Tag: <span>contaminant control</span>

Today, many if not all of the major pharmaceutical companies have specific budgets for large research and development pipelines for new biologics including vaccines, monoclonal antibodies, recombinant proteins and even gene therapy projects. In addition, small innovative companies are continually presenting us with novel treatment opportunities which hold great promise for the future. The reason for such huge optimism in the field of biologics is that there are now a number of ā€œblockbusterā€ drugs for which the safety profile has been very successfully managed. This success has been achieved following a considerable amount of time and financial investment by both the innovators and the regulators…

Biologics Production Risk Analysis and Management

Monoclonal antibodies and recombinant proteins have increased in importance and gained success as therapeutic agents in treating various diseases. Biomanufacturing of such a biopharmaceutical product by cell culture follows a main route. Upstream processing is strictly biology-driven, while on the other hand, purification is engineering driven. Fermentation is setting the pace. To some extent, that pace is a result of recent advances in cell culture, greatly increasing the densities of cells along with cell-related contaminantsā€¦

Manufacturing

Analytical tools for the characterization of protein identity and structure are fundamental to many fields of biochemical research. For the development of protein biopharmaceuticals, it is particularly important to measure modifications of the structure that may affect safety and efficacy. This application requires the analysis of large numbers of samples during process development. Small quantities of modifications must be detected in samples that are in the presence of more abundant native protein. Many kinds of analytical techniques are applied to this problem including peptide mapping, bioassays, liquid chromatography, spectroscopy, and so on. One of the most attractive tools is mass spectrometry, since essentially any change in the molecule is accompanied by a change in molecular weight. With the recent advent of readily accessible mass spectrometers capable of routine exact mass measurement, it is appropriate to consider the detailed requirements for this applicationā€¦

Biologics Production

Many precautions are taken in a typical research lab to ensure the integrity of biological specimens. Temperature, storage, and personnel access, among others, are all tightly controlled, and codified into standard operating procedures (SOPs), if not almost biblical law. And no wonder ā€” companies have millions invested in biotech solutions whose progress is often measured in years and decades. Scientists have their lifeā€™s work on the line. So, it is with some surprise that the diligence most companies exercise during the research and development process is not always maintained during specimen transport. Every time a specimen leaves the lab, be it for further analytical testing or investigational purposes, it runs a heightened risk of contamination, especially from fluctuating temperatures. Ensuring that this does not happen should be the responsibility and concern of everyone with a stake in a biological productā€™s successā€¦

Research Risk Analysis and Management

Biopharmaceutical manufacturers are constantly seeking new ways to lower production costs, while simultaneously increasing cost effectiveness without sacrificing quality. The U.S. biotech industry has grown from $8 billion in 1992 to $30 billion in 2002. As productivity in biopharmaceutical manufacturing has increased, pressures to contain costs have mounted in the healthcare industry, coupled with increased demands by investors, which results in increased cost containment pressures on the industry as a whole. Some biotechnology products need to be produced in large quantities (hundreds of kilograms per year) to meet both current and expected demand. This requires significant manufacturing capacity, and makes the types of incremental process improvements commonly sought in chemical pharmaceutical processing an attractive proposition for biopharmaceutical manufacturingā€¦

Manufacturing

A program for control of biopharmaceutical raw materials is a critical quality system that helps assure patient safety and contributes to product quality. The systems for testing and acceptance must be scientifically based, and meet global regulatory requirements and standards. When a new raw material is sourced, it is important to quickly establish the quality profiles for the supplier and the raw material. Among the numerous challenges that confront a company attempting to establish an effective, compliant, raw materials program, this paper will address the following: ā€¢ Challenges in sourcing and tracing raw materials that are suitable for use in human therapeutics ā€¢ Challenges and obstacles in qualifying suppliers ā€¢ Special challenges faced by a firm that has outsourced its manufacturing and/or quality control (QC) testing…

Manufacturing

Optimal process development creates unit operations that effectively generate, separate, and concentrate a broad array of products. Historically, tangential flow filtration (TFF) process capabilities have been limited by technological and flow restrictions. Recent innovations in TFF module design have dramatically increased the capabilities of TFF to better achieve processing objectives. NCSRT has established a best practices protocol for developing clarification, fractionation, and concentration processes for mammalian, bacteria, yeast, insect, and virus based production systems. This article presents the development platform, supplemented with application-specific expertise…

Biologics Production

Manufacturers must demonstrate, with a very high degree of assurance, that biopharmaceutical products derived from mammalian cells or from human plasma are safe and free of viral contamination. Viruses can be physically removed from most proteins using filtration. Often air diffusion is used as a nondestructive test to ensure that a process filter is installed properly and free of defects that can compromise virus retention. In this article, theoretical models were used to relate air and liquid flow rates through integral and defective filters. The effect of defect diameter and defect density on the virus retentive ability of a filter was also modeled…

Manufacturing

Single-use, disposable components offer many advantages in the manufacturing of biologics. They are clean and ready to use when supplied, which obviates the need for sterilization and decreases the requirement for services such as water for irrigation (WFI) systems and steam generators. Disposable components are not used for subsequent operations, eliminating the chance of cross contamination between process runs. Long lead times for equipment installation can be avoided because the need for stainless steel equipment is reduced or eliminated. Systems are less complex, therefore engineering requirements are also reduced. There is no need for clean-in-place (CIP) or steam-in-place (SIP) operations, along with the associated piping, valves, controls, or pressure rating of vessels. Moreover, the use of disposable components reduces the complexity of validation…

Biologics Production Manufacturing

One of the biggest challenges in the production of recombinant therapeutic proteins, monoclonal antibodies, and vaccines is the clarification and separation of the product (typically a protein) from the cell culture or fermentation broth. The desired product is present in low concentrations and must be efficiently separated from the other components present in the bioreactor fluid. An overall objective in developing a clarification process is to achieve the highest level of product recovery (yield) and contaminant removal with the fewest number of unit processes. Understanding how each operational step affects the performance of the next step downstream is the challenge at hand. Centrifugation, in combination with depth filtration, is gaining acceptance as the preferred method for the removal of cells, cell debris, colloids, insoluble precipitants, aggregates, and other materials found in mammalian cell culture and bacterial fermentation fluids…

Biologics Production