KCAS is a solution-based company. We are focused on the delivery of high quality scientific and defendable data, able to meet or exceed client’s timelines and expectations. One of the main reasons we are able to deliver on even the most challenging projects and programs, is the technical breadth and depth of our scientific staff within the Regulatory LC-MS/MS Department for both small and large molecules. We offer an extensive portfolio of services, designed to help answer even the most difficult questions, with our arsenal of state-of-the-art instrumentation. The above coupled with our customer-focused approach, allows us to stand out as a solution based service provider. Below are a few examples of where we made a difference for our clients by providing answers that matter.
Incurred sample repeats (ISR) acceptability is one of the indications of a robust and reproducible method. It’s a requirement described in the May 2018 FDA guidance to investigate whenever there is an overall ISR failure. Root cause assessment is imperative in order to solve the issue and not throw the data “over the fence” for the Sponsor to resolve. One occurrence at KCAS involved a urine assay with two analytes – one parent analyte and one primary metabolite. Validation met acceptance criteria; however, upon biostudy analysis, the ISR failed for the parent analyte. Through a collaborative effort at KCAS, an investigation ensued, the root cause was discovered: a potential secondary metabolite was interfering at the retention time of the parent analyte. The client was unaware of the additional secondary metabolite, and this information led to a metabolite identification. It was also found that during the sample preparation, this metabolite would breakdown into the parent, showing an increase in parent drug that was not allowing ISR to pass. For the existing method preventative measures were put in place– pH and temperature control, this allowed for stabilization of the secondary metabolite. Upon re-analysis, the ISR assessment met acceptance criteria, as the stabilization steps allowed for an accurate assessment of the parent analyte successfully. The Sponsor was able to file with the respective agency.
KCAS is solution-based even in our software systems. We use Watson LIMS for sample tracking, regression, and reporting. Watson has capabilities to store all pertinent sample information. Watson also is capable of importing study designs from multiple sample tracking systems to ease in sample transfer and data transfers. We have the capability to report additional information outside the standard parameters: subject, timepoint, and concentration data. KCAS is proactive in ensuring Sponsor’s get the data they need. Oftentimes, there are changes that need to be made such as collection dates, times and visits after samples have been processed and the data is accepted in Watson, subsequently locking in the information. These changes often pose issues due to the software limitations; however, KCAS has outlined a process to enable these changes to be made by utilizing custom fields within Watson, which can be updated without impact to the accepted sample information and data. By providing this solution we are able to provide original information with updated information concurrently. Ensuring our Sponsor’s get the data they need in a timely manner is our top priority!
A 20-plex amino acid panel was needed for a sponsor by LC-MS/MS. The challenge was that amino acids are endogenous, and they reside in matrix at various levels. The key was to group the amino acids in their respective concentration ranges, and by doing so, the assay needed to have 3 different curve ranges. Fortunately, stable label internal standards were available for each amino acid. The method involved using protein precipitation with derivatization. After collaboration between groups and cross-training to ensure the science was passed on successfully, KCAS was able to successfully validate the method. We are the one of the only labs with a validated method for the 20 essential amino acids in a single panel, as most amino acid panels are only qualified at best. Due to its complexity, the data drove the acceptance criteria which produced a robust assay. This assay has been used for several different indications and is becoming a favored panel for PD biomarker assessment.
KCAS is not intimidated by difficult science. The creativity within the technical and scientific staff is strong, and there is a determination to solve any problem a Sponsor may have from hybrid protein LC-MS/MS work to sample collection issues with unstable compounds to actual reporting issues. We are dedicated and ready to be challenged.
If you have any questions about this or any other services from KCAS, we invite you to reach out using the form below!