Medical Gases E-Book

Hartwig Müller

• Herausgeber: Wiley-VCH
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 276

Veröffentlichungsjahr: 2015

Beschreibung

Covering the entire spectrum of medical gases, this ready reference offers a comprehensive overview of production, medical gas equipment, medical gas verification, and medical gas safety standards. With a clear focus throughout on safety, the text recommends environmentally responsible manufacturing practices during each step of the process: manufacture, storage, transport, distribution, and in applications. It also discusses standards and regulations, in particular those of the European Union. An essential guide for researchers and professionals whose work includes the manufacture, handling, or use of medical gases.

Leseprobe

Table of Contents

Cover

Title Page

Related Titles

Copyright

Preface

General Remarks

Medicinal Gases

Chapter 1: Medicinal Gases – Manufacturing

1.1 Where Do the Gases Come from?

Chapter 2: Pressure Vessels and Their Accessories

2.1 Transportable Pressure Receptacles: Pressure Cylinders

2.2 Non-transportable Pressure Receptacles: Stationary (Pressure) Tanks for Cryogenic Liquids

2.3 Medicinal Gas Pipeline Systems (MGPS)

Chapter 3: Analytical Methods for Gases (as Described in Ph. Eur.)

3.1 Sampling

3.2 Gas Analytical Methods

Chapter 4: Monographs for Gases in the European and National Pharmacopoeias

4.1 European Pharmacopoeia Specifications

Chapter 5: Production of Medical Gases — Special Handling to Comply with GMP Rulings

5.1 History – Gases Becoming Medicinal Products

5.2 Classification of Gases or Gas Mixtures as Medicinal Products

5.3 Basic Requirements (Volume 4, Part I) ([79] – GMP-Guidelines)

5.4 Basic Requirements for Active Substances Used as Starting Materials (Part II of the GMP-Guide)

5.5 GMP-Related Documents (Part III of the GMP Guide)

Chapter 6: Requirements of the New Good Distribution Practice (GDP)

6.1 Gas in Packages – No Difference from Other Medicinal Products

Chapter 7: Safe Handling of Gases

7.1 Safe Handling of Gases

7.2 Safety and Pressure

7.3 The Compound's Chemical Properties

7.4 Cryogenic Liquids: Low Temperature and Vast Development of Gas

7.5 Gases Tapped from Piping Systems: Cross-Contamination and Contamination by Insufficient Handling, Memory Effects

References

Abbreviations

Index

End User License Agreement

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Guide

Cover

Table of Contents

Preface

Begin Reading

List of Illustrations

Chapter 1: Medicinal Gases – Manufacturing

Figure 1.1 Jan Baptist van Helmont (1577–1644) [1].

Figure 1.2 Air separation: schematic drawing [8].

Figure 1.3 Different layers in the terrestrial atmosphere [10].

Figure 1.4 View of an air separation plant (Air Liquide).

Figure 1.5 Refilling LIN containers with cryogenic liquid (own picture).

Figure 1.6 Separation of krypton and xenon [13].

Figure 1.7 Separation of helium from natural gas [22].

Figure 1.8 Helium tank trailer (own picture).

Figure 1.9 Superconducting MRT (magnetic resonance tomography) (15).

Figure 1.10 Schematic of the steam reforming process (1).

Figure 1.11 Separation column for the purification of carbon monoxide [24].

Figure 1.12 Purification of carbon dioxide.

Figure 1.13 Synthesis of nitric oxide.

Figure 1.14 Synthesis of nitrous oxide (N

2

O).

Figure 1.15 Equations of state for carbon dioxide [32].

Figure 1.16 Calibration of instruments with calibration gases [33].

Chapter 2: Pressure Vessels and Their Accessories

Figure 2.1 Ratio content to package – improvement by development of materials [36].

Figure 2.2 Medicinal gas cylinders (Air Liquide Medical).

Figure 2.3 Manufacture of steel cylinders [37].

Figure 2.4 Schematic of Al cylinder process [45].

Figure 2.5 Cleaning methods for aluminum cylinders.

Figure 2.6 Small cryo-container [14].

Figure 2.7 Wrapped cylinder (own picture).

Figure 2.8 Cylinder contaminated with blood.

Figure 2.9 Pin-index-type valves [49].

Figure 2.10 Silhouettes of different valve types [49].

Figure 2.11 Typical washers for different gases, made from different materials, packed in plastic to avoid contamination with grease.

Figure 2.13 Ordinary standard valve [51].

Figure 2.12 Valve with RPV/NRV cartridge to avoid contamination during filling (own picture).

Figure 2.14 Integral valve (Air Liquide, [51]).

Figure 2.15 Integral valve (TAKEO®) with digital indicator for the residual content in the cylinder (Air Liquide, [52]).

Figure 2.16 Stationary container for cryoliquids [14].

Figure 2.17 Truck refilling a tank [50].

Figure 2.18 Transportable mini-container for cryoliquids [14].

Figure 2.19 Safety valves at a cryogenic tank [50].

Figure 2.20 Ice coating on a vaporizer.

Figure 2.21 Ice coating on a valve box.

Figure 2.22 Minimum distances for safe positioning of a cryogenic tank [50].

Figure 2.23 Scheme of an MGPS in a hospital (Graphics: Air Liquide).

Figure 2.24 Influence of forming gas on the inner surface of the pipes (a) good quality and (b) poor quality).

Figure 2.25 Key Elements a Medical Gas Pipeline System (own graphics).

Figure 2.26 Typical sourcing, picture shows the backup feed with cylinders.

Figure 2.27 Feeding unit from the outside/with open cover.

Figure 2.28 Copper piping in a hospital (during construction).

Figure 2.29 Shutoff valve and NIST connection in area control unit/control closing box (6).

Figure 2.30 Terminal units (German design, six corners for oxygen, four corners for medical air).

Chapter 3: Analytical Methods for Gases (as Described in Ph. Eur.)

Figure 3.1 Gas cylinder with a permanent gas.

Figure 3.2 Gas cylinder with liquefied gas under pressure and different filling rates [55].

Figure 3.3 Typical easily built sampling unit used both for liquid and permanent gases [54].

Figure 3.4 Tapping of liquid phase from a cylinder by turning it upside down, or by using a dip tube, or by using a dip tube and helium pressure [24].

Figure 3.5 Schematic Flow of a cryogenic sampler (Cosmodyne).

Figure 3.6 Hempel burette [56].

Figure 3.7 Principle of NDIR spectroscopy [59].

Figure 3.8 Typical chromatogram (hydrocarbons separated with a Porapak® Column) [62].

Figure 3.10 GC-Lab in the eighties of the last century (Air Liquide).

Figure 3.9 Typical GC switch port (right).

Figure 3.11 Principle of chemiluminescence spectroscopy [62].

Figure 3.12 Principle of a paramagnetic detector [66].

Figure 3.13 Principle of a P

2

O

5

H

2

O detector.

Figure 3.14 Schematic Flow-sheet of a fluorescence analyzer [68].

Figure 3.15 Drawing from the patent of Lamb and Hoover [70].

Figure 3.16 Examples for test tubes: single-layer and multiple-layer test tubes [70].

Figure 3.17 Dräger tube with ampoule inside [70].

Figure 3.18 Example for coloring of a tube [70].

Chapter 5: Production of Medical Gases — Special Handling to Comply with GMP Rulings

Figure 5.1 Medical oxygen filling in steel cylinders (early 1950', Picture: Messer).

Figure 5.2 Truck for liquid transport of oxygen in the early 1960s (Messer).

Figure 5.3 Preparation area in a medical filling plant.

Chapter 6: Requirements of the New Good Distribution Practice (GDP)

Figure 6.1 Cylinder truck.

Figure 6.3 Subcontractor's truck (Picture: Santrans GmbH, Germany).

Figure 6.2 Bulk tanker (own Picture: Air Liquide Healthcare).

Chapter 7: Safe Handling of Gases

Figure 7.1 Returning cylinders.

Figure 7.2 Cylinder label according to CLP [119] CLP-Symbols are replaced by ADR-placards.

Figure 7.3 Cylinder colors according EN 1089-3 indicating the primary danger.

1

Figure 7.4 Cylinder colors according EN 1089-3 for medicinal gases (cylinder always white).

1

Figure 7.6 Example for erosion after contact with cryogenic temperatures.

Figure 7.6 Warning sign: asphyxiation.

Figure 7.7 Nitrogen enrichment near the evaporation source (EIGA, [111]).

Figure 7.8 Control box for an MGPS (example for level box).

List of Tables

Chapter 1: Medicinal Gases – Manufacturing

Table 1.1 Composition of ambient air, typical components [4].

Table 1.2 Physical properties of gases (I, [14]).

Table 1.3 Exploitation of natural gas wells for helium [22].

Table 1.4 Physical properties of gases (II) [14].

Table 1.5 Physical properties of gases (III) [14].

Chapter 2: Pressure Vessels and Their Accessories

Table 2.1 Commonly used aluminum alloys (AA wxyz, acc. EN 1975:1999 + A1:2003).

Table 2.2 European Valve Connections (a, Continued).

Chapter 3: Analytical Methods for Gases (as Described in Ph. Eur.)

Table 3.1 Gas analytical methods as described in the Pharm. Eur. [57].

Table 3.2 Reference gases as described in the Ph. Eur.

Table 3.3 List of components, appropriate detectors, and columns for separation (Ph. Eur.).

Chapter 4: Monographs for Gases in the European and National Pharmacopoeias

Table 4.1 Monographs for medicinal gases in the European Pharmacopoeia (excerpt of the essentials).

Chapter 5: Production of Medical Gases — Special Handling to Comply with GMP Rulings

Table 5.1 Status of medicinal gases as medicinal products in the European Union (own source).

Table 5.2 Key features of QC [88], p. 2].

Table 5.3 Example for a protocol of a long-term stability program [88], p. 5].

Table 5.4 Example of sampling plans for cylinder filling.

Table 5.5 Procedures for quality defect investigation [90].

Table 5.6 Application of Part II to API manufacturing [92].

Table 5.7 Contents of the Site Master File (SMF, acc. [97]).

Table 5.8 Contents of the Batch Certificate.

a

Chapter 7: Safe Handling of Gases

Table 7.1 Risk evaluation matrix –

probability

– keywords in bold [109].

Table 7.2 Risk evaluation matrix –

severity

– key words in bold

Table 7.3 Example of an assessment matrix [109].

Table 7.4 Tare weights and dimensions of commonly used cylinder sizes

a

Table 7.5 Important H- and P-statements for common gases in German, English, and French.

Mozzarelli, A.A. (ed.)

Chemistry and Biochemistry of Oxygen Therapeutics – From Transfusion to Artificial Blood

2011

Print ISBN: 978-0-470-68668-3; also available in electronic formats

ISBN: 978-1-119-97542-7

ISBN: 978-1-119-97620-2

Blumberg, L.M.

Temperature-Programmed Gas Chromatography

2010

Print ISBN: 978-3-527-32642-6; also available in electronic formats

ISBN: 978-3-527-63214-5

Hartwig Müller

Medical Gases

Production, Applications and Safety

Author

Gartenstr. 24

47506 Neukirchen-Vluyn

Germany

Cover

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Preface

Medicinal gases are gases used in the medical environment. Their range is defined differently by the most important pharmacopoeias, the European, the American, and the Japanese Pharmacopoeia. The defined gases and the permitted concentrations of their main impurities differ slightly in most of the pharmacopoeias, as do the analytical methods.

This is quite surprising because medicinal gases are comparable simple molecules (or atoms, in the case of argon, helium, and xenon) and their manufacturing and purifying methods have been known for more than 100 years.

In spite of their widespread use, medicinal gases remained a part of specialist knowledge for over a century. Starting from the 1980s, major efforts were made in Europe, to tailor these gases with specific limits and properties, and this found a place in several national pharmacopoeias and the European Pharmacopoeia.

With the long experience of having worked with and worked in several expert groups for medicinal gases for more than 30 years, the author's aim is to summarize the different developments leading to the present status in the description of medicinal gases.

It is the intention of the author to introduce specialist knowledge of these gases to a new generation of pharmacists, engineers, and medical doctors. A fascinating class of substances, they require special handling to gain the full benefit of their unique properties.

The present book should help professionals keep things simple where required and to take special precautions where past experience has revealed risks, thus requiring a risk-oriented approach. The book is not to be taken as a set laws, but is meant for the purpose of guidance only.

August 2014Hartwig Müller Neukirchen-Vluyn

General Remarks

Medicinal Gases