Cover Image

Nonclinical development of biologics, vaccines and specialty biologics /

Nonclinical Development of Biologics, Vaccines and Specialty Biologics, Second Edition, is a complete reference devoted to the nonclinical safety assessment of novel biopharmaceuticals, vaccines, cell and gene therapies, and oncology therapeutics. Updated and revised, the new edition compares and co...

Full description

Bibliographic Details
Corporate Author: ScienceDirect (Online service)
Other Authors: Plitnick, Lisa M. (Editor), Fuller, Claudette L. (Editor)
Format: eBook
Language:English
Published: London : Academic Press, [2025]
Edition:Second edition.
Subjects:
Biologicals.
Biological products.
Biopharmaceutics.
Vaccines.
Biological Products
Biopharmaceutics
Vaccines
Médicaments biologiques.
Produits biologiques.
Biopharmacie.
Vaccins.
Electronic books.
Online Access:Connect to the full text of this electronic book
Table of Contents:
  • Front Cover
  • NONCLINICAL DEVELOPMENT OF BIOLOGICS, VACCINES AND SPECIALTY BIOLOGICS
  • NONCLINICAL DEVELOPMENT OF BIOLOGICS, VACCINES AND SPECIALTY BIOLOGICS
  • Copyright
  • Contents
  • Contributors
  • Preface
  • Acknowledgments
  • I
  • Development of biopharmaceuticals
  • 1
  • Overview of biopharmaceuticals and comparison with small-molecule drug development
  • Introduction
  • Routes of administration
  • Nonclinical species for toxicology testing
  • Carcinogenicity assessment
  • Best practices in toxicology program design in the wake of the COVID-19 pandemic
  • Classes of biopharmaceuticals
  • References
  • 2
  • Nonclinical development of monovalent and polyvalent biopharmaceuticals
  • Introduction
  • Monovalent biopharmaceuticals
  • Polyvalent biopharmaceuticals
  • Scientific rationale for PVBs
  • Technology and formats
  • Chemical cross-linking and hybridoma fusion approaches
  • Recombinant formats using engineered protein scaffolds
  • General challenges and considerations
  • Understanding expression, regulation, and distribution of all targets
  • Understanding target biology
  • Effector function
  • Species selection
  • Tissue cross-reactivity study
  • Pharmacokinetics
  • Molecular properties
  • Immunogenicity
  • Selection of starting dose
  • Summary of challenges
  • T cell-dependent bispecific antibody biotherapeutics
  • Catumaxomab (EpCAM/CD3 multitargeting full-length antibody)
  • MT110 (EpCAM/CD3 TDB, BiTE format)
  • Case Example 4: Formation of ADAs limited the conduct of sub-chronic (3-month) or chronic toxicology studies
  • Dual-targeting antibodies
  • Oncology
  • Coagulation disorder
  • Hemophilia
  • Ocular disease
  • Age-related macular degeneration
  • Bispecific antibodies of endogenous receptor ligands for CNS delivery of biotherapeutics across blood-brain barrier
  • Combination therapeutics.
  • Evaluation of immunotoxicity
  • Immunosuppressive biotherapeutics
  • Immunostimulatory biotherapeutics
  • Tumor lysis syndrome (TLS), first dose effect and cytokine release syndrome (CRS) induced by mAbs
  • TGN1412 case study
  • Hypersensitivity reactions
  • Can we better address potential off-target toxicity?
  • Hematologic toxicity
  • Bevacizumab case study
  • LY2541546 (antisclerostin) case study
  • Omalizumab case study
  • AMG X case study
  • mAbY.1 case study
  • Summary
  • References
  • Further reading
  • 5
  • Novel biopharmaceuticals: Pharmacokinetics, pharmacodynamics, and bioanalytics
  • Introduction
  • Absorption, distribution and elimination of biopharmaceuticals
  • Absorption
  • Distribution and elimination: Nonspecific processes
  • mAbs, mAb fragments, and mAb constructs
  • Therapeutic proteins and peptides
  • Distribution and elimination: Target-mediated processes
  • Monoclonal antibodies
  • Therapeutic proteins and peptides
  • Modifications and impact on PK and biodistribution
  • "Metabolism" and biodistribution for biopharmaceuticals
  • Immunogenicity and impact on PK and biodistribution
  • Pharmacokinetics and pharmacodynamics
  • PK methods
  • Representative PK for molecule types
  • Pharmacodynamics, PK/PD methods and examples
  • Model types and examples
  • Nonclinical to clinical translation
  • Human PK projections
  • Exposure response: Determining minimum and maximum targets for FIH dosing
  • Bioanalytics
  • Method development guidances and regulations
  • Methods and platforms
  • Immunoassays
  • LC-MS
  • Assays
  • Drug exposure
  • Biomarkers: Target engagement
  • Immunogenicity assessment
  • Summary
  • Acknowledgment
  • References
  • II
  • Vaccines
  • 6
  • Introduction to vaccines and adjuvants
  • Introduction
  • The two arms of the immune system
  • Regulation of vaccines
  • US FDA definition of a vaccine.
  • Impacts of current vaccines on human health
  • The science (and business) of vaccinology
  • Vaccine platforms can accelerate development and approval of new vaccines
  • Are adjuvant platforms feasible?
  • "Outbreaks, they're inevitable. But turning into a pandemic, that's optional"
  • WHO's 10 major threats to global health
  • Other vaccines needed for serious infectious diseases
  • Antimicrobial resistant bacteria
  • "There Was a Fungus Among Us"
  • Parasitic diseases
  • Therapeutic vaccines
  • Platforms for therapeutic vaccines
  • Complexity of vaccines from a product quality perspective
  • Nonclinical testing
  • Vaccine development using the Animal Rule
  • WHO threat #8-Vaccine hesitancy (and the importance of vaccinology education)
  • Summary
  • References
  • 7
  • Regulatory aspects of nonclinical vaccine development
  • Introduction
  • Regulatory guidelines (Table 7.1)
  • Alternate approaches
  • Repeat-dose toxicity evaluation (Table 7.2)
  • Developmental toxicity
  • Biodistribution
  • Environmental risk assessment
  • Genotoxicity and carcinogenicity
  • Safety pharmacology
  • Neurovirulence
  • Conclusion
  • References
  • 8
  • Special considerations for the nonclinical safety assessment of vaccines
  • Introduction
  • De-risking strategies for vaccines
  • General de-risking strategies for vaccines
  • De-risking strategies for specific vaccine types
  • Vaccines with adjuvants
  • Therapeutic vaccines
  • Pharmacokinetics and pharmacodynamics assessments
  • Assays
  • Ligand-binding assays
  • Cell-mediated immune response assays
  • Functional assays
  • Differences in the nonclinical safety assessment of vaccines and biopharmaceutical drugs
  • Summary
  • References
  • III
  • Specialty biologics and indications
  • 9
  • Preclinical development of viral vector gene therapies
  • Background: Vectors and applications.
  • Delivering gene therapy products: Nonviral and viral vectors
  • Nonviral vectors
  • Viral vectors
  • Nonintegrating viral vectors
  • Adenoviral vectors (AdV)
  • Adeno-associated vectors (AAV)
  • Integrating viral vectors
  • Therapeutic applications and beyond
  • General considerations regarding chemistry manufacturing and controls (CMC): Viral vectors manufacturing, characterization, ...
  • Early decisions regarding CMC
  • Vector development
  • Producer cell line selection (upstream process)
  • Product format and formulation (downstream process)
  • Product characterization and potency assays
  • Product characterization
  • quality attributes
  • Potency assays
  • Nonclinical development
  • Principles of nonclinical development
  • Selection of test article for nonclinical studies
  • Justification for route and method of administration for nonclinical studies
  • Selection of animal model and or species for nonclinical efficacy studies
  • Pharmacologic efficacy assessments
  • Study design, dose selection and justification of endpoints
  • Pharmacodynamics and pharmacokinetics
  • Pharmacodynamics and minimal efficacious dose (MED)
  • Pharmacokinetics
  • biodistribution, shedding, and persistence
  • Nonclinical safety evaluation
  • General toxicity
  • Justification of dose
  • Justification of delivery method
  • Justification of the test system
  • Considerations for study designs, safety endpoints and safety pharmacology
  • Considerations for immunogenicity in toxicology studies
  • Developmental and reproductive toxicity (DART)
  • Genotoxicity: Insertional mutagenesis, carcinogenicity, and germline transmission
  • Translating nonclinical data to regulatory success
  • An ever-evolving regulatory landscape
  • Considerations for dose extrapolation
  • Clinical trial design
  • Expansion cohort trial designs.