2013

Robots in the Laboratory

Whether cell-based or molecular biology focused, most assays performed in biopharmaceutical laboratories involve liquid solutions. Increasingly, automated liquid handlers (laboratory robotics) are demonstrating utility in these labs, especially for high-throughput screening and optimization of cell culture media, chromatography conditions, formulations, and so on. Some experts say that screening 100,000 samples/day will soon become routine. But the robots haven’t condemned all manual pipettes to the trash heap — far from it. With multichannel and electronic pipettes improving throughput and reproducibility of…

Process Improvements Increase Production Capacity of a Legacy Product

Implementation of postlicensure process improvements in the biopharmaceutical industry can benefit patients and drug manufacturers alike. Here we demonstrate through a case study how a change to the cell culture medium and process can be taken from proof of concept through scale-up to demonstration of feasibility. We further illustrate the scope and complexity of implementing a change in commercial manufacturing to realize significant benefits such as increased production capacity over an existing legacy process. The Importance of Postapproval Improvements Drug…

Impact of Process Interruption on Virus Retention of Small-Virus Filters

Manufacturers of biopharmaceuticals using mammalian cell culture must have processes in place to minimize the likelihood of virus contamination of their products. Regulatory agencies provide guidelines for testing strategies and best practices to assure raw-material safety and control of the manufacturing process. Safety assurance relies on an interdependent matrix of managed risks, including characterization and control of raw materials, extensive testing of process intermediates, and demonstration of the virus removal capabilities of purification unit operations Figure 1:  () A dedicated…

Effects of Pressure Sensor Calibration Offset on Filter Integrity Test Values

Food and Drug Administration (FDA) and European good manufacturing practices (GMPs) require integrity testing of sterilizing-grade filters for producing injectables and other biologics. The diffusion test (also called the forward-flow test) and bubble-point test (also called the disk test) of a sterilizing-grade filter are both filter-integrity tests. The accuracy of both relies on calibration of a pressure sensor in the respective integrity test unit. Calibration of the pressure sensor of a filter-integrity testing device is an essential part of quality…

Enhancing Antibody Production

Increasing demand for monoclonal antibodies (MAbs) — useful as immunodiagnostic reagents in basic research applications and potential immunotherapeutics — has created a need to optimize protein production techniques. Many developers have attempted to increase MAb output from cell culture by addressing both equipment and consumables. For example, recent advances in improved bioreactor designs and bioreactor operation have increased antibody outputs by increasing cell densities and extending cell life in culture. Materials and Methods () Bioreactors can operate in batch, perfusion,…

Government Medicaid Reporting

On 27 January 2012, the US Centers for Medicare and Medicaid Services (CMS) published a much-anticipated proposed average manufacturer price (AMP) rule for implementing related prescription drug provisions of the Patient Protection and Affordable Care Act (PPACA). The new rule will create serious financial, administrative, and operational challenges for the life-sciences industry. Nearly two years later, the final rule has not been issued. Without official direction, we can look back at the proposed rule’s purpose and recommendations for manufacturers based…

New Paradigms for Process Validation

    Both the United States and the European Union have recently evolved guidance on how to execute process validation (1, 2) with the prospect of a more appropriate life-cycle approach. It goes beyond the traditional three to five lots run at the center point of proposed ranges for operating parameters. New approaches leverage product design and process development information. They facilitate adapting the quality by design (QbD) paradigm to allow for a science- and risk-based selection of critical process…

Preparedness Ahead of Pandemic Outbreaks

Lively debate in 2012 concerned the risks and benefits of laboratory studies that created a contagious H5N1 avian pandemic influenza (flu) laboratory-strain virus. One benefit of the public debate is that it reminded governments of the increasingly likely and disastrous possibility of a devastating flu pandemic on the scale of the Spanish influenza outbreak of 1918. Natural evolution of circulating H5N1 viruses could lead to emergence of a deadly and contagious strain (1). Here we outline conventional flu vaccine options…

Cellular Communications

Like spectroscopy, as discussed in BPI Lab last month (1), cell signaling is not a laboratory technique but rather an area of scientific study. The environment of living cells — whether prokaryotic or eukaryotic, in vitro or in vivo — comprises not only water, nutrients, waste products, and metabolites, but also molecules released by other cells in response to intracellular events such as microbial infection and disease state or environmental factors such as temperature, osmolality, and pH. Receptor proteins on…