State of Research

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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Press Release: Allele Biotechnology & Pharmaceuticals Closes Purchase of cGMP Facility for Production of Clinical-Grade Cells for Cell Therapy Applications

SAN DIEGO–(BUSINESS WIRE)–Allele Biotechnology & Pharmaceuticals, Inc. (“Allele”), a leader in the development of specialized cells for pharmaceutical drug discovery and regenerative medicine, today announced that it has closed the purchase of a new facility intended for its cGMP (current good manufacturing practices) production of clinical-grade cells for cell therapy applications.

The 18,000 square-foot facility, located near the main headquarters of Allele in San Diego, California, will be the center of production of human induced pluripotent stem cells (hiPSCs) using Allele’s proprietary synthetic mRNA platform, a technology that generates hiPSCs with neither the random integration of foreign DNA nor the use of whole virus or virus-based elements, drawbacks that are common to other technologies for making hiPSCs. Such “footprint-free” cells will be produced by Allele for industrial and academic partnerships, as well as Allele’s own efforts in the area of cellular therapeutics.

hiPSCs, as cells that have the potential to become any cell in the human body, hold great promise for therapies that can alleviate or cure human disease. Towards this end, Allele has recently made a number of advances regarding the differentiation of hiPSCs towards cells of specific lineages, such as neural progenitor cells, neurons, astrocytes, mesenchymal stem cells, cardiomyocytes, skeletal muscle cells, hepatocytes, and adipocytes, including brown fat cells. These cells would also be produced in the cGMP facility when intended for specific therapies.

“This dedicated facility will help us to realize a number of our visions in bringing the benefits of pluripotent stem cells to society,” said Jiwu Wang, Ph.D., President and CEO of Allele. “The first step in helping people in need with all the stem cell technologies developed in labs is to clear a path to move them from bench to bedside, which requires high-quality, controlled production that can be monitored by the FDA. Together with our licensees, drug development partners, investors, and individuals who would like to participate in banking hiPSCs for research and therapy, we anticipate even faster pace in our business development in this area.”

Contacts

Allele Biotechnology & Pharmaceuticals, Inc.
Jiwu Wang, 858-587-6645
info@allelebiotech.com

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The NIH is one step closer to be short of $260 million from its 2011 budget

The National Institutes of Health (NIH) 2011 budget will be cut by $260 million in the budget that the House has just passed based on the last minute pact reached last Friday to avoid federal government shut down.

The NIH’s 2011 budget will be $30.7 billion, down 0.8% from its 2010 budget of $30.9 billion, according to news releases that can be found from various sources. Previously, the President proposed a $32.1 billion budget for the NIH and the House of Representatives allocated $29.4 billion to the agency. President Obama asked for a $1 billion increase for the NIH in 2012, which will be in new debate to start immediately. Chances are the 2012 budget for the agency will be less than what the administration wanted.

Combined with “the cliff effect” from the ending of the stimulus money the NIH has epically managed since 2009 to fund extra research projects, the negative growth of the NIH budget could mean less academic positions and tighter lab budgets ahead. Cutting-edge technology and cost effectiveness will be the key for survival of the fittest in the biomedical research jungle.

Promotion of the week: Save 10% on any purchase of feeder cells. Email brianahasey@allelebiotech.com with offer code : FDST11

New Product of the week: Damage-free cloning kit for difficult cloning projects—get recombined plasmids or failed ligation? Your DNA is damaged by purification bugger and/or UV, ask us how to deal with it oligo@allelebiotech.com

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Thursday, April 14th, 2011 NIH Budget and You, State of Research 1 Comment

State of the Biomedical Research–Not So Good for Pharma R&D

Exerpt from From Science News

Pfizer’s R&D budget, $9.3 billion in 2010, will drop to less than $8.5 billion this year and to between $6.5 billion and $7 billion in 2012, and the company will stop funding research in internal medicine, allergy and respiratory diseases, urology, and tissue repair.

In fact, the pharmaceutical industry as a whole faces financial pressures, as companies are producing fewer new drugs than in the past. In these conditions, even highly promising research has gotten the ax; in November, Roche cut its RNA interference research unit after spending $400 million over 3 years.

Drug companies also seem less wary nowadays about outsourcing. Among other examples, Eli Lilly began outsourcing animal toxicology studies in 2008, and Wyeth (purchased by Pfizer in 2009) began out sourcing data management for its clinical trials in 2003. In 2007, AstraZeneca even decided to move the production of many active pharmaceutical ingredients—perhaps the core activity of a drug company—to China.

These downsizing events are not particularly caused by still depressed economy, they have more to do with industry-specific patent expiration and productivity issues with large pharmas. What does it all mean to current graduate students and postdocs? Perhaps an even tighter job market than now for starting researchers for some years to come until the next round of sea change comes around. Be aware of what’s going on in smaller, more productive, and focused biotech companies.

New Product of the Week 020711-021311: Lentivirus expressing Luciferase 5 vial package

Promotion of the week 020711-021311: 10% off Luc Assays

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Thursday, February 10th, 2011 State of Research No Comments

Integration of Orbigen Products

Allele Biotech has been marketing products previously offered by Orbigen since July of 2008. In the process, Allele Biotech has transferred the majority of the Orbigen products to its own product lines, and left out a few that were no longer in demand, under proper license, or in some cases replaced with newer and better versions.

The biggest class of Orbigen products now under the Allele Biotech brand name are the polyclonal antibodies such as anti-EDG1 EDG2… EDG8 (catalogue numbers: PABs 10626, 10619, 10628, 10630, 10496, 1063), anti-BMRPs (catalogue numbers: PABs 10536, 10537, 10538). Other popular polyclonal antibodies from Orbigen include PAB-10983, PAB-10216, PAB-10683, PAB-11651, PAB-11141, PAB-10241, PAB-10469, PAB-10778, PAB-11248, PAB-11665, PAB-10563, PAB-10774. Orbigen antibodies have been tested in hundreds to thousands of labs over more than ten years.

One key product group developed by Orbigen is the baculovirus system, which includes the viral Sapphire genomic DNA and pOrb transfer vector plasmid for efficient packaging. We have further developed the pOrb vector into a bicistronic vector for dual expression or mammalian infections.

Retrovirus packaging cells, on the other hand, have been obtained from non-Orbigen sources and are now called Phoenix 2 as products under a new product line, the Gryphon retrovirus system. These cells have similar functions but were built by different researchers and further selected at Allele Biotech. Like all packaging cells we have experience with, these cells do not attach well after a freeze/thaw cycle. It is absolutely essential to wash away DMSO and better seed them in high quality, attachment enhancing dishes such as our EcoCulture plates.

Products previously under the Orbigen brand name are now included in Allele Biotech’s brand new shopcart (now beta-testing at shop.allelebiotech.com). We hope the new functionalities at the new site combined with the relevant knowledge and information you used to enjoy at our current allelebiotech.com site will provide you with an improved shopping experience.

    New Product of the Week 110810-111410:

Retroviral vector with drug resistance new version, ABP-PVL-IRES10P.

    Promotion of the Week 110810-111410:

GFP-Trap beads-immobilized camelid antibody for GFP fusion pull down. 15% off ACT-CM-GFA0050, any number of vials ordered this week. Use code SP110810.

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Wednesday, November 10th, 2010 Allele Mail Bag, State of Research No Comments