Handbook of Investigation and Effective CAPA Systems

Worldwide regulatory agencies perform many inspections annually, and all too often investigation and CAPA system violations are at the top of the list of infractions. Life-sciences regulated companies (not only FDA-regulated ones) must ensure their investigation and CAPA systems look beyond the ‘usual suspects' to identify other quality issues in order to minimize risks (including safe ones) and reduce costs.

Enhancements to this third edition include:

A new section linking the investigation and CAPA programs with the overall quality culture of the company

Fully updated, current versions of regulations including U.S. FDA, EU, ISO 9001, and ISO 13485

Updated inspectional observations from the U.S. FDA and U.K. MHRA

A revised investigation and CAPA processes chapter, which has an improved barrier analysis section, including detailed flowcharts describing the barrier analysis process

New charts and information related to the investigation of human errors; the human factor section includes information about training and competence

A new chapter devoted to analytical laboratory investigations, including a section covering the invalidation of testing results

Updated forms and examples of the different elements of the investigation and CAPA plan, including new case studies; a revised diagnostic tool used for investigating human error

Jose(Pepe) Rodrguez-Perez, PhD, is president of Business Excellence Consulting, Inc., (BEC), a Puerto Rico-based, consulting, training, and remediation firm that focuses on the areas of regulatory compliance, FDA-regulatory training, and risk management. He is a biologist with a doctoral degree in biology from the University of Granada (Spain). Over his career, he has served as an educator, a technical services manager, and as a science advisor to the FDA.

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Handbook of Pharmaceutical Manufacturing Formulations: Semisolids Products (Volume 4 of 6)

The fourth volume in the six-volume Handbook of Pharmaceutical Manufacturing Formulations, this book covers semi-solid drugs. It includes ointments, lotions, gels, and suppositories, from publicly available but widely dispersed information from FDA New Drug Applications (NDA), patent applications, and the BASF book of generic formulations. Each entry begins with a fully validated scaleable manufacturing formula that includes compendial specification requirement for each ingredient, in-process controls for manufacturing and release of product, a summary of manufacturing process, and details of packaging.

Quality Control Training Manual: Comprehensive Training Guide for API, Finished Pharmaceutical and Biotechnologies Laboratories

Written to help companies comply with GMP, GLP, and validation requirements imposed by the FDA and regulatory bodies worldwide, Quality Control Training Manual: Comprehensive Training Guide for API, Finished Pharmaceutical and Biotechnologies Laboratories presents cost-effective training courses that cover how to apply advances in the life sciences to produce commercially viable biotech products and services in terms of quality, safety, and efficacy. This book and its accompanying CD-ROM comprise detailed text, summaries, test papers, and answers to test papers, providing an administrative solution for management.

• Provides the FDA, Health Canada, WHO, and EMEA guidelines directly applicable to pharmaceutical laboratory-related issues

• Offers generic formats and styles that can be customized to any organization and help management build quality into routine operations to comply with regulatory requirements

• Contains ready-to-use training courses that supply a good source of training material for experienced and inexperienced practitioners in the biotechnology/biopharmaceutical industries

• Includes a CD with downloadable training courses that can be adopted and directly customized to a particular organization

• Supplies ready-to-use test papers that allow end users to record all raw data up to the issuance of the attached certificate

The biotechnology/bioscience industries are regulated worldwide to be in compliance with cGMP and GLP principles, with particular focus on safety issues. Each company must create a definite training matrix of its employees. The training procedures in this book enable end users to understand the principles and elements of manufacturing techniques and provide documentation language ranging from the generic to the specific. The training courses on the CD supply valuable tools for developing training matrices to achieve FDA, Health Canada, EMEA, MHRA UK, WHO, and GLP compliance. 

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21 Cfr Part 11: Complete Guide to International Computer Validation Compliance for the Pharmaceutical Industry

In the FDA regulated environment, it is not acceptable for programmers or their managers to deviate from standardized methodologies. Given the type of software commonly found in FDA regulated operations, the criticality and complexity of computer systems, the evolving regulatory climate, and the current industry best practices, validating computer systems can be problematic. Covering regulatory requirements stipulated by FDA and GAMP guidelines, 21 CFR 11: Complete Guide to International Computer Validation Compliance for the Pharmaceutical Industry delineates the organization, planning, verification, and documentation activities and procedural controls required for compliance. Whether you need to validate computer systems for pharmaceutical cosmetic, food, or medical devise applications, this book is indispensable. Discussing the regulatory requirements that are the foundation for any project, the book introduces a model that can be used to determine the Part 11 requirements for consideration during implementation. The book establishes a top-down approach to the integration of computer systems validation strategies in support of a computer systems validation project. It focuses on practical issues in computer systems implementation and operational life project management, including relevant activities to comply with Part 11, validation planning, and scheduling. The book reviews documentation in relation to CSV and procedural controls in regulated operations. The book shows how to enable compliance with computer systems validation requirements while highlighting and integrating Part 11 requirements into the entire computer validation program. The author places regulatory compliance within the context of quality assurance and emphasizes the importance of integrating validation into the system life cycle using a structured top-down approach. This systematic approach helps you efficiently develop compliant software and maintenance its compliance.

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Ensuring Safe Foods and Medical Products Through Stronger Regulatory Systems Abroad

This book describes the ways the United States can help strengthen regulatory systems in low and middle income countries and promote cross-border partnerships - including government, industry, and academia - to foster regulatory science and build a core of regulatory professionals. This report also emphasizes an array of practical approaches to ensure sound regulatory practices in today's interconnected world. 

A very high portion of the seafood we eat comes from abroad, mainly from China and Southeast Asia, and most of the active ingredients in medicines we take originate in other countries. Many low and middle income countries have lower labor costs and fewer and less stringent environmental regulations than the United States, making them attractive places to produce food and chemical ingredients for export. 

Safe Foods and Medical Products Through Stronger Regulatory Systems Abroad explains that the diversity and scale of imports makes it impractical for U.S. Food and Drug Administration (FDA) border inspections to be sufficient to ensure product purity and safety, and incidents such as American deaths due to adulterated heparin imported from China propelled the problem into public awareness. 

Contents

Acknowledgments

Acronyms and Abbreviations

Summary

Front Matter

Summary

1 Introduction

2 Core Elements of Regulatory Systems

3 Critical Issues

4 A Strategy to Building Food and Medical Product Regulatory Systems

5 International Action

6 Domestic Action

7 Conclusions and Priorities

Appendix A Glossary

Appendix В A Review of Tort Liability's Role in Food and Medical Product Regulation

Appendix С Food and Medical Product Regulatory Systems of South Africa, Brazil, India, and China

Appendix D Chinese Food Regulatory System

Appendix E Meeting Agendas

Appendix F Committee Member Biographies

Appendix G Analyzing Food Safety Alerts in European Union Rapid Alerts Systems for Food and Feed

Appendix H Strengthening Core Elements of Regulatory Systems in Developing Countries: Identifying Priorities and an Appropriate Role for the U.S. Food and Drug Administration

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New Drug Approval Process: The Global Challenge

"This text [is] a useful road map to understanding the requirements that a drug product must fulfill to achieve approval." -- Journal of Medicinal Chemistry

"…very valuable…

"…should be a required reading….highly recommended." -- Guarino

"…very valuable… "…should be a required reading for anyone entering the strait-jacket world of modern pharmaceutical development….highly recommended. -- Pharmaceutical Development and Technology

Oxford Pharmaceutical Resources, Inc., Totowa, NJ. Covers the new emphasis on over-the-counter drugs, latest techniques of institutional review boards, Good Clinical Practice standards set by the FDA, adverse drug reaction standards, and more. For professionals in pharmaceutical industry.

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Filtration in the Biopharmaceutical Industry

This timely resource offers comprehensive examinations of the most recent developments in the field, from prefiltration methods to final, gas, and tangential flow filtration techniques. Delineates filtration in a host of applications, including virus removal, protein binding, and sterility testing and introduces new, membrane-based technologies for the biopharmaceutical industry! Addressing quality, security, economic, process development, and regulatory topics, Filtration in the Biopharmaceutical Industry presents pre- and sterility grade filters, charge-modified filter media, and aids to filtration discusses filter quality assurance, pore size, extractables, and compatibilities in various filters examines filter design and construction analyzes integrity testing, test sensitivity, and automation furnishes novel filtration flow methods explains filter validation summarizes the U.S. Food and Drug Administration regulations governing filtration and more!

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Handbook of Pharmaceutical Manufacturing Formulations: Liquid Products (Volume 3 of 6)

The third volume in the six-volume Handbook of Pharmaceutical Manufacturing Formulations, this book covers liquid drugs, which include formulations of non-sterile drugs administered by any route in the form of solutions (monomeric and multimeric), suspensions (powder and liquid), drops, extracts, elixirs, tinctures, paints, sprays, colloidons, emulsions, aerosols, and other fluid preparations from publicly available but widely dispersed information from FDA New Drug Applications (NDA), patent applications, and other sources of generic and proprietary formulations. Each entry begins with a fully validated scaleable manufacturing formula and a summary of manufacturing process. The book provides a detailed discussion on the difficulties encountered in formulating and manufacturing liquid drugs, the common elements of formulation. The section on regulatory and manufacturing guidance deals with the topics of changes to approved NDAs and aNDAs, post-approval changes to semisolid drugs, global manufacturing practices and guidelines, compliance program guidance manual for FDA staff covering drug manufacturing inspections program, waiver of in vivo bioavailability studies for immediate release solid drugs based on a biopharmaceutics classification, in addition to providing quick tips on resolving the common problems in formulating uncompressed drugs.

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GMP/ISO Quality Audit Manual for Healthcare Manufacturers and Their Suppliers, Sixth Edition, (Volume 2 - Regulations, Standards, and Guidelines)

Volume 2 of this set contains the full text of the FDA regulations, EC and IPEC guidelines, and ISO/BSI standards referenced in the checklists furnished in Volume I. The book is presented in an convenient, easy-to-read format, organized to provide fast access to the guidelines and regulations of interest.

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GMP/ISO Quality Audit Manual for Healthcare Manufacturers and their Suppliers, Sixth Edition, (Volume 1 - With Checklis)

Volume 1 of this three-part package provides a complete set of checklists for internal and contract device and drug manufacturers and developers, contract software developers, and suppliers of chemical, printed material, electronic component, and general supplies. It also includes a simulated QSIT audit, and a new-product market launch. All of these are referenced to the relevant relevant FDA regulations, EC and IPEC guidelines, and ISO/BSI standards. The text also explains various audit types, do's and don'ts for auditors, and guidance for audit preparation, performance, conclusion, report derivation, and follow up activities. A CD-ROM packaged with the book contains all of the checklists in a customizable electronic format.

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Davis's Pocket Clinical Drug Reference

Make sure your students rely on a trusted reference! This handy pocket guide shows them how to safely administer medications to their adult, pediatric, and geriatric patients, as well as pregnant and lactating women, and those with renal impairments.

Every detail is designed to make it easy for your students to find the information they need in a snap. And, they can count on it for accuracy because it s drawn from Davis s Drug Guide database.

OUTSTANDING FEATURES:

*4 x 7 size fits in a scrub pocket.

*Nearly 1,000 abbreviated drug monographs, organized alphabetically by generic name, deliver must-know information, including...

Trade name

Indications

Drug class

Pregnancy categories

Contraindications

Adverse drug reactions and side effects

Interactions

Dosing information for adult, pediatric, and geriatric patients, pregnant and lactating women, and renal impairment

Generic availability

Monitoring information

*Very important or life-threatening information, such as FDA black box warnings or adverse drug reactions, appears in red type.

*A colored thumb tab makes it easy for your students to find information quickly.

*The appendices features Cytochrome P450 enzyme table, Pediatric IV, immunization guidelines, and more.

*Abbreviations key appears in the front of the book and at the bottom of each page.*

Notes section covers patient safety information.

*Index provides generic and trade drug names.

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Clinical Pharmacology & Therapeutics Journal ~ Volume 85, Issue 5, May 2009

This issue discusses drug delivery and how advances in the pharmaceutical sciences and other scientific fields have enabled substantial progress in this field. Targeting the best route or providing a variety of routes of drug administration presents an array of benefits, such as enhanced drug administration and bioavailability, improved patient acceptance and compliance, decreased toxicity, and precise therapeutic targeting. Technologies enabling drug delivery are now commonly used to create and extend markets, and the pharmaceutical industry is turning to drug delivery to extend the revenueearning lifetime of their biggest products. Growth opportunities for drug delivery systems extend into all therapeutic classes of pharmaceuticals and encompass a wide range of compounds and formulations, presenting many options in the world market. The discovery of better delivery systems in conjunction with the discovery of novel pharmacological compounds will advance disease diagnosis and treatment.

In This Issue

Top of pageRegulating combination products

The US Food and Drug Administration (FDA) guidance on medical devices ensures the safety, efficacy, and security of drugs released to the public. The introduction of combination products has convoluted the approach historically used by the FDA to regulate single-entity products. Lauritsen details the complications faced by the agency in regulating combination products and the most important issues that must be addressed. See page 468

Top of pageAppraising the safety and efficacy of drug-eluting stents

The use of drug-eluting stents (DESs) in procedures has significantly increased worldwide since their approval by the US Food and Drug Administration in 2003. Although DESs are considered superior to bare-metal stents, safety concerns remain in the wake of reports of late stent thrombosis and myocardial infarction. In response to these concerns, new-generation DESs have been approved and made available for use. Using published clinical data, Maluenda et al. appraise the safety and efficacy of several DESs. See page 474

Top of pageEffect of multiple alleles on efavirenz disposition

Efavirenz (EVF), a non-nucleoside reverse transcriptase inhibitor used for treatment of HIV-1 infection, is primarily metabolized by CYP2B6. Although CYP3A4/3A5 has also been associated with higher EVF exposure, the influence of CYP2A6 polymorphism on EVF pharmacokinetics has not yet been determined. Arab-Alameddine et al. discuss the impact of multiple alleles on EVF disposition. See page 485

Top of pageThe growing role of nanoparticles in brain tumor diagnosis and therapy

Nanoparticle-based contrast agents designed for use in diagnosing brain tumors using magnetic resonance imaging (MRI) are capable of providing better information on the extent of tumor. The potential to visualize portions of tumors usually not detectable with conventional MRI makes nanoparticles of interest for advancing the diagnosis, operative management, and adjuvant therapy of brain tumors. Orringer et al. discuss the application of nanoparticles to brain tumor diagnosis and therapy and the many reasons that nanoparticles offer the next frontier in the treatment of brain tumors. See page 531

Top of pageBiologics in cardiovascular regenerative medicine

Stem cell–based cardiovascular regenerative medicine plays an integral role in therapy aimed at achieving structural and functional repair of the myocardium. Although experience gained in the clinical setting has shown stem cell–based cardiovascular regenerative medicine to be feasible and safe, the structural and functional benefits of such therapy have not yet reached their full potential. The very low rate of cell retention by the recipient myocardial tissue justifies review of the accumulated data to guide future developments aimed at overcoming this limitation and achieving a better outcome of stem cell delivery. See page 548

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Handbook of Isolation and Characterization of Impurities in Pharmaceuticals

The United States Food and Drug Administration (FDA) and other regulatory bodies around the world require that impurities in drug substance and drug product levels recommended by the International Conference on Harmonisation (ICH) be isolated and characterized.

Identifying process-related impurities and degradation products also helps us to understand the production of impurities and assists in defining degradation mechanisms. When this process is performed at an early stage, there is ample time to address various aspects of drug development to prevent or control the production of impurities and degradation products well before the regulatory filing and thus assure production of a high-quality drug product.

This book, therefore, has been designed to meet the need for a reference text on the complex process of isolation and characterization of process-related (synthesis and formulation) impurities and degradation products to meet critical requlatory requirements.

It's objective is to provide guidance on isolating and characterizing impurities of pharmaceuticals such as drug candidates, drug substances, and drug products. The book outlines impurity identification processes and will be a key resource document for impurity analysis, isolation/synthesis, and characterization.

- Provides valuable information on isolation and characterization of impurities.
- Gives a regulatory perspective on the subject.
- Describes various considerations involved in meeting regulatory requirements.
- Discusses various sources of impurities and degredation products.

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Practical Design Control Implementation for Medical Devices

Bringing together, for the first time, the concepts of design control and reliability engineering, Practical Design Control Implementation helps you face the challenge of designing and developing products that comply with regulatory requirements and fulfill customer expectations. Written with all levels of management and technical personnel in mind, the authors demonstrate how successful design control implementation can result in fewer customer complaints and medical device reports, more satisfied customers, and faster time-to-market. Part One focuses on the practical aspects of design control implementation for medical devices. The fundamental concepts of design control are not new. What is new is the adoption by the FDA of these principles and their consequent enforcement. Also new to the medical device industry are the different technical concepts, tools, and techniques necessary to implement design control. In this section, each chapter provides practical advice and insight on the required FDA design control elements. Part Two explores the reliability of medical devices and how design control can influence that reliability. The book presents easy to understand examples of typical product design and development phases with the corresponding reliability and risk analysis tools such as failure modes and effects analysis (FMEA), hazard analysis, reliability planning, reliability prediction, design verification, and validation. The authors discuss the inter-relatedness of reliability engineering and design control and apply the concept to medical device design. Providing common sense explanations and guidance, Practical Design Control Implementation helps readers successfully execute design control and reliability engineering procedures that not only meet the FDA guidelines but also meet or exceed customer expectations.

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Good Laboratory Practice Regulations Vol 69

Fully updated and revised to include the latest information since publication of the first edition in 1989, the Second Edition of this highly praised reference covers all aspects of the Food and Drug Administration's (FDA) Good Laboratory Practice (GLP) regulations and techniques for implementation.

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Food and Drug Administration Advisory Committees

Like many other agencies of the federal government, the Food and Drug Administration (FDA) relies extensively on external advisory committees for independent scientific and technical advice. Recognizing that the existing advisory committee system is essentially sound, this volume recommends ways of enhancing the use of these committees in the evaluation of drugs, biological materials, and medical devices; strengthening the agency's management of the system; and increasing the accountability of the system to the public. In doing so, it examines and makes recommendations on such issues as the recruitment of committee members, the FDA's management of financial conflict of interest and intellectual bias among members, and the operations and management of the advisory committee system.

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A to Z Drug Facts: Published by Facts and Comparisons

This compact, portable, alphabetically organized drug reference provides quick access to current, reliable information on more than 4,500 commonly prescribed medications. Each drug monograph is divided into pharmacological and patient care considerations, and includes action, indications, contraindications, route/dosage, interactions, lab test interferences, adverse reactions, precautions/warnings, administration/storage, assessment/interventions, and patient/family education. Icons and a second color are used to help readers quickly locate the information they are looking for. A color identification section enables readers to identify drugs by appearance. Coverage includes the newest FDA approvals, investigational and orphan drugs, and indications for labeled, unlabeled, and orphan uses.

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The Pharmaceutical Regulatory Process, Second Edition

This Second Edition examines the mechanisms and means to establish regulatory compliance for pharmaceutical products and company practices. It focuses on major legislative revisions that impact requirements for drug safety reviews, product regulatory approvals, and marketing practices. Written by top industry professionals, practicing attorneys, and FDA regulators, it includes policies and procedures that pharmaceutical companies need to implement regulatory compliance post-approval.

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Microbial Limit and Bioburden Tests: Validation Approaches and Global Requirements,Second Edition

A Practical Guide to Microbial Limit Methodologies

In recent years, the field of pharmaceutical microbiology has experienced numerous technological advances, accompanied by the publication of new and harmonized compendial methods. It is therefore imperative for those who are responsible for monitoring the microbial quality of pharmaceutical/biopharmaceutical products to keep abreast of the latest changes. Microbial Limit and Bioburden Tests: Validation Approaches and Global Requirements guides readers through the various microbiological methods listed in the compendia with easy-to-follow diagrams and approaches to validations of such test methodologies.

Includes New and Updated Material

Now in its second edition, this work is the culmination of research and discussions with technical experts, as well as USP and FDA representatives on various topics of interest to the pharmaceutical microbiologist and those responsible for the microbial quality of products, materials, equipment, and manufacturing facilities. New in this edition is an entire chapter dedicated to the topic of biofilms and their impact on pharmaceutical and biopharmaceutical operations. The subject of rapid methods in microbiology has been expanded and includes a discussion on the validation of alternative microbiological methods and a case study on microbial identification in support of a product contamination investigation.

Substantially updated and revised, this book assists readers in understanding the fundamental issues associated with pharmaceutical microbiology and provides them with tools to create effective microbial contamination control and microbial testing programs for the areas under their responsibility.

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Technology Transfer: A Practical Guide

There can be few pharmaceutical companies over the last 15 years that have not undergone the maelstrom of take-overs, mergers, downsizing, centres of excellence or product rationalisation. All these events can, and frequently do, result in product or products being transferred between manufacturing sites. At best it will be a product or product type that the receiving site is familiar with, or at worst, one with which they are totally unfamiliar.
The challenges to effect technology transfer in a timely fashion, within budget and achieving savings that have probably been pre-commirted, at the requisite quality are approximately the same for each aspect. This guide provides a "ready reckoner" of the issues to be considered to achieve these objectives, ensuring that the regulatory issues from both a licensing and inspection
perspective are addressed, and maintaining the organisation's integrity for its products and with its shareholders. In considering the technology transfer process reference is made to the situation within the European Union (EU) in the main; however, where useful guides or proposals are available from other regulatory authorities, notably the FDA, these have been included for completeness.

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