BioProcessing Journal

Improving Biopharmaceutical Manufacturing Yield Using Neural Network Classification

Traditionally, the Six Sigma framework has underpinned quality improvement and assurance in biopharmaceutical manufacturing process management. This paper proposes a neural network (NN) approach to vaccine yield classification and compares it to an existing multiple linear regression approach. As part of the Six Sigma process, this paper shows how a data mining framework can be used to extract further value and insight from the data gathered during the manufacturing process, and how insights into yield classification can be used in the quality improvement process.

Bioinformatics Biologics Biologics Production Research

bioreactor crisp data mining design-of-experiments dm methodologies doe FDA machine learning mvda neural network nn pat pneumococcal vaccine process analytical technology six sigma vaccine yield classification who

Signaling Substances Used in Plant Defense: HPLC-MS/MS Analysis of Jasmonates

Plants must be capable of responding to climatic fluctuations, diurnal rhythms, available supplies of water and nutrients, and insect attacks and infestations. To ensure such responses, plants need a network of regulating substances called phytohormones. These substances enable plants to respond to both biotic and abiotic stresses by initiating a cascade of orchestrated actions, and to trigger development-specific processes. In this article, we will discuss a highly sensitive analytical method for quantitative determination of phytohormones. The main representatives of the plant hormones are jasmonic acid (JA), cytokines, auxins, abscisic acid, salicylic acid, gibberellins, and strigolactones.

Biologics Research

HPLC hplc-ms mass spectrometry nanoESI-MS plant signaling sartorius ultrapure water

Development of a Novel Flow Cytometry-Based Titration Assay to Quantify Herpes Simplex Virus Type 1 (HSV-1)

Plaque assays have traditionally been a reliable way to determine the titer of a lytic virus. However, this method has several shortcomings in that it is time-consuming, labor intensive, and suffers from limited sensitivity. In this article, we describe a novel flow cytometry-based titration assay to quantify green fluorescent protein-labeled herpes simplex virus type 1 (HSV-1-GFP). Using this assay, we were able to directly quantify ten-fold dilutions of the virus in which every GFP-positive cell could be counted. In a head-to-head comparison with a traditional plaque assay, the flow cytometry assay showed a greater linear range and was accomplished in less than half the time of the plaque assay.

Bioinformatics Biologics Biologics Production Regulatory Research

flow cytometry gfp green-fluorescent protein herpes simplex 1 hsv-2 plaque assay titration assay virus

Antibody-Dependent Cellular Phagocytosis: The Mechanism of Action That Gets No Respect A Discussion About Improving Bioassay Reproducibility

Antibody-dependent cellular phagocytosis (ADCP), which relies on macrophages to attack and devour tumor cells following antibody binding, is a potentially useful mechanism of action (MOA) for antibody drug developers and vaccine makers to consider in determining product efficacy. Unfortunately, it is often ignored in favor of more accessible MOAs driving biological function such as antibody-dependent cellular cytotoxicity (ADCC) because the assays are tedious to prepare, perform, and reproduce.

Biologics Biologics Production Regulatory

adcc antibody-dependent cellular cytotoxicity bioassays ind investigational new drug mab mechanism of action moa monoclonal antibody ph eur USP

The Contamination Triangle: A New Model for Assessing the Risk of Biological Process Contamination and Performing Investigations

Microbial contamination is of great concern in pharmaceutical and biotech manufacturing. Many organizations struggle with determining the root cause of contamination when it occurs, and identifying effective safeguards to prevent future contaminations. This article will introduce a new model for understanding microbial contamination in biopharmaceutical and sterile products and processes. The “Contamination Triangle” identifies the three factors necessary for microbial ingress into a sterile (or pure) system. The use of this model will provide guidance for contamination investigations, clarify the explanation of the contributing root causes in Non-Conformances, and assist in identifying risks and risk mitigation measures as part of a Failure Modes and Effects Analysis (FMEA) or other risk assessment method…

Biologics Biologics Production Bioreactor Scale-Up Cell & Gene Therapy Fed-Batch Bioreactor Process Mammalian Cell Culture Manufacturing Regulatory Viral Reference Materials Viral Vectors

biological contamination biopharmaceuticals biotech manufacturing contamination mitigation contamination triangle fmea microbial contamination microgial ingress risk assessment sterile processes sterile products

Regulatory and Monetary Drivers for Real-Time Analytics

Implementation of “real-time” analytics (RTA) in processes for biologics is challenging from a technological and timeline perspective. Therefore, there need to be significant drivers from both a regulatory (quality) and a monetary standpoint to justify investment. Understanding how regulatory agencies define real-time analytics and the expectations for implementations (how and when) is a key component to rational decision-making, and dovetailing process improvement and facility design is important in the planning and development process…

Biologics Production Cell & Gene Therapy Cell Lines Mammalian Cell Culture Manufacturing Regulatory Viral Reference Materials Viral Vectors

at-line analytics biolgics design space biologics cpp critical process parameters design-of-experiments doe fda guidance fmea in-line analytics ind investigational new drug mabs monoclonal antibodies on-line analytics pat process analytical technology real-time analytics regulatory considerations rta

Development and Assessment of a Novel Device for the Controlled, Dry Thawing of Cryopreserved Cell Products

While playing an integral role in biotechnology and medicine, cryopreservation (CP) is often viewed as a “simple tool” and is overlooked as a critical and evolving component of cell and tissue bioprocessing. Despite this, cryopreservation serves as an enabling technology in numerous areas including the latest cell therapies. For example, over one third of the cells used in clinical trials are cryopreserved using the traditional methods, which in many cases yield suboptimal outcomes. Further, researchers still rely on the assessment of cell survival immediately post-thaw (within a few hours), and fail to account for the impact of cryopreservation-induced delayed-onset cell death (CIDOCD) which continues to impact survival from hours to days post-thaw.

Biologics Biologics Production Bioreactor Scale-Up Cell & Gene Therapy Cell Lines Fed-Batch Bioreactor Process HEK293 Mammalian Cell Culture Manufacturing Regulatory Viral Reference Materials Viral Vectors

biodefense cell recovery cell repopulation cell research cell therapy cell viability cellular preservation cellular products cp cryopreservation cryothawing dmso dry thawing gene therapy high-throughput screening research science smartthaw stem cells water bath thawing

Fetal Bovine Serum: Risk Management

Safety is typically viewed, perhaps unconsciously, as the result of a collection of factors, conditions, or behaviors. For example, consider “safety” in the context of personal, financial, or travel. With each, safety is defined as a set of component risks that have been managed to satisfactory levels for a particular situation. The same is true for product safety and risk, whether it be for raw materials or finished goods. The “safe” use of fetal bovine serum (FBS) is achieved by the management of controllable risks to a level that is acceptable for each particular application. For example, risk reduction requirements for research applications are not as stringent as for diagnostic, therapeutic, or manufacturing applications. Each end-user must decide on the level of risk reduction that is appropriate for their application…

animal sera animal-derived materials biologics raw materials biotherapeutics cell culture cgmp fbs fetal bovine serum gamma irradiation geographical origins isia safe use serum serum traceability vaccines

Serum: What, When, and Where?

For over 80 years, fetal bovine serum (FBS) and other animal-derived materials have been widely used in the production of vaccines, and more recently, biotherapeutics, for both human and animal applications. Ever since FBS was initially developed as a cell culture reagent, there have been efforts made to avoid the use of this critical commodity. The International Serum Industry Association (ISIA) recognizes the requirement for robust risk assessment and management, and has several ongoing programs designed to help mitigate the risk of using animal-derived materials. This article will provide an outline of the state of the industry and of these programs…

animal sera animal-derived materials biologics raw materials biotherapeutics cell culture fbs fetal bovine serum isia serum traceability vaccines

Using Lifecycle and Quality by Design (QbD) Approaches to Define, Plan, and Execute Biopharmaceutical Projects

The world in general, and biopharmaceuticals in particular, are becoming increasingly complex and challenging. The ability to plan and execute a project to efficiently and effectively achieve a high-quality project goal is especially important for developing and manufacturing biopharmaceutical products. Managing projects ranging from product development, process characterization and validation, to building new manufacturing facilities requires straightforward, effective project management approaches and tools. But perhaps even more importantly, managing a project is a fundamental enabling skill required to manage both oneself as well as teams of people.

biologics enterprise biopharmaceuticals product lifecycle project lifecycle qbd quality by design sme subject matter enterprise

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