cGMP Small Molecules

Stem cell therapies are beginning to enter the clinic, and with the clinical phases of development being highly regulated, there is a requirement for cGMP (Current Good Manufacturing Practice) ancillary reagents (raw materials) to assure therapy safety and suitability. At Tocris we support this development from the research to clinical phase, by offering the first cGMP small molecules for stem cell therapy. Partner with Tocris today and let us, help you develop the next stem cell therapy.

To view Bio-Techne's complete solutions for Cell and Gene Therapy manufacturing, including all GMP-grade reagents and analytical instrumentation, please visit bio-techne.com.

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cGMP Compounds Available

Tocris currently offers compounds SB 431542 (TGF-β, ALK4 and ALK7 inhibitor), DAPT (γ-secretase inhibitor), Y-27632 (ROCK inhibitor) and CHIR 99021 (GSK-3 inhibitor) manufactured to cGMP specifications. SB 431542 and DAPT can be used in protocols for the differentiation of stem cells into neural cells, while SB 431542 can also be used as a replacement for SOX2 in the reprogramming of fibroblasts to iPSCs. CHIR 99021 enables reprogramming of human somatic cells into iPSCs, and Y-27632 increases the survival rate of hESCs and iPSC-BMECs undergoing cryopreservation. cGMP compound XAV 939 (tankyrase inhibitor) will be available in early 2019.

To register your interest, suggest a compound to be manufactured to cGMP, or to let us know your cGMP requirements, please fill out our cGMP Compound Register Interest form

cGMP Quality

The quality of stem cell therapies and other ATMPs (Advanced Therapy Medicinal Products) depend on the quality and safety of raw materials / ancillary reagents. It is best practice for these to adhere to cGMP specifications when being used for the development of stem cell therapies and other ATMPs. The Tocris range of cGMP small molecules is manufactured following relevant sections of ICH Q7 guidelines (Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients).

Our highly skilled team have full control over the cGMP process, meaning we can ensure from the outset:

  • Batch-to-batch consistency
  • Traceability from starting material to final product
  • Animal-free production

Safety

Safety considerations are of high importance when developing stem cell therapies and other ATMPs for use in the clinic. Our cGMP small molecules are classified tier 2 risk as per USP <1043>.

USP <1043> : Ancillary Materials for Cell, Gene, and Tissue-Engineered Products

AM Risk Tier 2: Low-Risk, Well Characterized Materials with Intended use as AMs, Produced in Compliance with cGMPs.

To ensure the safety of your stem cell therapy, we can ensure:

  • Traceability from starting materials to final product
  • Fully qualified vendors of raw materials for our production processes
  • Animal-free production
  • Endotoxin and bioburden tested compounds
  • Stringent QC testing

Security of Supply

It is vital to have a consistent and reliable supply of cGMP raw materials when developing ATMPs such as stem cell therapies. Any delay or quality issue can result in significant issues, including increased cost and risk to patient samples. At Tocris we are well known for our consistent and reliable resupply and can offer you:

  • Consistent and assured supply of cGMP materials
  • Supply agreements and batch reservations
  • A point of contact at all times throughout your development process
  • Ability to scale up

Why not contact us today to discuss a supply agreement, reserve your batch, and let us know your scale of manufacturing requirements.

Stringent QA and QC

To ensure the highest quality our cGMP compounds are synthesized under a quality assured manufacturing system and subjected to stringent quality control.

Analytical Tests:

  • Purity - HPLC
  • Product identification - NMR and Mass Spectrometry
  • Water content - Karl Fischer
  • Residue on Ignition
  • Residual solvents
  • Solubility

Microbiological Tests:

  • Bioburden
  • Endotoxin

Product Specific Documentation:

  • Certificate of Analysis (CofA)
  • Safety Data Sheet (SDS)
  • TSE/BSE statement (Transmissible Spongiform Encephalopathy / Bovine Spongiform Encephalopathy)
  • Product Specifications

These documents are available on request.

Transition from Pre-clinical to Cell Therapy

An important consideration when developing a cell therapy is when to transition raw materials from research use only (RUO) to cGMP. Although the quality and safety of raw materials is less important during the pre-clinical stages of development, the cost and freedom of change increases and decreases respectively, as the clinical phase of development is advanced. We would recommend identifying a reliable supplier of your required cGMP raw materials early in the preclinical development stage, and transitioning from RUO to cGMP as early as possible during development. This will avoid the need to conduct time-consuming and expensive comparative studies during the latter stages of clinical development.

Regulatory Support

We offer the following regulatory support on request for our cGMP product line:

  • Auditing of our manufacturing facility (we are based in Bristol, UK)
  • Change notifications
  • Additional product data

FAQs:

What is the difference between RUO and cGMP small molecules?

Our cGMP small molecules are manufactured following relevant sections of ICH Q7 guidelines. They are also categorized in the risk tier 2 classification (low risk, well characterized materials with intended use as AMs, produced in compliance with cGMP) of USP <1043>. Our RUO products, along with the RUO products of other suppliers, are categorized in the risk tier 3 classification (moderate-risk materials not intended for use as AMs) of USP <1043>.

Each vial is weighed to a precise and specific amount. The appropriate volume of solvent can be injected directly through the septum into the vial. We would recommend passing the solution through a 0.2 μm filter.

We also carry out microbiological testing on our cGMP small molecules, specifically endotoxin and bioburden testing.

Are cGMP small molecules animal free?

Yes, our cGMP small molecules are animal free

Can cGMP small molecules be used as therapeutics?

No, our cGMP small molecules should only be used as raw materials / ancillary reagents for further ATMP manufacture, such as stem cell therapies.

Why has Tocris developed a cGMP product line?

Stem cell therapies are beginning to enter the clinic. As the clinical phases of cell therapy development are highly regulated, there is now a requirement to use cGMP compounds as ancillary reagents, to ensure the safety, suitability and reduced risk of the stem cell therapy being developed. By introducing a cGMP product line, Tocris is fulfilling its commitment to provide the life science community with the latest and most relevant reagents available, to make new discoveries possible.

Literature for cGMP Small Molecules

Tocris offers the following scientific literature for cGMP Small Molecules to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


Stem Cells

Stem Cells Scientific Review

Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.

Stem Cell Workflow

Stem Cell Workflow Poster

Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.

Stem Cells

Stem Cells Poster

Written by Rebecca Quelch and Stefan Przyborski from Durham University (UK), this poster describes the isolation of pluripotent stem cells, their maintenance in culture, differentiation, and the generation and potential uses of organoids.