By Christoph Frick and Nicola Spiggelkötter. Creating a Master Plan for Drug Warehousing, Transportation and Distribution

Transcription

1 By Christoph Frick and Nicola Spiggelkötter Creating a Master Plan for Drug Warehousing, Transportation and Distribution

2 ISBN: Where a product trademark, registration mark, or other protected mark is made in the text, ownership of the mark remains with the lawful owner of the mark. No claim, intentional or otherwise, is made by reference to any such marks in this book. While every effort has been made by Maas & Peither AG GMP Publishing, to ensure the accuracy of the information contained in this book, this organisation accepts no responsibilty for errors or omissions. Copyright 2014 by Maas & Peither AG GMP Publishing, All Rights Reserved This book is based on a chapter of the GMP MANUAL, Good Manufacturing Practice and Implementation. The material has been adapted and edited incollaboration with the FDAnews, 300 N. Washington St., Suite 200, Falls Church, VA Maas & Peither AG GMP Publishing Karlstrasse Schopfheim Germany Neither this e-book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording or by any information storage and retrieval system without permission in writing from the publisher.

3 Creating a Master Plan for Drug Warehousing, Transportation and Distribution Table of Contents About the Authors...2 Introduction...3 Regulatory Principles: EU, U.S., Canada and WHO...5 Transport Conditions: Transport As Mobile Storage...15 Transport Vehicles and Transport Packaging...22 Modes of Transportation: Guidelines and Quality Standards for Land Transportation...30 Monitoring Transport Temperatures...38 Risk Management in Transportation...45 Qualification of Large-Scale Active Systems (Trailers)...50 Qualification of Passive Insulation Boxes...58 Logistics Service Providers...68 Transport Validation...84 References...94

4 About the Authors Christoph Frick is the head of pharmaceutical development at Kohlpharma in Germany. He has worked for years at Kohlpharma and other companies with a focus on quality assurance, good manufacturing practice, good documentation practice, cool chain processes, risk management, qualification and validation, auditing, business development and regulatory affairs. Nicola Spiggelkötter is a pharma consultant with years of experience in quality assurance and API sourcing, cold chain, process optimization, audits, staff training and risk management.

5 Introduction Creating a Master Plan for Drug Warehousing, Transportation and Distribution The production of high-quality, safe medicinal products is the objective of every pharmaceutical company and is subject to GMP rules. Even though a medicinal product may be of impeccable quality when it leaves the manufacturing facility, during transport to the consumer it is exposed to many influences beyond the manufacturer s control that can compromise the product s quality. Therefore, it is not surprising that pharmaceutical transport or carriage in accordance with good distribution practice has recently become a topic of steadily growing importance. This change in awareness can be observed in inspections by authorities and in the quality assurance departments of pharmaceutical companies. However, the requirements made in the usual regulatory structures are not homogenous. Numerous guidelines are undergoing revision and new ones are being issued. For example, the revised EU GDP guidelines became effective Nov. 24, The catchphrase supply chain integrity is making the rounds, and refers to a closely knit supply chain as it relates to the infiltration of falsified medicinal products. Keeping falsified medicinal products from infiltrating the distribution chain is a core objective that affects the following aspects of transport processes: Admission/access control during the transport process Authentication and verification of sources of supply and delivery addresses Documentation of the individual delivery steps along the lines of a drug pedigree However, in terms of medicinal product safety, preventing the infiltration of falsified medicinal products into the distribution chain (or the theft of medicinal products from the distribution chain) is not the only aspect of pharmaceutical transport to be considered. Maintaining the required temperatures during transport poses another major challenge. Temperature during transport can greatly affect the quality of the products that reach consumers, as the following practical example illustrates: Wholesale distributors often use frozen cool packs for shipments of medicinal products that require refrigeration, and they generally do so regardless of prevailing outside temperatures. The likelihood that the refrigerated medicinal product will warm up is viewed as the sole risk factor, while little attention is paid to the other extreme, namely freezing. But it is this very drop to below the temperature range of 2 C to 8 C that can be extremely critical. Only a few minutes of exposure of an aluminum adsorbate vaccine to below-freezing temperatures can cause irreversible damage to the product (denaturation). Failure to deal with the problem entails the risk of compromising the product s safety and endangering the patient. This can undermine all GMP-compliant activities of a pharmaceutical company down to the last few steps in the distribution chain. Increasing awareness of transport and temperature is all the more important in light of the fact that one-fifth of the global pharmaceuticals market is occupied by preparations that are subject to cold chain requirements and the trend is growing. 1 Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use (2013/C ), 3

6 Creating a Master Plan for Drug Transportation and Distribution Medicinal products subject to the cold chain are generally high-priced medicines. If workflows are not scrutinized and validated adequately, transport damage could well lead to revenue and sales losses amounting to millions. Measured against a financial risk of this magnitude, the effort involved in transport validation is reasonable and economically feasible. Intermediate storage under a third party s responsibility may become necessary in the course of distribution, for instance on Sundays or holidays. Performing a prospective and/or retrospective qualification of a cold-storage facility is therefore also an important prerequisite for controlled storage conditions. Several cooperation partners are usually involved in the distribution chain. However, there may be marked differences in their GMP background and the regulatory structures applying to them. Each one, however, is responsible for pharmaceutical safety. Coordinating a distribution chain of this nature represents a major challenge that must be met. 4

7 Creating a Master Plan for Drug Warehousing, Transportation and Distribution Regulatory Principles: EU, U.S., Canada and WHO The revised Guidelines on Good Distribution Practice of Medicinal Products for Human Use became effective Nov. 24, Implementation of the guidelines is intended to support wholesale distributors and to help prevent the infiltration of falsified medicinal products into the legal distribution chain. The safety and integrity of the supply chain is of paramount importance here. Others involved in the supply chain are expressly included: Relevant sections of these guidelines should also be adhered to by other actors involved in the distribution of medicinal products. Transportation providers top the list of those actors. EU GDP Guidelines: Chapter 1 Quality Management Chapter 1 Quality Management deals with quality systems and the role played by management. A comprehensive quality assurance system should be implemented and documented. The demand that principles of quality risk management be applied here presents a challenge to many wholesale distributors. This risk-oriented approach is a theme that runs throughout the guidelines. Explicit references to ICH Q9: Quality Risk Management are also made. A quality assurance system has six key tasks assigned to it: Procurement, storage, delivery and export of medicinal products in conformity with good distribution practices Definition of managerial competence and responsibility Shipment of medicinal products Prompt provision of documentation Documentation and follow-up on deviations Initiation of CAPA actions Chapter 2 Personnel The appointment of a responsible person and that person s ideal qualification ( A degree in pharmacy is desirable ) have clearly raised the standard of desirable qualifications. Here, too, the proximity to the GMP-regulated sector becomes clearly evident. Furthermore, the guideline says constant availability (24/7) of the responsible person is expected, especially when it comes to product recalls. This requirement may entail rerouting phone calls and being on call, so to speak. For example, for some time now this has been customary practice for issuing alerts, when the monitoring system detects a failure or a deviation from the specified temperature. Some of the key tasks are: Implementing and maintaining a quality management system Monitoring processes and workflows that have been approved 5