From The Editor | February 13, 2019

Inside PDA's Technical Report No. 81


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

Parenteral Drug Association (PDA)

Parenteral Drug Association (PDA) recently released Technical Report No. 81, “Cell-Based Therapy Control Strategy,” written by PDA’s Cell and Gene Therapy Task Force. Michael Blackton, Global Head of Quality at adaptimmune and PDA’s Co-Chair of the Cell and Gene Therapy Interest Group co-authored the report. Blackton’s also a member of the Biopharmaceutical Advisory Board and International Board of Directors. Here, he breaks down Technical Report No. 81 and explains the report’s biggest takeaways.

Explain the why behind Technical Report No. 81 (TR 81), Cell-Based Therapy Control Strategy.

Blackton: Control Strategy is the critical element of the product development life cycle. Control strategy is essentially all the parameters of your product and process — of your product’s process, and, ergo, your product — in order to characterize what that product does such that you could transition through the life cycle to approval and beyond.

There has been a great deal of discussion about these products because they’re so new, that the question exists, “Does the life cycle even apply to these products?” The reason we wrote this TR is to illustrate how that life cycle applies through the control strategy, and all those elements required to get to the control strategy, such that we can understand what is required to shepherd these products through approval and beyond.

What I mean by “approval and beyond” is, once you characterize your product and get it through approval, you must constantly look at that product as it goes through its life. That may require you to go back and revise certain aspects of your product definition as embodied within the control strategy. Really, the control strategy is one element of the life cycle — the critical element of the life cycle that drives all the actions you make as you shepherd the product through.

It’s also important to note that the control strategy is not simply one-and-done. It is something that is maintained from the beginning, and its rigor is based on how much scientific knowledge you have of your product and process. This report’s scope ends with the setting up of a draft control strategy, but it starts with those strategic and tactical decisions we make as we define what our product is. That’s what we call, in section three of the document, the product profile document.

Once you have a product profile, then you start looking at what’s critical about that profile or what are those attributes, and then defining what your control strategy is from that. It was like the first step.

Why is Control Strategy so important?

Blackton:  It is incredibly important that people in cell therapy and gene therapy apply the life cycle to their products. I really believe, in this day and age, if you want to get a drug approved — and cell therapy is no different — then you must have a robust control strategy that allows you to understand where your flexibility lies and where you need to focus on highly critical areas, or else you will be very hard pressed — in fact, I believe it to be impossible — to get a product commercialized.


Explain and define TR 81’s biggest takeaways.

Blackton:  The first takeaway is that life cycle applies to these products. The second is that the scientific method and exercising science is germane to this and to the life cycle.

The third takeaway is that this is a somewhat methodical process that is rather complex.  For cell therapy products we have the vector and the product. This helps the reader understand the role of vector in developing a control strategy for cell therapy.

When considering cell therapy, we talk about critical material attributes and how we identify and evaluate raw materials associated with the control strategy or the process as we develop the control strategy.

We have a specific section on primary cells as starting materials and vector starting materials that puts it in its context. At the time that we wrote this report, the following was unknown: What is vector? How does it fit into cell therapy processes? Is vector akin to active pharmaceutical ingredient, or is it a starting material? It’s both. But we state in the report that it’s like a critical starting material, and now it’s embodied at later conferences, where the FDA has stated the same thing — that it is critical, but they do require full process validation for a vector, which is outside the scope of this TR.

But vector is important, and you must develop its process, just like you must develop your cell therapy process.

The fourth takeaway is knowing that this space is highly academic, and the academic community doesn’t have much exposure to product development life cycle as defined by the FDA and other world regulators.

Finally, hopefully this report will help highly academic people shape their development processes or how they conceptualize new products, or how they transfer products out of universities and into the industry as well.

Who has access to TR 81?

Blackton: Anyone can purchase the report from the PDA, but members have access to an online portal where they can access the reports. You cannot print them from the online portal. When the report is released, members may download the documents for free for a specific period. After that, a fee applies for both members and non-members.

Who is the audience for this report?

Blackton: The audience for this report includes academic researchers who intend to define an entity that can then be commercialized. If academics use this report, it could help in their efforts to commercialize a product, because they would anticipate the data required to transfer to industry.

But academics are a secondary audience. The primary audience are those people in quality, development, manufacturing, and research within companies that are in early phase trials, anticipating moving into phase II and through commercialization of their products. It is important for them to look at this document, as well as the other docket TRs.