■Purpose of this book
◎This book was explained based on the experience of the author, who has been involved in PV work and guidance for many years at a major pharmaceutical company.
From the author's point of view, this book introduces the method of introducing QMS according to the process approach, the method used in the process, and the key points.
It presents an overview of methods and tools that the author considers particularly useful for a variety of measures.
 

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■By the “INTRODUCTION”

                The EU GVP Module I -Pharmacovigilance systems and their quality systems (hereinafter referred to as Module I) is a guideline that describes the requirements related to the quality system (hereinafter referred to as the quality system) in pharmacovigilance (PV) and has been published for over seven years. The PV departments of pharmaceutical companies with head offices or branches in the EU, the PV departments of their license partners, which have authorized medicines for human use  in the EU, and the companies that outsource all or part of PV operations related to these medicines, (hereinafter, the PV Department of Pharmaceutical Company and the company outsourced PV operations are collectively referred to as an organization) developed a quality system according to Module I provision as a legal obligation.

                 However, many organizations have not yet fully introduced or maintained the quality system, and there are cases where fully understanding the requirements of Module I is not considered essential. Therefore, the quality system required by Module I and its construction are explained in this book.

                 The quality system referred to in Module I is substantially equivalent to the quality management system, and it is difficult to build and maintain the required level of the quality system from the requirements of Module I. Therefore, as supplementation with ISO9001 is indispensable, ISO9001, which is consistent with Module I, is used to compensate for the shortage. With the revision from 2008 to 2015 edition, incorporating recommendations into the requirements, deleting some requirements, reorganizing the clauses, etc. were conducted, but the essence has not changed since the 2008 edition.

                 This book is not an in-depth article explanation of Module I and ISO9001. However, it is organized according to the actual flow in building and operating PV systems and processes in the process approach. It would be greatly appreciated if the organizations that will build and operate PV systems and processes in the future, as well as those that have operated them, can review the current systems, process structures, and operations with reference to this book.

CHAPTER 1　OVERVIEW OF ISO9001 AND MODULE I

1.　ISO standards
2.　Overview of ISO9001
2.1　Quality
2.1.1　Requirements
2.1.2　Quality in terms of product life cycle
2.1.3　Quality from the customer’s perspective
2.2　Management and management systems
2.2.1　Management （system） and quality management （system）
2.2.2　Study of the introduction of QMS
2.3　Assurance
2.3.1　Changes in requirement levels
2.3.2　Quality assurance in the process approach
3.　Outline of Module I
3.1　Configuration of Module I
3.2　Relationship between PV systems and quality systems
4.　Comparison between ISO9001：2008 and Module I
4.1　Similarities between ISO9001：2008 and Module I
4.2　Differences between ISO9001：2008 and Module I
5.　Documentation and recordkeeping
5.1　Documentation
5.2　Retention of records
6.　Management review


CHAPTER 2　Establishment of PV business management systems and construction of quality systems
1.　Mission, product, customer, interested party, environmental trend
1.1　PV product
1.2　Customer and interested party determination and understanding of expectations and requirements
1.3　Understanding the environment
1.4　Key points of the survey and analysis
2.　Quality policy and objectives
2.1　What is quality?
2.2　What is quality in PV regulations?
2.3　Quality policy and quality objectives
2.3.1　The role of quality policy and quality objectives
2.3.2　Setting quality objectives
2.3.2.1　Setting an appropriate timeline
2.3.2.2　Setting quality objectives
2.3.2.3　Means for achievement
2.4　Drafting an execution plan for quality objectives（quality plan）
2.5　Risk
2.6　Execution control of quality plan
2.6.1　Executing the plan
2.6.2　Gantt chart and arrow diagram
2.6.3　How to prepare an arrow diagram
3.　Process development
3.1　Difference between process and procedure
3.2　Management on an organizational basis and a process basis
3.3　Interaction between production process and other processes
3.4　Process development and arrangement
A）Clarification of PV system configuration
A）-1　Clarification of regulations and requirements
A）-2　Product clarification
A）-3　Clarification of the required process
A）-4　Clarification of input and products in required processes, and interrelationships in the processes
B）Product design
B）-1　Extraction of quality requirements for the product and process
B）-2　Quality planning and designing
B）-2.1　Quality function deployment
B）-2.2　Case of quality design
B）-2.3　Deployment of required quality according to a tree diagram
B）-2.4　Deployment to quality elements
B）-2.5　Preparation of quality table
B）-3　Examination of mechanism/parts group that constitute the product and elements work/parts thereof
C）Deployment to process and preparation of procedure
C）-1　Deployment to process
C）-1.1　Drafting of the process and peripheral information
C）-1.2　Turtle diagram
C）-2　Analysis of necessary technology and resources
C）-3　Key point for quality assurance in the process
C）-4　Preparation of procedural document
C）-4.1　Operation standard in PV
C）-4.2　Considerations in preparation
C）-4.3　Reviewing risks in procedures
4.　System and process operation
4.1　Resource management
A）Personnel
A）-1　Preparation of job description
B）Facilities, Equipment and Apparatus
C）External resources
4.2　Procedural training
4.2.1　Process operation to prevent procedure violation
4.2.2　Implementation of procedural training
4.3　Ensuring compliance with procedure
4.3.1　Case of an accident due to non-compliance with procedures（1）4）
4.3.2　Case of accident due to non-compliance with procedures（2）5,6）
4.4　Error measure
4.4.1　Error caused by human characteristics
4.4.1.2　Error by social loafing
4.4.1.3　Other factors
4.4.2　Error elimination 
4.5　Monitoring
4.5.1　Purpose of monitoring
4.5.2　Monitoring according to process characteristics
4.5.3　Control chart
4.5.3.1　X-R control chart
4.5.3.2　T-type matrix
4.6　Early process control
4.7　Variation point control
4.8　Change control
5.　Audit
5.1　Audit plan
A）Strategic level audit planning
B）Tactical level audit planning
C）Operational level audit planning
5.2　Implementation of audit
A）Preparation of an audit agenda
B）Opening meeting
C）Interviews and review of documents and records
D）Closing meeting
5.3　Reporting of audit results
5.4　Analysis of audit results
5.5　Training of auditor
A）Qualification
B）Qualities
C）Work experience
D）Knowledge
E）Skills
6.　Improvement（handling abnormalities, problems, and unfavorable situations：CAPA）
6.1　Problems in the preparation and management of CAPA
6.1.1　Problems in CAPA preparation
6.1.2　Problems in CAPA management
6.2　Understanding the actual situation and status of the problem
6.3　Correction
6.4　Root cause analysis and impact assessment
6.5　Corrective action
6.5.1Response to recurrence prevention
6.5.2　Addressing root causes
6.5.3　Planning and implementation of corrective action 
6.6　Preventive action
6.7　Execution of CAPA
6.8　Evaluation of CAPA effectiveness