As part of our role advising biosimilar clients, we have encountered both mature and budding companies who are trying to either extend their portfolio or enter the biosimilars space. These companies often ask us to help them with the evaluation of either an existing process that has been launched in semi-regulated markets or the evaluation of cell line developers for the purpose of acquiring clones for internal development.
The most common issue with products that have already been developed is that the buyer is stuck with sub-standard cell lines and processes. In many situations, there is a need to rework the process to further align with similarity and other CQA characteristics.
This post will focus on the latter case, where companies have asked us to help them select a cell line developer as well as a clone. Over the past five years we have put together some lessons learned that we review with each client and would like to share the key elements of our learning with you.
As part of our lessons learned we have chosen According to Amita Goel, CEO of Celltheon and AETOS BIO in California to help us further elucidate some of the learnings and areas of opportunity.
Picking A Cell Line Developer
Lesson (1) – Global Regulatory
(1) Prior to selecting any provider/partner, there needs to be assurance that this company understands the regulatory requirements for the final product. We often see companies who are very focused on just developing the cell lines without giving any thought to the documentation and controls required to support global submission and commercialization. This lack of understanding also leads to decision making that may hamper the molecule from becoming a biosimilar candidate.
Lesson (2) – QTPP and CQA
(2) In addition to having a global understanding of the regulatory factors, it is vital that the company has a good handle on the Quality Target Product Profile and Critical Quality Attributes in early development of the cell lines and R& D scale process. Decisions that are made at these early stages will have a big impact on the development lifecycle of the product, development costs and even the market success of the product.
Lesson (3) Strong Technology is a must have
(3) Once there is an understanding of the regulations and product attributes, next comes the most important element for commercialization: the ability to create a clone with high productivity. This is easier said than done.
According to Amita Goel, CEO of Celltheon and AETOS BIO in California: “A cell line developer must have both strong expression technologies and should be able to approach the cell titer/productivity at the genetic level.” In this case she further explains that “it is vital that the developer has good understanding of strong molecular biology tools such as optimized vectors, engineered cells, signal sequences, etc.”
Lesson (4) Knowledge of Cell Line
(4) As is often the case, timeline is crucial in the selection of both the developers and clone selection. It is vital for a potential buyer to explore how the cell line developers intend to develop or has developed clones.
In speaking to Amita on this topic she explains it further.
She says: “as you proceed in the decision-making process, pick someone with expertise in process development. These developers will be able to deliver you initial process that can be scaled and allow to accelerate timeline into the clinical trials.” She continues by emphasizing that “a cell line developer must know their host cell line better than anyone. It’s important to ask the developers how long they have spent optimizing their platform and what they typically expect for standard molecules with regard to expression and CQAs..”
Lesson (5) Leverage Know-How – Buy the Process not the RCB
(5) Another caution in this case is thinking about what exactly do you need. Some of our clients often request a research cell bank (RCB) with minimal process and quality characteristics. These clients typically have an in-house development team that plans to further develop the process. A missing element that often gets lost is the expertise that sits in the cell line developers’ hands. At the time of RCB creation they have a significant understanding of the critical parameters and process that is required to achieve the expected result.
Amita shared that when the client just buys the RCB without the process they fail to take advantage of the experience and know-how of the developer.
The clients lack of understanding of process and its relationship between the critical process parameters and CQA(s) often leads to lengthy trial and errors experiments by buyer that can take years to resolve.
Amita recommends that it is better and most cost effective to have the cell line developer deliver a full process at some mid-level scale that can be transferred and quickly scaled for analytical similarity assessment.
She indicated that based on her experience this could save the client years since the cell line developers understand the cell line and process better than anyone at this stage.
She recommends that a fully characterized process is developed keeping in mind the critical quality attributes required to achieve similarity
The selection of a cell line provider seems like a very straightforward process, especially in light of so many companies that are in this arena. Our experience has shown that there are ample opportunities for improving this process. These are detailed above but are summarized below. Your cell line provider/partner must:
(1) Have Full regulatory and product understanding
(2) Have Proven vectors and deep experience in creating expression technologies
(3) Provide a fully developed process at mid scale (10-50L) that has met a most of the similarity criteria.
We like to thank Amita Goal from AetosBio ( firstname.lastname@example.org) for her expert opinions and sharing her experiences in this complex field.