The Science of Laboratory and Project Management in Regulated Bioanalysis

Abstract

Pharmaceutical drug development is a complex and lengthy process, requiring excellent project and laboratory management skills. Bioanalysis anchors drug safety and efficacy with systemic and site of action exposures. Development of scientific talent and a willingness to innovate or adopt new technology is essential. Taking unnecessary risks, however, should be avoided. Scientists must strategically assess all risks and find means to minimize or negate them. Laboratory Managers must keep abreast of ever-changing technology. Investments in instrumentation and laboratory design are critical catalysts to efficiency and safety. Matrix management requires regular communication between Project Managers and Laboratory Managers. When properly executed, it aligns the best resources at the right times for a successful outcome. Attention to detail is a critical aspect that separates excellent laboratories. Each assay is unique and requires attention in its development, validation and execution. Methods, training and facilities are the foundation of a bioanalytical laboratory.

Application of Multiplexed Pharmacokinetic Immunoassay to Quantify In Vivo Drug Forms and Coadministered Biologics

“…A trend toward increased development of complex biological molecules as well as the popularity of combination therapies represents an ongoing challenge to bioanalytical laboratories. Bioanalytical labs are tasked with providing sensitive and robust methods in the face of accelerated turnaround demands without sacrificing high-quality study data [17,18]. During the discovery stage for lead candidate selection of complex modalities, quite often multiple drug forms (intact and associated degraded forms) will have to be monitored during in vivo animal studies to establish a relationship between PK/PD, toxicity and biotransformation [19,20].…”

Making Methods Rugged for Regulated Bioanalysis

“…Additionally, all efforts should be made to prevent hemolysis of the plasma. We previously reported the heme-mediated oxidation of mesalamine (5-aminosalicylic acid) and N-desethyloxybutynin in hemolyzed plasma [28]. Release of intracellular components of RBCs can also exacerbate the oxidative instability of apomorphine.…”

“…Our laboratory ensures that a method can provide accurate quantitation up to 4% hemolysis (1100 mg/dl). In those rare occasions when it cannot, the cause has generally been associated with hememediated oxidation of an amine and not due to a direct interference [28]. When applicable, laboratories should test stability during method development under this extreme environment.…”

“…Ensuring equilibration and starting blood stability studies at 37ºC is the preferred approach for most compounds. Drugs having targeted chemistry for blood components can have excessively long equilibration times, confounding a stability assessment [28]. These cases are generally infrequent and are often predicted from the mechanism of action.…”

“…Compounds with slow on/off rates for plasma protein binding are one example where equilibration times need to be increased [28]. Blood assays of compounds with slow RBC penetration are another.…”