We recently finished our Ask the Expert discussion, “GMP Proteins for Cell Therapy Manufacturing”. During this Ask the Expert session, we discussed differences between research use only and GMP proteins. Specific topics included quality testing, FDA support, supplier responsibility, and transitioning from research use only to GMP proteins.

GMP (Good Manufacturing Practice) growth factors and cytokines designed for therapeutic manufacturing are a critical component in defined medias. To date, the cell therapy industry has accepted the term GMP for this reagent class despite the fact that there is no direct oversight by regulatory authorities. These proteins are intended to be used during further manufacturing and do not come in direct contact with the patient. In fact, cell therapy manufacturers need to take steps to ensure that reagents used for further manufacturing are removed before the cells can be used in the clinic. In addition, FDA-regulated, clinical grade proteins that can be directly used as therapeutics may also be described as GMP, leading to confusion of the term “GMP” within different contexts.

We recently published a blog, “GMP Proteins for Cell Therapy Manufacturing: Top 6 Things to Know,” that discusses what you should look for in a supplier. It was a popular piece with readers, so we asked the author, Tim Manning, Product Manager for Proteins at R&D Systems, A Bio-Techne brand, if he would host an Ask the Expert session on the topic. Tim was kind enough to agree to answer questions from readers on the topic of GMP protein manufacturing. Tim has an extensive knowledge of protein production and manufacturing, quality control, and GMP guidelines. Before joining Bio-Techne, Tim received his PhD in from the University of Alabama at Birmingham and was a Postdoctoral Fellow at the University of California, San Diego.

Below is a sneak peek of the discussion, for a full transcript, please see – Ask the Expert – GMP Proteins for Cell Therapy Manufacturing.

Question:

As I move my research toward a translational therapy, when should I transition to GMP?

Answer:

I would suggest moving to GMP as early as possible, potentially even during R&D work. This is especially the case if you are using cytokines or growth factors from a supplier that doesn’t also offer GMP for further manufacturing. Proteins are made in biological systems and are, therefore, susceptible to variability. Growth factors from different suppliers can appear identical on a Certificate of Analysis (C of A), yet still exhibit differences in folding, glycosylation, or impurities that can impact activity in your system. The earlier you incorporate the appropriate materials into your process, the easier and less expensive it is to make changes if they become necessary. Often cost is the main reason for delay. In order to keep costs down, work with your supplier to develop supply agreements that take into account bulk purchases, or bundling of other reagents and instrumentation.

Question:

I work in an academic lab and we have talked about using higher quality proteins in our research just to avoid lot variability, but it would involve a cost increase. Are there any other benefits to using GMP proteins in a research setting?

Answer:

As you indicate, one of the main reasons for shifting to GMP is to ensure consistency. This comes from all of the extra analytical testing, documentation, and oversite of the manufacturing process. Protein inconsistencies can lead to negative results and missed opportunities, false positives that lead you down an incorrect path, or results that simply can’t be repeated. All are incredibly frustrating to the researcher and, in the long run, can be more expensive than spending a bit more up front. However, cost is always a factor and must be considered. One suggestion I can make, if you haven’t already, is to develop a relationship with your vendor’s sales representative. At R&D Systems, our reps do an excellent job at finding ways for researchers to save. You might find that shifting to GMP is not as expensive as you think.

Question:

What kind of support is available for FDA filings. We are beginning to think about moving to GMP what should we expect from suppliers?

Answer:

Some basic things to expect include a lot-specific Certificate of Analysis that will detail the identity of the protein and analytical testing that has been done to ensure the material is meeting specifications. A Certificate of Origin may be obtained that provides traceability of the materials used in manufacturing of the protein. This would be key document for those wanting to establish they are working with animal-free raw materials. Drug Master Files (DMFs) may also be submitted to regulatory authorities by the supplier. DMFs provide details about manufacturing process and can be referenced during filing. They also provide a mechanism for submitting proprietary information. A supplier should be very open to audits of their facilities where you can review batch records that provide critical information about lot-to-lot consistency. Lastly, look for someone with experience. Chances are they’ve run across most questions, and they can be an asset as you move through the process.