This book provides an understanding of what is required to engineer and manufacture drug products. It bridges established concepts and provides for a new outlook by concentrating and creating new linkages in the implementation of manufacturing, quality assurance, and business practices related to drug manufacturing and healthcare products.
This book fills a gap by providing a connection between drug production and regulated applications. It focuses on drug manufacturing, quality techniques in oral solid dosage, and capsule filling including equipment and critical systems, to control production and the finished products. The book offers a correlation between design strategies and a step-by-step process to ensure the reliability, safety, and efficacy of healthcare products. Fundamentals of techniques, quality by design, risk assessment, and management are covered along with a scientific method approach to continuous improvement in the usage of computerized manufacturing and dependence on information technology and control operations through data and metrics.
Manufacturing and Quality Assurance of Oral Pharmaceutical Products: Processing and Safe Handling of Active Pharmaceutical Ingredients (API) is of interest to professionals and engineers in the fields of manufacturing engineering, quality assurance, reliability, business management, process, and continuous improvement, life cycle management, healthcare products manufacturing, pharmaceutical processing, and computerized manufacturing.
Author(s): Sam A. Hout
Publisher: CRC Press
Year: 2022
Language: English
Pages: 208
City: Boca Raton
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
