Mathematical Models of the Cell and Cell Associated Objects

Author: Viktor V. Ivanov,Natalya V. Ivanova

Publisher: Elsevier

ISBN: 9780080462721

Category: Mathematics

Page: 354

View: 3122


This book gives the reader a survey of hundreds results in the field of the cell and cell associated objects modeling. Applications to modeling in the areas of AIDS, cancers and life longevity are investigated in this book. Introduces and proves fundamental properties of evolutionary systems on optimal distribution of their various resources on their internal and external functions Gives detailed analysis of applications to modeling AIDS, cancers, and life longevity Introducing and grounding the respective numerical algorithms and software Detailed analysis of hundreds of scientific works in the field of mathematical modeling of the cell and cell associated objects

Pharmaceutical Biotechnology

Drug Discovery and Clinical Applications

Author: Oliver Kayser,Rainer H. Müller

Publisher: John Wiley & Sons

ISBN: 3527605525

Category: Science

Page: 336

View: 1928


With its focus on industrial pharmaceutical research, written by international experts from the industry, this book fills in a gap in the existing literature. It reflects the combination of such pharmaceutical interests as drug delivery, drug targeting, quality and safety management, drug approval and regulation, patenting issues and biotechnology fundamentals. Thus it provides practitioners in pharmaceutical biotechnology with all the relevant information from the shelf. The first part offers a comprehensive survey and review of the rapidly increasing array of biopharmaceuticals derived from the molecular biological approaches now widely available. This is followed by an extra section devoted to the very critical patenting and drug regulation issues. The whole is rounded off by detailed monographs of biotechnologically developed drugs that are already on the market. With a foreword of by Robert Langer, Kenneth J Germeshausen Professor of Chemical and Biomedical Engineering at the Massachusetts Institute of Technology. In 2002, he received the Charles Stark Draper Prize, the highest recognition for an engineer. Professor Langer is member of all three national academies - the Institute of Medicine, the National Academy of Engineering, and the National Academy of Sciences: "The book attempts to provide a balanced view of the biotechnological industry and the number of experts from industry sharing their knowledge and experience with the audience gives the book an outstanding value. All contributors provide with each chapter an up-to-date review on key topics in pharmaceutical biotechnology. This work is not only a valuable tool for the industrial expert but also for all pharmacists and scientists from related areas who wish to work with biotech drugs."

The Journal of Cell Biology

Author: N.A

Publisher: N.A


Category: Cytology

Page: N.A

View: 8098


No. 2, pt. 2 of November issue each year from v. 19 (1963)-47 (1970) and v. 55 (1972)- contain the Abstracts of papers presented at the Annual Meeting of the American Society for Cell Biology, 3d (1963)-10th (1970) and 12th (1972)-

Handbook of Pharmaceutical Manufacturing Formulations

Sterile Products

Author: Safaraz K. Niazi

Publisher: CRC Press

ISBN: 1420081314

Category: Medical

Page: 464

View: 6757


No other area of regulatory compliance receives more attention and scrutiny by regulatory authorities than the regulation of sterile products, for obvious reasons. With the increasing number of potent products, particularly the new line of small protein products, joining the long list of proven sterile products, the technology of manufacturing sterile products has evolved into a very sophisticated industry. Highlights from Sterile Products, Volume Six include: formulations of sterile dosage forms, regulatory filing requirements of sterile preparations, and cGMP compliance, all of which are tied together in the final preparation of the CMC sections of regulatory applications specifications of a manufacturing facility to manufacture compliant sterile products NDA or aNDA filing requirements of sterile products an alphabetical presentation of formulations of pharmaceutical products based on their generic names

Handbook of Pharmaceutical Manafacturing Formulations, 2nd Ed, Sarfaraz K. Niazi, 2009

Handbook of Pharmaceutical Manafacturing Formulations

Author: Informa Healthcare

Publisher: Bukupedia


Category: Business & Economics

Page: 2738

View: 6540


The science and the art of pharmaceutical formulation keeps evolving as new materials, methods, and machines become readily available to produce more reliable, stable, and releasecontrolled formulations. At the same time, globalization of sourcing of raw and finished pharmaceuticals brings challenges to regulatory authorities and results in more frequent revisions to the current good manufacturing practices, regulatory approval dossier requirements, and the growing need for cost optimization. Since the publication of the first edition of this book, a lot has changed in all of these areas of importance to pharmaceutical manufacturers. The second edition builds on the dynamic nature of the science and art of formulations and provides an evermore useful handbook that should be highly welcomed by the industry, the regulatory authorities, as well as the teaching institutions. The first edition of this book was a great success as it brought under one umbrella the myriad of choices available to formulators. The readers were very responsive and communicated withmefrequently pointing out to the weaknesses as well as the strengths of the book. The second edition totally revised attempts to achieve these by making major changes to the text, some of which include: 1. Complete, revised errors corrected and subject matter reorganized for easy reference. Whereas this series has six volumes differentiated on the basis of the type of dosage form and a separate inclusion of the U.S. OTC products, ideally the entire collection is needed to benefit from the myriad of topics relating to formulations, regulatory compliance, and dossier preparation. 2. Total number of pages is increased from 1684 to 2726. 3. Total number of formulations is expanded by about 30% with many newly approved formulations. 4. Novel formulations are now provided for a variety of drugs; these data are collected from the massive intellectual property data and suggest toward the future trend of formulations. While some of these formulations may not have been approved in the United States or Europe, these do provide additional choices, particularly for the NDA preparation. As always, it is the responsibility of the manufacturer to assure that the intellectual property rights are not violated. 5. A significant change in this edition is the inclusion of commercial products; while most of this information is culled out from the open source such as the FOIA (, I have made attempts to reconstruct the critical portions of it based on what I call the generally acceptable standards. The drug companies are advised to assure that any intellectual property rights are not violated and this applies to all information contained in this book. The freedom of information act (FOIA) is an extremely useful conduit for reliable information and manufacturers are strongly urged to make use of this information. Whereas this information is provided free of charge, the process of obtaining the information may be cumbersome, in which case, commercial sources of these databases can prove useful, particularly for the non-U.S. companies. 6. Also included are the new Good Manufacturing Guidelines (2007) with amendments (2008) for the United States and similar updates for European Union and WHO; it is strongly urged that the companies discontinue using all old documents as there are significant changes in the revised form, and many of them are likely to reduce the cost of GMP compliance. 7. Details on design of clean rooms is a new entry that will be of great use to sterile product manufacturers; whereas the design and flow of personnel and material flow is of critical nature, regulatory agencies view these differently and the manufacturer is advised always to comply with most stringent requirements. 8. Addition of a self-auditing template in each volume of the series. While the cGMP compliance is a complex issue and the requirements diversified across the globe, the basic compliance remains universal. I have chosen the European Union guidelines (as these are more in tune with the ICH) to prepare a self-audit module that I recommend that every manufacturer adopt as a routine to assure GMP compliance. In most instances reading the template by those responsible for compliance with keep them sensitive to the needs of GMP. 9. OTC products cross-referenced in other volumes where appropriate. This was necessary since the regulatory authorities worldwide define this class of drug differently. It is important to iterate that regardless of the prescription or the OTC status of a product, the requirements for compliance with the cGMP apply equally. 10. OTCmonograph status is anew section added to theOTC volume and this should allow manufacturers to chose appropriate formulations that may not require a filing with the regulatory agencies; it is important to iterate that an approved OTC monograph includes details of formulation including the types and quantities of active drug and excipients, labeling, and presentation. To qualify the exemption, the manufacturer must comply with the monograph in its entirety. However, subtle modifications that are merely cosmetic in nature and where there is an evidence that the modification will not affect the safety and efficacy of the products can be made but require prior approval of the regulatory agencies and generally these approvals are granted. 11. Expanded discussion on critical factors in the manufacturing of formulations provided; from basic shortcuts to smart modifications now extend to all dosage forms. Pharmaceutical compounding is one of the oldest professions and whereas the art of formulations has been v vi Preface to the Series—Second Edition relegated to more objective parameters, the art nevertheless remains. An experienced formulator, like an artist, would know what goes with what and why; he avoids the pitfalls and stays with conservative choices. These sections of the book present advice that is time tested, although it may appear random at times; this is intended for experienced formulators. 12. Expanded details on critical steps in the manufacturing processes provided but to keep the size of the book manageable, and these are included for prototype formulations. The reader is advised to browse through similar formulations to gain more insight. Where multiple formulations are provided for the same drug, it intended to show the variety of possibilities in formulating a drug and whereas it pertains to a single drug, the basic formulation practices can be extended to many drugs of same class or even of diversified classes. Readers have often requested that more details be provided in the Manufacturing Direction sections. Whereas sufficient details are provided, this is restricted to prototype formulations to keep the size of the book manageable and to reduce redundancy. 13. Addition of a listing of approved excipients and the level allowed by regulatory authorities. This new section allows formulators a clear choice on which excipients to choose; the excipients are reported in each volume pertaining to the formulation type covered. The listing is drawn from the FDA-approved entities. For the developers of an ANDA, it is critical that the level of excipients be kept within the range generally approved to avoid large expense in justifying any unapproved level. The only category for which the listing is not provided separately is theOTCvolume since it contains many dosage forms and the reader is referred to dosage form–specific title of the series. The choice of excipients forms keeps increasing with many new choices that can provide many special release characteristics to the dosage forms. Choosing correct excipients is thus a tedious exercise and requires sophisticated multivariate statistical analysis. Whereas the formulator may choose any number of novel or classical components, it is important to know the levels of excipients that are generally allowed in various formulations to reduce the cost of redundant exercises; I have therefore included, as an appendix to each volume, a list of all excipients that are currently approved by the U.S. FDA along their appropriate levels. I suggest that a formulator consult this table before deciding on which level of excipient to use; it does not mean that the excipient cannot be used outside this range but it obviates the need for a validation and lengthy justification studies in the submission of NDAs. 14. Expanded section on bioequivalence submission was required to highlight the recent changes in these requirements. New entries include a comprehensive listing of bioequivalence protocols in abbreviated form as approved by the U.S. FDA; these descriptions are provided in each volume where pertinent. To receive approval for an ANDA, an applicant must generally demonstrate, among other things, equivalence of the active ingredient, dosage form, strength, route of administration and conditions of use as the listed drug, and that the proposed drug product is bioequivalent to the reference listed drug [21 USC 355(j)(2)(A); 21 CFR 314.94(a)]. Bioequivalent drug products show no significant difference in the rate and extent of absorption of the therapeutic ingredient [21 U.S.C. 355(j)(8); 21 CFR 320.1(e)]. BE studies are undertaken in support of ANDA submissions with the goal of demonstrating BE between a proposed generic drug product and its reference listed drug. The regulations governing BE are provided at 21 CFR in part 320. The U.S. FDA has recently begun to promulgate individual bioequivalence requirements. To streamline the process for making guidance available to the public on how to design product-specific BE studies, the U.S. FDA will be issuing product-specific BE recommendations ( To make this vital information available, an appendix to each volume includes a summary of all currently approved products by the U.S. FDA where a recommendation on conducting bioequivalence studies is made available by the U.S. FDA. When filing an NDA or an ANDA, the filer is faced with the choice of defending the methods used to justify the bioavailability or bioequivalence data. The U.S. FDA now allows application for waiver of bioequivalence requirement; a new chapter on this topic has been added along with details of the dissolution tests, where applicable, approved for various dosage forms. 15. Dissolution testing requirements are included for all dosage forms where this testing is required by the FDA. Surrogate testing to prove efficacy and compliance is getting more acceptance at regulatory agencies; in my experience, a well-designed dissolution test is the best measure of continuous compliance. Coupled with chapters on waivers of bioequivalence testing, this information on dissolution testing should be great value to all manufacturers; it is recommended that manufacturers develop their own in-house specifications, more stringent than those allowed in these listings and the USP. 16. Best-selling products (top 200 prescription products) are identified with an asterisk and a brand name where applicable; in all instances, composition of these products is provided and formulation of generic equivalents. Despite the vast expansion of pharmaceutical sales and shifting of categories of blockbuster drugs, basic drugs affecting gastrointestinal tract, vascular system, and brain remain most widely prescribed. 17. Updated list of approved coloring agents in the United States, Canada, European Union, and Japan is included to allow manufactures to design products for worldwide distribution. 18. Tablet-coating formulations that meet worldwide requirements of color selection are included in the Volume 1 (compressed solids) and Volume 5 (OTC) because these represent the products often coated. 19. Guidelines on preparing regulatory filings are now dispersed throughout the series depending on where these guidelines are more crucial. However, the reader would, as before, need access to all volumes to benefit from the advice and guidelines provided. As always, comments and criticism from the readers are welcomed and these can be sent to me at [email protected] .com or [email protected] I would try to respond to any inquiries requiring clarification of the information enclosed in these volumes. I would like to express deep gratitude to Sherri R. Niziolek and Michelle Schmitt-DeBonis at Informa, the publisher of Preface to the Series—Second Edition vii this work, for seeing an immediate value to the readers in publishing the second edition of this book and allowing me enough time to prepare this work. The diligent editing and composing staff at Informa, particularly Joseph Stubenrauch, Baljinder Kaur and others are highly appreciated. Regardless, all errors and omissions remain altogether mine. In the first edition, I had dedicated each volume to one of my mentors; the second edition continues the dedication to these great teachers. Sarfaraz K. Niazi, Ph.D. Deerfield, Illinois, U.S.A