ABSTRACT
The high throughput is routinely used for the first steps of drug development such as drug discovery screening and toxicity. However, for PK analysis of regulated studies, the requirements and difficulties to achieve high-throughput analysis are more demanding due to regulatory guidelines that are not needed for early steps of drug discovery. High-throughput analysis can be required for any drug type from small molecules to larger ones. Contract research organizations must be prepared to deliver the results associated to these studies in a fast turnaround. Herein, we will describe the challenges encountered by a laboratory in order to go from low- to high-throughput analysis.
Subject(s)
Drug Discovery/methods , High-Throughput Screening Assays/methods , HumansABSTRACT
In 2012 with the issuance of its Guideline on Bioanalytical Method Validation, the European Medicine Agency (EMA) made the incurred sample reproducibility (ISR) assessment a requirement for studies to be submitted to European authorities. Since then 2012, European agencies have started to issue deficiencies to pharmaceutical companies for lack of ISRs in studies submitted recently but performed prior to the issuance of the 2012 Guideline. It now becomes the applicant's responsibility to justify scientifically the departure from the new guideline even for less recent studies. This article details the different strategies to provide an adequate justification for the absence of ISR data in studies performed prior to February 2012 but submitted to European agencies after that date.
Subject(s)
Chemistry Techniques, Analytical/standards , Pharmaceutical Preparations/analysis , Half-Life , Laboratories , Pharmacokinetics , Quality Control , Reproducibility of ResultsABSTRACT
The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the draft FDA Guidance, and to build unified comments to be provided to the FDA.
Subject(s)
Chemistry Techniques, Analytical/standards , Guidelines as Topic , Validation Studies as Topic , Biomarkers/analysis , Calibration , Ligands , Limit of Detection , Reagent Kits, Diagnostic , Reproducibility of Results , United States , United States Food and Drug AdministrationSubject(s)
Biomarkers/analysis , Biosimilar Pharmaceuticals/analysis , Pharmaceutical Preparations/analysis , Biosimilar Pharmaceuticals/pharmacokinetics , Biosimilar Pharmaceuticals/standards , Chromatography, High Pressure Liquid/standards , Drug Industry , Mass Spectrometry/standards , Pharmaceutical Preparations/standards , Quality Control , Reference StandardsABSTRACT
The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters. Recent 483s and agency findings, as well as issues on method carryover, were also part of the topics discussed.
Subject(s)
Chemistry Techniques, Analytical/standards , Guidelines as Topic , Organizations, Nonprofit/standards , United States Food and Drug Administration/standards , Analytic Sample Preparation Methods , Calibration , Chemistry, Pharmaceutical , Documentation , Drug Combinations , Drug Stability , Europe , Reference Standards , Reproducibility of Results , United StatesABSTRACT
"The Global CRO Council (GCC) for Bioanalysis was formed in an effort to bring together many CRO leaders to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry"
Subject(s)
Biopharmaceutics/standards , Chemistry Techniques, Analytical/standards , Reference Standards , Chemistry Techniques, Analytical/methods , Drug Stability , International Cooperation , Quality ControlABSTRACT
Incurred sample reanalysis (ISR) is now commonly practiced in regulated bioanalytical laboratories. With an average ISR success rate of 95% or higher and an increasing number of ISR tests being conducted, more and more situations deserve scientific evaluation or investigation for the unmatched reassay results revealed in ISR tests even though they meet the acceptance criteria. First, should an investigation be initiated when an ISR test is acceptable? How large a discrepancy or what situation would warrant an investigation? What would be the impact on a study? How would investigations regarding unmatched reassay results be conducted? What are the main root causes identified? Can normal random errors cause a large discrepancy in unfavorable combinations? How could the timeline and cost be affected? All these questions are addressed in this paper with five real case examples.
