Downstream Processing

The number of biotechnology-based human therapeutic products in the late-stage pipeline, and the average cost to commercialize a biotech product, have steadily increased. This has required biotech companies to use economic analysis as a tool during process development and for making decisions about process design. Process development efforts now aim to create processes that are economical, as well as optimal and robust.

If a company wants to reduce costs, it should consider outsourcing some manufacturing and analytical testing to low-cost sites.

This article shows how Probabilistic Tolerance Intervals of the form, "We are 99% confident that 99% of the measurements will fall within the calculated tolerance limits" can be used to set acceptance limits using production data that are approximately Normally distributed. If the production measurements are concentrations of residual compounds that are present in very low concentrations, it may be appropriate to set acceptance limits by fitting a Poisson or an Exponential Distribution.

We often assume we know what success looks like for our partner, but we never ask them, or take the time to write it down.

It is important to ensure that flow decay during processing is comparable to that observed during retention studies.

Formulations for pulmonary inhalation comprise spherical, porous particles that are 1–3 microns in diameter.

Established, fully validated methodology and SOPs are required prior to initiation of any training activities.

Development reports document process development and support the design of validation experiments, yet in many firms training is not provided nor are expectations established. This article describes how project managers can help scientists master the art of report-writing.

SOPs are written job aids that detail the procedure of how to do a specific job task correctly.

Nothing beats a good dictionary. It can clarify doubts, settle an argument, or prompt exploration into new areas of learning.

Case studies were run to test Process Analytical Technology applications for protein refolding, diafiltration, and cation exchange chromatography. It is shown that it is feasible to design control schemes that rely on measurement of product quality attributes and thereby enable real-time decisions.

Disposables require less space than conventional equipment, and they can be assembled offsite into complete process trains.

A symposium at the AAPS National Biotechnology Conference in Boston, June 19-22, 2006, addressed key concerns and new developments in manufacturing biologic products in a sterile environment.

"Clinical data is the gold standard" for setting manufacturing specifications, said Patrick Swann, PhD, acting deputy director of the Division of Monoclonal Antibodies at FDA, at a session on specification setting at the AAPS National Biotechnology Conference that was held June 19-21 in Boston.

On August 12, 2003, Johnson & Johnson began recalling certain batches of its anemia drug, Eprex (epoetin alfa, sold as Procrit in the US), in most countries outside of the United States.

The polishing process-unlike capturing-is beginning to benefit from technological advances.

The purpose of the PAT initiative is to move analytical laboratory functions close to the manufacturing process to improve manufacturing efficiency and product quality.

Biotech companies are running into production bottlenecks because standard purification and separation technologies lack the capability to remove the elevated levels of biomass from high titer solutions. Recent developments in filter technology offer the biotech industry a cost-effective solution to processing challenges by reducing bottlenecks, thereby accelerating the time-to-market of new drugs.

Using packed columns in process development activities limits the scope for appraising a large and diverse range of media.

Downstream process design can increase facility output through improved overall process yield or higher batch capacity in mass and volume.

The overall average flux rate for the concentration and diafiltration step was 41 L m–2 h–1.

Air filtration also needs a filter integrity test method to guarantee the sterility of critical parameters.

Transgenics can substantially reduce capital investment and lower production costs through economies of scale and more flexible scale-up.

Disposables can be used for media preparation, clarification, filling in downstream processes . . .

The sugars used to stabilize lyophilized proteins often have not been subjected to appropriate cGMP standards.

The type of reactive moiety controls the site and stability of the covalent link and also the total number of PEGylation sites on a given protein.

In the pharmaceutical industry, ultrafiltration (UF) membranes are used extensively in the downstream purification of recombinant proteins or monoclonal antibodies. However, the fouling of membranes after a unit operation?especially when recombinant proteins or monoclonal antibodies are highly concentrated?is a common problem. Typically, normalized water permeability (NWP) of a membrane can be reduced to about 20 percent of its original permeability at the end of an ultrafiltration-diafiltration (UF-DF) operation.

Extra column effects must be accounted for to make a valid comparison

br> Sterilizing grade, 0.2-µm rated membrane filters are used in many biopharmaceutical processes to ensure the absence of particles and microorganisms from the filtered fluid (1, 2, 3). These filters must meet particular performance criteria in specifically defined applications. For this reason, during filter design, one performance criterion often is enhanced at the expense of another. Consequently, critical process and flow parameters must be defined appropriately to identify the optimal flow membrane filter for a specific application. This paper describes such an evaluation schematic and tests, as well as some common misconceptions.

Cleaning validation is a critical consideration in the pharmaceutical industry. Inadequate cleaning can result in contamination of drug products with bacteria, endotoxins, active pharmaceuticals from previous batch runs, and cleaning solution residues. Such contaminants must be reduced to safe levels, both for regulatory approval and to ensure patient safety.