Product and Process Variants & Impurities

More documents

Recommendations

Info

Monday, October 21, 2013 (continued)Well Characterized BiologicalsBiological Assay Development Strategies3:45 CASE STUDY/UNPUBLISHED DATA Case Study for the Developmentof Potency Assays to Support the Characterization of aMonoclonal Antibody Reflecting Antibody Dependent CellMediated Phagocytosis (ADCP) As a Presumed Mechanismof ActionAt Biogen Idec, a phase-based approach is applied to the selection of assayformats to measure the biological activity of protein therapeutics. Forearly phase clinical programs, a binding assay is used for batch release andstability testing, followed by development of a cell-based functional assay,relevant to the therapeutics’ mechanism of action, as the program advancesto late stage. In this presentation, a case study describing the developmentand evaluation of several orthogonal assays used to characterize theAntibody Dependent Cell Mediated Phagocytosis (ADCP) activity of amonoclonal antibody is presented. In addition, development of a novelADCP assay that reflects this challenging MOA is described. The rationalefor usage of each individual assay and strategy for cross-over studiesbetween assays is discussed.Carl Co, Ph.D., Scientist, Analytical Development, Biogen Idec4:15 CASE STUDY/UNPUBLISHED DATA Application of Equivalency TestingTo Variable BioassaysEquivalency testing for bioassays circumvents some of the issues observedwith other parallel-line analysis statistics, but presents its own challenges.A statistical method from USP was applied to a binding assayand a cell based bioassay. Application of the method to the binding assaywas relatively straightforward. The bioassay, on the other hand, showedmuch more variability in its readout, requiring additional testing duringdevelopment to establish confidence interval goal posts. During validationand assay transfer, additional variation was observed necessitating a furtheradjustment of the goal posts. This case study demonstrates that settingequivalency testing goal posts requires reiteration. The USP chapter outlinesthe fundamentals of equivalency testing, however there are points to keep inmind from this application for future bioassay development.Edward Rocnik, Ph.D., Scientist II, Analytical Development – Biologics,Millennium, The Takeda Oncology Company4:45 Engineering Potency Assay Solutions for Complex MOAsAbstract not available at time of print.Please visit www.IBCLifeSciences.com/WCB for updates.Kendall D. Carey, Ph.D., QC Scientist, Genentech, Inc., A member of theRoche Group5:15 FDA Perspective Serologic Assays Used in VaccineDevelopment for Bacterial DiseasesThe US Food and Drug Administration, Center for Biologics Evaluationand Research, Office of Vaccines Research and Review (OVRR) evaluatesthe safety and efficacy of vaccines for therapeutic and vaccine preventablediseases in the U. S. Serologic assays may be used as correlates ofprotection to clinically evaluate effectiveness of a vaccine when diseasecannot be measured. This presentation will review why, when, and how it isappropriate to develop serologic assays. Meningococcal vaccines (Neisseriameningitidis) with use of the serum bactericidal activity (SBA) assay, andpneumococcal vaccines (Streptococcus pneumoniae) with the use ofopsonophagocytic assay (OPA) will be presented as examples.Cara Fiore, Ph.D., Master Reviewer, Office of Vaccines Research andReview, CBER, US FDA5:45 Close of Day OneProduct and Process Variants & Impurities3:45 Establishing Well-Controlled Manufacturing Processes forProcess-Related ImpuritiesTwo case studies on the investigation and resolution of disulfide bond-relatedfragmentation in monoclonal antibodies: In the pursuit of gaining better processunderstanding for rapid decision-making during drug development, the needfor analytical real-time monitoring tools becomes a critical factor in identifyingproblems before they have a serious impact on programs. Two unique case studieswill be presented where disulfide bond-related fragmentation was observed inthe production of monoclonal antibody therapeutics. The presentation describesthe discovery of the fragmentation issue using rapid high-throughput analyticaltools capable of analyzing crude cell cultures for critical attributes, the varioustheories and experiments carried out to explore root cause, as well as the solutionsimplemented to successfully eliminate the fragmentation and improve the process.The two case studies were approached in two very different manners, one with afocus on the upstream process, and one with a focus on the downstream process.However, in both cases, the fragmentation issue has been resolved through thepurposeful and strategic use of available analytical technology.Jason Kuo, Ph.D., Sr. Associate, Process Science, Boehringer Ingelheim4:15 Validating a Biological Manufacturing Platform to IdentifyVariants and Control ImpuritiesGene therapies and oncolytic viruses are seeing resurgence in the industry,and a number of those compounds are currently in Phase III development.This session will focus on SAFC’s development and implementation of itsMaster Validation Plan (MVP) in support of one of its Phase III clients forits commercial validation project. The discussion will focus on the topic ofprocess validation, product purity, and clearance of contaminants as subsetsto the MVP. The SAFC strategy and methodology is to use validation toolssuch as a detailed process description and flow chart to identify processvariables and critical control parameters, a risk assessment to assign relativevalues to the control parameters and product quality attributes, and a gapanalysis between the known process and the historical data to identify areaswhere additional characterization is needed for the purposes of establishingan optimal design space for each unit operation of the process.Kevin Briggs, Head of Manufacturing, SAFC Carlsbad4:45 Panel Discussion:Biophysical Methods for the Detection of ImpuritiesModerator:Indresh Srivastava, Ph.D., Vice President, Product Realization and Senior,Project Manager, Protein Sciences CorporationPanelists:Christopher Cowan, Staff Engineer, Preclinical Manufacturing ProcessDevelopment, Regeneron PharmaceuticalsPauline M. Rudd, Professor, NIBRT Research Professor of Glycobiology,Dublin-Oxford Glycobiology Laboratory, NIBRT, IrelandJudith Shimoni, Senior Scientist / Group Leader, Protein AnalyticalChemistry, GenentechWei Xu, Ph.D., Principal Scientist, Bioprocess Development Extended,Characterization, Merck Research Laboratories5:15 Close of Day One“Both the organizers and the presenters did an excellentjob – great content, variety and relevance to today’sindustry needs…”– James D. Mendoza, Staff Scientist, Beckman, Coulter, Inc.Divide and ConquerIt’s a fact – attendees walk away with the most value when theyexperience it with a peer – there is just too much informationavailable for one person to capture it all. As a result, we are pleasedto offer a buy 3 get 1 free offer. For more information call our groupsales advocate at 646-895-7445.6 www.IBCLifeSciences.com/WCB www.IBCLifeSciences.com/Variants
Tuesday, October 22, 2013Well Characterized Biologicals8:00 Chairwoman’s RemarksSuzanne Kiani, Associate Director, Regulatory CMC, MedImmuneAnalytical Strategies for Diverse Products8:15 Characterization Strategies for BiologicalsShara M. Dellatore, Ph.D., Principal Scientist, BioProcess ExtendedCharacterization, Merck & Co, Inc.8:45 Control Strategies for Drug Delivery Devices: RegulatoryConsiderations for Testing and Analytical CharacterizationThe regulatory classification of combination product brings with itsubsequent requirements for Risk Management, Design Controls andPurchasing Controls. This presentation will summarize steps that you cantake to incorporate device centric elements to design a control strategy thatis reflective of the combination product as a system.Suzanne Kiani, Associate Director, Regulatory CMC, MedImmune9:15 CASE STUDY/UNPUBLISHED DATA Don’t Go into the Light!Investigating the Changes in Color of a Therapeutic IgG1Antibody after Exposure to LightColor is an important product quality attribute to consider for release,stability, and comparability testing of biologics. In this study, a therapeuticIgG1 antibody was observed to increase in color upon exposure to light,indicating a light sensitivity and stability risk. Through a combination ofchromatographic, spectrophotometric, and mass spectrometry techniques,photosensitizing advanced glycation endproducts (AGE’s), resulting inphoto-induced protein oxidation and crosslinking, were implicated in theantibody’s light sensitivity/color change pathway.Galahad Deperalta, Scientist, Protein Analytical Chemistry, Genentech, Inc.,A member of the Roche Group9:45 Networking Refreshment Break and Exhibit/Poster ViewingFeatured Presentation10:15 FDA Perspective Top 10 List of AnalyticalInadequacies in IND or BLA SubmissionsProcedures to support the identity, strength, quality, purityand potency of drug products and drug substances are animportant component of new product applications reviewed bythe FDA. Inadequacies commonly encountered in these submissions involveprocedural details, system suitability tests, representative instrumentaloutputs, types of validation characteristics, linearity in sample matrix,verification of “compendial” procedures, robustness of critical assayparameters, accuracy calculations, precision and accuracy across intendedrange and factors in intermediate precision. FDA expectations for analyticalprocedures and validations will be discussed.Alfred Del Grosso, Team Leader, Analytical Chemistry,Division of Biological Standards and Quality Control, CBER, US FDA11:00 Oral Poster Presentation SessionSeveral poster presenters will be chosen to provide a short presentation tointroduce their work using a single slide to the entire conference. Submityour poster abstract today at www.IBCLifeSciences.com/WCB for a chanceto be selected for this opportunity.11:45 Technology WorkshopNew Tools and Methods for Label-FreeCharacterization of Biotherapeutic MoleculesTo address the large number of biotherapeutic molecules in development,biopharmaceutical companies are adopting a new generation of rapid,high-sensitivity analytical techniques for molecular characterization andbioprocess monitoring. In this seminar, we will review recent advances inlabel-free methods for biopharmaceutical molecules. Specific topics willinclude new tools for the quantitation of cell culture samples, impurityanalysis such as residual protein A and HCP, and activity monitoring ofmolecules throughout bioprocess to quality control.Rashi Takkar, Marketing Application Scientist, ForteBio,A Division of Pall Life SciencesProduct and Process Variants & Impurities8:00 Chairman’s Opening RemarksDean Ripple, Ph.D., Leader, Bioprocess Measurements Group,National Institute of Standards and TechnologyRegulatory and Scientific Organization andIndustry Perspectives on Process Variants andImpurity CharacterizationFeatured Presentation8:15 FDA Perspective Changing the Manufacturing Process toRemove Impurities and Monitoring Product Quality UsingRelevant Lot Release AssaysProcess- and product-related impurities in therapeutic products can leadto adverse events. When CMC information related to the adverse events areavailable, the potential risk could be reduced by controlling the levels of theimplicated impurities through changes in the manufacturing process andmonitoring of the quality of the product using relevant lot release assays.Mikhail V. Ovanesov, Ph.D., Visiting Scientist, Principal Investigator,Laboratory of Hemostasis/Division of Hematology, Office of BloodResearch and Review, CBER, US FDA8:45 Current Approaches for Standardization andCompendial ProceduresThis presentation discusses the U.S. Pharmacopeia’s efforts on developingrecommended practices for identifying and controlling product and processvariants and impurities during the lifecycle of a biologic product.Fouad Atouf, Ph.D., Director, Biologics and Biotechnology, US Pharmacopeia9:15 UNPUBLISHED DATA The National Institute of Standards andTechnology (NIST) Subvisible Particle Round-RobinComparison: Results and Lessons LearnedNIST has conducted a round-robin comparison for sizing and countingsubvisible particles from 1 µm to 25 µm, using a polydisperse polymersuspension that closely mimics actual protein particles. Twenty-fourlaboratories from industry, government, and academic institutionsparticipated. The results give a snapshot of the level of agreement betweendifferent laboratories and for different particle counting instruments.Dean Ripple, Ph.D., Leader, Bioprocess Measurements Group,National Institute of Standards and Technology9:45 Networking Refreshment Break and Exhibit/Poster Viewing10:15 CASE STUDY/UNPUBLISHED DATA Identification and Control ofProcess Impurities and Product Related Variants in theDevelopment and Manufacture of a GlycoproteinProcess improvements in CHO cell expression of a glycoprotein involvesbioreactor conditions that impose biophysical and biochemical pressures oncellular biosynthetic and biochemical pathways. Upstream and downstreamstrategies have been used to control glycan variation. An upstream goalis for harvested material to contain the desired product profile. However,product variation exists that include glycan species with less preferredcharacterization, i.e., complex heterogeneity and other CHO glycoproteinimpurities that together can challenge the process and product profile.This presentation will discuss examples of CHO glycoprotein variants andimpurities encountered in the development and manufacturing process.Kirk J. Leister, Ph.D., Director of New Technology,Bristol Myers Squibb Company12:15 Networking Luncheon and Exhibit/Poster Viewingwww.IBCLifeSciences.com/WCB www.IBCLifeSciences.com/Variants 7
Page 2 and 3: Find Practical Strategies and New T
Page 5: Monday, October 21, 2013 (continued
Page 9 and 10: Tuesday, October 22, 2013 (continue
Page 11 and 12: 3EASY WAYSTO REGISTER:@CALLEMAIL800

Product and Process Variants & Impurities

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?