Integrating an exploratory BM in an early clinical stage in Pharma R&D

Size: px
Start display at page:

Download "Integrating an exploratory BM in an early clinical stage in Pharma R&D"

Transcription

1 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

2 Content of Workshop 1. Introduction 2. Getting information about BM1: Assay request process (Biology of the BM and intended use) 3. Translation into a bioanalytical strategy: Choice of an analytical method for BM1 4. Validation of the BM assay for the first phase I study 5. Sample measurement: results and data evaluation 6. Outcome and consequences on the further development U. Kunz, June

3 Overview of the (ideal) Process of identifying BM for early clinical studies at BI Lead Optimization Literature Research Teams Clinical development Plan Disease Indication Teams Biomarker Medical Subteam (responsible for BM strategy, Pk, Pharmacometrics, Statistics, Clinical, Preclinical, Research, lead: TMCP) TMCP-Plan Project strategy early clinical development Outlook on late stage clinical development (planned studies, population, which BM and why) Contacts to external researchers Translatorical Studies Bioanalytical support (assay feasibility, search for methods, reagents, assay development, validation, measurement of samples transfer to other sites) Start of clinical development U. Kunz, June

4 Flow for biomarker method establishment BM Medical Subteam, Translational Medicine and BM expert: BM strategy Assay request process Understanding biology and intended use of BM TM & CP plan CTP (Expl. BM) + Analyt. Workplan Analyze samples 1. phase I study Fail Bioanalyst + Sponsor: Qualify BM assumptions + evaluate assay performance Validation plan Success Bioanalyst + Sponsor (TMBE): Translation into a Bioanalytical strategy and assay design Feasibility study/ method set up and validation Level 3/Screening assay Bioanalyst + Sponsor: Agree on future intended use of BM and assay requirements Continuing clinical and analytical interpretation of data from further studies (monitoring of assay performance) CTP (Expl. BM) + Analyt. Workplan Analyze samples Phase II study (Re-) Validation plan + Validation Report Set up/modify and validate the level 2/qualified assay U. Kunz, June

5 Assay request process Sponsor (Translational Medicine and Biomarker Experts) has to provide sufficient information prior to start of any lab activities Comprehensive questionaire to fill out: General status of method, BM and scope of analytical activities Structure and Biology of BM Intended use of BM results Prerequisites for the analytical method Planned clinical studies Thereafter, joint discussion between sponsor and bioanalyst: Practical aspects of requested lab support U. Kunz, June

6 BI tiered method validation approach for BM assays Tiered approach: Validation level may change dependent on: intended use of data, clinical qualification status of BM and knowledge about BM-assay and BM Level 3 (Screening assay) Level 2 (Qualified assay) Explorative biomarker To gain experience with the biomarker and the biomarker assay Comparability within a single study (narrow time window) Explorative and probable valid biomarker Comparability within a central lab over several studies (e.g. whole development) Level 1 (Cross) validated assay) Confirmatory biomarker (probable valid, valid) Comparability between labs External by diagnostic companies or CRO labs with extensive cross validation, Global reference system established and proven metrological traceability Advantages: Fast, flexible and cost effective (avoid frontloading of work) U. Kunz, June

7 How BM1 was nominated as explorative BM for phase I clinical study - very late, phase I clinical trail has already started - BI Research Teams Start of phase I clinical trial Literature BM1 Disease Indication Teams Biomarker Medical Subteam (responsible for BM strategy, lead: TMCP) Contacts to external researchers Translatorical Studies Interim analysis planned Clinical development Plan Amendment to Clinical Trial Protocol 1. Phase 1 study TMCP-Plan Version 2 Bioanalytical support (search for methods, validation, measurement of samples) U. Kunz, June

8 TMCP Plan The Translational and Biomarker strategy for this program has two main objectives: 1. Identify disease specific markers that change early after treatment with drug and correlate with clinical endpoints. 2. Identify mechanistic or disease specific markers that can predict clinical response to treatment with drug Efficacy Markers in the target tissue:... Disease Markers in Peripheral Blood : BM1 is a marker shown to be highly expressed in both the target tissue and serum of patients and higher levels correlated with higher clinical symptoms. Changes in serum levels of BM1 will also be assessed for PK/PD correlations. BIOMARKER ANALYSIS STRATEGY In collaboration with TransMed Experts and biomarker groups model-based analysis of efficacy or safety biomarker data may be conducted. The impact of serum levels of BM1 protein concentrations on the longitudinal, population model-based analysis of clinical outcomes is planned as an exploratory analysis using study data. U. Kunz, June

9 Assay request: Biology of BM1 Structure of BM (link to proteome database) relevant literature Biological Variability within and between populations (e.g. Differences Healthy Volunteers Patients) Presence in biological context, e.g. monomer, multimer (mono-, hetero-), splice variants, homologies, chemical isomers Interaction with other matrix compounds (binding proteins, receptor, drug...) Circadian rhythm known? Influence of extrinsic factors (e.g. fasted non-fasted, coagulation...)? Stability of BM (any hints for instability?) Preferred matrix Protein MW: 6 kda, cationic, cystein rich Some available about use of BM1 as biomarker in clinical studies Lit: Patient level > healthy volunteers (< 1ng/mL) Variability between patients high, correlation with disease status Several similar proteins present in blood, no info about multimers, commercial available anti-bm1 antibodies and kits states selectivity regarding BM1 Unknown, interaction with anionic peptides possible Lit: no evidence observed in healthy serum BM1 levels Lit: no large differences found in serum samples taken from the same individuum after a two year interval!! Serum and plasma (depending on what aliquots are remaining for BM1) U. Kunz, June

10 Assay request: Intended use of BM1 Biomarker category Known: Physiological Response Pd-Biomarker Option: Outcome Related Pd-Biomarker? Planned evaluation of results (for details please see: Trial Statistical Analysis Plan) Intended purpose What is the expected effect during treatment? not known about 50% 1-50% % % >1000% Which Lower Limit Of Quantification of the assay is needed? 1. Relative change from baseline levels during treatment 2. Correlation of baseline levels and clinical symptoms Outcome related BM: 1. How much reduction of peripheral levels of BM1 at week X do we need to achieve a 80% reduction in clinical symptoms at week 12? 2. Are baseline levels of BM1 predictive of clinical response? 3. Is BM1 a surrogate marker for clinical symptoms, independent of mechanism specific intervention? PK/PD with BM1 data. Reduction > 50% = 1-50% of baseline Healthy volunteer levels (Lit: about 1ng/mL) Information about existing analytical methods and current experience Lit about use of commercial kits and own ELISAs Kits from multiple vendors available U. Kunz, June

11 Assay request: Intended use of BM1 1. Expected number of samples in first studies? 2. Timelines of first studies 3. Interim analysis necessary? Use in further studies? Useful in other indications/projects? 1. About 300 in phase I, about 1000 in phase II (per indication) 2. Already running, about 3 month from now on (for interim)!!!!! 3. Yes after third dose cohort Yes, most likely phase II, support PK/PD modelling through expansion of kinetic data (together with mrna expression) Yes, data might support the transition into alternative indication/diseases U. Kunz, June

12 Question 1 1. Was the available information about BM1 and its intended use sufficient? What was missing? What assay format would you choose? U. Kunz, June

13 Translation into the bioanalytical strategy for (running) phase I and beyond (sponsor + bioanalyst) Biomarker of interest (incl. details about special isoforms or interesting epitopes or assay conditions) Necessary grade of quantification Total BM1 (no infos about isoforms, special selectivity of assays used in lit.) Relative quantitative (comparison of pre-dose levels necessary) Validation level for first study Level 3 (explorative BM, proof of hypothesis from lit, test of assay suitability, no inhouse experience with assay so far = not used in pre-clinic) Special requirements for assay development or validation, (e.g. sampling)? No (nothing known about needs for special sampling procedures, instabilities) Selected technology First choice: commercial ELISA kit (already available, high sensitivity not necessary) in principle LC-MS might be an option Patient samples available (contact)? Location of sample analysis (internal lab, external CRO) Some banked patient samples available Internal until end of phase I (quick results needed) Request to bioanalytical lab: Feasibility and selection out of various commercial assays Validation (level 3) Measurement of phase I samples (serum and plasma) U. Kunz, June

14 Selection of assay/assay feasibility Various BM 1 ELISA kits from different vendors available Several anti-bm1 antibodies and recombinant BM1 available Feasibility test of 6 different ELISA kits from 6 different vendors Tested parameter: Calibration range, curve fitting, signal to noise ratio lowest C/blank Reactivity of two external calibration standards (rec. Protein, synthetic peptide) Test of three individual sera from healthy volunteers + corresponding EDTA plasma in three dilutions (1:1 1:5) Test of a patient serum with expected high endogenous level in several dilutions U. Kunz, June

15 Selection of ELISA kit - Assay feasibility Calibration range, curve fitting, signal to noise ratio lowest C/blank Reactivity of two separate calibration standards (rec. Protein, synthetic peptide) Test of three individual sera from healthy volunteers + corresponding EDTA plasma in three dilutions (1:1 1:5) Test of a patient serum with expected high endogenous level in several dilutions ok ok ok No curve! ok Only 4 calibrators Parallel curves Non parallel Serum>plas ma Parallel curves Non parallel Serum>plas ma Non parallel Parallel 1:5 1:50 Parallel curves Non parallel Serum>plas ma - Conc. Independent response = blank!? - High signals, cannot be blocked with anti-bm1 antibody Parallel curves Sensitivity not sufficient Non parallel - - Non parallel Within replicate precision worth ok ok - ok ok comment preferred Kit does not work What does this kit measure? U. Kunz, June

16 Question 2 2. Has the intended use of BM1 data been translated adequately into the bioanalytical strategy? (choose of assay, feasibility experiments, plans for future validation and analyzing strategy)? U. Kunz, June

17 Assay validation plan, commercial kit#2, validation level 3 Validation plan experiment Calculation, method acceptance VCs (validation samples) Precision Calibration range, LLOQ, ULOQ Parallelism Baseline range Healthy Volunteers Short term stability endog. Analyte Three individual sera (low, mid, high) and EDTA plasma, aliquoted and stored frozen At least 3 runs at 3 day, VCs in independent duplicates Data from at least 3 runs at 3 days, whole curve + blank 4 individuals serum ( Healthy and patients), 4 individuals plasma Tabulate and calculate overall precision (CV), optimal: <30% CV Tabulated back calculated results of Cs, LLOQ = lowest valid C that can be distinguished from blank, ULOQ = highest valid C * highest valid dilution in parallelism exp. linear regression of log transformed values (0.8 < slope < 1.2, r²>0.98) N=12 serum and EDTA plasma Just report mean, min, max, CV, ratio plasma/serum 24h RT, +1, +3 freeze/thaw cycles (-20 C) Two individual samples (2 serum + 2 plasma) in duplicates (VCs), Expected BM effect >50% decrease Relative deviation stressed aliquots vs. frozen reference < 30% U. Kunz, June

18 Assay validation results Validation plan Precision Calibration range, LLOQ, ULOQ Parallelism Baseline range Healthy Volunteers Short term stability endog. Analyte experiment Calculation, acceptance Results 4 runs at 3 days, VCs in independent duplicates 4 runs at 3 days, whole curve + blank 4 individuals serum and 4 plasma N=12 serum and EDTA plasma 24h RT, +1, +3 freeze/thaw cycles (-20 C) Two individual samples in duplicates (VCs), Tabulate and calculate overall precision (CV), target: <30% CV Tabulated back calculated results of Cs, LLOQ = lowest valid C that can be distinguished from blank, ULOQ = highest valid C * highest valid dilution in parallelism exp. linear regression of log transformed values (0.8 < slope < 1.2, r²>0.98) Just report mean, min, max, CV Relative deviation stressed aliquots vs. frozen one < 30% Serum: 4-11% CV (N=8), Plasma: 5-13%CV (N=8) ng eq/ml ok, CV <4% (N=4), %dev: -3% - +5% LLOQ = 0.31 ng eq/ml (1:10) ULOQ = 750 ng eq/ml (1:500) 2 out of 4 non-parallel serum 3 out of 4 non-parallel plasma Serum: Mean 2.6 ng eq/ml (N=11), Min 0.62, Max 6.1, inter-indiv. CV = 71% Plasma: Mean 2.2 ng eq/ml (N=11), Min 0.63, Max 5.1, inter-indiv. CV = 69% Plasma/Serum = 0.85 Serum: stable 24h RT, +1, +3 freeze/thaw cycles (-20 C) Plasma: stable 24h RT, +1, +3 freeze/thaw cycles (-20 C) U. Kunz, June

19 Validation results - Precision Run Date Kit Lot# Curve Number QC Low (ng eq/ml) QC Mid (ng eq/ml) QC High (ng eq/ml) ratio Low/Mid ratio High/Mid 24-Aug-13 #2 V_ Aug-13 #2 V_ Aug-13 #2 V_ Aug-13 #2 V_ mean sd CV 11.0% 3.8% 8.6% 8.1% 9.1% U. Kunz, June

20 Validation results - Parallelism sample: concentrati [ng eq/ml] dilution 1: #P1 #P2 #P3 #P4 #S1 #S2 #S3 #S CV 10% 15% 7% 19% 16% 13% 13% 20% rel. Range 24% 37% 16% 41% 37% 28% 33% 46% linear regression log (1/dilution) log(conc.) slope r² Acceptance criteria: 0.8 < slope < 1.2 AND r² > 0.98 Parallel? Failed! U. Kunz, June

21 Questions 3 3. Has the assay been sufficiently proven/validated prior to start of sample measurements? What experiments are missing, not adequate? U. Kunz, June

22 Discussion with sponsor 1. Assay feasibility tests went fine (kit lot#1) But validation failed (due to different kit lot #2?) -> Consultation with the kit supplier (old lot #1 no longer available, third lot failed too) 2. Unfortunately, not sufficient time for an alternative assay, clinical study has already started -> Consultation with sponsor (Translational Medicine and Biomarker Expert) 3. Decision to continue with this assay as a quasi-quantitative assay. U. Kunz, June

23 Consequence for bioanalysis Keep the validation as it is Avoid reporting of relative concentration values (misleading) Pre-screening of pre-dose samples in various dilutions, titer determination (LLOQ = cut-off), reporting of titers for pre-dose samples only Selection of optimal individual dilution for each subject (upper range of calibration curve) Measurement of all samples of a subject in the fixed optimal dilution Calculation and reporting of post-/pre-dose ratio for post-dose samples -> Discussed in the validation summary and as part of the Analytical Workplan for BM1 measurement in the first study U. Kunz, June

24 Question 4 4. Assay acceptance after validation. What about the consequences of the failed parallelism experiment? quasi-quantitative evaluation of data ok? U. Kunz, June

25 In-study acceptance criteria (technical) General, all samples Is the CV of the response values of the dependent replicates (one preparation of sample in multiple wells) above 25%? IF yes THEN deactivate the whole sample (automatically done by Watson). Dynamic range = Check of calibration curve Are there calibration standards with a relative deviation from nominal/target of more than 20%? IF yes THEN deactivate the whole standard (all replicates). Recalculation of calibration curve Calibration range is truncated if lowest or highest standard failed. IF more than 25% of all replicates were excluded OR less than 5 valid calibration standards are remaining OR r² < 0.98 THEN the plate/run failed; Reject the run; STOP. ELSE continue No target values for QCs! QC results will be monitored and evaluated retrospectively (concentrations + ratios between QC results within 30% of mean). -> focus on comparability of runs not on relative accuracy U. Kunz, June

26 Measurement of study samples Retrospective QC evaluation and run acceptance Run Date Kit Lot# Curve Number QC Low (ng eq/ml) QC Mid (ng eq/ml) QC High (ng eq/ml) ratio Low/Mid ratio High/Mid 30-Sep-13 #2 S_ Sep-13 #2 S_ Sep-13 #2 S_ Oct-13 #2 S_ Oct-13 #2 S_ Jun-14 #4 S_ Jun-14 #4 S_ mean sd CV 9.4% 8.4% 10.1% 9.2% 7.2% mean -30% mean +30% Red values = outliers > 3 * inter-quartile range 1. Test of normal distribution 2. All batches fulfills +-30% acceptance criterion vs. mean of all study runs. All batches are considered comparable and valid. U. Kunz, June

27 Results, Data Transfer and Reporting 1/ PTNO CPEVENT DILUTION RESULT TITER RESULT RATIO PKQ RUN 209 VISIT P735_ VISIT P735_ VISIT P735_ VISIT NOS P735_ VISIT P735_ VISIT P735_ VISIT P735_ VISIT NOS P735_ VISIT P735_ VISIT P735_ VISIT P735_ VISIT NOS P735_ VISIT P735_ VISIT NOS P735_ VISIT P735_ VISIT P735_ VISIT P735_ VISIT P735_ VISIT P735_ VISIT P735_0006 Visit 2 = pre-dose NOS = no sample U. Kunz, June

28 Questions 5 5. Would you agree with the level3 in-study validation concept in which runs are preliminary accepted based on calibration curve data only and QC results are compared retrospectively to identify outlier runs? U. Kunz, June

29 Evaluation of BM1 results Significant dose dependent effect BM1 correlates with physiological effect Hints for an outcome related biomarker (early prediction of efficacy) U. Kunz, June

30 Planning for phase II BM 1 confirmed as very promising physiological response biomarker and maybe outcome related biomarker Team decision to measure BM1 in all phase II studies also in other indications Consequences for bioanalysis: Phase I approach is too much effort for the expected number of samples (Pre-screening/titer determination of pre-dose samples from each subject in order to define optimal dilution) Decision to invest in a complete new inhouse assay development using commercial antibodies MSD for a broader dynamic range Selection of antibodies and calibration standard to increase parallelism and enable a relative quantitative assay Serum only U. Kunz, June

31 Validation of the new MSD BM1 assay, level 2 Validation plan level 2 VCs (validation samples) Precision Calibration range, LLOQ, ULOQ Parallelism Baseline range Healthy Volunteers Short term stability endog. Analyte Calibration sample stability Stock solution stability, banked calibration standard Long term stability serum Sampling robustness Banking of sample control (monitoring samples) experiment Three individual sera (low, mid, high) aliquoted and stored frozen, additional LLOQ sample = higher diluted serum At least 6 runs at 4 days, VCs in independent triplicates Mean values are target for in-study batch acceptance Tabulation of back-calculated results 6 individuals sera ( Healthy and patients) N=24 sera 24h RT, +1, +3, +5 freeze/thaw cycles (-20 C) Three individual samples in triplicates (VCs) Ready-to-use diluted, 2h RT Thawed aliquot in the refrigerator, long-term monitoring at -70 C and -150 C Isochronic sample sets (stressed vs C), 3 individuals Fresh-blood stability, serum coagulation time, interference of hemolysed blood cells Use for long term trends and lot bridging experiments U. Kunz, June

32 Questions After first data available. Decision to develop a complete new assay: overkill or ok? 7. Has this been a typical case study or something special? U. Kunz, June

33 Questions for discussion 1. Was the available information about BM1 and its intended use sufficient? What was missing? 2. Was the intended use of BM1 data translated adequately into the bioanalytical strategy? (choose of assay, feasibility experiments, plans for future validation and analyzing strategy) 3. Has the assay been sufficiently proven/validated prior to start of sample measurements? What experiments are missing, not adequate. 4. Assay acceptance after validation. What about the consequences of the failed parallelism experiment? quasi-quantitative evaluation of data ok? 5. Would you agree with the level3 in-study validation concept in which runs are preliminary accepted based on calibration curve data only and QC results are compared retrospectively to identify outlier runs? 6. After first data available. Decision to develop a complete new assay: overkill or ok? 7. Has this been a typical case study or something special? U. Kunz, June

Considerations for Successful Biomarker Bioanalysis in Regulated Environment

Considerations 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 information

Current Best Practices in Commercial Kit Evaluation and Validation for Biomarker Assays

Current Best Practices in Commercial Kit Evaluation and Validation for Biomarker Assays Current Best Practices in Commercial Kit Evaluation and Validation for Biomarker Assays 10th Workshop on Recent Issues in Bioanalysis, 2016 Paul Rhyne, Ph.D. - Director of Immunoassay Services Copyright

More information

FDA Draft Guidance on Immunogenicity Testing

FDA Draft Guidance on Immunogenicity Testing FDA Draft Guidance on Immunogenicity Testing Susan Kirshner, Ph.D. Associate Chief, Laboratory of Immunology Division of Therapeutic Proteins OBP/CDER/FDA EBF 2010 Guidance for Industry Assay Development

More information

Guideline/Guidance Comparison on Ligand Binding Assays (LBA)

Guideline/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 information

Guideline/Guidance Comparison on Ligand Binding Assays (LBA)

Guideline/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 information

CRYSTAL CITY V REDUX: GUIDANCE FOR INDUSTRY BIOANALYTICAL METHOD VALIDATION DRAFT GUIDANCE (2013) VI. ADDITIONAL ISSUES

CRYSTAL CITY V REDUX: GUIDANCE FOR INDUSTRY BIOANALYTICAL METHOD VALIDATION DRAFT GUIDANCE (2013) VI. ADDITIONAL ISSUES CRYSTAL CITY V REDUX: GUIDANCE FOR INDUSTRY BIOANALYTICAL METHOD VALIDATION DRAFT GUIDANCE (2013) VI. ADDITIONAL ISSUES DELAWARE VALLEY DRUG METABOLISM DISCUSSION GROUP STEVE PICCOLI, BMS RAND JENKINS,

More information

Guideline/guidance Comparison on Large Molecule Bioanalysis

Guideline/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 information

Ligand Binding Assays: Summary and Consensus from the Bioanalytical Workshop (CC V)

Ligand 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 information

FGF23 (C-terminal) multi-matrix ELISA

FGF23 (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 information

Bioanalytical Concentrations Below the LLOQ:

Bioanalytical Concentrations Below the LLOQ: 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

More information

AlphaLISA - a no wash high-throughput alternative to ELISA for PK, PD and immunogenicity measurement during drug development?

AlphaLISA - a no wash high-throughput alternative to ELISA for PK, PD and immunogenicity measurement during drug development? AlphaLISA - a no wash high-throughput alternative to ELISA for PK, PD and immunogenicity measurement during drug development? EBF 3 rd Focus Meeting, 12-13 June 2012 Denise Sickert 13.June.2012 Agenda

More information

Outcomes 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 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 information

6 th EBF Open meeting, Barcelona November 21st, 2013

6 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 information

Ligand 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 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 information

Submission preparation what to watch out for

Submission 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 information

Biomarker Assay Validation a status update on the EBF Recommendation and discussions in Industry. Marianne Scheel Fjording, on behalf of the EBF

Biomarker Assay Validation a status update on the EBF Recommendation and discussions in Industry. Marianne Scheel Fjording, on behalf of the EBF Biomarker Assay Validation a status update on the EBF Recommendation and discussions in Industry Marianne Scheel Fjording, on behalf of the EBF EBF Focus Workshop Biomarkers Lisbon 9/10 June 2016 Outline

More information

Immunogenicity. How to deal with? Nathalie Macé Sanofi, Biomarkers & Biological analyses Unit

Immunogenicity. How to deal with? Nathalie Macé Sanofi, Biomarkers & Biological analyses Unit Immunogenicity How to deal with? Nathalie Macé Sanofi, Biomarkers & Biological analyses Unit Club Phase I, 22 March 2016 1 Outline Introduction to immunogenicity Analytical challenges for immunogenicity

More information

Validation of a concentration assay using Biacore C

Validation 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 information

Technical Guidance on Development of In Vitro Companion Diagnostics and Corresponding Therapeutic Products

Technical Guidance on Development of In Vitro Companion Diagnostics and Corresponding Therapeutic Products Administrative Notice December 26, 2013 To: Division of Pharmaceutical Affairs, Prefectural Health Department (Bureau) From: Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau Ministry

More information

Your bridge to. better medicines

Your bridge to. better medicines Your bridge to better medicines At a Glance Anapharm Bioanalytics is a client-oriented, GLP-certified, FDA-inspected, GCP-compliant and ANVISA-certified bioanalytical contract research organization (CRO)

More information

Development, Optimization and Validation of Luminex based cytokine assays

Development, 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 information

Development of an ELISA for the measurement of TNF-alpha in clinical samples

Development of an ELISA for the measurement of TNF-alpha in clinical samples Development of an ELISA for the measurement of TNF-alpha in clinical samples Liz Hickford, Senior Scientist, Bioanalytical Sciences, UCB EBF Young Scientist Symposium 17.NOV.15 Agenda TNF-alpha as a clinical

More information

REPEATABILITY, REPRODUCIBILITY AND ANALYTIC STANDARDS FOR BIOMARKER DEVELOPMENT

REPEATABILITY, REPRODUCIBILITY AND ANALYTIC STANDARDS FOR BIOMARKER DEVELOPMENT REPEATABILITY, REPRODUCIBILITY AND ANALYTIC STANDARDS FOR BIOMARKER DEVELOPMENT ABBAS BANDUKWALA BIOMARKER QUALIFICATION PROGRAM ABBAS.BANDUKWALA@FDA.HHS.GOV May 17, 2018 1 Disclaimer This presentation

More information

Validation of Immunoassays for Biomarker Detection at Sequani.

Validation of Immunoassays for Biomarker Detection at Sequani. White Paper Validation of Immunoassays for Biomarker Detection at Sequani. Brenda A Finney, PhD Principal Scientist, Biological Sciences, Sequani Limited This paper is intended to review the literature

More information

Case Studies on ultra-sensitive immunoanalytics based on Imperacer (Immuno-PCR) in clinical settings. Jan Detmers, Ph.D. (Chimera Biotec GmbH)

Case Studies on ultra-sensitive immunoanalytics based on Imperacer (Immuno-PCR) in clinical settings. Jan Detmers, Ph.D. (Chimera Biotec GmbH) Case Studies on ultra-sensitive immunoanalytics based on Imperacer (Immuno-PCR) in clinical settings. Jan Detmers, Ph.D. (Chimera Biotec GmbH) Agenda 1.Overview Platforms 2.Immuno-PCR (Imperacer ) Technology

More information

Fit-for-purpose limits and Tolerance intervals: connecting the assay performance to the clinical trial

Fit-for-purpose limits and Tolerance intervals: connecting the assay performance to the clinical trial Fit-for-purpose limits and Tolerance intervals: connecting the assay performance to the clinical trial Astrid Jullion & Bruno Boulanger Exploratory Statistics Pharmacometrics Lou, living with epilepsy

More information

Applying Affimers. Dr Amanda Nicholl at Avacta Life Sciences. Improving Antibody PK Assay Development

Applying Affimers. Dr Amanda Nicholl at Avacta Life Sciences. Improving Antibody PK Assay Development Improving Pharmacokinetic Assays in a Regulatory Bioanalysis Setting Applying Affimers With an increasing number of antibody-based therapeutics entering the clinic, the need for validated anti-idiotypic

More information

Paving the way for Non-Clinical Bioanalytical Partnerships Louise Angell

Paving the way for Non-Clinical Bioanalytical Partnerships Louise Angell Paving the way for Non-Clinical Bioanalytical Partnerships Louise Angell Content Overview of non-clinical immunogenicity testing for biologics Regulatory guidance Bioanalytical considerations Risk based

More information

Biomarker Measurement- Maximum Information from Limited Volume Barcelona, Spain 16 th November 2011 John Chappell, Immunoassay Services UK

Biomarker Measurement- Maximum Information from Limited Volume Barcelona, Spain 16 th November 2011 John Chappell, Immunoassay Services UK Biomarker Measurement- Maximum Information from Limited Volume Barcelona, Spain 16 th November 2011 John Chappell, Immunoassay Services UK Biomarker Services Equipment : MSD Sector Imager 2400 (3) Gyros

More information

Regulatory Reflections on the BMV Guideline/Guidance Harmonization

Regulatory 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 information

Specialty Lab Services. Deep science at scale

Specialty Lab Services. Deep science at scale Specialty Lab Services Deep science at scale Advancing biomarker research Our broad expertise and global laboratory footprint deliver deep science at scale Specialty assays drive insight into preclinical

More information

Gyrolab ADA assay protocol

Gyrolab ADA assay protocol Gyrolab ADA assay protocol Gyrolab ADA assay protocol D0016561/G, June 2017 Table of Contents Abbreviations... 2 Introduction... 2 Prerequisites... 3 Procedure... 4 Gyrolab ADA protocol overview... 4 Without

More information

Bioanalytical method validation: An updated review

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 information

Successful transfer of ligand binding assays between different laboratories

Successful transfer of ligand binding assays between different laboratories Successful transfer of ligand binding assays between different laboratories Debbie McManus Team Leader, Department of Biomarkers, Bioanalysis and Clinical Sciences 10 th EBF Open Symposium Hesperia Tower,

More information

Ready, Set, Test! AACC Conference Mass Spectrometry in the Clinical Lab: Best Practice and Current Applications September 17-18, 2013 St.

Ready, 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 information

WAIT! Ready, Set, Test! Financial Disclosure. Research/Educational grants/consulting/salary support

WAIT! 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 information

EBF Position on Biomarker Assay validation

EBF Position on Biomarker Assay validation EBF Position on Biomarker Assay validation Presenters: Philip Timmerman/Marianne Scheel Fjording on behalf of the EBF 7 th JBF Meeting March 2016 Tokyo, Japan Outline 1. Biomarkers and EBF 2012 (Philip)

More information

Validation 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. 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 information

BIOEQUIVALENCE TRIAL INFORMATION FORM (Medicines and Allied Substances Act [No. 3] of 2013 Part V Section 39)

BIOEQUIVALENCE 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 information

SMCxPRO Immunoassay System Sensitivity You Can Count On

SMCxPRO Immunoassay System Sensitivity You Can Count On SMCxPRO Immunoassay System Sensitivity You Can Count On The life science business of Merck operates as MilliporeSigma in the U.S. and Canada. Fit for Your Purpose Protein detection at every level. Your

More information

Fit-for-Purpose Biomarker Assay Validation: From Concept to Practices

Fit-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 information

The use of sensitivity analysis to set acceptance criteria in the validation of biomarker assays. Graham Healey, Chief Statistician, Oncimmune, UK

The use of sensitivity analysis to set acceptance criteria in the validation of biomarker assays. Graham Healey, Chief Statistician, Oncimmune, UK The use of sensitivity analysis to set acceptance criteria in the validation of biomarker assays Graham Healey, Chief Statistician, Oncimmune, UK SECTION 1 Introduction Autoantibody panel diagnostic test

More information

Evaluation 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 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 information

BIOSTATISTICAL METHODS

BIOSTATISTICAL METHODS BIOSTATISTICAL METHODS FOR TRANSLATIONAL & CLINICAL RESEARCH Phase 0 Trials: EARLY-PHASE CLINICAL TRIALS Steps to New Drug Discovery Get idea for drug target Develop a bioassay Screen chemical compounds

More information

Qualifying SPR immunogenicity assays Dr. Christian Kühne

Qualifying SPR immunogenicity assays Dr. Christian Kühne Qualifying SPR immunogenicity assays Dr. Christian Kühne Bioagilytix / IPM Biotech global CRO for large molecule bioanalysis supporting pre-clinical & clinical studies Biomarker, Pharmacokinetics, Immunogenicity

More information

BIOSTATISTICAL METHODS FOR TRANSLATIONAL & CLINICAL RESEARCH

BIOSTATISTICAL METHODS FOR TRANSLATIONAL & CLINICAL RESEARCH BIOSTATISTICAL METHODS FOR TRANSLATIONAL & CLINICAL RESEARCH Phase 0 Trials: EARLY-PHASE CLINICAL TRIALS CLINICAL PHASE Clinical Studies: Class of all scientific approaches to evaluate Disease Prevention,

More information

CLSI C60: Assay Validation & Post-Validation Monitoring

CLSI 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 information

Deer insulin-like growth factors 1 (IGF-1) ELISA Kit. This package insert must be read in its entirety before using this product.

Deer insulin-like growth factors 1 (IGF-1) ELISA Kit. This package insert must be read in its entirety before using this product. Deer insulin-like growth factors 1 (IGF-1) ELISA Kit Catalog Number. For the quantitative determination of deer insulin-like growth factors 1 (IGF-1) concentrations in serum, plasma, tissue homogenates.

More information

Human nuclear matrix protein 22 (NMP-22) ELISA Kit. MyBioSource.com

Human nuclear matrix protein 22 (NMP-22) ELISA Kit. MyBioSource.com Human nuclear matrix protein 22 (NMP-22) ELISA Kit Catalog Number. For the quantitative determination of human nuclear matrix protein 22 (NMP-22) concentrations in serum, plasma and urine. This package

More information

Qualification / validation of new lots of critical reagents for ADA assays: some practical examples

Qualification / validation of new lots of critical reagents for ADA assays: some practical examples PK SCIENCES Clinical Bioanalytics and Regulatory Science Qualification / validation of new lots of critical reagents for ADA assays: some practical examples Lydia Michaut EBF Training Day: Critical Reagents

More information

CASE-STUDY- VALIDATION of PCR based methodology. Beata Surmacz-Cordle Senior Analytical Development Scientist

CASE-STUDY- VALIDATION of PCR based methodology. Beata Surmacz-Cordle Senior Analytical Development Scientist CASE-STUDY- VALIDATION of PCR based methodology Beata Surmacz-Cordle Senior Analytical Development Scientist UK RMP Pluripotent Stem Cell Platform Validation Workshop 2 nd June 2016 RT-qPCR assay for detection

More information

Case Examples Highlighting Multi- Centre Clinical Trial Issues

Case Examples Highlighting Multi- Centre Clinical Trial Issues Case Examples Highlighting Multi- Centre Clinical Trial Issues Presenter: Carolyn Mailer (on behalf of EBF TT-12) 5 th EBF Open Symposium 14-16 November 2012 Hisperia Towers, Barcelona http://www.europeanbioanalysisforum.eu

More information

Reflection paper on co-development of pharmacogenomic biomarkers and Assays in the context of drug development

Reflection paper on co-development of pharmacogenomic biomarkers and Assays in the context of drug development 1 2 3 24 June 2010 EMA/CHMP/641298/2008 Committee for Medicinal Products for Human Use (CHMP) 4 5 6 7 Reflection paper on co-development of pharmacogenomic biomarkers and Assays in the context of drug

More information

Using Ligang-Binding Assay Sensitivity for Improved Matrix Tolerance and Related Parameters by Tailored Sample Dilution.

Using Ligang-Binding Assay Sensitivity for Improved Matrix Tolerance and Related Parameters by Tailored Sample Dilution. Using Ligang-Binding Assay Sensitivity for Improved Matrix Tolerance and Related Parameters by Tailored Sample Dilution. Dr. Mark Spengler, Chimera Biotec Chimera Biotec Company Overview Bioanalytical

More information

colorimetric sandwich ELISA kit datasheet

colorimetric sandwich ELISA kit datasheet colorimetric sandwich ELISA kit datasheet For the quantitative detection of human ENO2 concentrations in serum, plasma and cell culture supernatants. general information Catalogue Number Product Name Species

More information

Medicines Control Authority Of Zimbabwe

Medicines Control Authority Of Zimbabwe Medicines Control Authority Of Zimbabwe BIOEQUIVALENCE APPLICATION FORM Form: EVF03 This application form is designed to facilitate information exchange between the Applicant and the MCAZ for bioequivalence

More information

HARMONIZATION TEAM A6 (STABILITY) UPDATE. Yoshiaki Ohtsu 8 March 2012

HARMONIZATION 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 information

How Targets Are Chosen. Chris Wayman 12 th April 2012

How Targets Are Chosen. Chris Wayman 12 th April 2012 How Targets Are Chosen Chris Wayman 12 th April 2012 A few questions How many ideas does it take to make a medicine? 10 20 20-50 50-100 A few questions How long does it take to bring a product from bench

More information

A Streamlined Data Capture and Exchange Partnership that Delivers Faster Decisions

A Streamlined Data Capture and Exchange Partnership that Delivers Faster Decisions A Streamlined Data Capture and Exchange Partnership that Delivers Faster Decisions 2011 SAS Health & Life Sciences Conference Michelle Combs, PhD, VP, Clinical Pharmacology Sciences, Celerion Bernd Doetzkies,

More information

Bovine IgG-Ab ELISA Kit

Bovine IgG-Ab ELISA Kit Bovine IgG-Ab ELISA Kit For the quantitative in vitro determination of Bovine Immunoglobulin G Antibody concentrations in serum - plasma - tissue homogenates - other biological fluids FOR LABORATORY RESEARCH

More information

Regulatory Issues and Drug Product Approval for Biopharmaceuticals

Regulatory Issues and Drug Product Approval for Biopharmaceuticals Regulatory Issues and Drug Product Approval for Biopharmaceuticals Vinod P. Shah, Ph. D. FIP Scientific Secretary Biotech 2007 Southern African Regional and International Regulatory Biotechnology Workshop

More information

06/03/2009. Overview. Preclinical Support for Exploratory Phase I Clinical Trials. Micro-dosing IND. Pharmacological Active Single Dose IND

06/03/2009. Overview. Preclinical Support for Exploratory Phase I Clinical Trials. Micro-dosing IND. Pharmacological Active Single Dose IND Preclinical Support for Exploratory Phase I Clinical Trials Clive Joseph, DSRD Sandwich Overview Identify the most appropriate development paradigm - traditional vs alternative IND approach Confidence

More information

Human CTRP5 ELISA Kit

Human CTRP5 ELISA Kit Human CTRP5 ELISA Kit For the quantitative in vitro determination of Human C1q And Tumor Necrosis Factor Related Protein 5 concentrations in serum - plasma - tissue homogenates - other biological fluids

More information

BIOEQUIVALENCE TRIAL INFORMATION

BIOEQUIVALENCE 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 information

Shaping the future of bioassays

Shaping the future of bioassays Shaping the future of bioassays Company French Company Founded in 2010 Backed up by investment funds Situated in a business park dedicated to health developments projects within the environment of the

More information

ELISA White Paper - Quantitative Allergen Immunoassay Kit. October Developed and Manufactured by

ELISA White Paper - Quantitative Allergen Immunoassay Kit. October Developed and Manufactured by ELISA 2.0 Quantitative Allergen Immunoassay Kit - White Paper - October 2015 Developed and Manufactured by INTRODUCTION Enzyme Linked Immunosorbent Assay (ELISA) is a method used to measure an analyte

More information

Guinea pig 25-OH-VD ELISA Kit

Guinea pig 25-OH-VD ELISA Kit Guinea pig 25-OH-VD ELISA Kit For the quantitative in vitro determination of Guinea pig 25-Dihydroxy vitamin D concentrations in serum - plasma - tissue homogenates - other biological fluids FOR LABORATORY

More information

Guideline for the quality, safety and efficacy of follow-on biological medicinal products

Guideline for the quality, safety and efficacy of follow-on biological medicinal products Guideline for the quality, safety and efficacy of follow-on biological medicinal products 1. Introduction A follow-on biological medicinal product (hereinafter referred to as FOBMP) is considered as a

More information

Unique PK-PD properties of biotechnology-based therapeutics [mabs] and First In Human dose considerations. [mabs -monoclonal antibodies ] Peter Lloyd

Unique PK-PD properties of biotechnology-based therapeutics [mabs] and First In Human dose considerations. [mabs -monoclonal antibodies ] Peter Lloyd Unique PK-PD properties of biotechnology-based therapeutics [mabs] and First In Human dose considerations [mabs -monoclonal antibodies ] Peter Lloyd Head of Pharmacokinetics-Pharmacodynamics Novartis Biologics

More information

HOST CELL PROTEIN & BIOPROCESSING REAGENT DEVELOPMENT

HOST CELL PROTEIN & BIOPROCESSING REAGENT DEVELOPMENT HOST CELL PROTEIN & BIOPROCESSING REAGENT DEVELOPMENT INTRODUCTION Biopharmaceuticals require products to be free of residual host cell protein (HCP) contaminants from the bioprocessing workflow. To evaluate

More information

Bovine anti-mullerian hormone (AMH) ELISA Kit

Bovine anti-mullerian hormone (AMH) ELISA Kit Bovine anti-mullerian hormone (AMH) ELISA Kit Catalog Number. CSB-E13406B For the quantitative determination of bovine anti-mullerian hormone (AMH) concentrations in serum, plasma, tissue homogenates.

More information

Case 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 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 information

PPS (Human) ELISA Kit

PPS (Human) ELISA Kit PPS (Human) ELISA Kit Cat. No.:DEIA4080 Pkg.Size:96T Intended use Immunoassay for quantitative determination of the content of Pentosan Polysulfate (PPS) in human plasma General Description Pentosan Polysulfate

More information

Laboratory Developed Tests. William Castellani, MD Inter-regional Commissioner Clinical Pathologist, Penn State Hershey Medical Center

Laboratory Developed Tests. William Castellani, MD Inter-regional Commissioner Clinical Pathologist, Penn State Hershey Medical Center Laboratory Developed Tests William Castellani, MD Inter-regional Commissioner Clinical Pathologist, Penn State Hershey Medical Center Objectives Compare and contrast new test validation requirements for

More information

Mouse thyroxine(t4) ELISA Kit

Mouse thyroxine(t4) ELISA Kit Mouse thyroxine(t4) ELISA Kit Catalog Number. CSB-E05083m For the quantitative determination of endogenic mouse thyroxine(t4) concentrations in serum, plasma, tissue homogenates. This package insert must

More information

Revised Immunogenicity Guideline: Assays and methods- Presentation of the draft guideline and introduction of the topics for discussion

Revised Immunogenicity Guideline: Assays and methods- Presentation of the draft guideline and introduction of the topics for discussion Revised Immunogenicity Guideline: Assays and methods- Presentation of the draft guideline and introduction of the topics for discussion Robin Thorpe & Meenu Wadhwa Revised Guideline: Differences from original

More information

Measurement Uncertainty Guide. ISO Accreditation Program

Measurement Uncertainty Guide. ISO Accreditation Program Measurement Uncertainty Guide ISO 15189 Accreditation Program Background Why This is Necessary The ISO 15189:2012 standard contains enhanced expectations regarding measurement uncertainty (MU) in clause

More information

Technical Assessment (TA) Summary Form (M00116)

Technical 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 information

Food and. Re: Docket Bioanalytica. that keep. majority of. the world. market. only a small. since the. standard. on the draft. Sincerely, Affairs

Food 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 information

BioPhysics Assay Laboratory, Inc. ٠ 80 Webster Street ٠ Worcester MA ٠ Phone (508) ٠ Fax (508) ٠

BioPhysics Assay Laboratory, Inc. ٠ 80 Webster Street ٠ Worcester MA ٠ Phone (508) ٠ Fax (508) ٠ Introduction In this report, we describe and present the performance characteristics of an immunoassay (ELISA) method to measure the concentration of iohexol in collected samples to obtain a mgfr value.

More information

QUESTIONS AND ANSWERS TO ICH S3A: NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT OF SYSTEMIC EXPOSURE IN TOXICITY STUDIES FOCUS ON MICROSAMPLING

QUESTIONS AND ANSWERS TO ICH S3A: NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT OF SYSTEMIC EXPOSURE IN TOXICITY STUDIES FOCUS ON MICROSAMPLING INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED GUIDELINE QUESTIONS AND ANSWERS TO ICH S3A: NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT

More information

QUANTITATIVE DETERMINATION OF HUMAN EPIDIDYMIS PROTEIN 4

QUANTITATIVE DETERMINATION OF HUMAN EPIDIDYMIS PROTEIN 4 QUANTITATIVE DETERMINATION OF HUMAN EPIDIDYMIS PROTEIN 4 NEW PRODUCT Human Epididymis Protein 4 () ELISA High sensitivity (0.15 pmol/l) Excellent analytical characteristics Validated for human serum samples,

More information

What s the difference? Challenges in pre-clinical development of biologics

What s the difference? Challenges in pre-clinical development of biologics Biologics vs Small MW NCEs What s the difference? Challenges in pre-clinical development of biologics Peter Lloyd Joint Conference of EU Human Pharmacological Societies and 20 th Anniversary of AGAH 31

More information

Bio-Plex suspension array system

Bio-Plex suspension array system Multiplex Assays Bio-Plex suspension array system tech note 64 Profiling of Human, Canine, and Rat Urine Samples Using Bio-Plex Pro RBM Kidney Toxicity Assays L. Stephen, H. Schnaars, K. Marshall, H. Akey,

More information

A2LA. R231 Specific Requirements: Threat Agent Testing Laboratory Accreditation Program. December 6, 2017

A2LA. R231 Specific Requirements: Threat Agent Testing Laboratory Accreditation Program. December 6, 2017 Laboratory Page 1 of 17 Laboratory December 6, 2017 2017 by A2LA All rights reserved. No part of this document may be reproduced in any form or by any means without the prior written permission of A2LA.

More information

Placement of Biomarker Analysis in a CLIA or Bioanalytical Laboratory

Placement of Biomarker Analysis in a CLIA or Bioanalytical Laboratory Placement of Biomarker Analysis in a CLIA or Bioanalytical Laboratory Patrick Bennett, PPD Panel Discussion 29 March 2017 Agenda + Industry Overview + Biomarker Labs Overview + Biomarker Intended Use and

More information

Challenges for Flow Cytometry in Regulated Bioanalysis

Challenges for Flow Cytometry in Regulated Bioanalysis Challenges for Flow Cytometry in Regulated Bioanalysis Minesh Patel Merck Millipore Discovery & Development Solutions. Oxford, UK. Overview Flow cytometry principles Current uses and regulatory environments

More information

Rabbit immunoglobulin M(IgM) ELISA Kit

Rabbit immunoglobulin M(IgM) ELISA Kit Rabbit immunoglobulin M(IgM) ELISA Kit Catalog Number. CSB-E06950Rb For the quantitative determination of rabbit immunoglobulin M (IgM) concentrations in serum, plasma. This package insert must be read

More information

Exploratory clinical trials workshop

Exploratory clinical trials workshop Exploratory clinical trials workshop Yves Donazzolo, Grenoble / Lyon Dominique Tremblay, Paris AGAH / Club Phase I meeting Lyon, April 28 & 29, 2009 Topics Introduction Definitions Nonclinical safety studies

More information

Immunogenicity Assay Strategies for Antibody-Drug Conjugates

Immunogenicity Assay Strategies for Antibody-Drug Conjugates Immunogenicity Assay Strategies for Antibody-Drug Conjugates 8th World ADC Conference, San Diego 20 Sep 2017 Seema Kumar, PhD Associate Scientific Director Global Early Development (GED) EMD Serono Research

More information

Human Cytokine Assay Products from Meso Scale Discovery

Human Cytokine Assay Products from Meso Scale Discovery Human Cytokine Assay Products from Meso Scale Discovery Paul F. Grulich, David H. Stewart, Pankaj Oberoi, Rob Calamunci, George Sigal and Jacob N. Wohlstadter In this poster, we present a collection of

More information