ebook img

Challenges in Protein Product Development PDF

596 Pages·2018·10.777 MB·English
Save to my drive
Quick download
Download
Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.

Preview Challenges in Protein Product Development

AAPS Advances in the Pharmaceutical Sciences Series 38 Nicholas W. Warne Hanns-Christian Mahler Editors Challenges in Protein Product Development AAPS Advances in the Pharmaceutical Sciences Series Volume 38 Series Editor Yvonne Perrie, Strathclyde Institute of Pharmacy, University of Strathclyde, Bearsden, Dunbartonshire, UK The AAPS Advances in the Pharmaceutical Sciences Series, published in partnership with the American Association of Pharmaceutical Scientists, is designed to deliver volumes authored by opinion leaders and authorities from around the globe, addressing innovations in drug research and development, and best practice for scientists and industry professionals in the pharma and biotech industries. More information about this series at http://www.springer.com/series/8825 Nicholas W. Warne Hanns-Christian Mahler (cid:129) Editors Challenges in Protein Product Development 123 Editors NicholasW. Warne Hanns-Christian Mahler BioTherapeuticsResearchandDevelopment Lonza AG PharmaceuticsResearchandDevelopment Drug ProductServices PfizerInc. Basel, BaselStadt Andover,MA Switzerland USA ISSN 2210-7371 ISSN 2210-738X (electronic) AAPS Advances inthe Pharmaceutical SciencesSeries ISBN978-3-319-90601-0 ISBN978-3-319-90603-4 (eBook) https://doi.org/10.1007/978-3-319-90603-4 LibraryofCongressControlNumber:2018939307 ©AmericanAssociationofPharmaceuticalScientists2018 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission orinformationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfrom therelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontainedhereinor for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations. Printedonacid-freepaper ThisSpringerimprintispublishedbytheregisteredcompanySpringerInternationalPublishingAG partofSpringerNature Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Preface The use of therapeutic proteins continues to increase, with most of these protein drugproductsbeingusedtotreatseverediseasessuchasvarioustypesofcanceror inflammation. As the field of recombinant therapeutic proteins enters its fourth decade and the market for biopharmaceuticals becomes increasingly competitive, companies are increasingly dedicating resources to develop innovative biophar- maceuticals to address unmet medical needs. Often, the pharmaceutical development scientist encounters challenging phar- maceutical properties of a given protein, the demands placed on the product by stability, manufacturing and preclinical or clinical expectations, as well as the evolving regulatory expectations and competitive landscape. Further, there have been new findings that require close assessment, for example, related to excipient quality, processing, viscosity and device compatibility and administration, solu- bility and opalescence and container-closure selection. The literature varies widely initsdiscussionofthesecriticalelements,andconsensusdoesnotexist.Thisbook aims to serve to provide a broad overview, yet deep insight, into these different topics. We seek to discuss several of these and other challenges currently faced in biotechnology dosage form development to provide guidance, shared experience and thoughtful reflection on how best to address these potential concerns. Inordertodevelopanadequatedrugproductofatherapeuticprotein,significant considerations need to be made to the formulation, container-closure system, and processing. Only the combination of all yields an acceptable drug product. Firstly, Part 2 provides some insights into the formulation development of biologics. Recently, the degradation and quality of surfactants such as polysorbates have received significant attention. Furthermore, the use of excipients for formulations will impact not only protein stability but also the products’ pharmaceutical parameters such as pH, viscosity, and osmolality. Excipients can crystallize under frozen conditions and may subsequently lead to challenges related to protein sta- bility in the frozen state. In order to enable self-administration or improve conve- nience, high-concentration protein formulations are often required. Part 3 will discuss high-concentration protein formulations, related theoretical considerations, product considerations, including opalescence, appearance, and particulate matter, v vi Preface but also analytical and predictive tools as well as impact and practical considera- tions related to protein concentration, such as viscosity and relation to device functionality. In most R&D portfolios, there are increasingly more “novel con- structs” in research and development and less focus on “traditional” monoclonal antibodies. Part 4 will introduce different categories of novel therapeutic protein constructs, including antibody drug conjugates, fusion proteins, and strategies for half-life extension. Significant focus during the development of drug products includes the devel- opment and selection of the container closure, required to provide protection and possiblefunctionalityforagivenproduct.Historically,glassvials,rubberstoppers, and aluminum crimp caps are used for therapeutic protein injectables where self-administration is not desired or required. Increasingly, combination products are used, including syringes with needle-safety devices or autoinjector, injection pens or infusion (mini) pumps. Part 5 will introduce various technologies and discuss possible challenges related to primary packaging and device, including container-closure integrity testing, delamination, functionality of syringes and clogging,impactofsiliconeandtungstenandrelatedanalytics.Finally,thestability of a given product also needs to be ensured during preparation and administration andsomeconsiderationstoin-usestability,includingmicrobiologicalstability,will be provided. Finally, processing is being introduced and discussed in Part 6. Challenges for the “seemingly simple fill/finish process” are many: extractables and leachables, hold times, material (in)compatibility, sterile filtration, processing residuals (e.g., vaporizedhydrogenperoxide)impactonstability,QbDconsiderations,techtransfer challenges, and GMP drug product manufacturing segregation concerns, e.g., ADCs, cytotoxics, growth hormones, or some antibiotics. The final section, Part 7, will discuss strategies and options for life-cycle management. This may include changing the route of administration (e.g., IV to SC), changing the formulation or dosage form (e.g., replacing excipients, changes from lyophilisate to liquid), or the use of devices. Given the span of topics, we believe this book is of significant interest for colleagues in the biotechnology and pharmaceutical industry, as well as academic researchersandregulatoryagenciesglobally, mayit bebusiness orprojectleaders, researchers,scientistsinformulationandprocessdevelopment,analyticalscientists, QC/QA colleagues, regulatory staff, and manufacturing leaders. Enjoy reading! Cambridge, USA Nicholas W. Warne Basel, Switzerland Hanns-Christian Mahler Contents Part I Formulation Development of Biologics 1 Introduction into Formulation Development of Biologics . . . . . . . . 3 Daniel Weinbuch, Andrea Hawe, Wim Jiskoot and Wolfgang Friess Part II Challenges with Excipients 2 Polysorbate Degradation and Quality . . . . . . . . . . . . . . . . . . . . . . . 25 Kishore S. K. Ravuri 3 Sucrose and Trehalose in Therapeutic Protein Formulations . . . . . 63 Satish K. Singh Part III High Concentration Proteins 4 Introduction to High-Concentration Proteins . . . . . . . . . . . . . . . . . 99 Wei Wang, Arun Alphonse Ignatius, Satoshi Ohtake and Teng-Chieh Yang 5 Solubility, Opalescence, and Particulate Matter . . . . . . . . . . . . . . . 125 Hanns-Christian Mahler and Anja Matter 6 Analytical Characterization and Predictive Tools for Highly Concentrated Protein Formulations . . . . . . . . . . . . . . . . . . . . . . . . 139 Andrea Allmendinger, Stefan Fischer and Robert Mueller 7 Practical Considerations for High Concentration Protein Formulations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 Deirdre Murphy Piedmonte, Jian Hua Gu, Stephen R. Brych and Monica M. Goss vii viii Contents Part IV Container-Closure Systems 8 Parenteral Container Closure Systems . . . . . . . . . . . . . . . . . . . . . . 191 Roman Mathaes and Alexander Streubel 9 Development of Prefilled Syringe Combination Products for Biologics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 MarianaN.Dimitrova,JaredS.Bee,LingLuandJasonE.Fernandez 10 Special Topics in Analytics of Pre-filled Syringes . . . . . . . . . . . . . . 225 Atanas Koulov 11 C Mini-pumps. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 Dirk Gläser, Jürg Liniger and Daniel Peter 12 Container Closure Integrity Testing of Primary Containers for Parenteral Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257 Shu-Chen Chen 13 Chemical Durability of Glass—Delamination . . . . . . . . . . . . . . . . . 291 Holger Roehl, Philippe Lam and Dominique Ditter 14 Fogging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305 Holger Roehl, Philippe Lam and Dominique Ditter Part V Processing Considerations 15 Bulk Protein Solution: Freeze–Thaw Process, Storage and Shipping Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 Parag Kolhe and Sumit Goswami 16 Leachables and Extractables: From Regulatory Expectations to Laboratory Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 Michael Jahn 17 Biotherapeutic Drug Product Manufacturing and Process Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353 Daniel Dixon and Anthony Gudinas 18 Line Sterilization Considerations and VHP. . . . . . . . . . . . . . . . . . . 385 Ulla Grauschopf, Katherine Thomas, Joerg Luemkemann, Sebastian Schneider, Ada Hui, Y. John Wang and Kirk Eppler 19 Lyophilization: Process Design, Robustness, and Risk Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407 Daniel Dixon, Serguei Tchessalov and Bakul Bhatnagar 20 Scientific Approaches for the Application of QbD Principles in Lyophilization Process Development . . . . . . . . . . . . . . . . . . . . . . . . 441 Vinay Radhakrishnan, Penny Davis and David Hiebert Contents ix 21 Manufacturing of Highly Potent Drug Product in a Clinical Multi-Product Aseptic Facility and Transfer of Principles to Antibiotic Drug Product . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473 Karoline Bechtold-Peters and Silke Mohl Part VI Novel Constructs 22 Introduction into Novel Constructs. . . . . . . . . . . . . . . . . . . . . . . . . 497 Susanne Joerg, Kapil Gupta and Margarida Rodrigues 23 Novel Constructs—Half-Life Extensions . . . . . . . . . . . . . . . . . . . . . 527 Jeonghoon Sun and Mark Michaels 24 “Fc Fusion Proteins”. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545 Carole Heath and Dean Pettit Part VII Lifecycle Management 25 Lifecycle Management of Biotherapeutic Dosage Forms . . . . . . . . . 561 Nicholas Warne, Bryan Balthazor and William Parr 26 SwitchingfromanIVtoanSCFormulation—Considerationsfor Formulation Development and Formulation Bridging. . . . . . . . . . . 579 Claudia Mueller and Michael Adler Index .... .... .... .... .... ..... .... .... .... .... .... ..... .... 591

See more

The list of books you might like

Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.