Allele Biotech

cGMP Compliance: What Does It Mean for Your Cell Lines?

As the promise for cell-based therapy grows, the interest in making clinically relevant cell lines has skyrocketed for industrial and academic researchers alike. For translation into human therapies, cell-based products must be made following current Good Manufacturing Practice (cGMP). Many groups have already claimed to generate cell lines that are “cGMP-compliant,” “cGMP-ready,” or “certifiable under cGMP.” But what does it take to be truly cGMP-compliant, and what practices can you introduce in your lab to comply with cGMP standards?

A common misconception in the United States is that a facility is granted a ‘cGMP license’ from the government to manufacture cGMP-grade products. Rather, the Food and Drug Administration (FDA) evaluates the manufacturing process for each product to determine if it is compliant with cGMP standards. The primary concern when it comes to deriving cell-based products for therapies is making sure that the product is derived in a safe and reproducible manner. To ensure maximum quality assurance, researchers should

• choose reliable, xenogeneic-free raw materials,
• establish and monitor a clean environment,
• qualify all equipment and software,
• remove variation in laboratory procedures by creating detailed Standard Operating Procedures (SOPs) and by providing rigid process validation at each step.

Nevertheless, even establishing robust quality assurance does not imply that the process is scalable for commercial production. In the world of biologics, “the product is the process.” A requisite step to ensure a smooth transition to cGMP practice is to ensure that the process of manufacturing is not altered due to changes in production scale. For example, depending on the therapy, millions or billions of cells may be required for a single patient. Therefore, it is in the best interest of the researchers to develop a scalable method at the beginning to avoid revamping the entire process (e.g., changing from adherent cells to suspension). Along these lines, the quality control (QC) requirements of cell-based products should be carefully considered and not have to include difficult-to-assay tests. For example, some cell lines have been qualified as cGMP-compliant upon conversion from research-grade conditions to cGMP quality standards. Rigorous tests were performed on the converted lines to ensure that the cells were free of contamination. Even though strict measures were carried out to ensure cGMP compliancy, deriving cell lines in this manner makes scalability and reproducibility a challenge. Ideally, the entire process of deriving cell products for clinical use should be performed under cGMP conditions: from the acquisition of human tissue to the manufacturing, testing, and storage of derivative cell products.

Another important consideration when instituting cGMP-compliance is documentation. Each process must be described with rigorous SOPs, the training of individual manufacturing operators must be well-documented, and the entire established process must be validated and well noted. Failure to document—in the eyes of the FDA—is often equated with failure to perform the underlying activity. It is equally important to remain ‘current.’ The FDA expects manufacturing processes to stay up-to-date with current regulations, even as policies change.

For an academic lab, closely aligning with cGMP standards can ensure that the resulting cell lines are comparable to other truly cGMP-produced products used during clinical trials. It is in the best interest of academic researchers to establish rigorous SOPs and use qualified reagents and equipment, even if it is not possible to carry out all steps in a certified cleanroom. Whenever possible, it is advisable to acquire truly cGMP cell lines from appropriate sources for preclinical projects; if prohibited by costs or other reasons, it is recommended to use a protocol that is as close to cGMP as possible.

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Researchers use GFP nano antibody to study organ growth

Single-domain nano antibodies have a broad range of applications in biochemistry due to their small size, high affinity, and high specificity. Now, a team of researchers from the University of Basel and the University of Zurich has demonstrated that nano antibodies can be used for research in complex living organisms such as Drosophila, uncovering another new and exciting application for nano antibodies.

The team used nano antibodies to develop an assay for studying morphogens, molecules that regulate the pattern of tissue growth and the positions of various cell types within tissue. Morphogens form long-range concentration gradients from a localized source, ultimately determining the fate and arrangement of cells that respond to that gradient. Drosophila is a classic model system for understanding how morphogens regulate organ development. One morphogen called Dpp controls uniform proliferation and growth of the wing imaginal disc. Yet because Dpp is an extracellular, diffusible protein, it is difficult to immobilize in situ. Therefore, despite over 20 years of studying the role of Dpp as a morphogen, the lack of a dynamic system for controlling Dpp gradients has prevented researchers from understanding precisely how Dpp governs development of the wing disc.

By developing a novel synthetic system using nano antibodies, the researchers were able to modulate the concentration gradient of Dpp at the protein level. Their system—coined “morphotrap”—uses a membrane-bound GFP nano antibody to “trap” GFP-tagged Dpp at different locations along the wing imaginal disc. By tethering Dpp in a controlled spatial manner, researchers were able to determine how Dpp gradients affect wing disc development. They discovered that the gradient of Dpp is required for the patterning of the wing disc but not for lateral growth, disproving one of the field’s popular theories that address the role of Dpp. In addition to resolving the controversy with respect to the role of Dpp as a morphogen, this study pioneers a new method for using nano antibodies in situ.

“Dpp spreading is required for medial but not for lateral wing disc growth.”
Harmansa S., Hamaratoglu F., Affolter M., Caussinus E.
Nature. 2015 Nov 19;527(7578):317-22. doi: 10.1038/nature15712. Epub 2015 Nov 9.

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Allele Biotech Announces Opening of New Facility in San Diego

Class A biomedical labs with GMP plans.

Firsr Floor Multipurpose Lab

We’re happy to announce that after a long construction and moving process, Allele Biotech has passed its final inspection hurdle and is now officially open for business at our new location, a two-story building we recently purchased on Nancy Ridge Drive. This facility is located at the heart of the Sorrento Mesa biotechnology cluster and contains two floors of brand new lab space to support production and R&D, plus plenty of room for expansion. We’re also welcoming two tenants, Nano CELLect and MesaTech, as well as the non-profit research institute we helped launch earlier this year, the Scintillon Institute (

For our local colleagues and valued customers, please feel free to contact us to schedule a personal tour of our new facility and to meet with our esteemed group of experts who are always willing to discuss in person, your scientific needs

Keep an eye out on this blog for important dates, promotions and more news and photos from the new facility as we prepare for our upcoming open house! Hope to see many of you then if not sooner!

New Product Notes: iPS reprogramming and transdifferentiation product line including the Potent 6F mRNA Reprogramming Premix, IVT templates for Ascl1, Myt1l and neuro D2 mRNAs.

Allele Biotech Building Front

6404 Nancy Ridge Drive, San Diego, CA 92121

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Friday, November 16th, 2012 Allele Mail Bag No Comments

Why Allele?

Allele provides you with tools that you will find very helpful.  The two main motives for Allele developed products are:
1) To incorporate the most advanced technologies in the field
2) To provide equal utility as other companies’ equivalent products at a much more reasonable cost.

How did we do it?        By developing technologies internally, in most cases with government grant funding, by in-licensing others’ discoveries, and by listening to you, our customers.

What else do we do?      Conduct basic curiosity-driven research just like most of our customers. It helps to stay on the edge and connect to the community.

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Tuesday, July 28th, 2009 Customer Feedback, Open Forum No Comments

Our Message to Allele’s Followers

What we at Allele Biotech see ourselves doing in the sense of fulfilling an obligation to the society and our peers in scientific research: Salvation and success through innovation and diligence, reaching for a place of efficient sustainability where monopolies do not win and ordinary people have the chance to realize their dreams.

We don’t believe in dominance by a few big boys, because we don’t believe that they can provide researchers with the best value. We want people that deal with us to see that there is room for development by an individual or a small group of highly dedicated and talented persons, as your own group in academia or a small company can do. This is the beauty of our industry and our field.

We like to see our people challenge existing doctrine and hypothesize new ones, after all, isn‘t that how we are trained through grad school and postdoc training, but somehow and somewhere it starts to seem to difficult to do, especially when you try to get a paper accepted or a grant rated among the top 10%. We don’t want to lose our edge, even if we have to learn to better place it. We will continue to move this way, and we want you to come along for the ride.

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Tuesday, July 7th, 2009 Customer Feedback, Open Forum No Comments