Because recombinant protein therapeutics are genetically engineered, they have the potential to induce an immunogenic response in a patient. Immunogenicity risk, as defined by the formation of anti-drug antibodies (ADA), is a significant event that can compromise patient safety and ultimately sink a biologics program. With the increasing number of recombinant protein therapeutics in development, … Continue reading Predicting Immunogenicity of Protein Therapeutics
Significant numbers of therapeutic small molecule drugs–as many as 40% of marketed and 90% of clinical–pose dosing and formulation challenges due to solubility issues from their hydrophobic character. Now some of these compounds are being revisited using nanocrystal technology. Nanocrystal drug technology can improve solubility of hydrophobic drugs by increasing surface area-to-volume ratio and dissolution … Continue reading Nanocrystal technology can transform poorly soluble drugs into successful medicines
Capture of antibodies in biopharmaceutical processes is most commonly performed using affinity chromatography on Protein A. While Protein A works well, the commercially available chromatography resin is expensive and its use requires testing of the bulk drug substance for residual Protein A leached from the chromatography column during operation. There has been interest for a … Continue reading Engineering Micelles for Antibody Capture
A principal reason for why the manufacture of biologics is difficult is the structural complexity of the recombinant glycoproteins that are being produced. As biologics production moves from research and development to large-scale clinical and, ultimately, commercial production, critical variables–both upstream and downstream–must be controlled to ensure reproducibility of product. One variable is the product’s … Continue reading Taking Charge of Charge Variants
The annual “Antibodies to Watch” article series is celebrating its 10th anniversary. Published in the journal mAbs and widely anticipated at the beginning of the new year, these articles have provided updates on the development of clinical antibody therapeutics each year since 2010 and have given readers detailed insight into what is anticipated for the … Continue reading Antibodies to Watch 2019: 10 Years and Counting
Nancy Bradish Myers of Catalyst Healthcare Consulting in Washington, D.C., knows FDA well and recently assessed the impact of the US government shutdown on FDA. Here’s what is happening now, under the FDA shutdown: The FDA cannot accept any new drug, biologic, device, or generic applications that require payment of user fees until the shutdown … Continue reading The Impact of the Shutdown on FDA
Understanding the critical parameters that enable cells to grow to high density in a bioreactor is important to achieving a highly productive cell culture manufacturing process. Multi-omics, which is the use of metabolomics and proteomics combined with RNA-Seq, is a powerful analytical tool that provide a wealth of information. Previously these techniques were only applied … Continue reading Metabolite Analysis Can Increase Productivity in CHO Cell Culture Processes
We have covered biosimilars in this blog before. Biosimilars are biological products that are similar in potency, safety and efficacy to approved reference (or “innovator”) products, but are manufactured by other companies and are intended to compete for market share with the innovator product. Congress, through the Biologics Price Competition and Innovation Act (BPCI Act) … Continue reading Abbvie IP Deal with Sandoz Will Delay Humira Competitor
One of the hottest areas of medicine is cancer immunotherapy. The importance of this field to medicine was highlighted last month with the announcement of the 2018 Nobel Prize winners in Physiology or Medicine. This year’s recipients are James Allison at the University of Texas MD Anderson Cancer Center in Houston and Tasuku Honjo at … Continue reading A Nobel Nod to Cancer Immunotherapy
CAR-T cells are a new and exciting drug class in which treatment involves the use of transformed immune cells for cancer therapy. A patient’s T- cells are removed, transduced and expanded ex vivo. The genetically modified T- cells are infused back to the patient where they bind and kill their cancer cell target. The basic principle … Continue reading CAR-T cells: Beyond CD19
We have discussed bispecific antibodies (BsAbs) in this blog before. Teneobio, Inc., a biotechnology company in Menlo Park, CA, is developing a BsAb as a potential therapeutic for the treatment of cancer. Chamow & Associates is assisting Teneobio to produce this novel therapy for clinical testing. This IgG4 BsAb is directed against a tumor associated … Continue reading An Alternative to Protein A for Efficient Capture of a Bispecific Antibody
Biologics are the fastest-growing class of therapeutic products in the United States. As products of genetic engineering technology, they were initially introduced in the 1980s and the segment has been expanding ever since. As many of these products have come off patent, “generic” forms of biologics, or biosimilars, have recently been introduced. Biosimilars are biological … Continue reading Biosimilars on the Sale Rack
Reported on 8 March by Eric Palmer from Fierce Pharma, 2018 marks a landmark event in the global biologics supply chain—for the first time, an FDA approved biologic will be manufactured in China for the U.S. market. WuXi Biologics will produce the HIV targeting-monoclonal antibody (mAb) Trogarzo. Trogarzo was developed by Taiwan-based TaiMed Biologics and … Continue reading Biologics from China
You may be aware of the diagnostic value of hemoglobin A1C in managing patients who are at risk of developing diabetes. Hemoglobin A1C is glycated hemoglobin that results from the non-enzymatic chemical reaction of hemoglobin with glucose in the blood. The same phenomenon can occur during cell culture production of biologics such as mAbs. How … Continue reading Can a Sugar High be a Problem in Cell Culture? You Betcha!
Cell growth and product expression are key operating parameters in the manufacture of biologics from CHO cells. Chemical additives such as sodium butyrate have been used to enhance product expression. Sodium butyrate acts to enhance gene expression, but it can have negative impacts on cell viability by increasing cytotoxicity and apotosis. Moreover, it can alter … Continue reading Boosting Protein Yield in CHO Culture
We report on antibody drug conjugates, another exciting drug class that is proving to be an important tool in the fight against cancer. Leukemias, lymphomas, and myelomas are among the most prevalent and difficult cancers to treat. Challenges include identification specific targets and delivery methods. These cancers also have significant percent of relapse and can … Continue reading Antibody Drug Conjugates: Converting Antibodies into Therapeutic Guided Missiles
We have reported before on the annual preview of mAb products published by the journal mAbs at the start of each new year. For 2018, Hélène Kaplon & Janice M. Reichert, in “Antibodies to watch in 2018”, reveal a surge of antibody therapeutics granted approval in the European Union or United States in 2017. Ten … Continue reading Antibodies to watch in 2018
The eagerly awaited Part 2 of our review of bispecific antibodies (bsAbs) entitled “Therapeutic IgG-Like Bispecific Antibodies-Modular Versatility and Manufacturing” appears in the January 2018 issue of BioProcess International. In this follow-up to Part 1, which highlighted the characteristics of bsAbs, we describe in detail upstream and downstream manufacturing considerations when producing bsAbs and how … Continue reading More fun with bispecific antibodies!
At Chamow & Associates we have an ongoing interest in therapeutic Fc-fusion proteins. We have published recently on the subject (A. Linderholm and S.M. Chamow, Immunoglobulin Fusion Proteins, Parts 1 and 2, Bioprocess International 12(9) 30-35, 2014 and 12(10) 20-27, 2014, respectively), and Dr. Chamow has presented at conferences including last month at PEPTALK 2018 … Continue reading Therapeutic Fc Fusion Proteins to Watch
Bioprocesses used to produce recombinant proteins are based on the growth and expansion of living cells in bioreactors. Using the tools of genetic engineering, scientists modify living cells, usually Chinese hamster ovary cells, to produce the protein of interest as they grow and divide. Once the cells reach maximum cell density, they are maintained by … Continue reading How Good are Assays for Host Cell Impurities?
Dr. Chamow is presenting at the PEPTALK 2018 conference in San Diego this week (Jan 8). His presentation is entitled “Making proteins “druggable”: Fc fusion proteins as a therapeutic class”. In this talk, Dr. Chamow highlights that the potential therapeutic value of many proteins—including enzymes, receptors, cytokines and peptides—can be realized by fusing these proteins … Continue reading Dr. Chamow at PEPTALK 2018
As multivalent antibodies find their way to the therapeutics market, the ability to evaluate affinity and avidity becomes a key step to their success. Separating individual binding units by cutting the molecule with enzymes is key to understanding affinity and avidity. Proteolytic cleavage of mAbs to generate Fab and Fc fragments is typically performed using … Continue reading Cutting mAbs with precision: GingisKHAN™
New this month, from Chamow & Associates’ Jennifer Bratt, Angela Linderholm, Bryan Monroe and Steven Chamow, is a review on bispecific antibodies (bsAbs) published in BioProcess International titled “Therapeutic IgG-like Bispecific Antibodies and Their Manufacturing Challenges, Part 1”. The authors assemble a detailed overview of a new class of therapeutics in the early stages of … Continue reading Bispecifics Abs: New Therapeutic on the Block
One of the first tasks necessary for recombinant production of a protein or mAb is synthesis of cDNA(s) that will encode the protein of interest. This is typically done by reverse translation of the amino acid sequence of the desired protein into a DNA sequence, followed by chemical synthesis of that sequence. It is widely … Continue reading Rare Codons Enhance Protein Folding and Translation Efficiency
We often blog about monoclonal antibodies and the increasingly important role of this drug class in modern medicine. Monoclonal antibodies were first made possible with the development of hybridoma technology in 1975 by Georges Kohler and Cesar Milstein. In the 1980s, hybridoma technology gave way to genetic engineering and recombinant monoclonal antibodies were born. It … Continue reading Oligoclonal Antibodies Offer a Multi-Pronged Attack Against Disease
Until a few years ago, millions of American gout sufferers could buy colchicine, a long-established prescription drug to treat the painful ailment, for about $0.09 a pill. But in 2010, the price soared to about $4.50 a pill for the same medication, which had been used safely and effectively since the 1800s. The reason for … Continue reading The Cost Implications of the FDA’s Unapproved Drugs Initiative
Success in targeted delivery of therapeutics often relies on formulation. The ability to get biomolecules to where they are needed and taken in by the correct cell types requires strategic design. One technology currently drawing interest among pharmaceutical scientists is the use of exosomes as a transporter of therapeutics. Exosomes are membrane vesicles released into … Continue reading Exosomes – Nature’s Packaging
Multiple Myeloma (MM) is a plasma cell malignancy that accounts for approximately 1% of all cancers. The disease often involves bone and kidney, causing morbidity from pathological fractures, bone pain, spinal cord compression and renal failure. In the past decade, intensive research into the biology of myeloma has exposed many new potential therapeutic targets. In … Continue reading A new and exciting Monoclonal Antibody for Multiple Myeloma: Daratumumab
Monoclonal antibodies (mAbs) are remarkable proteins. Representing more than 50 FDA approved products for a variety medical indications, mAbs are the fastest growing class of new biologics today. Produced naturally by immune cells, these protein molecules function as the first line of defense for our immune systems to control infection and cancer–to eliminate invasive agents … Continue reading Antibodies to watch in 2017
The field of immuno-oncology has rapidly expanded since the 2011 approval of ipilimumab, the first monoclonal antibody that acts as an immune checkpoint inhibitor and is effective in treating cancer. The predicted market size in the US for immuno-oncology products is $35 billion by 2023, according to J.P. Morgan. The concept of utilizing the immune system as … Continue reading Exciting Developments in Cancer Immunotherapy
Precision medicine is the cutting edge of diagnosis and treatment; it encompasses medical practices and products that are tailored to individual patients. Aligned with that is the development of novel therapeutics which utilize many different technological strategies that target specific cell processes or structures. New drugs are being developed that have better specificity for receptors … Continue reading Pushing the treatment frontier in biologics
In October/November 2014, we published a pair of articles in Bioprocess International that examined how the potential therapeutic value of many proteins — including enzymes, receptors, cytokines, blood factors and peptides — can be realized by fusing them to the Fc region of human immunoglobulin G. These engineered proteins are known as “Fc fusion proteins”. … Continue reading Published Articles – Immunoglobulin Fc-Fusion Proteins
President Donald Trump’s choice to head the US Department of Health and Human Services, Tom Price, doesn’t like Medicare experiments in which physicians, hospitals, and patients have no choice but to participate. This means that the mandatory bundled payment models just approved by the Centers for Medicare & Medicaid Services (CMS) are on a collision … Continue reading Tom Price May Not Like Medicare Experiments
Patients today are receiving personalized treatment regimens that include a wide variety of medications ranging from standard-of-care antibiotics to advanced therapies such as monoclonal antibodies. Increasing demand for therapeutic proteins has pushed the biologics manufacturing industry to develop methods to improve product titers and streamline downstream purification. In a recent article in the journal mAbs, … Continue reading New Filter Technology May Transform mAb Downstream Processes
We co-authored this article with David Green at Angus Chemical. In the article, we outline the importance of selecting the appropriate buffers for biologic manufacturing. We define the chemical properties, types of buffers and the role they play in the production of biologics in both upstream and downstream processes. We also describe in the article … Continue reading Published Article – Buffers in Biologics Manufacturing
The Biologics Price Competition and Innovation Act (BPCIA) was enacted as one of the lesser known provisions of the controversial Patient Protection and Affordable Care Act (PPACA) which was signed into law by President Obama on March 23, 2010. The Act provided a legislative framework giving the Food and Drug Administration (FDA) the power to … Continue reading Congress needs to be cognizant of the biosimilars act as it considers changes to the PPACA.
Companies developing monoclonal antibodies face major challenges in developing and implementing a suitable manufacturing strategy and securing adequate capacity. Planning for products that are under development, and possibly years away from commercialization, entails uncertainty and risk. Establishing a manufacturing strategy that aligns with the company’s business objectives, considers risks and challenges, and prioritizes timing and … Continue reading The Process of CMO Selection for Antibody Development
Researchers have found a consistent association between a higher intake of the provitamin A carotenoid β-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, but the molecular basis for this association has been elusive—until now. BCX is responsible for a plants bright red, yellow and orange hues. The provitiman is found primarily in … Continue reading BCX link in Reduction of Lung Cancer Tumors
Gone are the days when people communicate by posting a letter and waiting for a response. Many people these days have given up home “land lines”; most people carry cell phones with them at all times and are easily reachable no matter where they are. Communication in the 21st Century has moved to instant post … Continue reading Manufacturing Efficiency: Making it in the 21st Century
Recently there has been uproar about increases in pricing of EpiPen, a prescription drug product enabling rapid injection of epinephrine. EpiPen is marketed by Mylan N.V. Since 2007, the price for a two-pack has gone up from $93.88 to $608.61, an increase of more than 500%. We thought we would investigate the story behind the … Continue reading Competition for EpiPen? Not really.
Can continuous manufacturing achieve efficient yield and product quality? Automation of manufacturing processes has been around for industrial applications for many decades. In 1913, Ford Motor Company introduced the assembly line, which can be considered one of the first forms of automation in manufacturing, for car production. It boosted Ford Motor’s production rates, as well … Continue reading Let it Flow