Pharmaceutical Packaging Handbook provides a complete overview of the role that packaging plays in the development and delivery of pharmaceuticals and medical devices. Supplying a thorough examination of the industry in size and scope, the book covers drug dosage forms, vaccines, biologically produced products, and medical foods.
Features:
- Discusses how packaging is designed and integrated into the product development cycle
- Provides an overview of the regulatory environment procedures
- Describes the materials used to package pharmaceuticals, including glass, metal, plastics, flexible films, rubber, and elastomers
- Examines new hybrids used for packaging
- Explores the processing techniques used with the materials to produce pharmaceutical containers
- Discusses some of the strengths and weaknesses of the processes used for container fabrication
- Explains retort, aseptic, gas, and radiation sterilization of product
- Reviews labeling and design for pharmaceuticals, including how labels are produced, materials used, and production techniques
Complete and straightforward, the book lists information in an easy to follow fashion, making it a complete standalone reference for anyone working in the pharmaceutical industry.
Preface
Introduction to the Pharmaceutical Industry: An Overview
Introduction
General Aspects of Drug Packaging
Brief History
General Business Overview of the Pharmaceutical Industry
General Industry Challenges and Trends
The Evolution and Structure of the Pharmaceutical Business
Therapeutic Areas of Concentration
General Worldwide Pharmaceutical Trends
Cost and Pricing Trends
Generic Products
OTC Products
Definition of a Drug
The Differences between Pharmaceutical and Food Packaging
Drug Regulations
The Function of Packaging
Trends in Pharmaceutical Packaging
Current Trends in Packaging
Influences Impacting Packaging
Summary
References
Pharmaceutical Dosage Forms and Their Packaging
Requirements
Introduction
Stability
Chemical Change
Thermal Protection
Chemical Reactions
Moisture Protection—Protecting the API from
Hydrolysis
Oxidation—Reactions with Oxygen
Light Protection
Mathematical Methods and Accelerated Methods for Assessing
Shelf Life
Purity and Sterility
Drug Purity
Quality Assurance
Drug Sterility
Drug Physiology
Oral Administration of Drug Products—Gastrointestinal
Methods
Direct Injection of Drug Products
Topical Administration of Drugs, Transdermal Methods
Topical Administration
Administration of Drugs through Mucus Membranes, Inhalation, and Nasal Administration
Rectal Administration of Drugs
Dosage Forms of Drugs
Solids
Liquids
Gases
Summary
Further Reading
References
Vaccines and Biologically Produced Pharmaceuticals
Introduction
Biologic Products
Biologic Drugs
Vaccines
Types of Vaccines
Summary
Further Reading
References
Medical Foods
Introduction
History of Medical Foods
Regulatory Requirements of Medical Foods
Medical Foods
Composition and Formulation of Medical
Nutritional Products
Nutritionally Complete Products
Nutritionally Incomplete Products
Formulas for Metabolic or Genetic Disorders
Oral Rehydration Solutions
Enteral Packaging
Medical Food Administration to the Patient
Tube Feeding
Parenteral Nutrition
Parenteral Formulations for Intravenous Feeding
Infant Formulas
Prenatal Nutritional Products
Juvenile Nutritional Products
Medical Foods: Legislative Overview and Regulations
Infant Formula Regulation
Manufacture of Infant Formula and Medical
Nutritional Products
Retort Processing
Aseptic Processing
Cold Aseptic Sterilization—Aseptic Filtration
Aseptic Manufacturing Equipment
Aseptic Package Sterilization
Mechanical Processes
Thermal Processes
Irradiation Processes
Chemical Processes
Combination Processes
Aseptic Packaging Systems
Fill and Seal
Erect, Fill, and Seal
Form, Fill, and Seal
Thermoform, Fill, and Seal
Blow Mold, Fill, and Seal
Bulk Storage and Packaging
Basic Principles of Thermal Processing
Thermobacteriology
Heat Exchange/Heat Transfer
Deaeration
Aseptic Surge Tanks
Processing Authority
The U.S. FDA/CFSAN Grade A Pasteurized Milk
Ordinance
USDA Requirements
Sterilization Technologies under Development
Future Trends
Further Reading
References
The Regulatory Environment
Introduction
Stages in the Identification and Qualification of a Drug
Drug Discovery
Preclinical Testing
Investigational New Drug Review
Clinical Trials
Phase I Clinical Trials
Phase II Clinical Trials
Phase III Clinical Trials
FDA Approval
Post-Marketing Surveillance and Phase IV Studies
The Regulatory Arena
The United States Food and Drug Administration
A General Overview of the Drug Approval Process
The Drug Packaging Approval Process
Current Good Manufacturing Practices
Validation
Electronic Data Submission, Electronic Specifications
Systems, Elimination of Paper Records 21 CFR Part 11
Electronic Records
Change Control
Structured Product Labeling: Enterprise Content Management,
Digital Asset Management
The United States Pharmacopeia-National Formulary
The United States Pharmacopeia Dictionary
Consumer Product Safety Commission
Summary
Further Reading
References
Pharmaceutical Packaging Materials
Introduction
Glass Pharmaceutical Packaging
Glass Composition
Types of Glass Used for Pharmaceutical Packaging
USP Type I Glass
USP Type II Glass
USP Type III Glass
USP Designation NP Glass
Glass as a Pharmaceutical Packaging Material
Metal Pharmaceutical Packaging
Tinplate
Can Coatings for Tinplate and Aluminum Cans
Aluminum
Metals as Pharmaceutical Packaging Materials
Aerosol Cans
Plastic Pharmaceutical Packaging
Plastics Overview and Definition
Introduction to Plastics
A Plastic Primer
Polymer Descriptions
Classes of Polymers
Determinants of a Polymer’s Properties
Chemical Attributes of Polymers
Chemical Bonding
Molecular Shape and Intramolecular Forces
Viscoelastic Behavior
Physical Properties of Polymers
Temperature Dependence on Reaction Rates
Plastics as Drug Packaging Materials
Density Differences/Consumer Preference for
Plastic/Easy Handling
Design Freedom
Plastic Disadvantages
Chemical Inertness/Stress Cracking/Additives/Electrical
Properties
Common Plastic Pharmaceutical Packaging Materials
Polyethylene Polymers
High-Density Polyethylene
Low-Density Polyethylene
Linear Low-Density Polyethylene
Polyethylene Restrictions in Drug Packaging
Other Ethylene Polymers
Ethylene Vinyl Acetate
Ethylene Acrylic Acid
Ionomers
Ethylene Vinyl Alcohol
Polyvinyl Alcohol
Polypropylene
Catalyst Background for Ethylene and Propylene Polymers
Polyvinyl Chloride
Polyvinylidene Chloride Copolymers
Fluoropolymers
Polystyrene
Other Styrene-Modified Copolymers
Polyamides (Nylon)
Polyester
Polyethylene Terephthalate
Amorphous PET
Crystallized PET
PET Films
Glycol-Modified Polyester
Polyethylene Naphthalate
Polycarbonate
Polyurethane
Acrylonitrile Polymers
Rubbers and Elastomers
Summary
Further Reading
References
Medical Device Packaging
Introduction
Regulation of Medical Devices
Medical Device Definitions and Testing Standards
510 (k) Pre-market Notification
Pre-market Approval of a Medical Device
Good Manufacturing Compliance (CGMP)
Establishment Registration
Medical Device Reporting
Harmonization of Standards for Terminally Sterilized Medical
Device Packaging—United States and Europe
An Overview of a Package Validation
Major Elements of a Package Validation
Validation Testing, Process Sampling, and Validation Reporting
Sample Size Testing
Test Methods
Distribution Testing
Accelerated Aging
ISO Standards
References
Container Fabrication
Introduction
Glass Containers
Blow Molding of Glass Containers
Annealing and Treating—Glass Finishing
Tubular Glass Fabrication—USP Type I Glass
Metal Containers—Cans
Draw–Redraw Cans
Draw and Iron Cans
Welded Cans—Three-Piece Cans
Metal Tubes
Plastic Containers
Bottles and Vials
Thermoforming of Pharmaceutical Containers
Blister Packaging
Large Thermoformed Packages—Strip, Tray, and Clamshell
Packages for Medical Devices
Pouches
Form, Fill, and Seal Bottles
Plastic Tubes
Laminated Tubes
Summary
Further Reading
References
Sterilization Technology
Introduction
Overview of Sterilization Requirements
Heat Sterilization Techniques
Sterilization Using Steam and Pressure (Autoclave)
Sterilization by Boiling
Dry Heat
Other Heat Sterilization Methods
Chemical Sterilization
EtO Sterilization
Other Chemical Sterilants
Radiation Sterilization
g-Ray Sterilization
X-Rays and Electron Beam (E-Beam) Sterilization
UV Light
Sterile Filtration
Regulatory Overview
Monitoring Sterilization Processes
Mechanical, Chemical, and Biologic Indicators
Summary
References
Container Closure Systems: Completing All Types of Filled
Pharmaceutical Containers
Introduction
Closure Functions
Protection
Containment
Complete and Positive Sealing
Access (The Ability to Open and Close a Package Repeatedly and Safely)
Consumer Communication
Display
Metering and Measuring
Types of Closures
Closures for Metal Cans
Bottles and Jars
Threaded Closures
Friction-Fit Closures
Crown Closures
Snap-Fit Closures
Press-on Vacuum Caps
Vial Stoppers
Flanged Plug Elastomeric Stoppers
Flanged Hollow Plug with Cutouts for Lyophilized Products
Flanged Elastomeric Plug with Plastic Overseal
Metal Closure with an Elastomeric Disk
Elastomeric Closure Performance
Tube Closures
Specialty Closures
Dispensing Closures and Closures with Applicators
Fitment Closures
Spray and Pump Dispensers
Single-Dose Closures
Compliance (Adherence)
Closure Liners
Composition of Closure Liners
Linerless Closures
Child-Resistant Closures
Child-Resistant Testing of Closures—An Overview
Design of Child-Resistant Closures
Combination Closures
Aerosol Closures
Non-Reclosable Packages
Pouches
Tamper-Evident Packaging Closures
Ease of Opening
Capsule Problems
Heat Sealing
Peelable Seals
Summary
References
Labels and Labeling
Introduction
History of Drug Labels
Labeling Requirements
Prescription Drug Labeling
Label Information
Drug Facts Labeling—OTC Pharmaceutical Products
NDC Number—The National Drug Code
Label Construction
Types of Labels
Label and Package Printing
Overview of Bar Code Administration: GS1 Designations
Universal Product Code Numbers
The Global Trade Item Number
Bar Codes
GS1 Standards Organization
EAN International Article Numbering Association and UCC
Two Dimensional Codes (2-D Data Matrix and other
Matrix Codes)
RSS Codes
RSS-14
RSS Limited
RSS Expanded
Composite Components of the Codes
Composite Code A (CC-A)
Composite Code B (CC-B)
Composite Component C (CC-C)
Code Category Overview
Narrow-Width Bar Code Symbologies
Pulse-Width Modulated Bar Code
Multi-Width Modular Codes
References
Issues Facing Modern Drug Packaging
Introduction
Compliance or Adherence to Drug Regimens
Unit Dose Packaging
Anticounterfeiting Packaging
Detailed Product Information
Transaction Details
Environmental Issues
Packaging and the Environment
United States Recycling Programs
Collection Methods for Recycling
European Recycling Programs
Plastic Packaging and the Environment
Recycling Rates for Plastic Packaging
U.S. Municipal Solid Waste: An Overview
Infectious Waste
Biodegradable Plastics
Biodegradable Materials
Starch-Based Plastics
Lactic Acid Polymers
Polyesters
Other Biodegradable Polymers
Naturally Occurring Biodegradable Polymers
Other Pharmaceutical Packaging Issues
References
Glossary of Terms
Bibliography
Index
Biography
Edward Bauer
