Bioanalytical Concentrations Below the LLOQ:
|
|
- Sherman Lindsey
- 5 years ago
- Views:
Transcription
1 Bioanalytical Concentrations Below the LLOQ: Should they be reported? arguments against What are regulatory and technical issues? What should we do to verify a lower LLOQ? Jeff Duggan and Jim Hilbert Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT The Case for and Against the Release of Bioanalytical Data Below the LLOQ AAPS 2015 Annual Meeting and Exposition, (#23), Wed., October 28, 2015
2 Possible Restrictions Technical and Scientific Sensitivity Selectivity Stability Absorptive phenomena Regulatory LLOQ defined in validation Assay range validated Supporting QCs (3x LLOQ) Other critical validated parameters
3 Verapamil, High Sensitivity Test Sensitivity to 50 pg/ml, linearity 50-10,000pg / ml 3
4 How far Below the LLOQ can we Go? (Beteween LLOQ and LOD) What are the limiting factors of our method?
5 Chromatographic Peak Signal to Noise LLOQ >= 5:1 S/N Baseline variation Sporadic noise Nearby interference Skewed baseline IS/Analyte Peak Area
6 Sensitivity and Chemical noise S/N Background Matrix 5 ng/ml Interferences 2 ng/ml
7 Accuracy and Precision Data from Validation: Supporting QCs QCs at 4 levels across the curve Accuracy (%bias) Precision (%CV) LLOQ QC set Verifies low end Statistically supported n= 5 or 6 X 3 runs P&A Interrun Precision and Accuracy for Drug XYZ in Human EDTA Plasma Assay Drug XYZ Concentration, nm 1 Nominal QC Batch ID LLOQ QC Low QC Mid QC High QC ULOQ QC Run Run Run NA NA NA NA Mean S.D %RSD %RE N
8 Response (CPS) Matrix Suppression: Sample and Method Inhibition, suppression or enhancement of the signal due to co-eluting matrix components A. SPE B. PP C. LLE D. 1-Docetaxel, 2-IS Time (min) Eluent pump Extracted Blank Injector Column 250 ul / min. Syringe pump Tee 20 ul / min. MS Source 8
9 Other Validation Criteria Selectivity: Can the method selectively measure the signal of the analyte in the presensce of other components Disease matrices Different populations Ion Suppression, Human Plasma Extracts Co-medicants Metabolites C P S 5000 PPT SS-LLE LLOQ Chromatogram Min. All of these effects can be amplified at high sensitivity
10 Stability and Adsorption Stability is tested only at low QC value during validation, what about: Freezer stability Room temperature stability Freeze thaw Extract and A/S stability Does analyte adsorb at sub LLOQ concentrations? Does the analyte signal become non-linear at low concentrations?
11 Stability BI xxxxxx Human Plasma Sample Concentrations after Hour Storage in Autosampler (~10 C) after Extraction BI xxxxxconcentration, nm Nominal QC Mean SD %RSD %RE Batch ID: HL29Oct2013a BI xxxxx Human Plasma Sample Concentrations after Four Cycles of Freezing and Thawing BI xxxxx Concentration, nm Nominal QC Batch ID:HL25Oct Mean SD %RSD %RE N 6 6 BI Human Plasma Sample Concentrations after 635 days Storage in the Freezer set at -20 C BI xxxxx Concentration, nm Nominal QC Batch ID: HL09Jul Mean SD %RSD %RE N 6 6 BI xxxxx Human Plasma Sample Concentrations after 96.5 hours Storage at Room Temperature under Normal Lab Lights BI xxxxx Concentration, nm Nominal QC Batch ID:HL03Feb Mean SD %RSD %RE N 6 6
12 Concentration related non-linearity Adsorptive affects Precipitation Matrix related affects Endogenous interferents
13 Typical Validation Runs Summary of Batches Performed Batch ID Run Number 1 Status 2 Description HL23Jul2013 NA Accepted Internal standard suitability evaluation HL25Oct Accepted HL28Oct Accepted HL29Oct Accepted Core Validation Run 1; Dil.QC, Freeze/Thaw Stability, Specificity Blank, and Specificity Zero are Included. Core Validation Run 2; Hemolysis effect samples and Lipemic samples are included. Core Validation Run 3; Thawed Matrix Stability and Run Size are included. HL29Oct2013a 5 Accepted Processed Sample Stability HL30Oct Accepted Freezer Stability of Plasma Samples HL22Nov2013 NA Accepted Stock freezer stability and room temperature stability test HL05Dec2013 NA Accepted Recovery and matrix effect test HL08Jan Accepted Freezer Stability of Plasma Samples HL03Feb Accepted Thawed Matrix Stability Extension
14 When to extend and When not to Extend the LLOQ Never: Comparative PK Studies: BE, BA, Food Effect, DDI Seldom: Sometimes : Studies with PK as primary endpoint Studies in which PK endpoint is not pivotal (SRD, MRD) Usually acceptable: Pharmacometric modeling studies Careful controls and cautions must be applied, things to be considered: The extent to which LLOQ extrapolation is made Expected ruggedness of method and matrix impact at sub-lloq concentrations Regulatory consequences: are the data use outside the study? will data be subject to regulatory scrutiny?
15 Recommendations for extending LLOQ Be sure extended values > LOD? With VerificationVia Partial Ways to verify sub-lloq values: Validation New and old curves should be combined (carry over) Extended STDs for lower concentrations. Add QC at new LLOQ Add QC at 3x New LLOQ, more if necessary Verify freezer stability at 3x New LLOQ Verify Selectivity (patient matrix) Cross analyte or co-med interference, if necessary Matrix Effect Verify other validation parameters as required A/S, Extract Stability F/T stability Recovery
Bioanalytical method validation: An updated review
Review Article www.phmethods.org Bioanalytical method validation: An updated review Abstract The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery
More informationA Sub-picogram Quantification Method for Desmopressin in Plasma using the AB SCIEX Triple Quad 6500 System
A Sub-picogram Quantification Method for Desmopressin in Plasma using the AB SCIEX Triple Quad 6500 System A high-throughput method for detecting ultra-low levels (0.5 pg/ml) of a therapeutic peptide in
More informationA Sub-picogram Quantification Method for Desmopressin in Plasma using the SCIEX Triple Quad 6500 System
A Sub-picogram Quantification Method for Desmopressin in Plasma using the SCIEX Triple Quad 6500 System A high-throughput method for detecting ultra-low levels (0.5 pg/ml) of a therapeutic peptide in human
More informationBackground. Ferring Pharmaceuticals
Background Ferring Pharmaceuticals Founded in 195 and have since then worked with peptides Today, focus are on peptides as well as proteins Many of our peptides are agonists targeting the oxytocin or vasopressin
More informationPractical Aspects of Dried Blood Spot (DBS) Bioanalytical Assay Development and Application. Qin C. Ji CASSS, 09 September 2010
Practical Aspects of Dried Blood Spot (DBS) Bioanalytical Assay Development and Application Qin C. Ji CASSS, 09 September 2010 1 Outline Introduction Potential advantages of DBS DBS assay development Result
More informationA TFC MS/MS Method for the Determination of the Cholinesterase Sensitive Analyte Rivastigmine in Human Plasma
White Paper A TFC MS/MS Method for the Determination of the Cholinesterase Sensitive Analyte Rivastigmine in Human Plasma Lars Neudert, MSc, Senior Scientist Method Development Laurence Meunier, PhD, Senior
More informationIntegrating an exploratory BM in an early clinical stage in Pharma R&D
Integrating an exploratory BM in an early clinical stage in Pharma R&D Ulrich Kunz, Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany Content
More informationQuantitatitive Analysis of Phosphorothioate Oligonucleotide in Human Plasma Using LC-MS/MS with On-Line Extraction
Laixin Wang, Sherry Liu, Qiuying Zhu, Scott Reuschel and Min Meng Tandem Labs Quantitatitive Analysis of Phosphorothioate Oligonucleotide in Human Plasma Using LC-MS/MS with On-Line Extraction Introduction
More informationMicroflow Liquid Chromatography Mass Spectrometry System. Nexera Mikros C146-E350
Microflow Liquid Chromatography Mass Spectrometry System Nexera Mikros C146-E35 Micro: Above and Beyond Nano The High Sensitivity You Expect from a Low Flow System with the Ruggedness of HPLC Covering
More information6 th EBF Open meeting, Barcelona November 21st, 2013
Validation of an immunoassay to selectively quantify the naked antibody of a new Sanofi Antibody Drug Conjugate: an additional tool for improvement of PK interpretation 6 th EBF Open meeting, Barcelona
More informationSmall molecule bioanalytical method development and transfer: is a plug and play approach possible?
Small molecule bioanalytical method development and transfer: is a plug and play approach possible? Luca Ferrari Clinical Pharmacology and Bioanalytical R&D, pred Pharmaceutical Sciences, Roche Innovation
More informationA8: Documentation. Team members: Interdependencies with other teams if any. Out of scope. Team lead. Other members
A8: Documentation Team members: Team lead Tom Verhaeghe Janssen R&D EU Other members Eric Woolf Merck NA Hollie Barton PPD NA Marian Kelley Mkelley Consulting NA Myriam Salvadori ChromAnalysis LA Richard
More informationA Sensitive and Robust Method for the Quantification of Goserelin in Plasma Using Micro-Elution Plates
A Sensitive and Robust Method for the Quantification of Goserelin in Plasma Using Micro-Elution Plates Tirupateswara B. Rao, P. Veeranjaneyulu, Sudarshan Mantha, and Dr. Gopal Vaidyanathan Waters Corporation,
More informationValidation of Analytical Method of Irbesartan Plasma in Vitro by High Performance Liquid Chromatography-Fluorescence
Journal of Life Sciences 6 (2012) 726-731 Validation of Analytical Method of Irbesartan Plasma in Vitro by High Performance Liquid Chromatography-Fluorescence Harmita, Yahdiana Harahap and I. Kadek Arya
More informationCase Studies Using the Singulex Erenna to Develop Sensitive Custom Biomarker Assays. Alison Joyce AAPS NBC 2015, San Francisco, CA
Case Studies Using the Singulex Erenna to Develop Sensitive Custom Biomarker Assays Alison Joyce AAPS NBC 2015, San Francisco, CA Outline Technology background Case Studies: -Assay 1: Bead-based homebrew
More informationFGF23 (C-terminal) multi-matrix ELISA
FGF23 (C-terminal) multi-matrix ELISA for the quantitative determination of human FGF23 (C-terminal) in serum, EDTA plasma, heparin plasma, and citrate plasma Cat. No. BI-20702. 12 x 8 tests CONTENTS ASSAY
More information10. Validated Normal Phase HPLC Method for the Determination. Fulvestrant is primarily used in the treatment of hormone receptor
229 10. Validated Normal Phase HPLC Method for the Determination of Fulvestrant in Pharmaceutical Dosage Forms 10.1 Introduction Fulvestrant is primarily used in the treatment of hormone receptor positive
More informationLigand Binding Assay strategies to support early drug development. Sarah Childs, Tina Panchal, Rose Edwards GlaxoSmithkline
Ligand Binding Assay strategies to support early drug development Sarah Childs, Tina Panchal, Rose Edwards GlaxoSmithkline Overview PK Study Design Bioanalytical Strategy Method Development Validation
More informationGuidance for Industry
Guidance for Industry Bioanalytical Methods Validation for Human Studies DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft
More informationEvaluation of a promising new homogenous assay technology (SPARCL) and comparisons with MSD, using FSH as test substance
Evaluation of a promising new homogenous assay technology (SPARCL) and comparisons with MSD, using FSH as test substance Karl Pettersson/ Ferring Pharmaceuticals A/S Background Bioanalysis department at
More informationRegulatory Reflections on the BMV Guideline/Guidance Harmonization
Regulatory Reflections on the BMV Guideline/Guidance Harmonization EBF - Focus Workshop: Industry input into ICH M10 September 25-27, 2014, Noriko Katori, PhD National Institute of Health Sciences, Japan
More informationDRUG DISCOVERY & 2 September 2010
LC-MS/MS QUANTITATION IN DRUG DISCOVERY & DEVELOPMENT Ludmila Alexandrova 2 September 2010 1 For personal use only. Please do not reuse or reproduce without the author s permission. 2 Presentation Outline
More informationMedicines inspections technical updates: Contract research organizations (CROs)
JOINT UNICEF, UNFPA & WHO MEETING WITH MANUFACTURERS AND SUPPLIERS OF CONTRACEPTIVE DEVICES, IN VITRO DIAGNOSTICS PRODUCTS, VACCINES, FINISHED PHARMACEUTICAL PRODUCTS, ACTIVE PHARMACEUTICAL INGREDIENTS
More informationValidation of Analytical Methods used for the Characterization, Physicochemical and Functional Analysis and of Biopharmaceuticals.
Validation of Analytical Methods used for the Characterization, Physicochemical and Functional Analysis and of Biopharmaceuticals. 1 Analytical Method Validation: 1..1 Philosophy: Method validation is
More informationCLSI C60: Assay Validation & Post-Validation Monitoring
CLSI C60: Assay Validation & Post-Validation Monitoring Ross J. Molinaro, MT(ASCP), PhD, DABCC, FACB Medical Director Core Laboratory, Emory University Hospital Midtown Emory Clinical Translational Research
More informationFood and. Re: Docket Bioanalytica. that keep. majority of. the world. market. only a small. since the. standard. on the draft. Sincerely, Affairs
Samata Veluvolu Manager, Regulatory Affairs December 11, 2013 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, rm. 1061 Rockville, MD 208522 Re: Docket No. FDA 2013
More informationSubmission preparation what to watch out for
Submission preparation what to watch out for EBF 2017 Boris Gorovits AAPS BIOTEC section Pfizer June 2017 Analytes Commonly Assessed for ADC PK Unconjugated Drug analyte Total Antibody analyte Conjugated
More informationSIMPLE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR DETERMINATION OF NORFLOXACIN IN PLASMA AND APPLICATION IN BIOEQUIVALENCE STUDY
Academic Sciences International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 4, Issue 3, 2012 Research Article SIMPLE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR DETERMINATION
More informationReady, Set, Test! AACC Conference Mass Spectrometry in the Clinical Lab: Best Practice and Current Applications September 17-18, 2013 St.
Ready, Set, Test! Ross Molinaro, PhD, MLS(ASCP) CM, DABCC, FACB Medical Director, Clinical Laboratories Emory University Hospital Midtown Emory Clinical Translational Research Laboratory AACC Conference
More informationWAIT! Ready, Set, Test! Financial Disclosure. Research/Educational grants/consulting/salary support
Ready, Set, Test! Ross Molinaro, PhD, MLS(ASCP) CM, DABCC, FACB Medical Director, Clinical Laboratories Emory University Hospital Midtown Emory Clinical Translational Research Laboratory AACC Conference
More informationDevelopment, Optimization and Validation of Luminex based cytokine assays
Introduction Luminex is a fluorescence covalent microbead immunosorbent assay, in which up to 500 analytes can be multiplexed in a single well. The advantages of Multiplexed bead- based immunoassays, which
More informationGuideline/Guidance Comparison on Ligand Binding Assays (LBA)
Guideline/Guidance Comparison on Ligand Binding Assays (LBA) vs EMA Guideline (2011, updated 2014) vs Scope This guideline is applicable to the validation of LBAs as analytical methods for the measurement
More informationGuideline/Guidance Comparison on Ligand Binding Assays (LBA)
http://bioanalysisforum.jp/ Guideline/Guidance Comparison on Ligand Binding Assays (LBA) vs EMA Guideline (2011, updated 2014) vs Scope This guideline is applicable to the validation of LBAs as analytical
More informationCurrent practices on metabolite profiling and quantification in Drug Development at Boehringer-Ingelheim
Current practices on metabolite profiling and quantification in Drug Development at Boehringer-Ingelheim S Blech EBF Focus Workshop: Metabolite Profiling and Quantification Strategies in Drug R&D Sep 25,
More informationFunctionality. Normal Operation
Application Note Automating EPA Method 200.8 using the SDXHPLD High Performance Liquid Dilution System Jim Maximovich, Teledyne CETAC Technologies, Omaha, NE, USA, Jim.Maximovich@Teledyne.com The SDX HPLD
More informationVerifying the Reliability of EPA Method 314 to Measure Perchlorate at Sub ppb Levels vs New EPA Method Options
Verifying the Reliability of EPA Method 314 to Measure Perchlorate at Sub ppb Levels vs New EPA Method Options Andrew Eaton, Ph.D. MWH Labs Region 6 QA Conference - 10/21/04 Why Do We Care About Accuracy
More informationOnline LC Sample Preparation with BioTrap 500 C18
Online LC Sample Preparation with BioTrap 500 C18 Jörgen Hermansson Anders Grahn Inger Hermansson ChromTech AB Stockholm, Sweden Phone: 08-464-8020 Fax: 08-464-7020 E-mail: ct@chromtech.se http://www.chromtech.
More informationTechnical Assessment (TA) Summary Form (M00116)
Technical Assessment (TA) Summary Form (M00116) Please complete the following 2 table summarization of the dossier. Table 1. Summary of Evidence Validation Element For each cell below, please provide the
More informationBIOEQUIVALENCE TRIAL INFORMATION FORM (Medicines and Allied Substances Act [No. 3] of 2013 Part V Section 39)
ZAMRA BTIF BIOEQUIVALENCE TRIAL INFORMATION FORM (Medicines and Allied Substances Act [No. 3] of 2013 Part V Section 39) The Guidelines on Bioequivalence Studies to be consulted in completing this form.
More informationThe AAPS Journal 2007; 9 (1) Article 4 (http://www.aapsj.org).
Themed Issue: Bioanalytical Method Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays Guest Editors - Mario L. Rocci Jr., Vinod P. Shah, Mark J. Rose, Jeffrey M.
More informationGary A. Schultz, Advion BioServices, Inc. Ithaca, NY 14850
Validation of an immunoprecipitation, digestion and immunoaffinity LC/LC/nanoLC-MS/MS assay for human b-nerve growth factor (NGF) and implementation in support of clinical trials Gary A. Schultz, schultzg@advion.com
More informationHigh Speed, Ultra-High Sensitivity, and Robustness Needed for the Quantitation of Pharmaceuticals in Blood Plasma. Application Note. Authors.
High Speed, Ultra-High Sensitivity, and Robustness Needed for the Quantitation of Pharmaceuticals in Blood Plasma Application Note Drug discovery and development: Drug metabolism and pharmacokinetics (DMPK)
More informationAgilent New 6470 Triple Quadrupole LC/MS System
Agilent New 6470 Triple Quadrupole LC/MS System ROCK SOLID Performance For Confident Quantitation Na Pi Parra, Ph.D Product Manager for Triple Quadrupole LC/MS 1 Overview of Topics The New 6470 QQQ LC/MS
More informationAppNote 5/2006 ABSTRACT
AppNote 5/26 Stir Bar Sorptive Extraction Based on Restricted Access Material for the Direct Extraction of Drugs and Metabolites in Biological Fluids Wayne M. Mullett and Elizabeth Kwong Merck Frosst,
More informationGuideline/guidance Comparison on Large Molecule Bioanalysis
Guideline/guidance Comparison on Large Molecule Bioanalysis 6th JBF Symposium 2014.2.26 Jun Hosogi Kyowa Hakko Kirin Co.,Ltd. MHLW/EMA/FDA BMV guidelines (LBA section) MHLW (LBA) 2014 EMA (7. LBA) 2011
More informationApplication Note. Author. Abstract. Pharmaceuticals. Detlef Wilhelm ANATOX GmbH & Co. KG. Fuerstenwalde, Germany mau
Development, validation, and comparison of an HPLC method to analyze paracetamol and related impurities according to the European Pharmacopoeia (EP) and USP using the Agilent 1120 Compact LC and the Agilent
More informationImproving Sensitivity in Bioanalysis using Trap-and-Elute MicroLC-MS
Improving Sensitivity in Bioanalysis using Trap-and-Elute MicroLC-MS Using the SCIEX M3 MicroLC system for Increased Sensitivity in Antibody Quantitation Remco van Soest and Lei Xiong SCIEX, Redwood City,
More informationBIOEQUIVALENCE TRIAL INFORMATION
PRESENTATION OF BIOEQUIVALENCE TRIAL INFORMATION BIOEQUIVALENCE TRIAL INFORMATION GENERAL INSTRUCTIONS: Please review all the instructions thoroughly and carefully prior to completing the Bioequivalence
More informationImproving Sensitivity for an Immunocapture LC-MS Assay of Infliximab in Rat Plasma Using Trap-and-Elute MicroLC-MS
Improving Sensitivity for an Immunocapture LC-MS Assay of in Rat Plasma Using Trap-and-Elute MicroLC-MS Using the SCIEX M3 MicroLC system for Increased Sensitivity in Antibody Quantitation Remco van Soest
More informationLigand Binding Assays: Summary and Consensus from the Bioanalytical Workshop (CC V)
Ligand Binding Assays: Summary and Consensus from the Bioanalytical Workshop (CC V) Binodh DeSilva Executive Director Immunochemistry and Biomarker Development Bristol-Myers Squibb Contributors Lauren
More informationICH Q2(R1) A Primer. cgmp. GxP PIC/S SOP ISO QA/QC LOD/LOQ. Validation of Analytical Methods API EP FDA OECD GCP
USP ICH Q2(R1) A Primer GxP cgmp PIC/S SOP ISO 17025 QA/QC LOD/LOQ API EP Validation of Analytical Methods FDA OECD GCP Validation of Analytical Methods Ludwig Huber Contents Preface...............................................
More informationDinesh Khokal, PhD, Singapore
GaBI Educational Workshops 5 August 2018, Furama Resort Da Nang, Vietnam 1st ASEAN Overview Workshop on GMP for BIOLOGICALS/BIOSIMILARS Dinesh Khokal, PhD, Singapore Director, External Affairs, Corporate
More informationCommon Pitfalls to Avoid LC/MS/MS
Wednesday April 5, 2017 2:45pm Common Pitfalls to Avoid LC/MS/MS Kathy Nucifora, MPH, MT(ASCP) COLA, Accreditation Division Director Columbia, MD DESCRIPTION: Kathy Nucifora, COLA Accreditation Division
More informationComposition Analysis of Animal Feed by HR ICP-OES
Composition Analysis of Animal Feed by HR ICP-OES Abstract The High-Resolution Array ICP-OES equipped with Standard-Kit was used for the analysis of Al, B, Ca, Co, Cr, Cu, Fe, I, K, Na, Mn, Mg, Mo, Ni,
More informationValidation of a concentration assay using Biacore C
GE Healthcare Application Note 48 Biacore systems Validation of a concentration assay using Biacore C Guideline for development of a GxP - compliant concentration assay Support for informed decision-making
More informationAnalysis of steel and its alloys using the GB/T standard and an Agilent 5100 ICP-OES in dual view mode
Analysis of steel and its alloys using the GB/T 20125-2006 standard and an Agilent 5100 ICP-OES in dual view mode Application note Metals analysis and production Authors John Cauduro Agilent Technologies
More informationExploring Extra Sensitivity Using ionkey/ms with the Xevo G2-XS Q-Tof HRMS for Small Molecule Pharmaceutical Analysis in Human Plasma
Exploring Extra Sensitivity Using ionkey/ms with the Xevo G2-XS Q-Tof HRMS for Small Molecule Pharmaceutical Analysis in Human Plasma Yun Wang Alelyunas, Mark D. Wrona, Jim Murphy, Angela Doneanu, Gregory
More informationAnalysis of Heavy Metals in Iron-based Fertilizers by HR ICP-OES
Analysis of Heavy Metals in Iron-based Fertilizers by HR ICP-OES Abstract The analysis of Iron-rich samples by ICP-OES is often very demanding since prominent Iron-based spectral interferences affect many
More informationA Simple Rapid and Sensitive Method Development for Quantification of Quetiapine Fumarate in Bulk and Dosage Forms Using RP-HPLC
Human Journals Research Article February 2018 Vol.:11, Issue:3 All rights are reserved by Priyanka Teepoju et al. A Simple Rapid and Sensitive Method Development for Quantification of Quetiapine Fumarate
More informationValidation of a Dual Wavelength Size Exclusion HPLC Method with Improved Sensitivity to Detect Aggregates of a Monoclonal Antibody Biotherapeutic
Validation of a Dual Wavelength Size Exclusion HPLC Method with Improved Sensitivity to Detect Aggregates of a Monoclonal Antibody Biotherapeutic By J. Tompkins1, T. Spurgeon 1, R. Tobias 1, J. Anders1,
More informationAbraxis Method 546 Guide
Abraxis Method 546 Guide Analysis Batch Controls Laboratory Reagent Blank Description: Control that is used to determine if any interferences are introduced during analysis. It is an aliquot of reagent
More informationOptiFlow Quant Solution for High-Sensitivity Quantitation
OptiFlow Quant Solution for High-Sensitivity Quantitation The Intelligent Union of Sensitivity, Ease-of-Use, and Robustness MicroFlow Sensitivity Analytical Flow Usability Transform Your Quantitation Microflow
More informationA Practical Example of CLSI C60 in Action: Vitamins and Hormones
A Practical Example of CLSI C60 in Action: Vitamins and Hormones Lorin Bachmann, Ph.D., DABCC Assistant Professor, Pathology Virginia Commonwealth University lbachmann@mcvh-vcu.edu AACC Conference-Mass
More informationProtocol for Quantitative Determination of Residual Solvents in Cannabis Concentrates Prepared by: Amanda Rigdon, May 23 rd, 2016
Protocol for Quantitative Determination of Residual Solvents in Cannabis Concentrates Prepared by: Amanda Rigdon, May 23 rd, 2016 1.0 Method background: This method employs full evaporation technique headspace
More informationFit-for-Purpose Biomarker Assay Validation: From Concept to Practices
Fit-for-Purpose Biomarker Assay Validation: From Concept to Practices Jean Lee, Ph.D., FAAPS Consultant BioQualQuan, LLC 6 th Japan Bioanalysis Forum Symposium February 25, 2015 Outline of discussions
More informationConsiderations for Successful Biomarker Bioanalysis in Regulated Environment
Considerations for Successful Biomarker Bioanalysis in Regulated Environment Darshana Jani, M.Sc. Darshana.Jani@pfizer.com 10 th European Bioanalysis Forum November 15, 2017 1 Disclaimer The contents of
More informationMultiQuant Software 2.0 with the SignalFinder Algorithm
MultiQuant Software 2.0 with the SignalFinder Algorithm The Next Generation in Quantitative Data Processing Quantitative analysis using LC/MS/MS has benefited from a number of advancements that have led
More informationRevision of 30 April 2013 draft, 4 November 2013
GUIDANCE DOCUMENT FOR SINGLE LABORATORY VALIDATION OF QUANTITATIVE ANALYTICAL METHODS USED IN SUPPORT OF PRE- AND POST-REGISTRATION DATA REQUIREMENTS FOR PLANT PROTECTION AND BIOCIDAL PRODUCTS INTRODUCTION
More informationAutomation for Improving the Workflows for LC-MS/MS. Francois Espourteille, Ph.D. Manager, Applications
Automation for Improving the Workflows for LC-MS/MS Francois Espourteille, Ph.D. Manager, Applications Discussion Overview Challenges of sample preparation in LC-MS analysis TurboFlow Technology Multiplexing
More informationInternational Journal of ChemTech Research CODEN (USA): IJCRGG, ISSN: , ISSN(Online): Vol.10 No.6, pp , 2017
International Journal of ChemTech Research CODEN (USA): IJCRGG, ISSN: 0974-4290, ISSN(Online):2455-9555 Vol.10 No.6, pp 1073-1082, 2017 Cost Effective Stabilty Indicating Reverse Phase High Performance
More informationL2: Large Molecule Specific Assay Operation
L2: Large Molecule Specific Assay Operation Team members: Team lead Lauren Stevenson (NA) Other members Clare Kinglsey (EU) Karolina Oesterlund (EU) Marian Kelley (NA) Heather Myler (NA) Boris Gorovits
More informationDried Blood Spot Analysis From The Clinic To The Laboratory
Dried Blood Spot Analysis From The Clinic To The Laboratory Joanne Mather, Pharmaceutical Life Sciences Waters Corporation 211 Waters Corporation 1 From The Clinic To The Lab Blood Spot Sampling First
More informationGUIDANCE NOTES ON ANALYTICAL METHOD VALIDATION
ON ANALYTICAL METHOD VALIDATION HSA September 2004 Reproduction prohibited for commercial purposes. Reproduction for internal use is authorised, provided the source is acknowledged. MQA Dir: DISK1\GUIDE-MQA-012A-004.doc
More informationEVOLUTE ABN FOR EXTRACTION OF DRUGS FROM BIOLOGICAL FLUIDS
Technical ote 3 EVLUTE AB FR EXTRACTI F DRUGS FRM BILGICAL FLUIDS EVLUTE Sample Preparation Products are a new generation of advanced polymeric solid phase extraction sorbents for the high throughput extraction
More informationVICH Topic GL49. at step 4 GUIDELINES FOR THE VALIDATION OF ANALYTICAL METHODS USED IN RESIDUE DEPLETION STUDIES
European Medicines Agency Veterinary Medicines and Inspections London, 14 December 2009 Doc. Ref. EMEA/CVMP/VICH/463202/2009-CONSULTATION VICH Topic GL49 at step 4 GUIDELINES FOR THE VALIDATION OF ANALYTICAL
More informationOn-line SPE-LC/MS/MS to Detect Organonitrogen and Triazine Pesticides at 10ng/L in Drinking Water
application note On-line SPE-LC/MS/MS of Pesticides On-line SPE-LC/MS/MS to Detect Organonitrogen and Triazine Pesticides at 10ng/L in Drinking Water API 3200 LC/MS/MS System Overview The feasibility of
More informationPhase Appropriate Method Validation
Phase Appropriate Method Validation Aryo Nikopour Irvine, California January 12, 2017 The Southern California Pharmaceutical Discussion Group (SCPDG) of AAPS OUTLINE What is Validation Guidelines Method
More informationHARMONIZATION TEAM A6 (STABILITY) UPDATE. Yoshiaki Ohtsu 8 March 2012
HARMONIZATION TEAM A6 (STABILITY) UPDATE Yoshiaki Ohtsu 8 March 2012 Contents 1. General update 2. Scientific discussion point 1. Stability of presence of co administered or co formulated drugs 2. Incurred
More informationCAMAG DBS-MS 500 DRIED BLOOD SPOT EXTRACTION SYSTEM FOR LC-MS
CAMAG DBS-MS 500 DRIED BLOOD SPOT EXTRACTION SYSTEM FOR LC-MS Direct Analysis FULLY AUTOMATED DBS EXTRACTION SYSTEM FOR MASS SPECTROMETRY Dried blood spot sampling was introduced around 40 years ago. It
More informationBIOANALYSIS CONSUMABLE SOLUTIONS. Sample Preparation and Liquid Chromatography Solutions for Quantitative BIOANALYSIS
BIOANALYSIS CONSUMABLE SOLUTIONS Sample Preparation and Liquid Chromatography Solutions for Quantitative BIOANALYSIS At Waters, we understand the unique challenges faced by the bioanalytical community,
More informationSequential Protein and Peptide Immunoaffinity Capture for Mass Spectrometry- Pfizer Inc, 1 Burtt Road, Andover, Massachusetts, 01810, United States
SUPPORTING INFORMATION Sequential Protein and Peptide Immunoaffinity Capture for Mass Spectrometry- Based Quantification of Total Human Beta-Nerve Growth Factor Hendrik Neubert *, David Muirhead, Musarat
More informationUniversal Solution for Monoclonal Antibody Quantification in Biological Fluids Using Trap-Elute MicroLC-MS Method
Universal Solution for Monoclonal Antibody Quantification in Biological Fluids Using Trap-Elute MicroLC-MS Method Featuring the SCIEX QTRAP 6500+ LC-MS/MS System with OptiFlow Turbo V source and M5 MicroLC
More informationEmerging Technologies for Personalized Medicine: The Impact on the Clinical Laboratory and the Future of Patient Care
Emerging Technologies for Personalized Medicine: The Impact on the Clinical Laboratory and the Future of Patient Care Mike S. Lee! Milestone Development Services!! Gary Valaskovic! New Objective!! Kenneth
More informationPoints to Consider Document:
Points to Consider Document: Scientific and Regulatory Considerations for the Analytical Validation of Assays Used in the Qualification of Biomarkers in Biological Matrices Biomarker Assay Collaborative
More informationUltra-Sensitive Quantification of Trastuzumab Emtansine in Mouse Plasma using Trap-Elute MicroLC MS Method
Ultra-Sensitive Quantification of Trastuzumab Emtansine in Mouse Plasma using Trap-Elute MicroLC MS Method Featuring SCIEX QTRAP 6500+ System with OptiFlow Turbo V source and M5 MicroLC system Lei Xiong,
More informationVALIDATION OF ANALYTICAL PROCEDURES: METHODOLOGY *)
VALIDATION OF ANALYTICAL PROCEDURES: METHODOLOGY *) Guideline Title Validation of Analytical Procedures: Methodology Legislative basis Directive 75/318/EEC as amended Date of first adoption December 1996
More informationAgilent 6490 Triple Quadrupole LC/MS System REACH ULTIMATE SENSITIVITY WITH BREAKTHROUGH IFUNNEL TECHNOLOGY
Agilent 6490 Triple Quadrupole LC/MS System REACH ULTIMATE SENSITIVITY WITH BREAKTHROUGH IFUNNEL TECHNOLOGY AGILENT 6490 TRIPLE QUADRUPOLE LC/MS SYSTEM WITH IFUNNEL TECHNOLOGY CLEARLY BETTER SENSITIVITY
More informationBIOANALYTICAL METHOD DEVELOPMENT AND ITS VALIDATION
321 P a g e International Standard Serial Number (ISSN): 2319-8141 International Journal of Universal Pharmacy and Bio Sciences 3(4): July-August 2014 INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND BIO
More informationEPA Drinking Water Method 544
OAWWA-2016 EPA Drinking Water Method 544 Jody A. Shoemaker, Daniel R. Tettenhorst, Armah de la Cruz Disclaimers: Mention of trade names or commercial products does not constitute endorsement or recommendation
More informationWaters Solutions for DMPK and Biomarker Analysis. Waters User Meeting ASMS 2011 Denver, Colorado. Stephen McDonald
Waters Solutions for DMPK and Biomarker Analysis Waters User Meeting ASMS 2011 Denver, Colorado Stephen McDonald 2011 Waters Corporation 1 Drug Development Process Pre-clinical testing R&D - 18 months
More informationMETHOD VALIDATION TECHNIQUES PREPARED FOR ENAO ASSESSOR CALIBRATION COURSE OCTOBER/NOVEMBER 2012
METHOD VALIDATION PREPARED FOR ENAO ASSESSOR CALIBRATION COURSE TECHNIQUES OCTOBER/NOVEMBER 2012 Prepared by for ENAO Assessor Calibration B SCOPE Introduction House Rules Central Tendency Statistics Population
More informationN. Tamilselvi *, Dona Sara Kurian. Department of Pharmaceutical Analysis. KMCH college of pharmacy Coimbatore
BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF PIRFENIDONE BY RPHPLC METHOD AND ITS APPLICATION TO THE DETERMINATION OF DRUG FOOD INTERACTION STUDY IN WISTER RATS ABSTRACT N. Tamilselvi *, Dona Sara
More informationSize Exclusion Chromatography of Biosimilar and Innovator Insulin Using the Agilent AdvanceBio SEC column
Size Exclusion Chromatography of Biosimilar and Innovator Insulin Using the Agilent AdvanceBio SEC column Application Note Bio-Pharmaceutical Authors M. Sundaram Palaniswamy and Andrew Coffey Agilent Technologies,
More informationOutcomes of the Global Bioanalysis Consortium s Recommendations: Large Molecule Discussion Topics. Binodh DeSilva on behalf of LM Harmonization Teams
Outcomes of the Global Bioanalysis Consortium s Recommendations: Large Molecule Discussion Topics Binodh DeSilva on behalf of LM Harmonization Teams TEAM LEADS TEAM Team Lead L1 Specific run Acceptance
More informationpharmaceutics ISSN
Pharmaceutics 2010, 2, 171 181; doi:10.3390/pharmaceutics2020171 Article OPE ACCESS pharmaceutics ISS 1999-4923 www.mdpi.com/journal/pharmaceutics Quantitative Determination of ABT-925 in Human Plasma
More informationAPPLICATION NOTE. UOP : Analysis of Trace CO and CO 2 in bulk H 2 and Light Gaseous Hydrocarbons by GC
UOP 63-13: Analysis of Trace CO and CO 2 in bulk H 2 and Light Gaseous Hydrocarbons by GC Fast Analysis in
More informationAnalytical Method of Limit Test for Hexachlorobenzene. in Picloram TC and Method Validation Data*
Analytical Method of Limit Test for Hexachlorobenzene in Picloram TC and Method Validation Data* Test Method (ABCTM-2010-01-07) 1. Apparatus Electronic Balance GC/MS System with NCI Ultrasonic Water Bath
More informationExtraction of Vitamin B7 (Biotin) from Serum Using EVOLUTE
Application Note AN880 Extraction of Vitamin B7 (Biotin) from Serum Using EVOLUTE EXPRESS ABN Prior to LC-MS/MS Analysis Page 1 Extraction of Vitamin B7 (Biotin) from Serum Using EVOLUTE EXPRESS ABN Prior
More informationMouse Sclerostin ELISA
Mouse Sclerostin ELISA For the quantitative determination of sclerostin in mouse serum and plasma. For Research use Only. Not For Use In Diagnostic Procedures. Catalog Number: Size: 41-SCLMS-E01 96 Wells
More informationExamples of regulatory expectations for analytical characterization and testing
Examples of regulatory expectations for analytical characterization and testing AT Europe 2016, 18 March 2016 Vicki Venizelos Quality RA B.V. Leiden, the Netherlands Overview What are the regulatory expectations?
More information