Xchange Alert

The measurement of the flow of liquids associated with bioprocessing has long been sought, and largely addressed, for the most part. The exception being the accurate and reliable measurement of liquid at ultra-low flow. However, this is fast becoming recognized by our industry as an exception no more. The Sonoflow IL sensors have proven capable of delivering the precise measurement (+/- 1%) of flow ranges below 10ml/min. These sensors accomplish this while complying with the first rule of bioprocessing when it comes to the cells, "do no harm". Learn More

This work is a proof of concept of how a sequence of industrial batch separation steps together are used to form an integrated autonomous downstream process. The sequence in this case study consisted of an anion chromatography step, virus inactivation and finally a hydrophobic chromatography step. Moving from batch to integrated separation minimizes hold-up times, storage tanks, and required equipment. The conversion from batch to integrated mode is achieved by extracting operating points and separation data from batch chromatograms. The integrated separation process is realized on an ÄKTA Pure controlled by an open research software... Learn More

To date, integrated continuous bioprocessing has not been realized as enabling technologies are nascent. In this work, a fully integrated continuous process is successfully demonstrated from pilot scale bioreactor to drug substance. Comparable product quality is observed between the continuous process and a 500 liter fed-batch conventional process. A throughput analysis shows that a fed-batch facility with four x twelve five hundred liter liter stainless steel bioreactors and purification train of the corresponding scale can be replaced by a continuous facility consisting of five x two thousand liter single use bioreactors and smaller purification train, with a cost reduction of 15%. Learn More

Biologic manufacturing processes typically employ clarification technologies like depth filtration to remove insoluble and soluble impurities. Conventional depth filtration media used in these processes contain naturally-derived components like diatomaceous earth and cellulose. These components may introduce performance variability and contribute extractable/leachable components like beta-glucans that could interfere with limulus amebocyte lysate endotoxin assays. Recently a novel, all-synthetic depth filtration media is developed (Millistak+® HC Pro X0SP) that may improve process consistency, efficiency, and drug substance product quality by reducing soluble process impurities... Learn More

The concept of continuous manufacturing has gained significant interest from the biopharmaceutical industry over the past several years. Benefits include increased manufacturing productivity, improved quality control, reduction in plant footprint, and more flexible management of facility capacity. There are several technologies currently available that enable continuous processing for chromatography and ultrafiltration. However, a single pass diafiltration design that meets the required small molecule clearance and has been integrated into a fully continuous monoclonal antibody purification process has not been previously published... Learn More

Automation and miniaturization is currently a hot topic in many industries, and the bioprocessing industry is no exception. The potential benefits to be had from automating and miniaturizing our process development work in microbial fermentation include reducing our process development timelines by improving our throughput and making better use of available resources. With these aims in mind, two systems have been implemented in UCB's fermentation process development laboratories, namely the Ambr250 Modular system from Sartorius and the Freedom Evo 200 from Tecan... Learn More

Recursive time series models are developed in this work for a fed-batch mammalian cell culture producing monoclonal antibodies, with key culture variables measured at different sampling frequencies. Glucose and glutamine feed rates are considered as inputs. The data required for parameter estimation are generated from simulated fed-batch experiments using a well-tested first principles model. The predictions for glucose, glutamine, and viable cell concentrations track very well the data for these, with the errors for the high prediction horizons considered being limited to 10% or less. The prediction accuracy can be increased further if data from prior experiments with dynamic similarities are available. Learn More

Recombinant proteins are revolutionizing present day therapeutics. They are generally expressed as insoluble inclusion bodies in the E. coli and mis-folding, loss of protein, high cost of down streaming are the hurdles in their recovery. For the first time, we are reporting the refolding with simultaneous purification of rhASP in E. coli using a single step utilizing Protein Folding - strong anion exchange chromatography (PF-SAX). The purification method is also standardized for optimal concentration of solution additives, pH and mobile phase composition. The results showed purification of rhASP with anion exchange chromatography was effective. Learn More

The use of cellular assays in drug screening continues to grow with over 50% of primary screens using cell-based formats in 2006. The majority of cells used in the drug discovery industry are fresh, using 'just in time' batch processing from in-house facilities. This process could give rise to a number of issues, namely batch variation, scheduling of cell production and capacity management. We describe the use of microcarrier technology in combination with a suitably configured bioreactor to provide a rapid, robust and reproducible approach to cell production. Cells cultured in this way can be removed from beads, cryopreserved in a single HTS batch size format and maintain assay capacity. Learn More

The pharmaceutical industry has proven it can successfully develop cell and gene therapies (CGTs). Eight CGTs are FDA approved: Gencidine, Oncorine, Rexin-G, Glybera, Neovasculgen, Imlygic, Strimvelis, and Zalmoxis.1 Over 400 therapies2 are in preclinical to Phase 3 development, and approximately 1,700 clinical studies are underway globally. Recent FDA approval of therapies based on chimeric antigen receptor - T-cells (CAR-T) has heightened interest and investment in CGTs. Notably, autologous cell therapies grew 65 percent from 2016 to 2017. Now it's time to tackle the challenges of sustainable and cost-effective commercial manufacturing of these emerging therapies. Learn More

Editors Choice from AspenXchange

In August of 2008, company representatives from Abbott, Amgen, Eli Lilly, Genentech, GSK, MedImmune and Pfizer were brought together to help advance the principles contained in ICH Q8 (R2), Q9 and Q10, focusing on the principles of Quality by design. Through a series of inter-company and regulatory interactions, the group set out to create a study that would stimulate discussion around how the core principles contained in these guidelines would be applied to product realization programs, with a multitude of real-world scenarios, as opposed to a singular approach. Learn More Editors Choice from AspenXchange

Monoclonal antibodies (mAbs) are important biopharmaceuticals for the treatment of many diseases. During manufacturing, the proteins tend to form aggregates, which reduce product yields, influence drug performance and safety. Environmental conditions during production in mammalian cell culture influence the formation of high molecular weight (HMW) species. In this report, we show how mAb aggregates can be detected directly in the cell culture supernatant using size exclusion chromatography (SEC) in a high pressure liquid chromatography (HPLC) system. We have investigated the impact of batch cultivation in different culture vessels, the addition of Valproic acid (VPA) as small molecule enhancer of protein production and the influence of the cell culture environment itself on the formation of mAb aggregates in Chinese hamster ovary (CHO) cell culture. Our results prove that aggregate formation can occur already during upstream processing (USP) due to intracellular and extracellular mechanisms and is not only a problem in downstream processing (DSP).
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Editors Choice from AspenXchange

This article is about pharmaceutical processing and flexible tubing; that is, tubing made from various polymeric materials, and in particular, silicone polymers. Flexible tubing has gained more acceptance in recent years as it offers low costs and simplicity, particularly for single-use applications where one can reduce costs associated with validation, cleaning-in-place (CIP) or sterilization-in-place (SIP) and disposal of contaminated waste waters. Many of the articles about flexible tubing for pharmaceutical processing are generated by suppliers, each one promoting their own attributes and advantages. Learn More This whitepaper, which appears in the ASPENXCHANGE, was selected by the Editor for its value as a seemingly timeless point of reference.

The adoption of single-use technologies in drug product manufacturing has introduced many benefits for the biopharma industry. It has also introduced the need for an entirely new way of thinking for a group of developing subject matter experts to deal with a fresh set of challenges. Many of the advantages of single-use technology have been well-characterized and discussed in literature, including the reduction of cross-contamination risks and cleaning validation program related resources, as well as faster changeover times on the production floor, lower capital investment costs on facility start-ups and less costs associated with routine cleaning and sterilization of product contacting parts. Often underplayed benefits are those associated with the reduction of microbiological contamination risks and overall improvements to sterility assurance for aseptically-filled products. Learn More