Manufacturing of Quality Oral Drug Products: Processing and Safe Handling of Active Pharmaceutical Ingredients (API)

Cover
Half Title
Title Page
Copyright Page
Table of Contents
Preface
Acknowledgments
Introduction
Authors
Chapter 1 Milling and Charging
	Milling
	Charging
Chapter 2 Granulation
	PK Blender Manufacturing Process
		Charging
		Granulating
		Milling
		Final Blending
		Post Blending
	Laboratory Analysis of Granulation
	Critical Elements of the Process
Chapter 3 Compression
	Core Compression Manufacturing Process
		Line Preparation and Sign-Off
		Laboratory Analysis of Cores
Chapter 4 Sub-coating
	Sub-coating Manufacturing Process
	Critical Elements and Trouble Shooting
Chapter 5 Membrane Coating
	Membrane-Coating Manufacturing Process: For Acetone-Based Solutions
	Critical Elements of Coating Process
		Aqueous Coaters
	Membrane-Coating Manufacturing Process: For Methylene Chloride-Based Solution
Chapter 6 Drilling
	In-Process Testing
	Critical Elements of the Drilling Process
Chapter 7 Drying
	Laboratory Analysis of Cores
Chapter 8 Overcoating
	Overcoating
	Color Overcoating
	Laboratory Analysis
	Critical Elements and Trouble Shooting
Chapter 9 Printing
Chapter 10 Sorting and Packing
	Critical Elements of the Sorting Process
	Packing Overview
Chapter 11 Capsule Filling
Chapter 12 Safe Handling of APIs and Drugs
	Definitions
	Hierarchy of Controls
	Administrative Controls
		Personal Protective Equipment (PPE)
	Hazard Assessment
	Risk Assessment
		Control Strategy
		Hazard Communication
	Industrial Hygiene (IH) Monitoring Guidelines
		Definitions
		Surrogate Monitoring
		Data Interpretation and Handling
		Further Notes
		References
	Cleaning of Glove Boxes and Biosafety Cabinets
		Definitions
	Facts about BSC
		Prevention of Exposure
	Personal Protective Equipment Requirements
	Pre-safety Checklist
	Cleaning and Decontamination
	Maintenance, Service, and Certification of BSCs
		References
	Facility/Infrastructure Considerations: Laboratory Operations
	Facility/Infrastructure Considerations: Production and Pilot Plant Operations
	Containment Control Guidelines/Engineering Matrix: Laboratory Operations
		Comment
	Containment Control Guidelines/Engineering Matrix: Production and Pilot Plant Operations
		Comment
Chapter 13 Data Integrity Compliance
	Process/Procedure: Inventory of Systems
	Process/Procedure: Determination of 21 CFR Part 11/Data Integrity Applicability
		Process/Procedure: 21 CFR Coverage Assessment
		Process/Procedure: 21 CFR Part 11/Data Integrity Gap Analysis
Chapter 14 Guidelines for Statistical Procedure
	Process Capability Analysis
	Long-Term Studies
	Acceptance Sampling
		Attribute and Variable Sampling Plans
		Variable Sampling Plans: ANSI Z1.9
		Normality
		Transformation of Non-normal Data (Normalization)
	Protocol Sampling
		Failure Mode and Effect Analysis (FMEA)
		Calculating or Recalculating Control Limits
Chapter 15 Calibration
	Contingency Plan/Disaster Recovery
Chapter 16 Clean-In-Place (CIP) Systems
	PTS
	Mix Tank and Discharge Piping
	STS Circuit
	Lifecycle Requirements
		Product and Process User Requirements
		Process Quality Requirements
		Process Parameter Requirements
		Installation User Requirements
		Operational Requirements
	Functions (FCT)
	Process Control System
	Equipment Alarms and Warnings
	Data
	Power Loss and Recovery
	Cleaning and Sanitizing
	Material/Waste Movement Requirements
	Maintenance Requirements
	Training and Documentation Requirements
Chapter 17 Cleaning Validation
	New Products and Product Changes
	Cleaning Processes and Changes
	Risk Assessment/Matrix Approach
	Matrix Development
	Cleaning Processes (Manual and Automated)
	Critical Process Parameters/Critical Quality Attributes
	Cleaning Validation Life Cycle: Cleaning Method Development
	Strategy for Process Controls
	Worst-Case Identification: Product/Component
		Equipment
	Validation Tests/Inspections: Visual Inspection
	Chemical Testing
	Microbiological Testing
	Endotoxin Testing
		Sampling Methods
			Direct Swab Sampling
			Rinse Sampling
	Coupon Testing
	Sampling Sites
		Acceptance Criteria
		Residual Levels
		Endotoxin Levels
		Microbiological Levels
			Cleaning Agents/Sanitizer Validation Studies
	Hold Time Development
		Dirty Hold Time
		Clean Hold Time
		Additional Hold Times/Cleaning Frequencies
	Continuous Process Verification
	Failure Investigations
Chapter 18 Manufacturing Process Validation
Chapter 19 Risk-Based Life Cycle Management
	Process Flow Diagram
	Essential Requirements (Requirements List)
	Linkage Document (Trace Matrix): Historical Document
	Process Failure Mode and Effects Analysis (pFMEA)
	Control Plan
		Assessment of Process Flow Diagram/pFMEA/ Control Plan Documents
		Assessment of Test Method Validation Documents
		Assessment of Process Validation and Manufacturing Instruction Documents
		Product Performance Data
		Production Process Data Collection (PPDC)
		Assessment of Risk Controls (Control Strategy)
			Maintaining “Living Documents” Updates to the Playbook Documentation
			Document Management
		Playbook Updates/Approvals (Live System)
		RBLCM Data Collection
Chapter 20 pFMEA Manufacturing Procedure
Chapter 21 Analytical Methods Development, Validation, and Transfer
	HPLC
		HPLC: Case Study
		Guidelines: Formulating Mobile Phases for Various Reversed Phase HPLC Columns
		Case Study: HPLC Columns Comparison
	HPLC Columns
		High Efficiency and Symmetrical Peaks
		Universal Reversed-Phase HPLC Column Simplifies
Method Development
	HPLC Troubleshooting and Guide
		Isolating Pump Problems
		Column Protection
		Getting the Most from Analytical Column
		Solving Detector Problems
		Column Heater, Recorder
		Keeping Accurate Records
		Further Recommendations
		Restoring Column’s Performance
		Nonbonded Silica Columns Exposed to Polar Solvent
		Performance Evaluation Mixes for HPLC Columns
		Preventing and Solving Common Hardware Problems
			Preventing Leaks
		Unclogging the Column Frit
Appendix I: API Terms
Appendix II: Impurities – FDA Directive
References
Bibliography
Index