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Stem cell therapies offer great potential for the treatment of several pathologies, including Parkinson’s disease, diabetes, and heart disease. The stem cell therapy market is undergoing a period of growth, with more and more therapies moving towards and entering the clinic. This has resulted in discussions as to the quality and suitability of the ancillary materials (AMs) being used during the cell therapy manufacturing process. In many instances the AMs available have only been manufactured to a quality suited for research and pre-clinical work, therefore careful risk assessments need to be undertaken as to their appropriateness for clinical development.
AMs are reagents that are used in the cell therapy manufacturing process but are not intended to be found in the final product. These include reagents that are used for stem cell culture, including reprogramming, expansion and differentiation processes. Small molecules and growth factors are examples of such AMs. Although AMs aren’t meant to be found in the final product, they do influence it's quality, and can therefore impact the safety, purity and thus suitability of the final cell product for clinical use.
It is vital that AMs are carefully qualified for use throughout the stem cell therapy manufacturing process. The focus should be on mitigating the risk to patient safety of the cell therapy, and it is critical that part of this conversation is selecting the correct and most suitable AMs to use at the different stages of therapy development.
Small molecules offer several advantages when compared to other ancillary materials for stem cell therapy manufacture.
Patient safety will always be the priority during the development of a stem cell therapy and regulators may ask how the risk of using AMs, as part of the production process, has been mitigated. It is worth carefully qualifying the suitability of an AM before moving into the clinic, to avoid having to switch to an alternative AM due to regulator feedback, which will inevitably lead to a loss of considerable time and money.
How do you know if your AM is suitable for use in stem cell manufacture?
Ancillary materials should be qualified based on source, purity, identity, safety and suitability. If using an AM where these factors are unknown, expensive and extensive qualification studies may be required to ensure that your chosen AM is suitable for use and won’t compromise the final cell therapy.
If you are using a small molecule as an AM, then the ICH and USP provide recognized frameworks: ICH Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients; and USP <1043>, Ancillary Materials for Cell, Gene and Tissue-Engineered Products.
Figure 1: Schematic of USP <1043> Ancillary Materials for Cell, Gene and Tissue-Engineered Products. GMP small molecules are considered low risk to the final cell therapy, and intended for use as AMs, whereas RUO small molecules are considered moderate risk, and not intended for use as AMs.
When should you be looking to transition from RUO to GMP materials?
Although pre-clinical development can be undertaken with RUO materials, it may be more cost effective and easier to start working with GMP AMs early in the development process. This is because switching from RUO to GMP materials will require validation and optimization studies to ensure processes remain consistent. Changing materials as the cell therapy is about to enter the clinic, will result in expensive comparative studies, and be subject to greater scrutiny than if the GMP material was validated earlier on. Validation studies are also time consuming, causing delays when there are often critical time pressures to move the cell therapy into the clinic.
By using GMP materials early in the development process, there will be no need for comparative studies at a later date, saving time and money, and ensuring a more seamless transition from the bench into clinical trials.
So, what’s next? Work with your supplier early in the development process to qualify your required AM and ensure that the AM meets regulatory requirements. Selecting a GMP supplier may be advisable to reduce the need for extensive qualification, and to ease your transition from the bench to the clinic.
Bio-Techne offers an innovative solution to your stem cell therapy manufacturing needs, with a portfolio that includes the largest range of GMP proteins, and the first off-the shelf GMP small molecules available on the market, as well GMP media and media supplements. Find out more about clinical solutions available from Bio-Techne today!
Solomon (2016) Current perspectives on the use of ancillary materials for the manufacture of cellular therapies. Cytotherapy. 41, 18. PMID: 26596503