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Agnes Shanley is senior editor of Pharmaceutical Technology.
Once described as “throwing processes over the wall,” tech transfer is evolving into close collaboration and communication, as potential problems are considered sooner, and new technology is applied. Joseph Szczesiul, director of technical services for UPM Pharmaceuticals, shares best practices.
Technology transfer is a difficult process, whether it occurs between R&D and manufacturing within a single company, between an academic lab and a corporation, or between a manufacturer and a contract development and manufacturing organization (CDMO). Pharma’s folklore is full of stories about tech transfer failures: analytical techniques or processes that worked perfectly in the lab, yet failed on the plant floor, costing partners significant time and money, and derailing promising development programs.
Where a few decades ago, research department staffers might speak glibly of throwing a process “over the wall” from R&D to scaleup and manufacturing, today most organizations realize how wasteful that approach has been and are approaching tech transfer in a much more systematic and collaborative way. Crossfunctional teams are usually the rule, with representatives from each major operational group (e.g., quality, business, research, and operations) at the sponsor group taking an active role in moving projects forward.
In addition, best practices often call for minimizing the number of tech transfers required involved in the development of a drug, says James Bernstein, principal of Live Oak Pharmaceutical Services. This approach depends on careful contract partner selection, he says, to ensure that the CDMO’s strengths are fully leveraged at each stage. Typically, he says, a sponsoring drug company will opt to work with a smaller contract partner for the initial development and formulation, then design the process so that only one tech transfer is required, he says, so the project can move straight from development to Phase III. “If we plan the process well, we can get away with only one tech transfer, but you’ll always have at least one,” he says.
Tech transfer is also the best time to consider scale-up type issues, and to take stock of risks based on the technologies and equipment that are available, says James Blackwell, principal of the Windshire Consulting Group. “By understanding the sensitivities and behaviors of your system, you can start to predict behavior,” he says.
Currently, a growing number of companies are starting to use novel technology to help improve and speed tech transfer. Merck, for example, tested the use of augmented reality to move an analytical process between sites, and found that it improved efficiency by 10% (1). By allowing partners in the transfer to interact directly, to troubleshoot and share “tribal knowledge” (i.e., expertise gained by people experienced in operating the equipment or working with the technology that cannot be written into a training manual or other typical documentation), the technology can help improve communication and eliminate travel time and expenses (2).
Joseph Szczesiul, director of technical services for UPM Pharmaceuticals, recently shared best practices for tech transfer with Pharmaceutical Technology.
PharmTech: What are the crucial elements to doing tech transfer correctly, and when should their foundations be established?
Szczesiul: The best foundation for tech transfer success is complete formulation and process development. You cannot correct formulation deficiencies during tech transfer, and process optimization can only provide limited improvement. An inadequate enteric coating, for example, or a wet granulation with insufficient binder, can only be improved incrementally by process changes. The big fix comes from formulation change, which needs to be done early in the development process.
To step back even further, a development project needs clear and complete goals, which then lead to a strategy, and then to a plan of work. The obvious goals are to succeed in the clinic, to file your application, get approval, and start selling product. But a product also needs to pass validation. It must also be physically and chemically stable, and will need to succeed in routine manufacturing and to meet regulatory requirements.
A good practice is to maintain a development narrative over the life of the project. This becomes a reference, but it is also a tool for periodic review. It should include the goals for each stage of development. It should list the batches made, their purpose, and their outcome, and also list all issues and problems encountered with each one.
All issues should be resolved before proceeding to the next development phase. At the end of each phase, call a team meeting, review the development against the goals for that phase, and determine whether the project is ready to move further down the path. In that way, you keep returning to your overall strategy, and your idea of big-picture success.
PharmTech: What are the biggest mistakes that pharmaceutical companies and inventors most often make when approaching tech transfer? What do they often appear to overlook or leave out?
Szczesiul: Incomplete knowledge transfer to the CDMO is a consistent problem with tech transfer projects, and projects are often delayed due to incomplete information being provided. Effective technology transfer requires access to relevant information about the process that is being transferred.
Client companies must provide as much information as possible to their CDMO, since the client possesses all of the documented and undocumented product and process knowledge at that phase of the project. Ideally, knowledge transfer takes place through the provision of a technology transfer document package, as well as through routine ongoing communication.
In addition to the ‘hard’ data transfer, it is important for client companies to transfer their peripheral and soft, experiential knowledge. The client’s experts that know manufacturing, analytical, and safety aspects of the product should be on the project team so they can provide continued review and input.
PharmTech: What should client companies ideally focus on, and how should they be staffing and managing these projects?
Szczesiul: Client companies should focus on information transfer, on having a clear regulatory strategy, and on developing an appropriate plan of work in conjunction with their CDMO. A tech transfer plan of work establishes the steps to be implemented to generate all of the information and data necessary for successful regulatory filing. It must meet regulatory agency expectations for the application and answer questions specific to the product being transferred.
PharmTech: Can you share any tech transfer war stories?
Szczesiul: Years ago, I worked on a project where nearly, but not quite all, of the required information was communicated by a sponsor. This project involved the site transfer of an approved Wurster-coated product. It was sustained-release, with the polymer dissolved in a flammable solvent.
Our fluid bed was from the same equipment manufacturer, it was explosion-proof, and it matched the bowl size of the fluid bed at the originating site, so it was assumed when the development contract was signed that no process development work would be needed, just a confirmation batch to verify a successful run using the parameters in the original batch record.
However, two significant issues arose after we finally received a copy of the batch record. First, the originating site used the same size bowl as our fluid bed, but it was connected to a different expansion chamber to a model that was two sizes larger than ours. This meant that our filter chamber was several feet shorter than theirs, so we had to reduce airflow, to avoid driving product up into the filter.
Second, we learned that the other site had a sealed air system with solvent recovery, and purged their system with nitrogen to prevent combustion of the solvent. We did not have either capability, and for safety and insurance reasons, our maximum spray rate could not exceed 40% of the original spray rate. A new coating process had to be developed. So the project exceeded its original scope, required unexpected process development work, and caused an unexpected delay for the client.
PharmTech: For virtual companies, and even nonvirtual companies that outsource most key functions, what is essential to coordinating efforts and ensuring success?
Szczesiul: The first step is to understand and analyze your own company’s limitations in terms of specific knowledge and experience for the project at hand. Then fill in your knowledge gaps with the appropriate consultants and the CDMO. A key component of your relationship with the right CDMO should be education: their technical leads should be able to explain not just what they are doing, but why, in the same way that that they should be able to explain to an auditor or FDA investigator what they have done, and why.
There should be a continual feedback loop of review and information to the client as the project progresses. Your knowledge and understanding of your product should grow throughout its development life. Look for a CDMO that can communicate technical and scientific information, and consider this an important part of the contract partner selection process.
Beyond that, evaluate the progress of your project against its development strategy. Work completed needs to be considered in the context of your overall goals. It is important to conduct gate-keeping reviews before starting significant steps, such as the manufacture of registration batches or validation batches, to verify that the project is ready to advance.
1. W. Forrest et al., J Pharm Sci, 106 (12) 3438–3441 (2017).
2. A. Shanley, “Mixed Reality Gains a Foothold in the Pharma Lab,” Pharmaceutical Technology Bio/Pharma Laboratory Best Practices eBook (November 2018).
Vol. 42, No. 12
Pages: 24–25, 48
When referring to this article, please cite it as A. Shanley, “Tech Transfer: Tearing Down the Wall," Pharmaceutical Technology 42 (12) 2018.