Bioprocessing Technology Transfer and Scale-up
Over the last few years, the bioprocessing industry has had a high throughput rate for new product candidates in its attempt to find the next pharmaceutical blockbusters. This had led to an acceleration in pharmaceutical outsourcing for process and analytical activities. Pharmaceutical outsourcing starts with a technology transfer, which is typically one of many during the life cycle of any biopharmaceutical product. Often this first technology transfer is from a research facility or process development group to a service provider for pre-clinical and clinical studies. This technology transfer from a sponsor to the first CGMP manufacturing site is often the time our Bioprocess Technology Consultants get involved with the technical aspects of a project for the first time as.
The technology transfer from process development to Phase I CGMP manufacturing can also be an in-house transfer. But looking at today’s demographic, multiple products are coming out of virtual or low infrastructure companies. Thus, the first technology transfer also often comes with the need to find the right partner to advance the product. As Bioprocess Technology Consultants, we are often tasked with helping to select the right partner (see previous blogs) and to assist with the technology transfer to a contract development manufacturing organization (CDMO).
Once a partner is selected, technology transfer from the sponsor to a service provider is initiated. The importance and duration of the technology transfer is unfortunately still widely underrated. Allocation of the right resources and time is often not fully considered, even though technology transfer is very important in the bioprocessing industry. ICH Q10 explains the importance of technology transfer as follows:
“The goal of technology transfer activities is to transfer product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realization. This knowledge forms the basis for the manufacturing process, control strategy, process validation approach, and ongoing continual improvement.”
At Bio-Processing Alliance, we have learned that concise documentation (including a technology transfer plan and report), as well as open communication between all involved parties, are the keys to success during bioprocessing technology transfer. We are often tasked as Bioprocess Technology Consultants to help generate a documentation package summarizing all relevant information for the process transfer, as well as to help planning the technical aspects of the technology transfer. In our experience, a good starting point for the technology transfer is the creation of a target product profile (TPP) that documents the intended use and quality targets of the developed product. An added benefit of the TPP is that it also provides a format for discussions between a sponsor and regulatory agencies, such as FDA, that can be used throughout the drug development process. Establishing a TPP early on helps to define product characteristics that are important to be maintained during any future technology transfer and biologics process scale-up. Generating the technology transfer package with the TPP in mind is critical in bioprocessing and allows the technology transfer plan to be better defined.
The technology transfer package should include enough details about each aspect of the product and bioprocessing unit which will allow the receiving pharmaceutical outsourcing partner to plan their receipt of the product accordingly. A typical table of contents to a technology transfer report that our Bioprocess Technology Consultants use includes the following topics, amongst others:
- Product background
- Cell line development
- Analytical development
- Bulk Drug Substance and Drug Product Specifications
- Process development program
- Process Flow Diagram
- Bill of Materials
- Process scale-up experience
- Critical Process Parameters (if known)
- Critical Quality Attributes (if known)
Once all the information is exchanged and the receiving party has had enough time to review the information, it is then a good time to initiate a project kick-off meeting to discuss the detailed plan for project realization. In many cases, this is the first time the sponsor and the pharmaceutical outsourcing service provider have the opportunity for a technical discussion and it is imperative to have the subject matter expert teams represented. Open communication between the parties is a key element of a successful technology transfer and the foundation for this is often built during the kick-off meeting.
The technology transfer plan should also include outlines about other aspects of the technology transfer in addition to the obvious technical information. An important part is the definition of project team members and their roles in the technology transfer. For example, it is important to put a governance structure in place so that challenges can be readily dealt with. A project manager on each side facilitates the technology transfer by ensuring proper buy-in from all parties, assisting with staff allocation and coordination of activities. A good communication structure between the sponsor and the pharmaceutical outsourcing service provider should be established. BPAI has tremendous experience with leading or assisting as Bioprocess Technology Consultant during technology transfer in many bioprocessing projects.
Often technology transfer goes hand in hand with bioprocessing scale-up. Typically, the process is originally developed at laboratory scale and then needs to be scaled-up to the manufacturing scale to produce enough GMP material to support clinical trials. The intended production scale in support of pre-clinical and clinical work is usually determined by several factors, with the main drivers being product requirements for clinical trials and the available scale at the pharmaceutical outsourcing service provider. Sometimes the required scale becomes a deciding factor in the selection of a bioprocessing partner. Different pharmaceutical outsourcing partners have different approaches for scale-up and thus it is important to openly discuss scale-up considerations and to come to an agreement between the sponsor and the service provider. In our experience, it typically comes down to balancing time and cost versus risk of failure and thus, it is important to get the buy-in from both the pharmaceutical outsourcing company and the sponsor. We have played pivotal roles in planning for successful scale-up as Bioprocess Technology Consultants by balancing risks with the typically aggressive timelines of the sponsor.
Although technology transfer and scale-up are important and unavoidable parts of a product life cycle in the bioprocessing industry, they are often erroneously underrated. It is important to remember that technology transfers are often part of pivotal stages in the life cycle of the product. For example, moving the process from development to CGMP manufacturing, increasing process capacity from Phase I to Phase II, or scale-up to commercial production. Therefore, it is important to plan for a successful technology transfer because failure usually leads to several weeks, if not months, of scrambling to recover. Not to mention that a failure can impact investor trust (sometimes to the point of complete breakdown of investor confidence) that ultimately harms both the sponsor and the pharmaceutical outsourcing company. Putting effort into preparing and executing the first technology transfer is definitely an approach that pays forward in our experience. Once the right strategy is developed, a similar system can be used for any future technology transfer.
Product equivalence at every significant change is also a fundamental regulatory requirement and thus introduction of the TPP early in the development process becomes an important feature. In our years as Bioprocess Technology Consultants we have witnessed some of the more common pitfalls of unsuccessful bioprocessing technology transfer due to poor planning, unconcise or ambiguous documentation, miscommunication, and much too aggressive timelines that leave little tolerance for unexpected issues. Though this blog is focused on the early stage technology transfer from a sponsor to a pharmaceutical outsourcing service provider, most aspects apply for later stage or in-house technology transfers.
So in summary: bioprocessing technology transfer and scale-up – do it right the first time!
Bio-Processing Alliance, Inc.