Development

The purpose of design validation is to demonstrate that a product performs as intended. The usual route to this goal is showing that every item on the specification has been achieved, but it is not an easy path. The specification itself can create difficulty if it includes statements like "as long as possible" or the real horror "to be decided." Verification tests can reveal so many problems that the design must change to such an extent that earlier tests are no longer relevant. And there is also the practical difficulty of obtaining sufficient samples to test when the manufacturing engineers have not completed their standard operating procedures, the product design is not fixed yet, the component suppliers are late, and the marketing department has taken all the samples to show to prospective customers.

In order to institute a GxP mindset across the organization, support and respect for quality systems should come from the top down.

When replacing an existing method, it may be necessary to compensate for a significant difference between the current and new method by adjusting the specifications.

The relationship between "valid" or "suitable and validated" is often overlooked, but there is a high price when "validated" test systems are simply inappropriate.

Filtration is one of the most commonly used unit operations in the manufacturing of biopharmaceuticals. This is the second part of the fourth article in the "Elements of Biopharmaceutical Production" series. In this second segment, Manoj Menon and Frank Riske present an approach for the development and optimization of a TFF application, followed by a contribution from Jennifer Campbell and Elizabeth Goodrich reviewing key issues involved in validation of a TFF step.

Filtration is one of the most commonly used unit operations in biopharmaceutical manufacturing. Available formats include direct or normal flow filtration (NFF) and cross or tangential flow filtration (TFF). These methods are used for sterilization and virus filtration, depth filtration or ultrafiltration, and diafiltration applications. Some common objectives include:

Networks are part of the compliance picture. Recent FDA warning letters show the agency considers network monitoring and qualification a necessary part of maintaining the security and integrity of electronic records.

Biotech companies are among the most intensive instrumentation users of any FDA-regulated business. Because of the complex nature of these companies' research and manufacturing, they typically have a larger number of instruments per employee.

Although gene therapy and DNA vaccination suggest promising new approaches to disease treatment - and nonviral vectors (which are cheap and easy to manufacture) afford low immunogenicity, better safety profiles, and improved stability - commercial-scale purification of plasmid DNA remains difficult, particularly if bovine-derived ribonuclease A is left out of the process. This article series reviews the benefits and limitations of current plasmid DNA purification and suggests an RNase-free downstream process that is scalable, robust, and meets the requirements set by industry regulators.