Regulatory Consideration for the Characterization of HOS in Biotechnology Products
|
|
- Oscar Mosley
- 6 years ago
- Views:
Transcription
1 Regulatory Consideration for the Characterization of HOS in Biotechnology Products Maria Teresa Gutierrez Lugo, Ph.D. OBP/CDER/FDA 5 th International Symposium on Higher Order Structure of Protein Therapeutics April 11 13, Long Beach, CA
2 Considerations for the characterization of Higher Order Structure (HOS) New biological entity Biosimilar Examples of methods used for HOS characterization Biosimilar applications Advantages and limitations of common methods used for HOS characterization Considerations for method selection Challenges Overview 2
3 Characterization of biotecnology products Structural Primary structure Higher order structure including aggregates Molecular weight Degree of heterogeneity (derived from enzymatic, unintended and intentional modifications) Functional Biological activity (i.e. potency) Functional domain Enzyme kinetics Receptor binding Protein target binding Fc effector function Impurity profiles Product related impurities Inactive protein variants generated during manufacture or storage Process related impurities Host cell proteins & DNA Media components Column leachates (e.g., protein A) Stability Degradation profiles under accelerated, stress (high temperature, freeze thaw, light exposure, agitation), forced conditions Collectively, these quality attributes can be used to define identity, purity, potency, and stability of the products, and if critical, they correlate with safety and efficacy 3
4 Characterization during product development 351(a), New Biological Entity 351(k), Biosimilar IND enabling, Initial Clinical Studies Additional Clinical Studies Licensure EXTENT OF CHARACTERIZATION Preliminary product characterization Extensive product characterization Sufficient data to support proposed product is similar to the reference product Strong evidence to support that proposed product is highly similar to the reference product. LOW DEGREE OF UNCERTAINTY
5 Hierarchy of protein structure Primary Secondary Tertiary Quaternary Asp His Ala Iso Val Gln Tyr Leu All need to be evaluated as part of the characterization of the product The three dimensional conformation of a protein is critical for its biological activity, specificity and stability 5
6 Correct protein conformation versus disordered aggregates Tyedmers J. et al (2010). Nature Reviews Molecular Cell Biology 11,
7 Characterization of HOS for NBEs Early in development, characterization of HOS is desirable (e.g. phase I) but it is not required. Functional studies (e.g. biological activity, target binding) could be used to support proper HOS Later in development, full characterization of HOS using orthogonal methods is expected. HOS is an integral part of product characterization. Assessment of aggregates is expected at all stages of development along with a risk assessment of their potential impact on safety and efficacy. 7
8 Characterization of HOS for biosimilars Characterization HOS is expected as part of the data supporting that the proposed biosimilar product is similar to the reference product. HOS can be affected by environmental conditions (e.g. formulation, container closure system). Some of these conditions may differ between the proposed biosimilar product and the reference product. Any differences in HOS between a proposed biosimilar and reference product should be evaluated in terms of a potential effect on protein function. Thus, functional assays are also critical tools for evaluating the integrity of the HOS. Guidance for Industry Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product. February
9 Characterization of HOS for biosimilars Evaluation of higher order structure adds to the body of information supporting biosimilarity The more comprehensive and robust the comparative structural and functional characterization, the stronger the scientific justification for a selective and targeted approach to animal and/or clinical testing to support a demonstration of biosimilarity Guidance for Industry Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product. February
10 Common methods 1 used for characterization of HOS Circular dichroism Far UV Near UV Fourier transform infrared spectroscopy Fluorescence spectroscopy Intrinsic Extrinsic (fluorescent probes) Nuclear magnetic resonance ID and 2D Disulfide bonding (MS) H/D exchange MS Differential scanning calorimetry Light scattering Analytical Ultracentrifugation Raman spectroscopy X ray crystallography 1 Methods used in regulatory applications 10
11 HOS methods used/proposed in biosimilar applications 1 Functional assays were also used to support higher order structure Most applications include assessment of disulfide bonds (MS) and free cysteine 1 Survey as of March
12 Advantages and limitations CD Method Advantages Disadvantages Small amount of protein Amenable to quantitative analysis Short acquisition and data analysis Small and large proteins Thermal stability and conformational flexibility Measure average of populations Difficult to determine the structural origin of changes Quality of deconvoluted data depends on the quality of the database used Artifacts associated with light scattering Fluorescence FT IR High signal to noise ratio Small amount of protein Fast acquisition time (suitable for folding/conformation studies) Sensitive to immediate environment of the probe (eg. Trp) which changes drastically upon unfolding Small and large proteins Able to detect proteins in dynamic equilibrium Thermal stability and conformational flexibility Measure average of populations Difficult to determine the structural origin of changes (it reports on the environment surrounding the probe) Does not provide information concerning the relative positioning of individual functional groups 12
13 Advantages and limitations Method Advantages Disadvantages DSC NMR Small amount of protein Suitable for conformational studies (stability) Sensitive to changes Sensitive to protein conformation changes 1 H NMR does not require labeling Suitable for structural fingerprinting analysis Provide information concerning the relative positioning of individual functional groups Complete assignment of 3D structure across the entire molecule in solution at atomic level resolution May be able to detect protein mixtures (?) Protein may denature at high or low temperature May not distinguish between different populations Limited to proteins < kda (?) Sensitivity depends on protein concentration Require large amount of protein (relative to the methods) Time consuming (not labeled proteins, 2D NMR). Resonance assignments are time consuming (if assignments have not been done previously) Expensive instrumentation HDX MS Small and large proteins Small amount of sample (nmol) Identify specific sites in the molecule Can be automated Difficult data analysis Interference of some formulation component (e.g. detergents) Day to day drift 13
14 Considerations for method selection Nature of protein being characterized MW, heterogeneity, solubility, etc. Knowledge regarding the structure Type, amount and quality of information needed E.g. Higher order structure characterization or understanding of conformational stability Small change in all molecules of a population (batch) Change in a small percentage of the population 14
15 Considerations for method selection Use of orthogonal methods, including functional assays Use high resolution separation methods to identify population of proteins with different conformations In analyzing results consider manipulations of the samples 15
16 Considerations for method selection Test used to characterize the products do not necessarily need to be validated for routine quality control purposes but should be: Scientifically sound Fit for the intended purpose Produce results that are reproducible and reliable Capable of identifying product differences Qualitative Quantitative Sensitive Analysis of stress or spiked samples 16
17 Challenges Assessment of HOS in highly heterogeneous or complex products (e.g. glycosylated products and large proteins) Evaluation of a small change (e.g. change of conformation in a specific domain) in all molecules of a population (batch) vs a change in a small percentage of the population (e.g. low level of incorrectly folded protein) Establish the link between HOS, functional activity and potential impact on safety and efficacy 17
18 Thank you for your attention 18
Value of DSC in characterization and optimization of protein stability as compared to other thermal stability assays
Value of DSC in characterization and optimization of protein stability as compared to other thermal stability assays 韩佩韦 Malvern Instruments 2016.02.28 Complex task of characterization and optimization
More informationRegulatory Perspectives on Higher Order Structure Evaluations for Protein Products. Emily Shacter, Ph.D.
Regulatory Perspectives on Higher Order Structure Evaluations for Protein Products Emily Shacter, Ph.D. Chief, Laboratory of Biochemistry U.S. Food and Drug Administration Center for Drug Evaluation and
More informationRegulatory Perspective on Analytical Method Validation During Product Development
Regulatory Perspective on Analytical Method Validation During Product Development CASSS CMC Strategy Forum 2018 Jacek Cieslak CDER/OPQ/OBP FDA Disclaimer This presentation reflects the views of the author
More informationMass Spectrometry for Characterization of Monoclonal Antibodies: Regulatory Considerations
Mass Spectrometry for Characterization of Monoclonal Antibodies: Regulatory Considerations Jun Park, Ph.D. Division of Monoclonal Antibodies Office of Biotechnology Products OPS/CDER Food and Drug Administration
More informationDegradation of Biological Products and Impact on Higher Order Structure
Degradation of Biological Products and Impact on Higher Order Jason K. Cheung, BioProcess Development Biologics and Vaccines Date: May 16, 2016 AAPS-NBC Sunrise Session Analytical Toolkit 2 Analytical
More informationAssistant Professor Mohammad A Alsenaidy, MSc, PhD, Saudi Arabia
GaBI Scientific Meetings First GCC Stakeholder Meeting on Approval Process, Interchangeability/Substitution and Safety of Biosimilars 20 November 2017, Holiday Inn Izdihar Riyadh, Saudi Arabia Assistant
More informationComparability to establish Biosimilarity
Comparability to establish Biosimilarity CMC Strategy Forum Europe 2014, Sorrento, Italy Jan Visser, Head Global Analytical Characterization & Bioanalytics Sandoz Biopharmaceuticals, Hexal AG, Germany
More informationThe Present State and Future Outlook for Characterizing the Higher Order Structure (HOS) of Protein Drugs in the Biopharmaceutical Industry
The Present State and Future Outlook for Characterizing the Higher Order Structure (HOS) of Protein Drugs in the Biopharmaceutical Industry Steven Berkowitz, Senior Principal Scientist Biogen Idec 2 nd
More informationZetasizer ZS Helix (DLS/Raman) For Characterization of Pharmaceuticals and Biopharmaceuticals
Zetasizer ZS Helix (DLS/Raman) For Characterization of Pharmaceuticals and Biopharmaceuticals Benefits of Zetasizer ZS Helix What it provides Develop mechanistic insight into oligomerization and aggregation
More informationDevelop A Highly Similar" Biosimilar Compound: Lessons Learnt
Develop A Highly Similar" Biosimilar Compound: Lessons Learnt Hui-Chun Li, Ph.D. Sr. Manager of Process Science 2015 Feb 05 3rd Biologics World Taiwan 2015 SPIN OFF ACQUISITION Development Center for Biotechnology
More informationTechnical Challenges in the Development of Biosimilars. E. Morrey Atkinson, PhD Interphex May 1, 2012
Technical Challenges in the Development of Biosimilars E. Morrey Atkinson, PhD Interphex May 1, 2012 FDA Guidance on Biosimilarity Guidance for Industry: Scientific Consideration in Demonstrating Biosimilarity
More informationDemonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product ICH Guidance
Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product ICH Guidance Derek Bradley M.Sc. BioClin Research Laboratories 13 th May 2016 Agenda Brief overview of biosimilars ICH
More informationChallenges in Optimizing Formulations for Multi- Antigen Vaccines
Engineering Conferences International ECI Digital Archives Vaccine Technology IV Proceedings Spring 5-22-212 Challenges in Optimizing Formulations for Multi- Antigen Vaccines Lakshmi Khandke Pfizer Global
More informationRegulatory 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 informationKinetics Review. Tonight at 7 PM Phys 204 We will do two problems on the board (additional ones than in the problem sets)
Quiz 1 Kinetics Review Tonight at 7 PM Phys 204 We will do two problems on the board (additional ones than in the problem sets) I will post the problems with solutions on Toolkit for those that can t make
More informationFDA recommendations for comparability studies to support manufacturing changes. Joslyn Brunelle, PhD Office of Biotechnology Products OPQ/CDER/FDA
FDA recommendations for comparability studies to support manufacturing changes Joslyn Brunelle, PhD Office of Biotechnology Products OPQ/CDER/FDA The views and opinions expressed here should not be used
More informationIntegrating HOS Techniques in CQA Assessment. Not all quality attributes are critical. Abbreviations
Integrating HS Techniques in CQA Assessment Tapan Das Biologics Development, Bristol-Myers Squibb April 5, 2017 6th International Symposium on Higher rder Structure of Protein Therapeutics. Gaithersburg
More informationARBRE-P4EU Consensus Protein Quality Guidelines for Biophysical and Biochemical Studies Minimal information to provide
ARBRE-P4EU Consensus Protein Quality Guidelines for Biophysical and Biochemical Studies Minimal information to provide Protein name and full primary structure, by providing a NCBI (or UniProt) accession
More informationTony Mire-Sluis Vice President, Corporate, Product and Device Quality Amgen Inc
The Regulatory Implications of the ever increasing power of Mass Spectrometry and its role in the Analysis of Biotechnology Products Where do we draw the line? Tony Mire-Sluis Vice President, Corporate,
More informationFDA Public Hearing: Approval Pathway for Biosimilar. Products. November 2-3, 2010
FDA Public Hearing: Approval Pathway for Biosimilar and Interchangeable Biological Products November 2-3, 2010 1 The Biotechnology Industry Organization Over 1,100 members, including biotechnology companies,
More informationProtein analysis. Dr. Mamoun Ahram Summer semester, Resources This lecture Campbell and Farrell s Biochemistry, Chapters 5
Protein analysis Dr. Mamoun Ahram Summer semester, 2015-2016 Resources This lecture Campbell and Farrell s Biochemistry, Chapters 5 Bases of protein separation Proteins can be purified on the basis Solubility
More informationAnalytical similarity: Lessons from the first US biosimilar
Analytical similarity: Lessons from the first US biosimilar 2nd FDA/PQRI Conference on Advancing Product Quality Oct. 5-7, 2015 Corinna Sonderegger, Head Pharmaceutical Development Sandoz Biopharmaceuticals,
More informationfor MA and Beyond John Gabrielson CASSS 2 nd International Symposium on Higher Order Structure of Protein Therapeutics
Higher Order Structure Characterization for MA and Beyond John Gabrielson CASSS 2 nd International Symposium on Higher Order Structure of Protein Therapeutics February 12, 2013 Proteins form multiple levels
More informationIntroduction to Protein Purification
Introduction to Protein Purification 1 Day 1) Introduction to Protein Purification. Input for Purification Protocol Development - Guidelines for Protein Purification Day 2) Sample Preparation before Chromatography
More informationBiosimilar Monoclonal Antibodies: Registration Requirements. Henry M. J. Leng
Biosimilar Monoclonal Antibodies: Registration Requirements Henry M. J. Leng Disclaimer This presentation is given in my personal capacity and represents only the author s personal views and does not represent
More informationThe Role of Mass Spectrometry for Developing Biotherapeutics: Regulatory Perspectives
The Role of Mass Spectrometry for Developing Biotherapeutics: Regulatory Perspectives Jun Park, Ph.D. Division of Monoclonal Antibodies Office of Biotechnology Products CDER/FDA CASSS, Applications of
More informationThe United States Pharmacopeia Strategy on Biotherapeutic Products Standards. Jaap Venema, Ph.D. Chief Science Officer & Chair, Council of Experts
The United States Pharmacopeia Strategy on Biotherapeutic Products Standards Jaap Venema, Ph.D. Chief Science Officer & Chair, Council of Experts U.S. Pharmacopeia Who We Are Scientific, independent, volunteer-driven,
More informationPractical challenges in the CMC development of biosimilars. Simon Hotchin Executive Director Regulatory Affairs Amgen Inc.
Practical challenges in the CMC development of biosimilars Simon Hotchin Executive Director Regulatory Affairs Amgen Inc. Overview Introduction Statistical methodologies in the assessment of analytical
More informationAPPLYING SCIENTIFIC CONSIDERATIONS AND STATISTICAL APPROACHES IN ANALYTICAL SIMILARITY ASSESSMENT
APPLYING SCIENTIFIC CONSIDERATIONS AND STATISTICAL APPROACHES IN ANALYTICAL SIMILARITY ASSESSMENT JENNIFER LIU CASSS CMC STRATEGY FORUM EUROPE 2017, MAY 22-24 BIOSIMILAR DEVELOPMENT BEGINS WITH THOROUGH
More informationLocalized Higher Order Structures of mabs and ADCs Investigated by MS-based Protein Footprinting
Localized Higher Order Structures of s and ADCs Investigated by MS-based Protein Footprinting Lucy Pan, John Valliere-Douglass and Oscar Salas-Solano 6 th International Symposium on the Higher Order Structure
More informationStability of Biological Products
Stability of Biological Products Dr Jurgen Lindner Principal, BioPharma Consulting & Executive Secretary, APIMAA Biological Products Functional Proteins or Polypeptides (mab s, enzymes & inhibitors, growth
More informationAnalysis of Protein Biopharmaceuticals
Analysis of Protein Biopharmaceuticals Comprehensive cgmp Services at Every Stage of Drug Development Amazing where you can go At Solvias, we work closely with you Solvias provides comprehensive services
More informationAdvanceBio Peptide Mapping
AdvanceBio Peptide Mapping An HPLC Column Technology for Faster Protein Biocharacterizations Tim Rice BioColumn Technical Specialist 1 What Is Peptide Mapping? The chemical or enzymatic treatment of a
More information3D Structure of Biologics in a Convenient Immunoassay Format
3D Structure of Biologics in a Convenient Immunoassay Format Xing Wang, Ph.D. Array Bridge Inc. 5/25/2017 1 Topics Covered Today Why New Technologies? Technology Development. Case Studies for Novel and
More informationAnalytical Methods Development and Validation
Understanding and Implementing Efficient Analytical Methods Development and Validation Jay Breaux, Kevin Jones, and Pierre Boulas Analytical methods development and validation play important roles in the
More informationPurification: Step 1. Lecture 11 Protein and Peptide Chemistry. Cells: Break them open! Crude Extract
Purification: Step 1 Lecture 11 Protein and Peptide Chemistry Cells: Break them open! Crude Extract Total contents of cell Margaret A. Daugherty Fall 2003 Big Problem: Crude extract is not the natural
More informationPurification: Step 1. Protein and Peptide Chemistry. Lecture 11. Big Problem: Crude extract is not the natural environment. Cells: Break them open!
Lecture 11 Protein and Peptide Chemistry Margaret A. Daugherty Fall 2003 Purification: Step 1 Cells: Break them open! Crude Extract Total contents of cell Big Problem: Crude extract is not the natural
More informationAnalytical Tools for Higher Order Structure Assessment in Comparability and Biosimilarity
Analytical Tools for Higher Order Structure Assessment in Comparability and Biosimilarity Brad Jordan, PhD Director, Global Regulatory and R&D Policy Amgen Inc. CASSS HOS 2018 Providence, RI How good are
More informationnanodsf 2bind: Your service provider for biophysical characterization of proteins Precisely revealing protein folding and stability
nanodsf Precisely revealing protein folding and stability 2bind: Your service provider for biophysical characterization of proteins This booklet was written and designed by 2bind 08 2015 Any reproduction
More informationAntibody-Drug Conjugate Characterization and Quality Assurance
Antibody-Drug Conjugate Characterization and Quality Assurance Sarah Kennett Division of Monoclonal Antibodies Office of Biotechnology Products OPS/CDER/FDA October 12, 2011 1 Disclaimer The views and
More informationComputational methods in bioinformatics: Lecture 1
Computational methods in bioinformatics: Lecture 1 Graham J.L. Kemp 2 November 2015 What is biology? Ecosystem Rain forest, desert, fresh water lake, digestive tract of an animal Community All species
More informationCryoconcentration effects during freeze/thaw processing of bulk protein, and possible consequences of frozen storage on protein aggregation
Cryoconcentration effects during freeze/thaw processing of bulk protein, and possible consequences of frozen storage on protein aggregation Satish K Singh 20 July 2010 Abstract Frozen storage of proteins
More informationExtracting Pure Proteins from Cells
Extracting Pure Proteins from Cells 0 Purification techniques focus mainly on size & charge 0 The first step is homogenization (grinding, Potter Elvejhem homogenizer, sonication, freezing and thawing,
More informationAli Yaghi. Tamara Wahbeh. Mamoun Ahram
28 Ali Yaghi Tamara Wahbeh Mamoun Ahram This sheet is a continuation of protein purification methods. Isoelectric focusing Separation of proteins based on Isoelectric points(charge),and it is a horizontal
More informationExpectations for Analytical Characterisation in the Evaluation of Biosimilarity: A Regulator`s Perspective
Expectations for Analytical Characterisation in the Evaluation of Biosimilarity: A Regulator`s Perspective Christian Mayer AGES - Austrian Agency for Health and Food Safety Analytical Technologies Europe
More informationHigh-throughput Biophysical Analysis of Protein Stability: Comparability Assessments and Formulation Development
High-throughput Biophysical Analysis of Protein Stability: Comparability Assessments and Formulation Development David B. Volkin Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization
More informationAn FDA Perspective on the Implementation of State-of-the-Art Analytical Methods for the Development of Therapeutic Proteins
An FDA Perspective on the Implementation of State-of-the-Art Analytical Methods for the Development of Therapeutic Proteins Marjorie Shapiro, Ph.D. Office of Biotechnology Products/FDA WCBP 2018 Technical
More informationExpert Consensus on Quality Control and Preclinical Evaluation of Antibody-Drug Conjugates
Expert Consensus on Quality Control and Preclinical Evaluation of Antibody-Drug Conjugates National Institutes for Food and Drug Control July 20 th, 2018 Contents 1. Overview... 3 2. Manufacturing... 4
More informationKupers Luc IMI webinar
Biomanufacturing 2020 (biomfg2020): Development of Innovative high throughput analytical tools and methods to characterize cell culture fluid during development and commercial cell culture processes Kupers
More informationRegulatory perspectives on setting relevant specifications in early development and throughout product life cycle
Regulatory perspectives on setting relevant specifications in early development and throughout product life cycle Ashutosh Rao, R. Ph., Ph.D. Principal Investigator/Product Quality Reviewer Division of
More informationPhysical Methods in Models of Cataract Disease. O. P. Srivastava Department of Vision Science University of Alabama at Birmingham
Physical Methods in Models of Cataract Disease O. P. Srivastava Department of Vision Science University of Alabama at Birmingham Function of the Lens: Refraction Lens Specific Structural Proteins (α-,
More informationEGA s Perspective on the Draft Quality Guideline
EGA s Perspective on the Draft Quality Guideline London, 31 October 2013 JOERG WINDISCH, Ph.D. Chief Science Officer, Sandoz Biopharmaceuticals Chair European Biosimilars Group (EBG), EGA Sector Group
More informationDevelopment. - Be Your Partner-
Development - Be Your Partner- 1 Product development and management 2 Product development and management A good product development is based on a strong product management. Mycenax sproject management
More informationEuropean Medicines Agency Evaluation of Medicines for Human Use
European Medicines Agency Evaluation of Medicines for Human Use London, 22 February 2006 EMEA/CHMP/BWP/49348/2005 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) GUIDELINE ON SIMILAR BIOLOGICAL MEDICINAL
More informationChanges to a Potency Bioassay for Biotechnology Products: a Regulatory Perspective Kathleen A. Clouse, Ph.D., Director Division of Monoclonal Antibodi
Changes to a Potency Bioassay for Biotechnology Products: a Regulatory Perspective Kathleen A. Clouse, Ph.D., Director Division of Monoclonal Antibodies Office of Biotechnology Products Center for Drug
More informationRegulatory Considerations on. Office of Biotechnology Products
Regulatory Considerations on Multiproduct t Facilities for Biotechnology Products Jun Park, Ph.D. Division of Monoclonal Antibodies Office of Biotechnology Products OPS/CDER/FDA 2011 CASSS CMC Strategy
More informationSolutions to Problem Set 1
MIT Department of Biology 7.014 Introductory Biology, Spring 004 Question 1 Solutions to 7.014 Problem Set 1 a) Describe the conditions of the atmosphere on prebiotic earth and how these conditions differ
More informationScientific and Regulatory Perspectives on Measuring Protein Aggregation of Biotechnology Products
Scientific and Regulatory Perspectives on Measuring Protein Aggregation of Biotechnology Products Ashutosh Rao, Ph.D. Chief, Laboratory of Applied Biochemistry Division of Biotechnology Review and Research
More informationPrometheus Series Product Information
Prometheus Series Product Information Prometheus Instruments for nanodsf www.nanotemper-technologies.com Prometheus Series NanoTemper Technologies offers nanodsf technology with the Prometheus Series.
More informationBest Practices in Formulation and Lyophilization Development Proteins, mabs and ADCs
Best Practices in Formulation and Lyophilization Development Proteins, mabs and ADCs Best Practices in Formulation and Lyophilization Development The ultimate goal of formulation development is a stable
More informationCharacterization of Biotechnology Products: A Regulatory Perspective
Characterization of Biotechnology Products: A Regulatory Perspective Laurie Graham Acting Team Leader FDA/CDER/OPS/OBP Division of Monoclonal Antibodies WCBP 2013 1 Disclaimer The views and opinions expressed
More informationGuidance for Industry
Reprinted from FDA s website by Guidance for Industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product DRAFT GUIDANCE This guidance document is being distributed for comment
More informationThe study of protein secondary structure and stability at equilibrium ABSTRACT
The study of protein secondary structure and stability at equilibrium Michelle Planicka Dept. of Physics, North Georgia College and State University, Dahlonega, GA REU, Dept. of Physics, University of
More informationCOPYRIGHTED MATERIAL QUALITY BY DESIGN: AN OVERVIEW OF THE BASIC CONCEPTS. Rohin Mhatre and Anurag S. Rathore 1.1 INTRODUCTION
1 1.1 INTRODUCTION QUALITY BY DESIGN: AN OVERVIEW OF THE BASIC CONCEPTS Rohin Mhatre and Anurag S. Rathore The premise of Quality by Design (QbD) is that the quality of the pharmaceutical product should
More informationSimple, Robust, High Quality Intact Mass Analysis A Biosimilars Case Study
3 Conjugation Site (ADC) 4 34 35 1 1 35 34 CASE STUDY 3 National Institute for Bioprocessing 3 4 Research and Training 1 35 31 5 31 3 6 9 3 9 5 6 7 7 6 8 8 3 1 19 16 17 19 18 7 9 11 11 5 17 9 7 3 1 9 9
More informationScientific Considerations in Demonstrating Biosimilarity to a Reference Product. Guidance for Industry
Scientific Considerations in Demonstrating Biosimilarity to a Reference Product Guidance for Industry U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation
More informationDevelopment of High Concentration cetuximab Formulations using Ultrafiltration and Precipitation Techniques
Dissertation zur Erlangung des Doktorgrades der Fakultat fur Chemie und Pharmazie der Ludwig-Maximilians-Universitat Munchen Development of High Concentration cetuximab Formulations using Ultrafiltration
More informationSeparation of Recombinant Human Erythropoietin (repo) Using Agilent Bio SEC-3
Separation of Recombinant Human Erythropoietin (repo) Using Agilent Bio SEC-3 Application Note BioPharma Authors Phu T Duong and James Martosella Agilent Technologies, Inc. 285 Centerville Rd, Wilmington,
More informationB05 - PEPTIDE MAPPING(Revision 1) INTRODUCTION
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 B05 - PEPTIDE MAPPING(Revision 1) INTRODUCTION Proteins can exist as large complex structures, with some molecules in the population
More informationChapter 6. Techniques of Protein and Nucleic Acid Purification
Chapter 6 Techniques of Protein and Nucleic Acid Purification Considerations in protein expression and purification Protein source Natural sources Recombinant sources Methods of lysis and solubilization
More informationOpportunities for Accelerating Cell Line Development and Beyond
Opportunities for Accelerating Cell Line Development and Beyond European CM&C Strategy Forum May 24, 2017 Christopher Frye, Ph.D. Research Advisor & Group Leader Bioprocess R&D Presentation Outline CM&C
More informationNotice Our file number:
June 15, 2015 Notice Our file number: 15-107053-353 Adoption of ICH 1 Guidance: Q5E: Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process Health Canada
More informationAntibody-Drug Conjugates The Road to the Current State. Nila Das, Ph.D. American Drug Delivery & Formulation Summit San Diego, CA June 13, 2016
Antibody-Drug Conjugates The Road to the Current State Nila Das, Ph.D. American Drug Delivery & Formulation Summit San Diego, CA June 13, 2016 1 Current Status of ADCs C&E News. 2014, 92(3): 13-21 2 Current
More informationAdvanced QA/QC characterization MS in QC : Multi Attribute Method
Advanced QA/QC characterization MS in QC : Multi Attribute Method Global BioPharma Summit The world leader in serving science A Complex Problem: Drug Safety and Quality Safety Is the product safe to use?
More informationRapid Kinetics with IR Protein folding examples
Rapid Kinetics with IR Protein folding examples Time dependent data with FTIR Stop-flow methods - msec limits so far Continuous, micro-flow methods - < 100 µsec Rapid scan FT-IR - msec Multichannel laser
More informationRegulatory perspective on setting clinically relevant specifications. Joslyn Brunelle, PhD Team Leader Office of Biotechnology Products
Regulatory perspective on setting clinically relevant specifications Joslyn Brunelle, PhD Team Leader Office of Biotechnology Products Disclaimer The views and opinions expressed should not be used in
More informationMolecular characterization, detection & quantitation of biological products Purin Charoensuksai, PhD
Molecular characterization, detection & quantitation of biological products Purin Charoensuksai, PhD Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University Example of critical checkpoints
More informationThermo Scientific MAbPac HIC Columns. Novel Hydrophobic Interaction HPLC Columns. Designed for Monoclonal Antibody Analysis
Thermo Scientific MAbPac HIC Columns Novel Hydrophobic Interaction HPLC Columns Designed for Monoclonal Antibody Analysis Introduction The Thermo Scientific MAbPac HIC column family is designed for separations
More informationSize-exclusion chromatography TT30 sample was analyzed using a Tosoh Haas TSK Gel G3000SW XL 7.8 mm 30cm column at 1 ml/min and 280 nm detection.
Analytical ultracentrifugation (AUC) and size exclusion chromatography (SEC-HPLC) were used to assess TT30 molecular weight distribution. The sedimentation distribution of TT30 is shown in Fig. S1A. The
More informationParadigm Shift in Comparability Assessment:
Paradigm Shift in Comparability Assessment: How Quality by Design (QbD) and Process Analytical Technology (PAT) can improve Structure-Activity Relationship (SAR) evaluation and its relevance to comparability
More informationUV Fluorescence Polarization as a Means to Investigate Protein Conformational and Mass Change
A p p l i c a t i o n N o t e UV Fluorescence Polarization as a Means to Investigate Protein Conformational and Mass Change Using Intrinsic Tryptophan Fluorescence in Conjunction with UV-capable Polarizers
More informationUtilizing novel technology for the analysis of therapeutic antibodies and host cell protein contamination
Utilizing novel technology for the analysis of therapeutic antibodies and host cell protein contamination Kelli Jonakin, Ph.D. Senior Field Application Scientist, Seattle, WA Eric Johansen, Ph.D. Senior
More informationThe mechanism(s) of protein folding. What is meant by mechanism. Experimental approaches
The mechanism(s) of protein folding What is meant by mechanism Computational approaches Experimental approaches Questions: What events occur and in what time sequence when a protein folds Is there a specified
More informationDesign and Interpretation of Accelerated Stability Studies of Biologics
Design and Interpretation of Accelerated Stability Studies of Biologics Sheila G. Magil, Ph.D. Cambridge Healthtech Institute s Fourth Annual The Bioprocessing Summit 2012 August 20-23, 2012 Boston, MA
More informationPreparing the CMC section of IMPD for biological/biotechnology derived substances
Preparing the CMC section of IMPD for biological/biotechnology derived substances Your Logo Dr. Una Moore Health Products Regulatory Authority, Ireland Presented by Una Moore on 16 th April 2014. Health
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 informationStructure formation and association of biomolecules. Prof. Dr. Martin Zacharias Lehrstuhl für Molekulardynamik (T38) Technische Universität München
Structure formation and association of biomolecules Prof. Dr. Martin Zacharias Lehrstuhl für Molekulardynamik (T38) Technische Universität München Motivation Many biomolecules are chemically synthesized
More informationStructural Aspects of Immunogenicity: Aggregates
Structural Aspects of Immunogenicity: Aggregates Ronald Smulders 19 November 2009 Pharmaceutical Sciences & Drug Metabolism EIP-Protein Characterization Subcommittee Mission of the EIP-PCS: To discuss
More informationFORMULATION & LYOPHILIZATION CYCLE DEVELOPMENT OF AN ADC
FORMULATION & LYOPHILIZATION CYCLE DEVELOPMENT OF AN ADC A Case Study Wendy Saffell-Clemmer Director, R&D Baxter BioPharma Solutions Antibody Drug Conjugates (ADCs) are complex molecules consisting of
More informationSolutions for the Core and Protein Laboratory: MassHunter Walkup
Solutions for the Core and Protein Laboratory: MassHunter Walkup Jade C. Byrd MS Software Product Manager Page 1 Common Challenges in Characterizing Biomolecules Molecular size (insulin is 5 kda, mabs
More informationCh Biophysical Chemistry
Ch 247.53. Biophysical Chemistry Nina Rosario L. Rojas 2012-2013 sem 1 Review of Protein Structure Why structure? Primary, secondary, tertiary structure Disulfide bonds scheme 2 STRUCTURE- REGULAR STRUCTURE
More informationBiosimilars Scientific and Regulatory Considerations
Biosimilars Scientific and Regulatory Considerations Gustavo Grampp Regulatory Policy Director, Amgen Presented at Maryland Pharmacists Association meeting January 31, 2016 Program objectives 1. Review
More informationTen Lessons for the Formulation Development of Monoclonal Antibodies from Multimodal Thermal Unfolding Case Studies
Ten Lessons for the Formulation Development of Monoclonal Antibodies from Multimodal Thermal Unfolding Case Studies Mark Brader Protein Pharmaceutical Development Biogen Idec PEGS Boston essential protein
More informationAdvanceBio HIC: a Hydrophobic HPLC Column for Monoclonal Antibody (mab) Variant Analysis
Application Note Biologics Development AdvanceBio HIC: a Hydrophobic HPLC Column for Monoclonal Antibody (mab) Variant Analysis Using the Agilent 16 Infinity II Bio-Inert LC Authors Andrew Coffey and Sandeep
More informationStreamlined and Complete LC-MS Workflow for MAM
Streamlined and Complete LC-MS Workflow for MAM Multiple Attribute Methodology (MAM) for Biotherapeutic Attribute Monitoring and Purity Testing BV MAM WORKFLOW Define Track Quantify Purity New Peaks Report
More informationIMPORTANCE OF CELL CULTURE MEDIA TO THE BIOPHARMACEUTICAL INDUSTRY
IMPORTANCE OF CELL CULTURE MEDIA TO THE BIOPHARMACEUTICAL INDUSTRY Research, development and production of biopharmaceuticals is growing rapidly, thanks to the increase of novel therapeutics and biosimilar
More informationZool 3200: Cell Biology Exam 3 3/6/15
Name: Trask Zool 3200: Cell Biology Exam 3 3/6/15 Answer each of the following questions in the space provided; circle the correct answer or answers for each multiple choice question and circle either
More informationReference Standards: Overview and Strategy for Development to Commercialization
Reference Standards: Overview and Strategy for Development to Commercialization John Ruesch Analytical Research and Development CASSS / WCBP CMC Strategy Forum: Reference Standards For Therapeutic Proteins
More informationComparability Analysis of Protein Therapeutics by Bottom-Up LC-MS with Stable Isotope-Tagged Reference Standards
Comparability Analysis of Protein Therapeutics by Bottom-Up LC-MS with Stable Isotope-Tagged Reference Standards 16 September 2011 Abbott Bioresearch Center, Worcester, MA USA Manuilov, A. V., C. H. Radziejewski
More informationRequirements for demonstrating biosimilarity of monoclonal antibodies
Requirements for demonstrating biosimilarity of monoclonal antibodies Dr. Steffen Gross Section Mono-/Polyclonal Antibodies Paul-Ehrlich-Institut Germany http://www.pei.de Outline Biosimilars Regulatory
More information