Laboratory Control System Operations in a GMP Environment. David M. Bliesner

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       Library of Congress Cataloging-in-Publication Data

      Names: Bliesner, David M., author.

      Title: Laboratory control system operations in a GMP environment / David M. Bliesner.

      Description: Hoboken, NJ : Wiley, [2020] | Includes bibliographical references and index.

      Identifiers: LCCN 2019052264 (print) | LCCN 2019052265 (ebook) | ISBN 9781119529231 (cloth) | ISBN 9781119529279 (adobe pdf) | ISBN 9781119529293 (epub)

      Subjects: LCSH: Medical laboratories--Quality control. | Laboratories--Management. | Pharmacy--Research. | Manufacturing processes--Quality control.

      Classification: LCC RB36.3.Q34 B55 2020 (print) | LCC RB36.3.Q34 (ebook) | DDC 610.28/4--dc23

      LC record available at https://lccn.loc.gov/2019052264

      LC ebook record available at https://lccn.loc.gov/2019052265

      Cover Design: Wiley

      Cover Image: © Image Journal-Photography/Getty Images

To my wife and best friend, Kathy.

Preface

      Regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) mandate that companies who manufacture drugs for human and animal use be operated in a state of control by employing conditions and controls commonly referred to as good manufacturing practices (GMPs). In the United States the GMPs or CGMPs (where C = current) are codified in 21 Code of Federal Regulations Parts 210 and 211. In the European Union the GMPs are described in EudraLex – Volume 4, the Good Manufacturing Practice (GMP) guidelines. Other Regulatory bodies, such as the World Health Organization (WHO) and the International Council for Harmonization (ICH) also provide requirements and guidelines with respect to GMPs.

      At the turn of the twenty-first century the FDA was actively engaged in regulatory actions against pharmaceutical companies whom they determined to be in significant violation of the CGMPs. As part of FDA's actions, several large companies entered into voluntary legal agreements referred to as Consent Decrees. These agreements existed for the expressed purpose of correcting the deficiencies related to CGMPs. Consent Decrees routinely require the contracting of independent third-party expert consultants. These consultants' duties include performing a baseline audit of the offending facilities, documenting their findings and helping the companies develop and implement corrective action plans.

      To help collect evidence to support regulatory actions, FDA began using a Quality Systems approach to evaluate a firm's level of GMP compliance.

      The Quality Systems approach is a scheme of systems for the manufacture of drugs and/or drug products. The general scheme of systems FDA used for auditing manufacture facilities consists of the following:

      1 Quality System

      2 Facilities and Equipment System

      3 Materials System

      4 Production System

      5 Packaging and Labeling System

      6 Laboratory Control System

According to FDA “The Quality System provides the foundation for the manufacturing systems that are linked and function within it.”¹

      This approach is commonly referred to as the six-system model and is still used today by the FDA to conduct inspections of GMP facilities.

      During this time, Delphi Analytical Services, Inc. (Delphi) served as one of the third-party expert consulting firms on several Consent Decrees at major pharmaceutical companies. Delphi's core competency is the practical understanding of workings of the laboratory control system (LCS), the sixth quality system mentioned in the FDA model. Delphi was extensively involved in performing third-party audits of quality control (QC) and research and development (R&D) laboratories for companies under Consent Decree.

      While executing these consulting assignments it became apparent that the CGMPs regulations, FDA Guidance Documents and FDA Internal Compliance Program Guides offered little direction or specifics of what was expected of a CGMP compliant LCS. Because of this, Delphi developed and documented a systematic means for performing the baseline audits, capturing deficiencies, reporting the results, and developing subsequent corrective action plans, for QC laboratories. In addition, Delphi also created instructional materials and began teaching courses on auditing QC laboratories at various client sites and scientific conferences.

      Due to the inherent complexity of the LCS, Delphi divided it into seven sub systems or sub elements. These included the following:

      1 Laboratory Managerial and Administrative Systems

      2 Laboratory Documentation Practices and Standard Operating Procedures

      3 Laboratory Equipment Qualification and Calibration

      4 Laboratory Facilities

      5 Methods Validation and Technology Transfer

      6 Laboratory Computer