Ask the Expert – GMP Proteins for Cell Therapy Manufacturing

Sponsored by: Bio-techne
Session ends: May 12th, 2017, 3:00pm MST
Answers by: Tim Manning , R&D Systems


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.


This session is sponsored by

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, if he would host an Ask the Expert session on the topic. Tim was kind enough to agree to answer questions from readers this week on the topic of GMP protein manufacturing.

Tim Manning is the Product Manager for Proteins at R&D Systems, a Bio-Techne brand.  He 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.

This should be of interest to anyone interested in cell therapy research or those manufacturing cells that will be used as therapeutics.

ask the expert

Questions & Answers

What system do you use to produce your recombinant proteins?

If by system, you mean cell culture vessels, this is highly dependent on the type of cell lines used and the protein being expressed. Currently these include a combination of glass, stainless steel, CellSTACK, and WAVE systems. If you mean the source, this also very dependent on the protein. In most cases we use an […]» Read More

How are your GMP products packaged, to be sure they are stable and sterile?

Unless requested differently, our GMP proteins are lyophilized in glass vials, which is typically very stable. We have environmentally controlled stability chambers that are in continuous use to ensure that there is a documented understanding of protein stability during storage. Although GMP proteins as not labeled as sterile, microbial testing is done on all bulk […]» Read More

I am interested in your recommendations for setting up secondary suppliers. What if the GMP version is hard to source? Is it ok to have a research use only as a secondary or tertiary?

It is OK to use research use only (RUO) reagents, even as a primary source when GMP for manufacturing isn’t available. If this is the case, you should still be asking the same questions of the supplier that you would if they were manufacturing using GMP for cell therapy. You still have the same concerns […]» Read More

We have been having some trouble with mycoplasma in our lab, we feel we are doing all the right things for good lab practices, is there any chance this be coming from our raw materials?

As you know, mycoplasma can be very hard to deal with. They are resistant to some antibiotics, may be small enough to slip through typical lab filters, and they can linger on surfaces and equipment. Some potential sources of introduction are shared cell lines between labs, contaminated reagents such as serum or natural proteins, or […]» Read More

I seem to recall seeing something about the variation of animal sourced growth factors and cytokines having unexpected impacts on various cell types. Is this something you have experience with?

The vast majority of discussions we have about animal-free vs animal-sourced growth factors involve the risk of introducing pathogens. However, there are other points of variability that could be introduced by using animal-derived materials. “Animal-sourced” might mean that the natural growth factor is purified from a preparation like plasma. It may also refer to recombinant […]» Read More

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?

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 […]» Read More

Do you run cell based assays to test cytokine performance?

Yes. Each cytokine is tested for performance using cell-based bioassays that include proliferation, induced cytokine secretion, cytotoxicity, and others. Before a cytokine is released to the public, a bioactivity specification is established based on the consistent performance of a minimum of three bulk lots. After that, each new bulk lot must meet this defined activity. […]» Read More