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Monday, August 15, 2011

Dilute Nitride Semiconductors

by: Mohamed Henini

Dilute Nitride Semiconductors library.nu #16914

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Book Description:
# This book contains full account of the advances made in the dilute nitrides, providing an excellent starting point for workers entering the field. # It gives the reader easier access and better evaluation of future trends, Conveying important results and current ideas # Includes a generous list of references at the end of each chapter, providing a useful reference to the III-V-N based semiconductors research community. The high speed lasers operating at wavelength of 1.3 m and 1.55 m are very important light sources in optical communications since the optical fiber used as a transport media of light has dispersion and attenuation minima, respectively, at these wavelengths. These long wavelengths are exclusively made of InP-based material InGaAsP/InP. However, there are several problems with this material system. Therefore, there has been considerable effort for many years to fabricate long wavelength laser structures on other substrates, especially GaAs. The manufacturing costs of GaAs-based components are lower and the processing techniques are well developed. In 1996 a novel quaternary material GaInAsN was proposed which could avoid several problems with the existing technology of long wavelength lasers. In this book, several leaders in the field of dilute nitrides will cover the growth and processing, experimental characterization, theoretical understanding, and device design and fabrication of this recently developed class of semiconductor alloys. They will review their current status of research and development. Dilute Nitrides (III-N-V) Semiconductors: Physics and Technology organises the most current available data, providing a ready source of information on a wide range of topics, making this book essential reading for all post graduate students, researchers and practitioners in the fields of Semiconductors and Optoelectronics.
Collection name: Electronics & Electrical
Table of Contents
* Cover
* Frontmatter
o Half Title Page
o Copyright
o Title Page
o Copyright
o Preface
o Contents
* Chapter 1. MBE Growth and Characterization of Long Wavelength Dilute Nitride III V Alloys
o 1.1. INTRODUCTION
o 1.2. MBE GROWTH OF DILUTE III V NITRIDES
o 1.3. DILUTE NITRIDE CHARACTERIZATION
o 1.4. ENERGY BAND AND CARRIER TRANSPORT PROPERTIES
o 1.5. ANNEALING AND N In NEAREST NEIGHBOR EFFECTS
o 1.6. SUMMARY
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 2. Epitaxial Growth of Dilute Nitrides by Metal-Organic Vapour Phase Epitaxy
o 2.1. INTRODUCTION
o 2.2. EPITAXIAL GROWTH OF GaInAsN-BASED STRUCTURES
o 2.3. LONG WAVELENGTH GaAs-BASED LASER PERFORMANCES
o 2.4. CONCLUSION
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 3. The Chemical Beam Epitaxy of Dilute Nitride Alloy Semiconductors
o 3.1. INTRODUCTION TO DILUTE NITRIDE SEMICONDUCTORS
o 3.2. THE CHEMICAL BEAM EPITAXIAL/METALORGANIC MOLECULAR BEAM EPITAXIAL (CBE/MOMBE) GROWTH PROCESS
o 3.3. CBE OF DILUTE NITRIDE SEMICONDUCTORS
o 3.4. FUNDAMENTAL STUDIES OF GaNxAs(1-x) BAND STRUCTURE
o 3.5. THE COMPOSITIONS AND PROPERTIES OF DILUTE NITRIDES GROWN BY CBE
o 3.6. CBE-GROWN DILUTE NITRIDE DEVICES
o 3.7. THE POTENTIAL FOR PRODUCTION CBE OF DILUTE NITRIDES
o 3.8. CONCLUSIONS
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 4. MOMBE Growth and Characterization of III V-N Compounds and Application to InAs Quantum Dots
o ABSTRACT
o 4.1. INTRODUCTION
o 4.2. MOMBE GROWTH AND CHARACTERIZATION OF GaAsN
o 4.3. RELATION OF In AND N INCORPORATIONS IN THE GROWTH OF GaInNAs
o 4.4. GROWTH AND CHARACTERIZATION OF GaAsNSe NEW ALLOY
o 4.5. APPLICATION OF GaAsN TO InAs QUANTUM DOTS
o 4.6. SUMMARY
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 5. Recent Progress in Dilute Nitride Quantum Dots
o 5.1. SELF-ORGANIZED QUANTUM DOTS
o 5.2. DILUTE NITRIDE QUANTUM DOTS
o 5.3. RECENT EXPERIMENTAL PROGRESS IN GaInNAs QDs
o 5.4. OTHER KINDS OF DILUTE NITRIDE QDs
o 5.5. SUMMARY AND FUTURE CHALLENGES IN DILUTE NITRIDE QDs
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 6. Physics of Isoelectronic Dopants in GaAs
o 6.1. NITROGEN ISOELECTRONIC IMPURITIES
o 6.2. THE FAILURE OF THE VIRTUAL CRYSTAL APPROXIMATION
o 6.3. PREVALENT THEORETICAL MODELS ON DILUTE NITRIDES
o 6.4. ELECTROREFLECTANCE STUDY OF GaAsN
o 6.5. RESONANT RAMAN SCATTERING STUDY OF CONDUCTION BAND STATES
o 6.6. COMPATIBILITY WITH OTHER EXPERIMENTAL RESULTS
o 6.7. A COMPLEMENTARY ALLOY: GaAsBi
o 6.8. SUMMARY
o 6.9. CONCLUSION
o REFERENCES
* Chapter 7. Measurement of Carrier Localization Degree, Electron Effective Mass, and Exciton Size in InxGa1 xAs1 yNy Alloys
o ABSTRACT
o 7.1. INTRODUCTION
o 7.2. EXPERIMENTAL
o 7.3. SINGLE CARRIER LOCALIZATION IN InxGa1 xAs1 yNy
o 7.4. MEASUREMENT OF THE ELECTRON EFFECTIVE MASS AND EXCITON WAVE FUNCTION SIZE
o 7.5. CONCLUSIONS
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 8. Probing the Unusual Band Structure of Dilute Ga(AsN) Quantum Wells by Magneto-Tunnelling Spectroscopy and Other Techniques
o 8.1. INTRODUCTION
o 8.2. RESONANT TUNNELLING DIODES BASED ON DILUTE NITRIDES
o 8.3. MAGNETO-TUNNELLING SPECTROSCOPY TO PROBE THE CONDUCTION BAND STRUCTURE OF DILUTE NITRIDES
o 8.4. ELECTRONIC PROPERTIES: FROM THE VERY DILUTE REGIME ( 0.1%) TO THE DILUTE REGIME
o 8.5. CONDUCTION IN DILUTE NITRIDES AND FUTURE PROSPECTS
o 8.6. SUMMARY AND CONCLUSIONS
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 9. Photo- and Electro-reflectance of III V-N Compounds and Low Dimensional Structures
o 9.1. PRINCIPLES OF ELECTROMODULATION IN ELECTRO- AND PHOTO-REFLECTANCE SPECTROSCOPY
o 9.2. BAND STRUCTURE OF (Ga,In)(As,Sb,N) BULK-LIKE LAYERS
o 9.3. (Ga,In)(As,Sb,N)-BASED QUANTUM WELL STRUCTURES
o 9.4. THE INFLUENCE OF POST-GROWN ANNEALING ON GaInNAs STRUCTURES
o 9.5. PHOTOREFLECTANCE INVESTIGATION OF THE EXCITON BINDING ENERGY
o 9.6. MANIFESTATION OF THE CARRIER LOCALIZATION EFFECT IN PHOTOREFLECTANCE SPECTROSCOPY
o REFERENCES
* Chapter 10. Band Anticrossing and Related Electronic Structure in III-N-V Alloys
o 10.1. INTRODUCTION
o 10.2. BAND ANTICROSSING MODEL
o 10.3. EXPERIMENTAL EVIDENCE OF BAND SPLITTING AND ANTICROSSING CHARACTERISTICS
o 10.4. NOVEL ELECTRONIC AND TRANSPORT PROPERTIES OF III-N-V ALLOYS
o 10.5. CONCLUSIONS
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 11. A Tight-binding Based Analysis of the Band Anti-Crossing Model and Its Application in Ga(In)NAs Alloys
o ABSTRACT
o 11.1. INTRODUCTION
o 11.2. NITROGEN RESONANT STATES IN ORDERED GaNxAs1 x STRUCTURES
o 11.3. ANALYTICAL MODEL FOR QUANTUM WELL CONFINED STATE ENERGIES AND DISPERSION
o 11.4. INFLUENCE OF DISORDER ON NITROGEN RESONANT STATES, E AND E IN GaNxAs1 x
o 11.5. CONDUCTION BAND STRUCTURE AND EFFECTIVE MASS IN DISORDERED GaNxAs1 x
o 11.6. ALLOY SCATTERING AND MOBILITY IN DILUTE NITRIDE ALLOYS
o 11.7. CONCLUSIONS
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 12. Electronic Structure Evolution of Dilute III V Nitride Alloys
o 12.1. INTRODUCTION
o 12.2. PHENOMENOLOGY OF DILUTE III V NITRIDES
o 12.3. EMPIRICAL PSEUDOPOTENTIAL METHODOLOGY
o 12.4. ELECTRONIC STRUCTURE EVOLUTION OF DILUTE NITRIDES
o 12.5. SUMMARY OF ELECTRONIC STRUCTURE EVOLUTION
o 12.6. PHENOMENOLOGY OF DILUTE NITRIDE QUATERNARIES
o 12.7. FUTURE CHALLENGES OF NEW NITRIDE MATERIALS
o 12.8. CONCLUSIONS
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 13. Theory of Nitrogen Hydrogen Complexes in N-containing III V Alloys
o 13.1. INTRODUCTION
o 13.2. THEORETICAL METHODS
o 13.3. N H COMPLEXES IN GaAsN ALLOYS
o 13.4. INTRINSIC N AND H IMPURITIES IN GaP AND GaAs
o 13.5. N H COMPLEXES IN InGaAsN
o 13.6. N H COMPLEXES IN GaPN
o 13.7. CONCLUSIONS
o REFERENCES
* Chapter 14. Dislocation-free III V-N Alloy Layers on Si Substrates and Their Device Applications
o ABSTRACT
o 14.1. INTRODUCTION
o 14.2. DISLOCATION GENERATION MECHANISMS IN LATTICE-MISMATCHED HETEROEPITAXY
o 14.3. LATTICE-MATCHED HETEROEPITAXY OF III V-N ALLOYS ON III V COMPOUND SEMICONDUCTORS
o 14.4. GROWTH OF DISLOCATION-FREE III V-N ALLOY LAYERS ON Si SUBSTRATES
o 14.5. DEVICE APPLICATIONS
o 14.6. SUMMARY
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 15. GaNAsSb Alloy and Its Potential for Device Applications
o ABSTRACT
o 15.1. INTRODUCTION
o 15.2. MBE OF THE GaNAsSb ALLOY
o 15.3. BANDS
o 15.4. ANNEALING EFFECT
o 15.5. QUINARY ALLOY
o 15.6. LONG-WAVELENGTH GaAs-BASED LASER
o 15.7. HBT
o 15.8. CONCLUSIONS
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 16. A Comparative Look at 1.3 m InGaAsN-based VCSELs for Fiber-optical Communication Systems
o ABSTRACT5
o 16.1. INTRODUCTION: 0.85 m VERSUS 1.3 m VCSELs
o 16.2. APPROACHES TO ACHIEVE 1.3 m VCSELs
o 16.3. 1.3 m VCSELs BASED ON InGaAsN
o 16.4. OUTLOOK
o 16.5. CONCLUSION
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 17. Long-wavelength Dilute Nitride Antimonide Lasers
o 17.1. INTRODUCTION
o 17.2. EPITAXIAL GROWTH SYSTEMS: MOVPE AND MBE
o 17.3. ION DAMAGE AND ANNEALING BEHAVIOR
o 17.4. GaInNAsSb EDGE-EMITTING LASERS
o 17.5. SPONTANEOUS EMISSION STUDIES
o 17.6. GaInNAsSb VCSELs
o 17.7. HIGH POWER LASERS BASED ON GaInNAs(Sb)
o 17.8. RELATIVE INTENSITY NOISE
o 17.9. GaInNAsSb ELECTROABSORPTION MODULATORS AND SATURABLE ABSORBERS
o 17.10. LASER RELIABILITY
o 17.11. SUMMARY
o ACKNOWLEDGEMENTS
o REFERENCES
* Chapter 18. Application of Dilute Nitride Materials to Heterojunction Bipolar Transistors
o ABSTRACT
o 18.1. INTRODUCTION
o 18.2. DESIGN CONSIDERATIONS FOR GaInNAs BASE HBTs
o 18.3. MATERIAL GROWTH AND DEVICE PROCESSING
o 18.4. GaInNAs HBT RESULTS
o 18.5. CIRCUIT APPLICATIONS FOR GaInNAs HBTs
o 18.6. FUTURE OUTLOOK
o ACKNOWLEDGEMENTS
o REFERENCES
* Index

Extraction Techniques in Analytical Sciences (Analytical Techniques in the Sciences (AnTs) *)

by: John R. Dean

Extraction Techniques in Analytical Sciences (Analytical Techniques in the Sciences (AnTs) *) library.nu #196142

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This book covers one of the most important areas in analytical sciences, i.e. that of extraction techniques for organic compounds in environmental and related matrices, e.g. food. This text discusses all of the key stages for analysing a sample for organic compounds from the initial sampling protocols through to the range of different extraction techniques used for solid, liquid and air samples and finally through to the final chromatographic analysis. The text provides detailed information on specific extraction techniques to prepare samples for organic compound analysis.

The topics covered include the following:

Initial steps for solid, aqueous and air sampling.
Extraction techniques for aqueous samples, including LLE, purge and trap, SPE, SPME, SBSE, SDME, membrane microextraction and MEPS.
Extraction techniques for solid samples, including Soxhlet, "Soxtec", shake-flask, sonication, PFE, MAE, SFE and MSPD.
Extraction techniques for air sampling, including whole air, enrichment approaches and desorption techniques.
Pre-concentration approaches for post-extraction.
Practical aspects for chromatographic analysis (GC and HPLC) of organic compounds.
Quality assurance aspects of analysis.
Health and safety considerations.

Key features include the following:

Up-to-date information on the latest development in extraction techniques for organic compounds in environmental and food matrices.
Written in the AnTS style, it is ideal for use as a self-study guide, as the basis of a taught course or guided reading for new "early-career" researchers.
Includes a resources section to guide the reader to other sources of information.

Extraction Techniques in Analytical Sciences should prove invaluable to students who are studying university-level courses – "undergraduate- to postgraduate-taught". The text will also prove invaluable as a key starting point for individuals undertaking applied research in the fields of analytical, bioanalytical, environmental and food sciences.

The Analytical Techniques in the Sciences series of books provides coverage of all of the major analytical techniques and their application in the most important areas of physical, life and material sciences. Each text is presented in an open learning/distance learning style, in which the learning objectives are clearly identified. The reader's understanding of the material is constantly evaluated by the use of self-assessment and discussion questions. Series Editor: David J. Ando

Aromatic Chemistry (Basic Concepts In Chemistry)

by: John D. Hepworth, David R. Waring, Michael J. Waring

Aromatic Chemistry (Basic Concepts In Chemistry) library.nu #21375

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Aromatic Chemistry (Basic Concepts In Chemistry)
By John D. Hepworth, David R. Waring, Michael J. Waring

Publisher: Wiley-RSC
Number Of Pages: 168
Publication Date: 2003-12-05
ISBN-10 / ASIN: 0471549312
ISBN-13 / EAN: 9780471549314
Binding: Paperback

Book Description:

This book provides an up-to-date and comprehensive account of aromatic chemistry. A series of chapters describes the synthesis and reactions of the major functional derivatives of benzene and the more common polycyclic systems. The concepts of aromaticity and the mechanism of aromatic substitution are discussed, as is the use of metals in the synthesis of aromatic compounds. Throughout, emphasis is placed on mechanisms. Worked problems and questions are provided to aid understanding.

In addition to providing material required by an undergraduate studying chemistry, Aromatic Chemistry is also ideal for industrial chemists seeking to update their knowledge of this important aspect of chemistry.

Amino Acids, Peptides and Proteins in Organic Chemistry: Volume 4 - Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis (Amino Acids, Peptides and Proteins in Organic Chemistry (VCH))

by: Andrew B. Hughes

Amino Acids, Peptides and Proteins in Organic Chemistry: Volume 4 - Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis (Amino Acids, Peptides and Proteins in Organic Chemistry (VCH)) library.nu #415939

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Closing a gap in the literature, this is the only book series in 6 volumes to cover this important topic in organic and biochemistry. Drawing upon the combined expertise of the international "who's who" in amino acid research, this series is a real benchmark for amino acid chemistry, providing a comprehensive discussion of the occurrence, uses and applications of amino acids and, by extension, their polymeric forms, peptides and proteins. The practical value of each volume is heightened by the inclusion of experimental procedures.
Volume 1: Origins and Synthesis of Amino Acids
Volume 2: Modifi ed Amino Acids, Organocatalysis and Enzymes
Volume 3: Building Blocks, Catalysis and Coupling Chemistry
Volume 4: Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis
Volume 5: Analysis and Function of Amino Acids and Peptides
Volume 6: Peptide Natural Products and Amino Acid Chemistry Development
The fourth volume in this six-volume series is structured in three main sections. The first section is about protection reactions and amino acid based peptidomimetics. The second, and most extensive, part is devoted to the medicinal chemistry of amino acids. It includes, among others,
the chemistry of alpha- and beta amino acids, peptide drugs, and advances in N- and O-glycopeptide synthesis. The final part deals with amino acids in combinatorial synthesis. Methods, such as phage display, library peptide synthesis, and computational design are described.

Contents

List of Contributors.

1 Protection Reactions (Vommina V. Sureshbabu and Narasimhamurthy Narendra ).

1.1 General Considerations.

1.2 ^_α-Amino Protection (N^α Protection).

1.3 Carboxy Protection.

1.4 Side-Chain Protection.

1.5 Photocleavable Protections.

1.6 Conclusions.

1.7 Experimental Procedures.

References.

Part One Amino Acid-Based Peptidomimetics.

2 Huisgen Cycloaddition in Peptidomimetic Chemistry (Daniel Sejer Pedersen and Andrew David Abell ).

2.1 Introduction.

2.2 Huisgen [2 + 3] Cycloaddition Between Azides and Acetylenes.

2.3 Mechanistic Consideration for the Cu-Huisgen and Ru-Huisgen Cycloadditions.

2.4 Building Blocks for the Synthesis of Triazole-Modified Peptidomimetics.

2.5 Cyclic Triazole Peptidomimetics.

2.6 Acyclic Triazole Peptidomimetics.

2.7 Useful Experimental Procedures.

References.

3 Recent Advances in ß-Strand Mimetics (Wendy A. Loughlin and David P. Fairlie ).

3.1 Introduction.

3.2 Macrocyclic Peptidomimetics.

3.3 Acyclic Compounds.

3.4 Aliphatic and Aromatic Carbocycles.

3.5 Ligands Containing One Ring with One Heteroatom (N).

3.6 Ligands Containing One or Multiple Rings with One Heteroatom (O, S).

3.7 Ligands Containing One Ring with Two Heteroatoms (N,N).

3.8 Ligands Containing One Ring with Two Heteroatoms (N,S) or Three Heteroatoms (N,N,S or N,N,N).

3.9 Ligands Containing Two Rings with One Heteroatom (N or O).

3.10 Ligands Containing Two Rings with Two or Three Heteroatoms (N,N or N,S or N,N,N).

3.11 Conclusions.

References.

Part Two Medicinal Chemistry of Amino Acids.

4 Medicinal Chemistry of α-Amino Acids (Lennart Bunch and Povl Krogsgaard-Larsen ).

4.1 Introduction.

4.2 Glutamic Acid.

4.3 Conformational Restriction.

4.4 Bioisosterism,

4.5 Structure–Activity Studies.

4.6 Conclusions.

References.

5 Medicinal Chemistry of Alicyclic ß-Amino Acids (Nils Griebenow ).

5.1 Introduction.

5.2 Five-Membered Alicyclic ß-Amino Acids.

5.3 Six-Membered Alicyclic ß-Amino Acids.

References.

6 Medicinal Chemistry of a-Hydroxy-ß-Amino Acids (Zyta Ziora, Mariusz Skwarczynski, and Yoshiaki Kiso ).

6.1 Introduction.

6.2 α-Hydroxy-ß-Amino Acids.

6.3 Antibacterial Agents.

6.4 Inhibitors of Aminopeptidases.

6.5 Aspartyl Proteases Inhibitors.

6.6 Paclitaxel and its Derivatives.

References.

7 Peptide Drugs (Chiara Falciani, Alessandro Pini, and Luisa Bracci ).

7.1 Lights and Shades of Peptide and Protein Drugs.

7.2 Peptide Drugs Available on the Market.

7.3 Approved Peptides in Oncology.

7.4 Antimicrobial peptides.

7.5 Perspectives.

References.

8 Oral Bioavailability of Peptide and Peptidomimetic Drugs (Arik Dahan, Yasuhiro Tsume, Jing Sun, Jonathan M. Miller, and Gordon L. Amidon ).

8.1 Introduction.

8.2 Fundamental Considerations of Intestinal Absorption.

8.3 Barriers Limiting Oral Peptide/Peptidomimetic Drug Bioavailability.

8.4 Strategies to Improve Oral Bioavailability of Peptide-Based Drugs.

8.5 Conclusions.

References.

9 Asymmetric Synthesis of ß-Lactams via the Staudinger Reaction (Monika I. Konaklieva and Balbina J. Plotkin ).

9.1 Introduction.

9.2 Staudinger Reaction.

9.3 Influence of the Geometry of the Imine on Stereoselectivity in the Reaction.

9.4 Influence of the Polarity of the Solvent on Stereoselectivity of the Reaction.

9.5 Influence of the Isomerization of the Imine Prior to its Nucleophilic Attack onto the Ketene Stereoselectivity in the Reaction.

9.6 Influence of the Order of Addition of the Reactants to the Reaction.

9.7 Influence of Chiral Substituents on the Stereoselectivity of the Reaction.

9.8 Asymmetric Induction from the Imine Component.

9.9 Asymmetric Induction from the Ketene Component.

9.10 Double Asymmetric Cycloinduction.

9.11 Influence of Catalysts on the Stereoselectivity of the Reaction.

9.12 Conclusions.

References.

10 Advances in N- and O-Glycopeptide Synthesis – A Tool to Study Glycosylation and Develop New Therapeutics (Ulrika Westerlind and Horst Kunz ).

10.1 Introduction.

10.2 Synthesis of O-Glycopeptides.

10.3 Synthesis of N-Glycopeptides.

References.

11 Recent Developments in Neoglycopeptide Synthesis (Margaret A. Brimble, Nicole Miller, and Geoffrey M. Williams ).

11.1 Introduction.

11.2 Neoglycoside and Neoglycopeptide Synthesis.

11.3 Protein Side-Chain Modifications.

11.4 Cu(I)-Catalyzed Azide–Alkyne ‘‘Click’’ Cycloaddition.

11.5 Cross-Metathesis.

11.6 Application of Neoglycopeptides as Synthetic Vaccines.

11.7 Enzymatic, Molecular, and Cell Biological Techniques.

References.

Part Three Amino Acids in Combinatorial Synthesis.

12 Combinatorial/Library Peptide Synthesis (Michal Lebl ).

12.1 Introduction.

12.2 High-Throughput Synthesis of Peptides.

12.3 Synthesis of Peptide Arrays.

12.4 Peptide Libraries.

12.5 Future of Peptide Libraries.

12.6 Synthetic Protocols.

References.

13 Phage-Displayed Combinatorial Peptides (Renhua Huang, Kritika Pershad, Malgorzata Kokoszka, and Brian K. Kay ).

13.1 Introduction.

13.2 Conclusions.

References.

14 Designing New Proteins (Michael I. Sadowski and James T. MacDonald ).

14.1 Introduction.

14.2 Protein Design Methods.

14.3 Protocol for Protein Design.

14.4 Conclusions.

References.

15 Amino Acid-Based Dendrimers (Zhengshuang Shi, Chunhui Zhou, Zhigang Liu, Filbert Totsingan, and Neville R. Kallenbach ).

15.1 Introduction.

15.2 Peptide Dendrimer Synthesis: Divergent and Convergent Approaches.

15.3 Applications of Peptide Dendrimers.

15.4 Conclusions.

References.

Index.

Sunday, August 7, 2011

Junhua Tao, Romas Joseph Kazlauskas, "Biocatalysis for Green Chemistry and Chemical Process Development"
W,..y | 2011 | ISBN: 0470437782 | 496 pages | PDF | 10,1 MB

Biocatalysis for Green Chemistry and Chemical Process Development offers an exciting alternative to today's complex, multidisciplinary approach to green chemistry by focusing exclusively on the most potent weapon in this field's arsenal—biocatalysis. In-depth coverage details the technological advances being made in biocatalysis-driven green syntheses of industrially important molecules, as well as how these advances show great promise in streamlining current chemical processes for reducing or eliminating hazardous substances. In addition, coverage of the biotechnological production of pharmaceuticals (small molecules, natural products and biologics), flavors, fragrance and cosmetics, fine chemicals, and more underscore the book's main goal of facilitating industrial applications of this powerful and pioneering green technology. Highlights include:
A variety of case studies, not only in pharmaceuticals and fine chemicals, but also specialty and bulk chemicals and polymers
A comprehensive overview of green chemistry applications of enzyme-driven transformations for a wide range of industries
A look at the application of biocatalysis across a wide range of chemical manufacturing fields, and why it is a good sustainable manufacturing option
Biocatalysis is emerging as a transformational technology uniquely suited to deliver green chemistry solutions for safer, efficient, and more cost-effective chemical synthesis. Biocatalysis for Green Chemistry and Chemical Process Development serves a key role in promoting this significant and potentially world-changing technology—and offers valuable perspective on achieving widespread sustainable industrial practices.

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The Art of Process Chemistry

Nobuyoshi Yasuda, "The Art of Process Chemistry".
Publisher: Wiley-VCH | ISBN 10: 3527324704 | 2010 | PDF | 298 pages | 2.1 MB

Providing must-have knowledge for the pharmaceutical industry and process chemists in industry, this ready reference offers solutions for saving time and money and supplying -- in a sustainable way -- valuable products. Application-oriented and well structured, each chapter presents successful strategies for the latest modern drugs, showing how to provide very fast bulk quantities of drug candidates. Throughout, the text illustrates how all the key factors are interwoven and dependent on one another in creating optimized methods for optimal products.

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Chemistry for Engineering Students (2nd Edition)

Enhanced with a remarkable number of new problems and applications, the Second Edition of Chemistry for Engineering Students provides a concise, thorough, and relevant introduction to chemistry that prepares students for further study in any engineering field. Updated with even more questions and applications specifically geared toward engineering students, the book emphasizes the connection between molecular properties and observable physical properties and the connections between chemistry and other subjects studied by engineering students, such as mathematics and physics. This new edition is now fully supported by OWL, the most widely-used online learning system for chemistry.

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Saturday, August 6, 2011

Indians are Hobbesian.(culture of self interest)

Must Read !

Indians are Hobbesian.(culture of self interest)

Corruption in India is a cultural aspect.
Indians seem to think nothing peculiar about corruption .
It is everywhere.
Indians tolerate corrupt individuals rather than correct them.
No race can be congenitally corrupt.
But can a race be corrupted by its culture?
To know why Indians are corrupt ,
look at their patterns and practices .
First:
Religion is transactional in India .
Indians give God cash and anticipate an out-of-turn reward.
Such a plea acknowledges that favours are needed for the undeserving.
In the world outside the temple walls,
such a transaction is named- “bribe”.
A wealthy Indian gives not cash to temples,
but gold crowns and such baubles.
His gifts can not feed the poor. His pay-off is for God.
He thinks it will be wasted if it goes to a needy man.
In June 2009, The Hindu published a report of Karnataka minister
G. Janardhan Reddy gifting a crown of gold and diamonds worth
Rs 45 crore to Tirupati.
India’s temples collect so much that
they don't know what to do with it.
Billions are gathering dust in temple vaults.
When Europeans came to India they built schools.
When Indians go to Europe & USA, they build temples.
Indians believe that if God accepts money for his favours,
then nothing is wrong in doing the same thing.
This is why Indians are so easily corruptible.
Indian culture accommodates such transactions morally.
There is no real stigma. An utterly corrupt Jaya Lalita can
make a comeback, just unthinkable in the West.
Second -
Indian moral ambiguity towards corruption is visible in its history.
Indian history tells of the capture of cities and kingdoms after guards
were paid off to open the gates, and commanders paid off to surrender.
This is unique to India .
Indians' corrupt nature has meant limited warfare on the subcontinent.
It is striking how little Indians have actually fought compared to
ancient Greece and modern Europe .
The Turks’ battles with Nadir Shah were vicious and fought to the finish.
In India fighting wasn't needed, bribing was enough to see off armies.
Any invader willing to spend cash could brush aside India ’s kings,
no matter how many tens of thousands soldiers were in their infantry.
Little resistance was given by the Indians at the “ Battle ” of Plassey.
Clive paid off Mir Jaffar and all of Bengal folded to an army of 3,000.
There was always a financial exchange to taking Indian forts.
Golconda was captured in 1687 after the secret back door was left open.
Mughals vanquished Marathas and Rajputs with nothing but bribes.
The Raja of Srinagar gave up Dara Shikoh’s son Sulaiman to
Aurangzeb after receiving a bribe.
There are many cases where Indians participated
on a large scale in treason due to bribery.
Question is: Why Indians have a transactional culture while
other 'civilized' nations don't?
Third -
Indians do not believe in the theory that they all can rise
if each of them behaves morally, because that is not
the message of their faith.
Their caste system separates them.
They don't believe that all men are equal.
This resulted in their division and migration to other religions .
Many Hindus started their own faith like Sikh, Jain, Buddha
and many converted to Christianity and Islam.
The result is that Indians don't trust one another .
There are no Indians in India ,there are
Hindus ,Christians, Muslims and what not.

Indians forget that 400 years ago they all belonged to one faith.
This division evolved an unhealthy culture.
The inequality has resulted in a corrupt society,
In India every one is thus against everyone else,
except God and even he must be bribed.

Thursday, August 4, 2011

Professional Cooking (Unbranded), College Version, 6th Edition

Wayne Gisslen, "Professional Cooking (Unbranded), College Version, 6th Edition"
W..ey Publishing | 2006 | ISBN: 0471959464, 0471663743 | 1088 pages | PDF | 40 MB

Wayne Gisslen's Professional Cooking has helped train hundreds of thousands of professional chefs. With clear, in-depth instruction on the cooking theories and techniques successful chefs need to meet the demands of the professional kitchen. Now, with 1,100 recipes and more information than ever before, this beautifully revised and updated 6th Edition helps culinary students and aspiring chefs gain the tools and confidence they need to succeed as they build their careers in one of the fastest growing and exciting fields today.
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* Completely revised, updated, and expanded vegetable chapters feature additional product identification and cooking techniques, as well as new recipes
* Revised and expanded Nutrition chapter features the new USDA nutritional guidelines
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* cooking with legumes, grains, and pastas; breakfast preparation; dairy; and beverages
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Organisation Behaviour

Organisation Behaviour
Publisher: New Age Publications (Academic) | 2007 | ISBN: 8122415504 | 326 pages | PDF | 12,23 MB

Organization Behaviour-Text and Cases including Internet Exercise provides the most contemporary topics and examples and is comprehensive in its presentation of research and practical advice for managers. This book opens with the appropriate background on current practices of people and organization behaviour and then flows from micro and macro concepts like 'e' organization, virtual team, empowerment, emerging issues, indigenisation of western management, Potential Performance Programming and Developmental thinking.
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Saturday, July 30, 2011

The road to hell may or may not be paved with good intentions, but the road to failure surely is. Take a good look at the people you work with, and you'll find lots of Good Starters — individuals who want to succeed, and have promising ideas for how to make that happen. They begin each new pursuit with enthusiasm, or at the very least, a commitment to getting the job done.

And then something happens. Somewhere along the way, they lose steam. They get bogged down with other projects. They start procrastinating and miss deadlines. Their projects take forever to finish, if they get finished at all.

Does all this sound familiar? Maybe a little too familiar? If you are guilty of being a Good Starter, but a lousy finisher — at work or in your personal life — you have a very common problem. After all, David Allen's Getting Things Done wouldn't be a huge bestseller if people could easily figure out how to get things done on their own.

More than anything else, becoming a Great Finisher is about staying motivated from a project's beginning to its end. Recent research has uncovered the reason why that can be so difficult, and a simple and effective strategy you can use to keep motivation high.

In their studies, University of Chicago psychologists Minjung Koo and Ayelet Fishbach examined how people pursuing goals were affected by focusing on either how far they had already come (to-date thinking) or what was left to be accomplished (to-go thinking). People routinely use both kinds of thinking to motivate themselves. A marathon runner may choose to think about the miles already traveled or the ones that lie ahead. A dieter who wants to lose 30 pounds may try to fight temptation by reminding themselves of the 20 pounds already lost, or the 10 left to go.

Intuitively, both approaches have their appeal. But too much to-date thinking, focusing on what you've accomplished so far, will actually undermine your motivation to finish rather than sustain it.

Koo and Fishbach's studies consistently show that when we are pursuing a goal and consider how far we've already come, we feel a premature sense of accomplishment and begin to slack off. For instance, in one study, college students studying for an exam in an important course were significantly more motivated to study after being told that they had 52% of the material left to cover, compared to being told that they had already completed 48%.

When we focus on progress made, we're also more likely to try to achieve a sense of "balance" by making progress on other important goals. This is classic Good Starter behavior — lots of pots on the stove, but nothing is ever ready to eat.

If, instead, we focus on how far we have left to go (to-go thinking), motivation is not only sustained, it's heightened. Fundamentally, this has to do with the way our brains are wired. To-go thinking helps us tune in to the presence of a discrepancy between where we are now and where we want to be. When the human brain detects a discrepancy, it reacts by throwing resources at it: attention, effort, deeper processing of information, and willpower.

In fact, it's the discrepancy that signals that an action is needed — to-date thinking masks that signal. You might feel good about the ground you've covered, but you probably won't cover much more.

Great Finishers force themselves to stay focused on the goal, and never congratulate themselves on a job half-done. Great managers create Great Finishers by reminding their employees to keep their eyes on the prize, and are careful to avoid giving effusive praise or rewards for hitting milestones "along the way." Encouragement is important, but to keep your team motivated, save the accolades for a job well — and completely — done.

Sunday, July 24, 2011

CATCH THE VIEWS OF QUALITY CONTROL(Presented by : Rajeswara Rao G)

REGULATORY AND GMP CONCERNS ON QUALITY CONTROLS OF DRUG SUBSTANCES

Specification

The specifications should be in accordance with the current general and specific Pharmacopoeia monographs.

Where the monograph has been shown not suitable to control the quality of the substance, and in particular the related substances, the additional analytical methods should be identified.

Any additional specifications to those of the monograph shall be justified.

If any of these specifications vary during operation, this change should be investigated and appropriate action taken.

At the time of filing it is unlikely that sufficient data will be available to assess process consistency.

Therefore it is considered inappropriate to establish acceptance criteria that tightly encompass the batch data at the time of filing.

Justification of Specification

It should be stated if supplementary or improved tests are needed.

Any additional specifications or deviations should be justified.

The possible need for a revision of the Pharmacopoeia monograph should be discussed.

Omission of Tests

Where the monograph mentions a test for a named impurity (metal catalyst/reagent/solvent) but which is not used during manufacture, the manufacturer may omit the test in the specifications which should be made clear in the DMF.

However, the substance should comply with the monograph, if tested.

Out of Specifications

Any out-of-specification result obtained should be investigated and documented according to a procedure.

This procedure should require analysis of the data, assessment of whether a significant problem exists, allocation of the tasks for corrective actions, and conclusions.

Any re-sampling and/or retesting after OOS results should be performed according to a documented procedure.

Out-of-specification (OOS) investigations are not normally needed for in-process tests that are performed for the purpose of monitoring and/or adjusting the process.

Out-Of-Specification batches should not be blended with other batches for the purpose of meeting specifications.

Each batch incorporated into the blend should have been manufactured using an established process and should have been individually tested and found to meet appropriate specifications prior to blending.

Field Alert Reports

For those products that are the subject of approved full and abbreviated new drug applications, regulations require submitting within 3 working days a field alert report (FAR) of information concerning any failure of a distributed batch to meet any of the specifications established in an application (21 CFR 314.81(b)(1)(ii)).

OOS test results on these products are considered to be one kind of "information concerning any failure” described in this regulation.

Unless the OOS result on the distributed batch is found to be invalid within 3 days, an initial FAR should be submitted.

A follow-up FAR should be submitted when the OOS investigation is completed.

NEEDS OF QUALITY CONTROLS FOR DRUG SUBSTANCES

Description / Appearance

Description can normally embrace colour and physical form.

The term “white” is not used without qualification since, if viewed against a standard white material, very few pharmaceutical materials will appear truly white.

It is, of course, not intended that such a comparison be made but experience shows that certain users of the pharmacopoeia may insist on doing so as part of a purchasing contract.

The term “white or almost white” is used instead.

Where positive colours are to be described this is done in terms of primary colours or combinations of primary colours.

A qualitative statement about the state (e.g. solid, liquid) and colour of the drug substance.

Visible

White to off-white, white to pale yellow, “JP white”, colour descriptions are available, including recommendation of “white to almost white”

Qualitative test only

Genuine issues (e.g. impurities, contaminants) should be dealt with via quantitative tests; appearance doesn’t need to be quantitative.

Testing during stability may need to be a slightly different process to that for release where trends do not need to be monitored.

Solution Clarity

During development for APIs for solution formulation (internal test)

Clarity and Degree of Opalescence (DP test)

Silica: Acid + Silica Filtration, Recrystallizein API

Filter Housing : Acid + Filter

Turbidity

Quantitative (with weaknesses)

Ball-park figure of ~ 2NTU; EP test solution for clear = ~2.8NTU

Other tests

Odour

Generally no

Depending on route of delivery may need to limit solvents to < ICH thresholds e.g. Pentane

Degradation products e.g. Sulphates or Toluene degradation product

Mass balance

Useful scientific guide for evaluating data, but is not achievable in all circumstances

WHO guidelines discuss this with reference to Degree of Opalescence only

Address as part of development if notice significant discrepancies

No taste

Identification

Identification testing should optimally be able to discriminate between compounds of closely related structure, which are likely to be present.

Identification tests should be specific for the new drug substance, e.g., Infrared Spectroscopy.

Identification solely by a single chromatographic retention time, for example, is not regarded as being specific.

However, the use of two chromatographic procedures, where the separation is based on different principles or a combination of tests into a single procedure, such as HPLC/ UV diode array, HPLC/ MS, or GC/ MS is generally acceptable.

If the drug substance is a salt, identification testing should be specific for the individual ions.

An identification test that is specific for the salt itself should suffice.

Drug substances that are optically active may also need specific identification testing or performance of a chiral assay.

Specific spectroscopic technique

e.g. FTIR

Generally best strategy

Easy to do ‘Identification testing on receipt’ etc..

Chiral test if required

Optical Rotation

Or may get chromatographic ‘for free’ è see Chiral impurity control

Racemates if also developing Enantiomer or Chiral preference may occur

If more than two Chiral centres then control of Starting Materials/ Reagents may be more appropriate

The first tells you if you have the right species, the second confirms which enantiomer

Salt form identity

Release test

Not required to be measured on stability

An IR test for the API may be specific for the Salt form also

If not, a test for the counter ion may be required (may also double as an assay test for the counter ion if required)

Salt form assay

Assay determination of the counter ion may be omitted from the release specification if batch data shows good stoichiometry routinely achieved.

If the, generally organic, counter ion degrades may need to determine on stability or if the counter ion degradation products need to be controlled

Hemi-maleate / Hemi-hydrochloride can transform to Maleatetrihydrate + HCl at high humidity

Solid form identity

Polymorph, Solvate, De-solvated Solvates, Amorphous

From experience, mean is 3-4 per compound; record = 75 ?

If development work shows that no other forms are feasible/relevant then not required on specification

Similarly for stability, if other forms would not be formed at relevant temperatures/ humidities or timescales (hydrates, amorphous crystallisation), then shouldn’t be required on stability

PXRD in early development, once characterised, DSC more widely available

Form assay

Reactivity in the amorphous state is greater than that in the crystalline state

Possible release test if observing batch-to-batch variation in degradation rates

PXRD can measure amorphous content down to ~5%

Racemic drugs

Can be racemic compounds 90-95% of cases (racemic crystals)

- (RSRSRSRSRS)

or racemic conglomerate 5-10% of cases (enantiomorphous mixture of crystals)

- (SSSSS RRRRR)

rarely pseudoracemate

- (RSSRSRRSRS)

Release test

Crystal habit

Can affect solubility, dissolution rate, degradation and formulation processing

Determine using microscopy

Develop final step to ensure control

Release test

Assay

A specific, stability-indicating assay to determine strength (content) should be included for all drug products.

In many cases it is possible to employ the same procedure (e.g., HPLC) for both assay of the new drug substance and quantitation of impurities.

Results of content uniformity testing for drug products can be used for quantitation of drug product strength, if the methods used for content uniformity are also appropriate as assays.

In cases where use of a non-specific assay is justified, other supporting analytical procedures should be used to achieve overall specificity.

For example, where titration is adopted to assay the drug substance for release, the combination of the assay and a suitable test for impurities can be used.

A specific procedure should be used when there is evidence of excipient interference with the non-specific assay.

Main component assay

ICH Q6A

Stability indicating; If non-specific test, may need to subtract impurities from the result

For chiral drugs, an achiral assay with control of the enantiomeric impurity is acceptable

General limits

Upper limit 102.0% (on an anhydrous basis or dried i.e. anhydrous and solvent free)

Lower limit 98.0% depending on levels of impurities

Racemic drugs

Essentially equal efficacy/safety –then can control as a total of the two

Tend to be denser and thus stable than chiral counterparts

Organic Impurities

Organic impurities arising from degradation of the drug substance and impurities that arise during the manufacturing process for the drug product should be monitored in the new drug product.

Acceptance limits should be stated for individual specified degradation products, which may include both identified and unidentified degradation products as appropriate, and total degradation products.

Process impurities from the drug substance synthesis are normally controlled during drug substance testing, and therefore are not included in the total impurities limit.

However, when a synthesis impurity is also a degradation product, its level should be monitored and included in the total degradation product limit.

When it has been conclusively demonstrated via appropriate analytical methodology, that the drug substance does not degrade in the specific formulation, and under the specific storage conditions proposed in the drug application, degradation product testing may be reduced or eliminated upon approval by the regulatory authorities.

Organic

Contaminants –addressed as GMP issues

Process related impurities to be controlled at the API stage –release testing only

In early development phase impurity limits may be set at thresholds

As per ICH Q3A,

Specification should include:

Each specified identified impurity

Each specified unidentified impurity•

Total Impurities”

Any unspecified impurity with an acceptance criterion of not more than (≤) the identification threshold

If maximum Daily Dose is < 2 g / day - Unknown Impurity is 0.10%

Reporting Threshold is 0.05%

Identification Threshold is 0.10% or 1.0 mg per day intake _{(whichever is lower)}

Qualification Threshold is 0.15% or 1.0 mg per day intake _{(whichever is lower)}

If maximum Daily Dose is > 2 g / day - Unknown Impurity is 0.05%

Reporting Threshold is 0.03%

Identification Threshold is 0.05%

Qualification Threshold is 0.05%

When identification of an impurity is not feasible, a summary of the laboratory studies demonstrating the unsuccessful effort should be included in the application.

Could control to the qualification threshold as an unidentified specified impurity

Where there is no safety concern, impurity acceptance criteria should be based on data generated on batches of the new drug substance manufactured by the proposed commercial process, allowing sufficient latitude to deal with normal manufacturing and analytical variation and the stability characteristics of the new drug substance.

Thus limits for degradants should not be bounded within actual data available at time of filing, although thresholds in Q3A apply.

ICH Q6A “estimate maximum increase in impurity at retest date”

Estimate maximum by extrapolation:- 3 x Standard Deviation of predictions from the three batches or the upper one-sided 95% confidence limit out to retest period desired.

Chiral Impurities

Can significantly affect physicochemical properties of pure enantiomers.

Release test; if development work (scientific analysis, stress testing) shows that opposite enantiomer is not a degradation product, shouldn’t need to test on stability

A racemic degradant could be controlled as two separate enantiomers each to ICH Q3A threshold

Impurities -Analytical Methodology

Chromatographic methods in development stability may need to be more powerful than (or in addition to) those transferred to manufacturing : Stress in acid led to brown gum - Polymerisation

Noted disappearance of PRI dimers on stability, disappearance not seen during stress testing

Found that adsorbed onto certain vial types –changed to end-capped vials/altered pH

Total Impurities

Essentially a quality test only (assay and individual impurities controls ensure efficacy and safety)

By specifying impurities, rather than having unspecified impurities control only, may help to set more appropriate limits

TLC only for a specified impurity and only as last resort.

Veterinary Medicine

Different thresholds

Genotoxic impurity

According to current regulatory practice it is assumed that (in vivo) genotoxic compounds have the potential to damage DNA at any level of exposure and that such damage may lead/contribute to tumour development.

Thus for genotoxic carcinogens it is prudent to assume that there is no discernible threshold and that any level of exposure carries a risk.

However, the existence of mechanisms leading to biologically meaningful threshold effects is increasingly acknowledged also for genotoxic events.

This holds true in particular for compounds interacting with non-DNA targets and also for potential mutagens, which are rapidly detoxified before coming into contact with critical targets.

The regulatory approach to such chemicals can be based on the identification of a critical No-Observed-Effect Level (NOEL) and use of uncertainty factors.

Even for compounds which are able to react with the DNA molecule, extrapolation in a linear manner from effects in high-dose studies to very low level (human) exposure may not be justified due to several protective mechanisms operating effectively at low doses.

However, at present it is extremely difficult to experimentally prove the existence of threshold for the genotoxicity of a given mutagen.

Thus, in the absence of appropriate evidence supporting the existence of a threshold for a genotoxic compound making it difficult to define a safe dose it is necessary to adopt a concept of a level of exposure that carries an acceptable risk.

The toxicological assessment of genotoxic impurities and the determination of acceptable limits for such impurities in active substances is a difficult issue and not addressed in sufficient detail in the existing ICH Q3X guidances.

The data set usually available for genotoxic impurities is quite variable and is the main factor that dictates the process used for the assessment of acceptable limits.

In the absence of data usually needed for the application of one of the established risk assessment methods,

i.e. data from carcinogenicity long-term studies or data providing evidence for a threshold mechanism of genotoxicity, implementation of a generally applicable approach as defined by the Threshold of Toxicological Concern (TTC) is proposed.

A TTC value of 1.5 µg/day intake of a genotoxic impurity is considered to be associated with an acceptable risk (excess cancer risk of <1 in 100,000 over a lifetime) for most pharmaceuticals.

From this threshold value, a permitted level in the active substance can be calculated based on the expected daily dose.

Higher limits may be justified under certain conditions such as short-term exposure periods.

The concentration limits in ppm of genotoxic impurity in drug substance derived from TTC can be calculated based on the expected daily dose to the patient using equation

TTC [mg / day]

Concentration Limit (ppm) = -------------------------------- Threshold of Toxicological Concern

Dose [g / day]

Inorganic Impurities

The need for inclusion of tests and acceptance criteria for inorganic impurities (e.g., catalysts) should be studied during development and based on knowledge of the manufacturing process.

Procedures and acceptance criteria for sulfated ash / residue on ignition should follow pharmacopoeial precedents; other inorganic impurities may be determined by other appropriate procedures, e.g., atomic absorption spectroscopy.

Inorganic Impurities (not on stability)

Heavy metals

Shouldn’t need to test if no Heavy metals used in route and RSMs/reagents are adequately understood/controlled.

Criteria and limits EP Technical Guide

Daily intake > 0.5 g/day, treatment < 30 days : Heavy metals test limit 20 ppm

Daily intake > 0.5 g/day, treatment > 30 days : Heavy metals test limit 10 ppm

Daily intake < 0.5 g/day, treatment > 30 days: Heavy metals test limit 10 ppm _{If it is used parenterally}

Heavy metals test limit 20 ppm _{Other wise}

Daily intake < 0.5 g/day, treatment < 30 days : No heavy metals test

Global Specifications

Pharmacopoeias: Heavy metals for an API in Japan

JP Heavy metals test not adequate temperature

Used modified (validated) EP test accepted

For API usually set out with good intentions, however some tests may be region specific e.g. arsenic for Japan, or may end up with different agreed limits for impurities in different regions.

Depending what is easiest for one’s supply chain, may test API for specific markets or have a tighter internal control document put in place meeting all region requirements…

Similarly for API intended for >1 dosage form type…

Specific Tests

Control of catalysts used during manufacturing process

Arsenic control for Japan may be required

Pharmacopoeial methodology or specific (but validated)

Information about Metal Residues

Residual metals used as process catalysts do not provide any therapeutic benefit and should therefore be evaluated and restricted on the foundation of safety- and quality-based criteria.

Metals will be classified in three categories based on their individual levels of safety concern and concentration limits will be set on the bases of the maximal daily dose, duration of treatment, route of administration and permitted daily exposure (PDE).

In the reviews the following assumptions and/or default values are used:

Body Weight (bw) of an adult: 50 Kg.

Breathing volume of an adult: 20 m₃per Day (24 Hr.).

Occupational (workplace) inhalation exposure: 8 Hr. per Day (24 Hr.).

Exposure limits were established using uncertainty factors as per ICH Q3.

For pragmatic reasons a number of uncertainty factors were adapted to arrive at a final safe and practical PDE setting - Q3 method for uncertainty factor (UF) calculation plus additional pragmatic factor for PDE calculation.

Acceptable Additional Lifetime Cancer Risk:

An increased cancer risk of 1 in 100,000 was identified as acceptable for genotoxic impurities in pharmaceuticals by the Committee for Human Medicinal Products (CHMP).

Limits set based on safety criteria may therefore be higher than limits set on the basis of GMP, process capabilities, or other suitable quality criteria.

Any interested party can make a request and submit relevant safety data.

Classification and limits may change as new safety data becomes available.

Metal catalysts and metal reagents are defined here as chemical substances that are used to change the rate of chemical reactions or which act on other chemical substances in chemical reactions.

Residues of metals can either be present as the original form of the metal or as a form of the metallic element altered by downstream chemical processing.

Excluded from this document are extraneous metal contaminants that should not occur in drug substances or excipients and are more appropriately addressed as Good Manufacturing Practice (GMP) issues.

Different limits are applied to oral and parenteral routes of administration due to limited oral bioavailability of many metals.

As different routes of exposure may have different toxicological properties, specific limits have been set for inhalation exposure to some metals.

When the exposure is short the PDE´s mentioned in this guideline may be adapted as indicated

Thursday, July 21, 2011

Chemistry Links

Laboratory Manual for Principles of General Chemistry, Beran, J.A. 9th ed. 2011 (Google Books)

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