biopharmaceuticals – Page 3 – BioProcessing Journal

Biosimilars in the Rest of the World: Developments in Lesser-Regulated Countries

Biosimilars, and related biopharmaceutical biobetters and biogenerics, are still relatively new, but are already starting to impact worldwide biopharmaceutical markets. Most discussions of biosimilars center on developed regions where markets are mature and manufacturing capabilities allow for the cost-efficient manufacture of these complex molecules. This article covers the development of these products outside the United States (US), European Union (EU), and other developed, generally rather affluent and high-technology economy-based countries. To start, we first offer some definitions…

Biologics Production

biologics regulations biopharmaceuticals biosimilars complex molecules eu regulatory GMP us fda regulatory

Microcarrier-Based Expansion of Adipose-Derived Mesenchymal Stem Cells in Shake Flasks

The expansion of stem cells, including mesenchymal stem cells (MSCs), has been successfully demonstrated using microcarrier-based small bioreactors such as spinner flasks. In this study, we explored a simple alternative for microcarrier-based MSC expansion using conventional shake flasks. This method relies on a new type of shaker with built-in CO2 gas control capability, the New Brunswick™ S41i incubator shaker. The expansion of adipose-derived mesenchymal stem cells (AdMSCs) was compared between shake and spinner flasks containing microcarriers. The AdMSCs were seeded at a density of 3 × 103 cells/cm2 in both setups, each containing 0.5 g of plastic microcarriers and 50 mL of stem cell growth medium. The cell culture experiments were conducted over 12 days with samples collected daily for cell growth, biochemistry, and metabolite analysis. The study revealed that AdMSCs cultured under shake flask conditions achieved excellent growth under 12-day batch-culture conditions. Finally, the AdMSCs expanded using the shake flask method retained high quality stem cell characteristics, as indicated by CD44 and CD90 stem cell marker assays, and the ability of these cells to differentiate into either adipocytes or osteocytes…

Biologics Production

adipocyte adipose-derived mesenchymal admsc batch culture biologics biopharmaceuticals cd44 cell differentiation incubator shaker mesenchymal stem cells microcarrier-based msc msc osteocyte stem cell characteristics stem cell expansion stem cell markers

Virus Clearance in Your Process from Start to Finish

The safety of biological products (biologics) derived from in vitro cultured cell lines of animal origin is dependent both on clinical studies to evaluate efficacy, and a matrix of controls throughout the manufacturing process to assure consistency, quality, and safety of the marketed product for human use. One major area of concern is virus safety. Through the combination of: (A) careful selection of raw materials; (B) testing of process intermediates; and (C) virus clearance evaluations of the individual steps in the manufacturing process; biologics manufacturers can demonstrate that their products are free from detectable adventitious and endogenous viruses. Comprehensive regulatory guidance suggests approaches for virus testing of biologics at early and later stages of clinical development and, although some countries have specific requirements, many of these approaches are harmonized worldwide. In general, regulatory authorities expect purification processes to include multiple steps with complementary, or orthogonal, methods for virus reduction including inactivation and separation or removal. Each step in the process may be more or less effective for reducing levels of different test viruses, and therefore selection of the appropriate panel of test viruses for the specific product is critical for viral clearance studies…

Biologics Production

biologics biopharmaceuticals cell culture mammalian cell culture raw materials purity viral clearance viral safety testing virus safety

Fetal Bovine Serum: What You Should Ask Your Supplier and Why

In today’s volatile sera market, it is critical that sera users worldwide thoroughly review their supply relationships and update sourcing and risk mitigation strategies. BioProcessing Journal’s recent article by Siegel and Foster highlighted the impact of selecting the appropriate country of origin as one criterion for purchasing decisions. Many more vital selection criteria exist to ensure a sera supplier provides long-term assurance of supply and integrity of supply. This article identifies critical questions sera users should ask their suppliers and explains why they should ask them…

Biologics Production

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Risk Assessment of Residual Genomic DNA in Therapeutic Proteins Using Gene Copy Number Application

Therapeutic proteins manufactured in cellular systems contain residual DNA derived from host cell substrates used in production. Risk assessment of the residual host cell DNA is necessary, as some of these DNA sequences may be potentially infectious or oncogenic. Oncogenic potential lies in transmission of the activated oncogenes to subjects receiving the product, thereby inducing oncogenic events. Therefore, it becomes essential for drug manufacturers to show clearance of genomic DNA (oncogenic sequences as well) throughout production processes and to confirm low levels of residual DNA in the final drug substance. This study attempted to estimate the oncogenes in the total residual DNA using a highly sensitive, specific, and robust method—quantitative polymerase chain reaction (qPCR). Routinely, total residual DNA is estimated using either the 18S ribosomal (r)DNA gene or Alu equivalent multicopy gene sequence as qPCR targets. We have determined the copy numbers of these qPCR targets along with the oncogene (Ras gene) and housekeeping genes (ACTB and GAPDH) and established a ratio of their presence in protein samples. Another objective of the study was to estimate the level of oncogenes from several in-process step samples in the manufacturing and purification process and check the clearance of total residual DNA including oncogenes. Upon quantification, the proportions of oncogenes present were one tenth of the quantified residual DNA levels (Ras gene:18S RNA) in the purification stage samples, providing information that the therapeutic protein product was safe from the presence of oncogenes in residual DNA by a factor of ten…

Biologics Production

biologics biopharmaceuticals DNA gene copy number oncogenic sequences purification process qpcr residual genomic dna risk assessments therapeutic proteins

Biobanking Operations: Contingency Planning and Disaster Recovery of Research Samples

Biobanking is a critical component to realizing the promises of translational research and personalized medicine. The proper collection, processing, storage, and tracking of human biological samples allows researchers to better link molecular and clinical information, which in theory, allows for the development of more targeted therapies for patients. Realizing the scientific potential of well-annotated, properly preserved sample collections has led to the proliferation of large-scale biobanks by biopharmaceutical companies, academic organizations, governments, and non-profit research organizations. To this point, conservative industry projections estimate that in the United States, there are at least 300 million tissue samples in biobanks with an estimated accrual rate of 20 million samples annually…

Biologics Production

biobanking biologics biopharmaceuticals contingency planning molecule information recovering research samples research samples

Continuous Bioprocessing and Perfusion: Wider Adoption Coming as Bioprocessing Matures

Batch processing has long been the predominant bioprocessing paradigm, both up- and downstream. Bioprocessing fluids are processed incrementally, piped as a bolus or transferred via vessels from one process and piece of equipment to the next. This continues to work well, including a number of technological advances resulting in improvements that continue to make bioprocessing more efficient. Upstream and overall process yields are essentially doubling about every five years, with this largely driven by improved cell lines, expression systems and genetic engineering, culture media, and equipment. Among the technologies now gaining increasing adoption and market share for biopharmaceutical manufacture is continuous (bio) processing, with perfusion currently the leading technology, in terms of adoption. The use of incremental, one-step-at-a-time, classic batch processing in biopharmaceutical manufacture is different than most other major products manufacturing and high-tech industries, where processing is generally more continuous. In this context, the move toward more continuous processing in manufacturing is a common characteristic of industries starting to reach maturity. Continuous processing is exemplified by assembly lines, and petroleum refining with processing involving a rather continuous flow of the material being manufactured from one unit operation to the next. Continuous processing generally follows and eventually replaces incremental manufacturing…

Biologics Production

batch processing biopharmaceuticals continuous bioprocessing continuous perfusion downstream bioprocessing expression systems genetic engineering process yields upstream processing

Rapid and Effective Monitoring of Baculovirus Concentrations in Bioprocess Fluid Using the ViroCyt® Virus Counter®

The licensing of recombinant vaccines produced using the baculovirus expression vector system (BEVS) has cleared the way for the production of a variety of biopharmaceuticals produced using this technology. Obtaining accurate estimates of both total and infectious baculovirus titer in upstream and downstream bioprocess fluids is one of many process controls that will need to be addressed during the development phase of a product’s lifecycle. Traditional plaque-titer methods require 5–7 days of incubation in order to reveal plaques that may be enumerated, and is further complicated by plaques created by multiple viruses that may be scored as a single plaque, thereby lowering the titer estimate. Titer assays based on polymerase chain reaction (PCR) have been developed, but they measure the presence of baculovirus genes, not virus particles. This often results in titers one or two logs higher than the actual titer. Immunoassays correlate with host cell infection and virus replication, but they too can be time-consuming and difficult to interpret. Our goal was to identify a method that would provide estimates of both total and infectious virus particles in as close to real-time as possible. We have evaluated the ViroCyt Virus Counter over the course of three years and have found it to provide accurate and reproducible estimates of both titer types in as little as 30 minutes. We have created an algorithm that converts total virus particle counts into estimates of infectious titer and tested these values in virus amplifications. The Virus Counter method of titer determination has also been used to track the quantity of virus particles in the culture supernatant of stirred-tank bioreactors infected with standard baculovirus stocks and with baculovirus-infected insect cells (BIIC)…

Biologics Production

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Contract Pharma Manufacturer Optimizes Quality Check Process With the Cubis Lab Balance

As a contract manufacturing organization (CMO) in this environment, it is essential for hameln pharma to deliver goods to their customers reliably, in terms of quantity, delivery time, and quality. Therefore, the topic of quality assurance plays a huge role— for both final packaged units as well as for bulk products. After a long-term analysis of the bulk product weighing process, hameln pharma’s objective was to significantly streamline the time-consuming process of manual counting and visual inspection. Moreover, taking cGMP standards into account, they wanted to optimize their existing process in order to remove any possibility of incomplete package volumes. Katrin Strasser, hameln pharma’s operational excellence expert, explained that: (1) packing box weights fluctuated with humidity levels during their manufacture; (2) labels for product packages varied; and (3) the actual number of items in a box carton were not always consistent

Biologics Production

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Failure Mode and Effect Analysis (FMEA) as a Quality by Design (QbD) Tool for Managing Biopharmaceutical Product Development and Manufacturing Risks

This paper examines FMEA as a QbD tool. If FMEA’s strengths are used and weaknesses understood, it can be effectively used within a QbD feedback algorithm to identify, analyze, prioritize, and remediate biopharmaceutical development and manufacturing risks…

Biologics Production

biopharmaceuticals failure mode fmea qbd quality by design

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