The FDA and Worldwide Current Good Manufacturing Practices and Quality System Requirements Guidebook for Finished Pharmaceuticals

Jose (Pepe) Rodriguez-Perez

Description

Good Manufacturing Practices (GMP) for human pharmaceuticals affects every patient taking a medicine. GMP covers all aspects of the manufacturing process, from defining manufacturing processes to systems for recall and investigation of complaints. Consumers expect that each batch of medicines they take will meet quality standards so that they will be safe and effective.
GMPs provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. This formal system of controls at a pharmaceutical company, if adequately put into practice, helps to prevent instances of contamination, mix-ups, deviations, failures, and errors. This assures that drug products meet their quality standards.
This guidance book is meant as a resource to manufacturers of pharmaceuticals, providing up-to-date information concerning required and recommended quality system practices. It should be used as a companion to the regulations/standards themselves and texts on the specific processes and activities contained within the QMS.
As a bonus, this package contains dozens of FDA guidance documents as well as international harmonization documents (WHO, PIC/S, and ICH). A check list for GMP audit is also included based on risk management criteria. An exam complements the extra material.

Sujets

• Business
• Qualité, hygiène, sécurité, environnement
• Total Quality Management
• Gestion et management
• risk management
• FDA
• Economics
• Food and Drug Administration

Informations

• Publié par: ASQ Quality Press
• Date de parution: 30 avril 2014
• Nombre de lectures: 1
• EAN13: 9780873898294
• Langue: English

Extrait

The FDA and Worldwide Current Good Manufacturing Practices and Quality System Requirements Guidebook for Finished Pharmaceuticals
José Rodríguez-Pérez
ASQ Quality Press
Milwaukee, Wisconsin
American Society for Quality, Quality Press, Milwaukee 53203
© 2014 by ASQ
All rights reserved.
Library of Congress Cataloging-in-Publication Data
Rodríguez Pérez, José, 1961–
The FDA and worldwide current good manufacturing practices and quality system requirements guidebook for finished pharmaceuticals / José Rodríguez-Pérez.
pages cm
Includes bibliographical references and index.
ISBN 978-0-87389-869-0 (alk. paper)
1. Pharmaceutical industry—Production standards—United States. 2. Pharmaceutical industry—United States—Quality control. 3. Drugs—Standards. I. Title.
RS192.R63 2014
338.4 ′ 76151—dc23
2014018745
No part of this book may be reproduced in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher.
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Managing Editor: Paul Daniel O’Mara
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This book is dedicated to all my associates at Business Excellence Consulting Inc. Thanks for your support and sharing our passion for quality.
Preface
Quality must be built into the product—testing alone cannot be relied on to ensure product quality.
G ood manufacturing practice (GMP) for human pharmaceuticals affects every individual who takes medicine. Consumers expect that the medicines they take will meet quality standards and will be safe and effective. Most people, however, are not aware of the existence of GMP or how government regulators ensure that drug manufacturing processes meet these basic objectives.
The original requirements for GMP from the World Health Organization (WHO) date back to 1975. The WHO defines GMP as “that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.” 1 Chapter 4 discusses WHO GMP requirements.
GMP covers all aspects of the manufacturing process: defined manufacturing process; validated critical manufacturing steps; suitable premises, storage, and transport; qualified and trained production and quality control personnel; adequate laboratory facilities; approved written procedures and instructions; records to show all steps of defined procedures were taken; full traceability of a product through batch processing records and distribution records; and systems for recall of product and investigation of complaints.
GMP constitutes the element of quality assurance that ensures products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by government authorization or product specification. GMPs are related to both production and quality control and they cannot be considered “best practices”; rather, they establish threshold or minimum standards that must be satisfied in order for a pharmaceutical manufacturing operation to be compliant.
GMP provides for systems that ensure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the GMP regulations ensures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations. This includes establishing strong quality management systems (QMSs), obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories. This formal system of controls at a pharmaceutical company, if adequately put into practice, helps prevent instances of contamination, mix-ups, deviations, failures, and errors. This ensures that drug products meet their quality standards.
The guiding principle of GMP is that quality is built into a product, not just tested into a finished product. Therefore, the assurance is that the product not only meets the final specifications but is made by the same procedures under the same conditions each and every time. There are many ways this is done, such as by controlling the quality of the facility and its systems, controlling the quality of the starting materials, controlling the quality of production at all stages, controlling the quality of the testing of the product, controlling the identity of materials by adequate labeling and segregation, controlling the quality of materials and products by adequate storage, and so on. All of these controls must follow prescribed, formal, and approved procedures or master formulae describing all the tasks carried out in the manufacturing and control processes.
The GMP requirements were established to be flexible in order to allow each manufacturer to decide individually how to best implement the necessary controls by using scientifically sound design, processing methods, and testing procedures. The flexibility in these regulations allows companies to use modern technologies and innovative approaches to achieve higher quality through continual improvement. Accordingly, the “c” in cGMP stands for “current,” requiring companies to use technologies and systems that are up to date in order to comply with the regulations.
Consumers usually cannot detect whether a drug product is safe or whether it will be effective. While cGMP requires testing, testing alone is not adequate to ensure quality. In most instances testing is done on a small sample of a batch (for example, a drug manufacturer may test a few dozen tablets from a batch that contains several million units) so that most of the batch can be used for patients rather than being destroyed by testing. Therefore, it is important that drugs are manufactured under conditions and practices established by the cGMP regulations to ensure that quality is built into the design and manufacturing process at every step. Facilities that are in good condition, equipment that is properly maintained and calibrated, employees who are qualified and fully trained, and processes that are reliable and reproducible are a few examples of how cGMP requirements help ensure the safety and efficacy of drug products.
It is generally agreed that the cGMP requirements applicable to the manufacture of veterinary medicinal products should be very similar (if not identical) to those for the manufacture of product for human use.
The first manufacturing and quality requirements, which later evolved into cGMPs, were issued in the 1940s in the United States by the Food and Drug Administration (FDA). In the 1969 general meeting of the WHO, the World Health Assembly issued a recommendation for the introduction of GMPs. Since then, most industrialized countries have passed laws on control procedures essential for the manufacture of drug products. The cGMP regulations originated from congressional concern that impure and otherwise adulterated drugs might escape detection under a system predicated only on seizure of drugs shown to be in fact adulterated.
In 1962, the US Congress enacted various amendments to the Federal Food, Drug, and Cosmetic (FD&C) Act of 1938 to “strengthen and broaden existing laws in the drug field so as to bring about better, safer medicine and to establish a more effective system of enforcement of the drug laws.” 2
Among the amendments was a section by which a drug is deemed adulterated if its packaging, processing, holding, or manufacturing fails to conform to “current good manufacturing practice (cGMP) to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.” The FDA issued its first regulations under this section in 1963, and in February 1976, it announced a proposal to revise and update the then-current GMP regulations.
The legal authority for the FDA to impose minimum manufacturing standards is set forth in the Federal FD&C Act, 21 U.S.C. sec. 301 et seq. Section 351(a)(2)(B) of 21 U.S.C. requires manufacturers of drugs to operate in conformance with manufacturing regulations established by the FDA. The regulations are primarily contained in Title 21 of the US Code of Federal Regulations (CFR), Parts 210 and 211, and are called the cGMP regulations. Drugs that are not manufactured in accordance with cGMP requirements, including the quality control and quality process mandates, are “adulterated” under the FD&C Act. The knowledge and understanding of cGMP establishes the foundation for drug product safety and quality, allowing for quality to be built into the design and production of pharmaceuticals.
GMP requirements are supported by a central objective: to create a system of programs, policies, processes, and facilities that prevent errors and defects. Senior managers in the pharmaceutical industry are responsible for the effectiveness of this system, which is known as the pharmaceutical quality system (PQS). A PQS is successful when it ensures an ongoing state of control. In a healthy PQS, managers establish a vigilant culture of quality in which timely