Process Control, Automation, and PAT

Federal regulations are broad and open to interpretation. Most have not caught up with advancements in technology.

For decades now, it has been said that "the process is the product" for biologics. Great care and consistency must be applied in their upstream manufacture-during fermentation, harvest, and early purification-to preserve their complex structure, which confers their activity and specificity. As the product moves to late-stage purification, however, the relative concentration of impurities and altered product forms is diminished. Also, the final dosage form of most large molecule biopharmaceuticals is the relatively simple liquid formulation of parenteral dosage form. In contrast, manufacturing the solid dosage forms common for small-molecule drugs involves more complex processes, such as mixing dry powders, granulation, manufacturing controlled-release matrices, and tableting.

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

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

The overhead expense that comes along with each new enterprise application adds up quickly, and can be somewhat invisible to owners of the system.

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

Minimum disruption and maximum gain result when adopting a distributed process control and data management system for a cell culture and fermentation lab.

PAT can be defined as a collection of real-time data in-line to make decisions about product quality early in the production process.

...each day a product is delayed is estimated to cost upwards of $1 million to $100 million.

The methods used in most microbiological test laboratories originated in the laboratories of Koch, Lister, and Pasteur. While numerous changes have occurred in the chemistry laboratory, there have been limited improvements in methods used for microbiological testing.

A well-understood, validated, and correctly maintained BAS reduces the chance of a critical room parameter slipping out of specification.

Three meetings of the BioPharma Operations Excellence Consortium, facilitated by Tefen Operations Management Consulting, were held recently. The east coast meeting was hosted by Genzyme at its headquarters in Cambridge, MA; the west coast Chapter met at the Genentech campus in South San Francisco, CA; and the European forum held its meeting in Frankfurt, hosted by Aventis.

by Demetri Petrides, Alexandros Koulouris, and Charles Siletti, Intelligen, Inc. Bottlenecks are everywhere, from the freeway overpass during the morning commute to the long lines at the supermarket. But bottlenecks in a manufacturing process are bad for business. Computer models can help you eliminate those conditions or situations that retard your progress. Whether the goal is strategic planning, evaluating alternatives, purchasing equipment, appraising a facility, or optimizing production processes, simulation tools can improve your analysis.