PrefaceContributorsIntroduction, Stanley H. NusimConsolidation and IntegrationQualityPotencyComputer Control and AutomationSummaryBulk Drugs: The Process Development Task, Carlos B. RosasIntroductionThe Bulk Drug Process as Part of the Drug Development ProgramFrom the Bench to the Pilot Plant and BeyondThe Physicochemical Attributes of the Bulk DrugThe Process Body of KnowledgeNew Trends and Their Probable Impact on Bulk Drug Process DevelopmentProcessing Responsibility in Bulk Drug Process DevelopmentOutsourcing in Bulk Drug Process DevelopmentIn ClosingReferencesBulk Drugs: Process Design, Technology Transfer, and First Manufacture, Carlos B. RosasIntroductionThe Process Design Task in Bulk DrugsTechnology Transfer of the Bulk Drug Process and First ManufactureIn Closing—The Processing Technologies of Bulk DrugsReferencesDesign and Construction of API Manufacturing Facilities, Steven MongiardoIntroductionProject Scope DevelopmentPreliminary Scope DevelopmentGMP ConsiderationsSafety and Environmental ConsiderationsDesign Strategy and Detailed DesignDesign DevelopmentSterile Process Facilities DesignConstruction ManagementConclusionsReferencesRegulatory Affairs: Requirements and Expectations, John CurranIntroductionHigh-Level Requirements for Submission of Regulatory CMC DocumentsContents of Regulatory Submissions—API SectionsRegistration SamplesThe Review and Approval ProcessPreapproval InspectionsPostapproval Change EvaluationsRegulatory Affairs: Guidelines, Evolving Strategies, and Issues, John CurranIntroductionGuidelines Issued by the International Conference on HarmonisationRegulatory Agency GuidelinesEvolving Strategies and IssuesThe FutureValidation of Active Pharmaceutical Ingredients, James Agalloco and Phil DeSantisHistoryDefinition of ValidationRegulationsApplication of ValidationLife Cycle ModelValidation of New ProductsValidation of Existing ProductsImplementationBulk Pharmaceutical Chemical ValidationIn-Process ControlsCleaning ValidationComputerized SystemsProcedures and PersonnelValidation of Sterile Bulk ProductionConclusionReferencesQuality of Active Pharmaceutical Ingredients, Michael C. Vander Zwan and Carlos YuraszeckIntroductionThe ProductThe ProcessThe FacilitiesThe PeopleThe Quality Management DepartmentThe Regulatory AuthoritiesThe RegulationsPart I: Defining and Ensuring the Quality of the Active Pharmaceutical IngredientPart II: The Regulations for QualityQ7 Section I: ‘‘Introduction’’Q7 Section 2: ‘‘Quality Management’’Q7 Section 3: ‘‘Personnel’’Q7 Section 4: ‘‘Buildings and Facilities’’Q7 Section 5: ‘‘Process Equipment’’ Q7 Section 6: ‘‘Documents and Records’’Q7 Section 7: ‘‘Materials Management’’Q7 Section 8: ‘‘Production and In-Process Controls’’Q7 Section 9: ‘‘Packaging and Identification Labeling of APIs and Intermediates’’Q7 Section 10: ‘‘Storage and Distribution’’Q7 Section 11: ‘‘Laboratory Controls’’Q7 Section 12: ‘‘Validation’’Q7 Section 13: ‘‘Change Control’’Q7 Section 14: ‘‘Rejection and Reuse of Materials’’ Q7 Section 15: ‘‘Complaints and Recalls’’Q7 Section 16: ‘‘Contract Manufacturers (Including Laboratories)’’Q7 Section 19: ‘‘APIS for Use in Clinical Trials’’Part III. The Quality Control and Quality Assurance DepartmentEnvironmental Control, Bruce WallingtonIntroductionLicense to OperateEnvironmental Management SystemsEnvironmental ScopingPermit Project SchedulesEnvironmental ProfileEnvironmental DossierApplicable Regulatory RequirementsControl Equipment PlanOperational FlexibilityManagement of ChangeSustainabilityGreen Chemistry InitiativesConclusionsReferencesThermochemical Process Safety—An Introduction, Carlos B. RosasPreambleHazards, Risks, and Consequences—Definitions and an Actual Thermochemical ExampleThermochemical Events and Their Basis—EnergyThermochemistry, Heat Effects in Chemical Reaction Processing, and CalorimetryThermochemical Hazards and Their AssessmentExothermic Reactions—Runaways and Unintended ReactionsThermochemical Hazard Avoidance, Prevention, and Risk ReductionIn ClosingReferencesDesign and Operating Practices for Safety, Stanley S. GrosselIntroductionFlammable/Combustible Liquids Storage and HandlingToxic Gas Storage and HandlingWater-Reactive ChemicalsCyanides Storage and HandlingHandling and Containment of APIsReactor Design and OperationPresure Relief and Effluent HandlingFire and Explosion ProtectionReferencesPlant Operations, Stanley H. NusimPlant OrganizationBatch Versus Continuous OperationsDedicated Versus Shared Manufacturing FacilitiesShift OperationsClean RoomCost ControlEmployee SafetySterile Bulk Active Pharmaceutical Ingredient Production, James Agalloco and Phil DeSantisIntroductionTypical Sterile Bulk Active Pharmaceuticals Ingredients and ExcipientsSterile Synthesis StepsConsiderations for Sterile Bulk Pharmaceutical ChemicalBuildings and FacilitiesPersonnel Training and QualificationContainer-Closure SystemsTime LimitationsAseptic Processing SimulationSterilizationLaboratory ControlsSterile ExcipientsIn-Process Sterilization of Bulk APIs and ExcipientsOther AttributesConclusionReferencesBiological Production of Active Pharmaceutical Intermediates, Max J. Kennedy, Randolph L. Greasham, and Stephen W. DrewIntroductionMicroorganismsBioreactorsFermentor DesignRegulation of Microbial Metabolism and Product FormationGrowth MediaMedium ComponentsMedium SterilizationGrowth KineticsSeed TrainReducing Variability and Throughput Time in Inoculum DevelopmentDownstream ProcessingSolvent ProcessingScale-Up to Manufacturing Strategies for Process Development and Scale-Up of Biological ProductsBioanalyticsProduction of a Recombinant Vaccine in Saccharomyces CerevisiaeTriggering Immune ResponseEstimates of Capital and Operating Costs for Manufacture from Fermentation or Cell CultureContract Manufacturers for API from Fermentation or Cell CultureContract Development Organizations and Contract Manufacturing Organizations for Fermentation and Cell Culture Biological ProductsWhat Happens if the Fermentation or Cell Culture Does not Perform as You Expect?ReferencesSupply Management, Victor J. CatalanoIntroduction to Supply ManagementProduction PlanningInventory ManagementPurchasing/Supply ManagementDistribution/TransportationInformation TechnologyQuality ManagementReferenceFurther ReadingEquipment Maintenance and Reliability, Kaizad P. SunavalaIntroductionStrategic Plan (2)Reliability Fundamentals Program SummaryReferencesIndex
