This Assay is the First to Gain FDA Approval for Drug Quality Control

Chemical Engineering Progress, Jul 2004 by D'Aquino, Rita

The U.S. Food and Drag Administration (FDA; Rock ville, MD; www.fda.gov) granted GlaxoSmithKline (GSK; Research Triangle Park, NC; www.gsk.com) approval to use Pall Corp.'s (East Hills, NY; www.pall.com) Pallchek Luminometer, a rapid microbiological detection (RMD) instrument, to monitor the quality of a prescription nasal spray product used to treat migraines, as part of its quality control process. GSK, which manufactures the product in its Parma, Italy, facility, is the first company to win approval for the commercial release of a pharmaceutical product using RMD technology under the PDA's Process Analytical Technologies (PAT) program, which was established to improve drug manufacturing and product safety.

The Pallchek detects the presence of microbiological contamination by measuring luminescence based on the presence of adenosine triphosphate (ATP), which is released from the microbes during their energy cycle. It uses proprietary reagents, including extradants to ensure the optimal release of intracellular ATP, and a highly efficient luciferin-luciferase enzyme system to detect ATP. "These reagents, combined with a highly sensitive photomultiplier tube, result in sensitivity levels of 10^sup -17^ moles of ATP in any type of filterable sample," says Peter Ball, technical marketing director at Pall.

In effect, the system can detect the presence of even one microorganism, including stressed cells and fungi, within 24 h vs. 3-5 d with microbial limits tests (MLT) using growth on solid media. For GSK, such efficiency will enable the release of the product to market up to 4 d earlier than if MLT methods were used. "This saves a typical pharmaceutical facility $300,000-$500,000 when considering costs of product testing, and upwards of $500,000 if the costs of environmental and water-quality monitoring are included.

"GSK's release of the spray using RMD is considered a benchmark of regulatory acceptance of these methods," says Ball. Other potential applications include cleaning validation and raw material evaluation.