QM: 4.2.2 Quality Manual, 4.2.3 Control of Documents & 4.2.4 Control of Records

Introduction

In pharmaceutical sector documentation system varies from company to company.  

Pharmaceutical documentation system can be divided into two functional classes for better understanding, segregation and control:

•      Product Documents
•      Process Documents

Product Documents:

Documents generated during the product life cycle (ICH Q10). This category include product development plan, developmental history reports, stability data, process validation data, preclinical reports and data, clinical trial reports and data, drug master files and dossiers, specifications (raw materials, intermediaries, finished products, container closure system), batch manufacturing procedures and records, batch testing procedures and records, Batch release records, batch dispatch records, post marketing surveillance, market complaints, product recall etc. For each product these documents are different and uniquely identified based on product code.

The makeup of these documents is defined by regulatory requirements for product & process and applicable GMP requirements.

Support Process Documents:

These are the documents of supporting processes required for proper product realization, quality compliance, regulatory compliance and customer satisfaction. The makeup of these processes may vary from organization to organization and are influenced by organizational size and structure. These processes/departments include:

Human Resource: Other than administrative function HR deals with the requirement of personnel as per GMP guidelines. Human resource ensures that the personnel performing work affecting the conformity to the product requirements shall be competent on the basis of appropriate education, training, skill and experience. They define job descriptions, job responsibilities and reporting pattern for each post and individual. In some organizations (instead of Quality Assurance) competence, training and awareness of the personnel are also included in Human Resource functions.

Purchase: Ensures that the purchased product confirms to specified purchase requirements and necessary resources are provided as per need and in time. These resources may include infrastructure, work environment, raw materials etc.

Warehouse and Dispatch: This process includes physical verification of purchased product, its identification and traceability. Approved materials are distributed for different product realization steps and their traceability is maintained.

Production (General): This includes operation and activities other than product manufacturing activities which supports and ensures that the production process is carried out as per GMP. This includes cleaning processes, facility and equipment operation and maintenance, personnel and material flows, waste disposal, biosafety, bio-security, containment, product changeover and campaign change, equipment qualification and calibration etc.

Quality Control: Testing and control procedures other than product testing. This includes raw and packaging material, Environmental Monitoring, Water system testing, Analytical Method validations, Microbiology, Good Laboratory Practices etc.

Quality Assurance: Control and supervision of all the production, testing and control activities. The process includes implementation of Quality and QMS system in an organization as per regulatory guidelines and applicable GMP standards.

Maintenance and Engineering: Ensures that the plant, equipment and machineries operate under total control and are maintained to minimize breakdown. Equipments are qualified and maintained as per schedule. All the instruments are calibrated as per defined frequency.

Documents of all the above processes/ departments shall be identified with a unique identification number to better control over documents.

4.2.2	Quality Manual
4.2.3	Control of Documents
4.2.4	Control of Records

4.2.2 Quality manual:

This Quality Manual is prepared in line with the requirements of ISO 9001:2008.  The Quality Manual supplemented by system documents describes company’s QMS. The scope and permissible exclusions of the QMS are described in section one (Scope) of this manual. Each section of the manual references documented QMS procedures relating to the requirements outlined in that section. The Process Flow provides a description of the processes and interaction between the processes within QMS system.

4.2.3 Control of document:

(The brief policy of the documentation control system shall be provided at this point. Introduction to process wise or department wise segregation of the documents practiced in the company can be provided.) For example:

For the purpose of control Documentation system is divided into two sections:

Product Documents

Support Process Documents

(Description of the sections can be given as above.)

(A detailed description of document control procedure or just an overview may be given in this paragraph.) Responsibility of document control and management is shared between QA and owner department of the document. The document control system is defined in SOP (cite procedure reference no) and ensures that:

• Approve documents for adequacy prior to issue
• Review, update as necessary and re-approve documents
• Ensuring that changes and current revision status of documents are identified
• Ensure that relevant revisions of applicable documents are available at points of use
• Ensure that documents remain legible, readily identifiable and retrievable
• Ensure that documents of external origin are identified and their distribution controlled
• Prevent the unintended use of obsolete documents, and apply suitable controls and identification measures if they are retained for any purpose

4.2.4 Control of Quality Records

The records are maintained as per SOP (cite procedure reference no) demonstrate conformance to specified requirements and the effective operation of the quality management system. The procedure specifies the methods for controlling quality system records, defines internal requirements for record keeping and requires that records are identified, collected, indexed, filed, stored and maintained in a manner that provides assurance that they are retrievable when required.

The records are also classified, maintained and archived as per paragraph 1 of 4.2.3 Control of document.

QM: 4.2 Documentation Requirements (4.2.1 General)

Introduction

This section provides the general outline the structure of documentation system maintained in an organization.

Types of documents in a pharmaceutical company can be:

• Quality Policy (a part of Quality Manual)
• Quality Objectives (Part of Quality manual, annexure to QM, or a separate document)
• Quality Manual
• Plans (Quality Plans, Test and Inspection Plans, Product Realization and Control Plan, Service realization and control plans,  Risk assessment and Mitigation plans etc)
• Procedures (Quality Procedures, Operating Procedures, Product Realization Procedures)
• QA/Control Procedures and Quality Specifications
• Design Standards (DSs)
• Manufacturing specifications
• Labeling and Packaging specifications
• Work Instructions and Forms
• Standards and Codes
• Technical Reference Materials
• Device Master Record/Master formulae Record
• Engineering documents, including drawings, specifications, procedures and other document defining products and system
• Customer engineering documents
• Records (Manufacturing and Processing records, Records of Internal Review, Records of Product realization, equipment operation, logbooks etc)
• Reports (Inspection and test report, audit reports, CAPA)

4.2	DOCUMENTATION REQUIREMENTS
4.2.1	General

4.2 Documentation requirements

4.2.1 General:

Company’s Quality Management System documentation includes:

• Documented statement of Quality Policy
• Documented statement of Quality Objectives
• Quality Manual
• Procedures and Work Instructions (Required for implementation, maintenance and control of QMS (including 6 mandatory procedures by ISO Standard, Procedures required for effective planning, operation and control of processes)
• Records (Records required by ISO Standard and those generated through planning, operation and control of processes)
• Standards and other technical reference materials
• Any documents specified by national or regional regulations

or

As classified by ISO template Quality Manual

• Level 1: Policies – key system objectives
• Level 2: Quality Manual – approach & responsibility
• Level 3: Procedures – methods (Who, What, Where & When)
• Level 4: Work Instructions – description of processes (How)
• Level 5: Forms, Data & Records – evidence of conformance

The term "document" is also used to name the information of a similar character stored in a computer. (Paper based documentation system and electronic documentation system shall be demarcated and explained in this section). The company ensures that personnel have access to QMS documentation and are aware of relevant procedures.

Subcontractors are provided access to applicable documents through document control distribution.

QM: 4 Quality Management System (4.1: Introduction)

Form this point onwards management’s commitment for implementation of QMS and policy adopted for fulfilment of each and every clause of the Standard are explained. Detail of the information provided in the quality manual (QM) depends upon the complexity of the organizations processes & interaction and structure & complexity of documentation system. For a simple documentation system all the quality procedures can be explained in detailed in a QM and thus the manual becomes the only document for implementation of QMS. In a complex documentation system, policy and brief description of implementation of requirements of each clause are given in the manual along with the reference of the document containing detailed description.

4	QUALITY MANAGEMENT SYSTEM
4.1	INTRODUCTION

4.1 Introduction:

The company has established, documented, implemented and maintains a Quality Management System in accordance with requirements of ISO 9001:2008 and applicable regulatory (FDA, EU, MHRA…) and statutory requirements.

or

This Quality Manual and its associated policies and procedures establish and document the means by which the company implement, maintain and continually improve its QMS. It is not a stand-alone system, but is integrated within companies operating discipline which encompasses the policies, requirements, and work processes of (applicable regulatory requirements- FDA, EU....), (applicable pharmacopeia BP/USP....), (applicable statutory and regulatory requirement of product), Environment (applicable laws), Health, Safety, Human Resources (applicable laws and rules) and Quality.

(Company’s design/model of QMS system) The system is maintained and continually improved through the use of the quality policy, quality objectives, audit results, analysis of data, corrective and preventive action and management review. The company also has a system in place to review, evaluate, and address customer satisfaction.

4.1.1 The processes needed for the QMS and their application throughout the organization have been determined (Description of the process flows can be given at this point or annexed to the manual).

4.1.2 The sequence and interaction of these processes has been determined. (Sequence of the interaction can be given at this point or annexed to the manual)

4.1.3 The company has determined criteria and methods needed to ensure that both the operation and the control of these processes are effective and documented them in quality plans, procedure and work instructions and controlled through Measuring, Monitoring and Analysis.

4.1.4 The management ensures the availability of resources and information necessary to achieve planned results and continual improvement of these processes, including the development of appropriate departments to handle defined responsibilities as part of the Quality Management System.

4.1.5 The company has established a system to monitor, measure, and analyze these processes.

4.1.6 The company has established processes for identification and implementation of actions necessary to achieve planned results, maintain effectiveness and continual improvement of these processes.

4.1.7 Additional processes may be added to the determined process, as new customer products and/ or regulatory requirements are introduced.

(Control over outsourced processes) The company ensures that outsourced processes are managed within the umbrella of QMS. All requirements and specifications of outsourced processes are identified for the better control over the outsourced processes. All outsource parties are selected and approved as per the supplier qualification procedure. Controls and requirements of outsourced processes are outlined in the applicable Supplier Qualification procedure(s) (Cite Procedure No).

Outsourced processes and services may include the following (provide list of outsources processes/services):

1.

2.

3.

Supplier history information is maintained and monitored. Records regarding the control of outsourced processes are maintained in the applicable supplier files. The company works closely and has regular communication with the suppliers of these outsourced services.

Process Flow and sequence of Interaction between the processes:

The process flow of each determined process within the umbrella of QMS can be prepared separately.  Process can be explained in a block diagram with interacting process in side arm, e.g.:

Or an exhaustive process flow depicting all the processes and their interactions can be prepared. 

Process interaction matrix chart can be prepared as follows:

QM: Introduction, 1 Scope and Exclusions, 2 References & 3 Terms and Definations

	INTRODUCTION
1	SCOPE
2	REFERENCES
3	TERMS & DEFINITIONS

Introduction 

The introduction page of the quality manual (QM) shall introduce the reader to the organization and provide evidence of its commitment towards QMS. Introduction may contain brief description of the following:

·                     Introduction to the organization

·                     Site Address and Contact Details

·                     Licenses and Approvals

·                     Company Products and Services

·                     Legal and Regulatory Obligations (product, process, environment etc)

·                     Why QMS is adopted by the organization, Organizations Mission and Vision

·                     Purpose of Quality manual and its section wise makeup

·                     Responsibilities: For implementation of QMS, Review of Quality Policy, Review          of Quality Objectives, review of Quality Manual.

Scope and Exclusions

First define the scope of QMS and then give exclusions along with justification.

            Scope:

            Exclusion:

            Clause:

            Justification:

ISO 9001:2008 standard states following requirements for Scope and Exclusion- ISO 9001:2008, 1.2 Application, Para 2 & 3: Where any requirement(s) of this International Standard cannot be applied due to the nature of an organization and its product, this can be considered for exclusion. Where exclusions are made, claims of conformity to this International Standard are not acceptable unless these exclusions are limited to requirements within Clause 7, and such exclusions do not affect the organization's ability, or responsibility, to provide product that meets customer and applicable statutory and regulatory requirements. ISO 9001:2008, 4.2.2 Quality manual The organization shall establish and maintain a quality manual that includes a) the scope of the quality management system, including details of and justification for any exclusions (see 1.2), This means, exclusions form the ISO 9001:2008 standard are acceptable however, these exclusions shall be limited to clause 7 (Product Realization). Entire clause or a sub clauses can be exempted if proper justification for exclusion is provided. The scope of Quality Manual shall include all the processes which are covered under QMS. Statement of scope should be relevant, complete in all sense, clear & unambiguous and precise. For certification purpose the organization is audited for the processes defined in a scope.

References

Documents, guidelines, regulations etc., which are referred during implementation of the QMS and preparation of QM, shall be enlisted in this column. These can be divided into two sub groups:

            Regulatory Requirements (if not given in introduction sub section Legal and Regulatory Obligations)

            Standards and guidelines

Terms and Definition

Explanation of terms and definitions used in the Quality Manual are given in this section. Standard vocabulary terms and definitions are available in ISO 9000:2005.

References:

ISO 9001:2008 Quality management systems — Requirements

ISO 9004:2009 Managing for the sustained success of an organization- A quality management approach

ISO 9000:2005 Quality management system: Fundamentals and Vocabulary 

Quality Manual: Format of Cover Page and Revision History.

A.           Cover Page with approvals

The design of the cover page varies form organization to organization. Here I have prepared a template of cover page of QM which can be applicable to all the other documents.

Quality Manual Header: Header shall be consistent in all the pages of the document. The annexes to the manual may have unique header.

Company Name and Logo
QUALITY MANUAL
(Site, Location and Owner Department of the Document)
QM001(Document number for QM)	Revision No:00
Supersedes: None	Page Number: 1 of 18

Quality Manual Approval Sheet Format:

	Prepared By:	Reviewed  and Approved By:		Authorized By:
Name:
Designation and Role:
Signature
Date
Effective Date: (To be filled in by blue pen)			Next Revision: (To be filled in by blue pen)

B.            Revision History Quality Manual(Amendment Record) Format:

Page 2 of the manual.

Revision Number:	Change Summary:
00	None

In case the document is revised give subsequent revision number and explain the nature of change and reason for change (including reference of change control if any) in the change summary column. A policy can be adopted for giving three to five recent change histories in this table.