently conducted throughout the product lifecycle. They require substantial resources, technical know-how, and organizational skills in both sending und receiving units. The transfer of biopharmaceuticals is particularly challenging and should be planned and executed by an experienced and skilled team.
Michael Firgens, Senior Consultant at Biopharma Excellence, summarizes why the following factors are pivotal for the success of technology transfer projects:
- Sending unit and receiving unit work closely with each other.
- Clear understanding of roles and responsibilities of both sending unit and receiving unit team members.
- Complete technology transfer package.
- Quality Risk Management.
- Effective knowledge transfer and training.
- Stage Gate Approach
The transfer of manufacturing processes and analytical procedures between facilities or laboratories is an essential technical activity during the product lifecycle, as outlined in ICH Q10. These “technology transfers” take the outputs of process and method development activities and transfer the knowledge (sending unit) to a different location where the process or analytical procedure should be operated in the future (receiving unit).
The transfer of technologies can be triggered by a variety of reasons considering business and regulatory rationales:
- Product life cycle management, from R&D through scale-up to routine manufacturing
- Post-approval changes to implement new process versions
- Need for additional manufacturing capacity driven by increased demand or risk mitigation
- Strategic requirements to relocate manufacturing sites for rationalization or economic advantages in different regions of the world (e.g. market access, supply chain optimization, contract manufacturing)
Technology transfers are complex projects and must overcome diverse technical and organizational challenges. From technical perspective, it is rarely possible to transfer and implement the same systems from the sending unit without adjustments in the receiving unit. In certain cases, the receiving unit might not have the required manufacturing and analytical capabilities yet, and new technologies must be implemented first. For the production of biopharmaceuticals, processes and materials show inherent variability so that the range and nature of the drug product and its byproducts can vary, making it challenging to establish the same product quality in different sites. Moreover, manufacturing processes must be optimized for site-specific equipment and materials to maximize product yield and to minimize impurity levels. During the transfer of analytical methods, specific technical challenges likely arise requiring in-depth trouble-shooting expertise. From organizational perspective, the technology transfer activities require significant resource commitment from all involved parties. Commonly, the teams are geographically separated, and language and cultural barriers exist. Cooperation between multiple teams from different organizations is also hampered by missing processes, lack of accountability or leadership.
Based on previous experiences with technology transfer projects, the following best practices can help to overcome challenges and reduce complexity, as summarized in Figure 1 and Table 1:
1. Sending unit and receiving unit work closely with each other
In any technology transfer project, sending unit and receiving unit together should act as a unified team. An aligned technology transfer plan created by collaboration of sending unit and receiving unit helps to ensure agreement on deliverables, success criteria, and ownership of the transfer at different stages. The transfer plan should also capture applicable regulatory requirements and critical technical decisions. It is beneficial to start technology transfer planning and anticipating potential issues as early as possible.
The project manager plays a pivotal role to guide the transfer team and should ideally be seen as relatively unbiased with strong directive leadership skills. The project manager must break down the overall project goals and strategy into defined work packages for the transfer team. Throughout the course of the project, each department must have a clear understanding about the required input so that the transfer plan is implemented accordingly. The project manager is also responsible to cope with changes in project scope, budget, timelines, risks, and other key assumptions and must escalate critical issues to relevant stakeholders to ensure alignment.
2. Clear understanding of roles and responsibilities of both sending unit and receiving unit team members
As multidisciplinary teams from different organizations collaborate with each other on each technology transfer project, transparent definition of roles and responsibilities is the basis for an efficient transfer process. In general, clear task assignment and streamlined communication routes can minimize redundancies and oversights. They also allocate decision rights in the team and help to avoid misunderstandings and conflicts. Roles and responsibilities should be defined for the technical aspects of the technology transfer process as well as for the overall business process and project governance.
Roles and responsibilities of sending unit and receiving unit teams should be documented appropriately and ideally should be fixed in a SOP on technology transfer, which also enforces accountability. Especially for the routine conduct of technology transfers, a transparent documentation of roles and responsibilities facilitates employing the same process consistently in all technology transfer projects and is helpful during quality audits.
3. Complete technology transfer package
A comprehensive technology transfer package comprising relevant information from the sending unit should be compiled for technical review, including process description, analytical methods and data, production equipment details, and historical process data. In particular, CQAs and the control strategy for both drug substance and drug product should be provided in final documented form by the sending unit. Once the technology transfer package is completed, the transfer team can use the data to work on the planning and writing of technical documents for the receiving unit. Based on the technology transfer package, the transfer team should also conduct a first high-level risk analysis.
4. Quality Risk Management
Technology transfer must consider principles of quality risk management, as outlined in ICH Q9. In the beginning and throughout the technology transfer process, it is beneficial to continuously analyze and reduce the risks to an acceptable level. For this purpose, detailed gap and risk assessments should be conducted to control and mitigate risks. Risk assessments likely are required at different stages of the technology transfer project and can focus on specific technical areas or issues. If needed, risk mitigation measures may employ experimentation and modifications of equipment or facilities. After finalization of the transfer plan and before introduction of drug substance, drug product, and related raw materials to the manufacturing facility, a change control should be initiated at the receiving unit.
5. Effective knowledge transfer and training
In the receiving unit, sufficient resources and time should be planned in to develop a good understanding of the sending unit’s process and product knowledge, especially for process steps, CQAs, operation parameters, and their impact on those quality attributes.
Small-scale verification and engineering runs are typically employed to test and implement all systems and processes in the receiving unit. In order to adequately build up experience and knowledge in the receiving unit, it might be necessary to train receiving unit staff at the sending unit.
6. Stage Gate Approach
Defined stage gate reviews can help to ensure that critical items of a project phase have been completed satisfactorily before proceeding to the next project phase. Typically a steering committee, consisting of key stakeholders, management representatives, and technical subject matter experts, performs stage gate reviews. If consistently applied, the stage gate approach can help to reduce risks during later project phases and facilitates decision-making and alignment.
Please do not hesitate to ask us if you need support in your technology transfer projects with:
- Development of integrated technology transfer plans and strategies
- Compilation of technology transfer packages and document preparation for regulatory submission
- Comprehensive project management and targeted support of the transfer team (e.g., during risk assessments, stage gate reviews, training)
- Creation of customized and streamlined operating procedures for technology transfers in your organization