2-1- purpose - elsmar and other manuals/… · web view2-1- purpose. this document ... which...

1. Company History

of 19

2-1- Purpose

This document defines quality system policies and procedures for governing the design & manufacture of all Sobhan Chemotherapeutical Co. products.

2-2- Scope

This quality manual provides details on the policies and procedures Sobhan Chemotherapeutical Co. uses to meet ISO 9001:2000 Quality management system requirements & applicable regulatory requirements (including requirements of Good manufacturing Practice). The intent of these policies and procedures is to demonstrate Sobhan Chemotherapeutical Co. ability to consistently provide products that meet customer and applicable regulatory requirements and to enhance customer satisfaction through the effective application of the quality management system processes.The scope of the quality management system is as the followings:[Insert the organization scope clearly including all products and a statement such as “Design and manufacturing of ….”]

2-3- Exclusions

ISO 9001:2000 Requirements EXCLUSION TABLEClause or Sub-clause Exclusion Justifications

7.5.4 (full) Customer Property

Sobhan Chemotherapeutical Co. does not use customer properties (including intellectual properties) in none of its products realization processes.

3-1- Definitions

The definitions and terms used in this quality manual are based on the following documents:

- (Insert relevant references which contains technical terms of pharmaceutical industry)

- ISO 9000:2005: Quality management systems – Fundamentals and Vocabulary

3-2- References

This manual is organized and written to comply with the following documents and standards:

ISO 9001:2000: Quality management systems - Requirements (Insert relevant regulatory bodies requirements that meeting theses requirements

are mandatory in pharmaceutical industry and organization specific products)Sobhan Chemotherapeutical Co. quality management system complies with the most recent edition of the aforementioned documents and standards. Necessary changes to quality management system are applied continuously by the organization to ensure compliance with applicable standards.All references to specific policies, procedures, or work instructions in this manual are the latest revision of these documents.

of 19

4- Quality management System

4-1- General Requirements

Quality management system in Sobhan Chemotherapeutical Company has been established, documented, and is continually improved in accordance with the requirements of ISO 9001: 2000. To implement the system, the following actions have been taken in the organization:

- The processes needed for the quality management system and their application throughout the organization; have been identified. These processes have been shown in process map (annex number…..). Other additional information related to each process including the inputs, the outputs, the sub-processes, the criteria needed for monitoring and measuring processes and methods used to control processes have been shown specifically in process identification table (SIPOC1) for each process individually.

- The sequence and interaction of these processes has been determined in process map (annex number …..).

- The criteria and methods needed to monitor and measure the effectiveness of processes have been identified as Key Performance Indicators (KPIs). These criteria and methods have been described for each processes and sub-processes in the determination of process criteria form.

- The resources and information necessary to support the operation and monitoring of the processes have been identified for each process in turtle diagrams.

- The identified processes have been regularly monitored, measured, and analyzed through internal audits, analysis of data meetings and management reviews.

- Actions necessary to achieve planned results and continual improvement of these processes are defined in accordance with the monitoring, measurement and analysis results.

These processes are managed in accordance with ISO 9001: 2000.Required controls over outsourced processes that affect product conformity with requirements are being done through the specified mechanisms for evaluation of sub-contractors performance mentioned in clause 7-4 of this quality manual. These processes are identified specifically within the quality management system.

4-2- Documentation requirements:

4-2-1- General

Quality management system documentation in Sobhan Chemotherapeutical Company includes:

- Quality policy- Quality objectives- Quality manual- Documented procedures required by ISO 9001:2000 and legal requirements such

as GMP- Documents needed by the organization in order to ensure the effective planning,

operation and control of processes- Records

1 Supplier, Input, Process, Output, Customer

of 19

QualityPolicy

Quality Manual

Standard Operating Procedures (SOPs)

Work Instructions

Forms, Lists, Records

- External documents such as relevant standards, guidelines and books in relevant fields according to external documents list

The levels of theses documents have been shown in figure 1-1 (hierarchy of documents)

Figure 1-1- Hierarchy of Documents

4-2-2- Quality Manual

Quality manual includes:- The scope of the quality management system (including justification for

exclusions of ISO 9001:2000 requirements) and details related to implementation of ISO 9001:2000 in organization.

- Reference to the documented procedures used in quality management system- Quality policy- Process map (including a description of quality management system processes

and the interaction of these processes)- Organizational chart- Company history

4-2-3- Control of documents:

of 19

Documents and records required by the quality management system are controlled. Document control procedure has been established to define the controls needed to:

- Approve documents for adequacy prior to issue- Review and update as necessary and re-approve documents- Ensure that changes and the current revision status of documents are identified- Ensure that relevant versions of applicable documents are available at points of

use- Ensure that documents remain legible and readily identifiable (Coding system of

documents)- Ensure that documents of external origin are identified and their distribution

controlled- Prevent the unintended use of obsolete documents, and to apply suitable

identification to them if they are retained for any purposeIn order to define the format and contents of SOP2s, SOPs preparation procedure has been prepared.

4-2-4- Control of Records

Records are established and maintained to provide evidence of conformity to requirements and of the effective operation of the quality management system.Records are legible, readily identifiable and retrievable.A documented procedure (Control of records procedure) has been established to define the controls needed for the identification, storage, protection, retrieval, retention time and disposition of records.

References of Clause 4:

- ISO 9001:2000 Standard- Process map- Processes Identification Table No. …………- Identification of Processes Indicators No. ………………..- Document Control Procedure, SP/QA-GE-001- SOPs Preparation Procedure, SP/QA-GE-002- Control of records Procedure No. …………..….

2 Standard Operating Procedures

of 19

5- Management Responsibility

5-1- Management Commitment

Sobhan Chemotherapeutical Company top management has provided evidence of its commitment to the development and implementation of the quality management system and continually improving its effectiveness by:

- Communicating to the organization the importance of meeting customer requirements as well as statutory and regulatory requirements through conducting regular meetings in all organizational levels and providing trainings for all personnel.

- Establishing the quality policy;- Ensuring that quality objectives are achieved and monitoring the trend of

achieving these objectives during management review meetings - Conducting management reviews in 6 months intervals- Ensuring the availability of resources

5-2- Customer Focus

The quality management system in Sobhan Chemotherapeutical Company has been designed with the focus on requirements of different customer groups (including patients, doctors, pharmacies, distribution companies and legal bodies such as Ministry of Health) as the main approach. Top management identifies changes that must be made to align the organization direction with customer needs. To achieve this objective, top management reviews and analyzes customer surveys, marketing reports and marketing department reports of on-sight visits (during management review meetings) and evaluates organization ability to meet customer needs.

5-3- Quality Policy

Sobhan Chemotherapeutical Company top management has documented the quality policy and encourages all personnel to follow this policy. The steering committee ensures that the policy is understood and implemented in all organizational levels. The quality policy is periodically reviewed during the management review meetings in order to ensure its continuing suitability and if necessary it will be republished. The quality policy is:

- Appropriate to organization vision and mission.- Includes management commitment to comply with quality management

requirements and continually improve its effectiveness- Provides a framework for establishing and reviewing quality objectives

5-4- Planning

5-4-1- Quality Objectives

The steering committee defines quality objectives for different areas of the organization according to the company management policies which are specified in quality policy statement annually. These objectives should be:

- Specific and clear- Measurable- Attainable

of 19

- Related to the quality policy- Time-bound

When determining quality objectives, product requirements, customer requirements and required resources needed to achieve the objectives are taken into consideration. After defining the objectives, responsible personnel in determined areas establish the objective achievement plan. This plan includes: time schedule, responsibilities, required resources, objective achievement monitoring methods and other relevant requirements. Quality objective plans should be approved by steering committee and committee is responsible to support the plan through providing the required resources.

5-4-2- Quality Management System Planning

Management representative is responsible for quality management system planning. Activities related to identification of all processes and supervision of developing documents and quality manual are also the responsibility of management representative.

5-5- Responsibility, Authority and Communications

5-5- 1-Responsibility and Authority

Job descriptions for all personnel in accordance with the Sobhan Chemotherapeutical Company organizational chart (which is attached to this quality manual) are prepared by Administration affairs manager cooperating with other managers and after being approved by managing director, job descriptions are submitted to all personnel in all organizational levels. Administration affairs manager has to ensure that responsibilities and authorities are defined in all organizational levels and are available for all personnel.

5-5-2- Management Representative

The top management has appointed the Information Technology chief as management representative. Who, irrespective of other responsibilities, has responsibilities that include:

- Ensuring that processes needed for the quality management system are established, implemented and maintained;

- Reporting to top management on the performance of the quality management system, and any need for improvement

- Ensuring of awareness - Supervising of communication processes to ensure the promotion of awareness of

customer requirements and needs throughout the organization- Acting as liaison with external parties on matters relating to the quality

management system

5-5-3- Communication

The steering committee is responsible for identifying the key communication processes in Sobhan Chemotherapeutical Company. Information communication and transfer methods are different according to the type of information and might include using computer systems, designed quality system documents and conducting internal meetings at different organizational levels. The type of these communicating methods is defined in quality management system.

5-6- Management Review

of 19

5-6-1- General

The quality management system is reviewed at 6 months intervals to ensure its continuing suitability, adequacy and effectiveness and also includes opportunities for improvement and required changes in quality policy and quality objective.Managing director, management representative, quality assurance manager, factory manager, commercial manager, sales and marketing manager, research and development manager and if necessary other relevant personnel participate in management review meetings.The management review procedure has been developed to describe management review process.

5-6-2- Management Review Inputs

Management review input includes:- Results of audits (Internal and external)- Customer feedback- Status of preventive and corrective actions- Quality policy and quality objectives- Recommendations for improvement- Process performance and product conformity- Planned changes that could affect the quality management system- Follow-up actions from earlier management reviews

5-6-3- Management Review Outputs

Output from management review includes any decisions and actions related to:- Improvement of the effectiveness of quality management system and its processes- Improvement of product related to customer requirements- Required resources

References of Clause 5

- Quality policy- Management review procedure No. …………….- Personnel job descriptions

of 19

6- Resource Management

6-1- Provision of resources

Sobhan Chemotherapeutical Company determines and provides in planned intervals, all resources needed to implement and improve the processes of the quality management system and to address customer satisfaction (including human resources, process equipment, utilities, etc). Evidences that required resources (in accordance with the requirement of customers and products requirements and organization development plans) have been provided are documented in the organization annual budget.

6-2- Human Resources

6-2-1- General

Personnel performing work affecting product quality are assigned to the described jobs in the organizational chart in accordance with the competencies (education, training, skills and experience) defined in job descriptions.

6-2-2- Competence, Awareness and Training

In Sobhan Chemotherapeutical Company:- The required competencies for personnel performing work affecting product

quality are defined in job descriptions in accordance with clause 6-2-1- All required trainings are provided in order to meet quality system requirements

and inserted needs in job descriptions in accordance with training procedure.- The effectiveness of trainings is evaluated according to the determined

mechanism mentioned in the training procedure. - Personnel in all levels shall be aware of:

Quality policy Quality management system requirements The importance of conformance with customer requirements, regulatory

bodies, organization commercial partners and organizational requirements How they contribute to the achievement of the quality objectives The impact of their work in quality The benefits of improved performance Their roles and responsibilities in achieving conformance The potential consequences of departure from the specified procedures

- All the relevant records of education, training, skills and work experiences are maintained by Administration affairs manager and training head.

6-3- Infrastructure

The infrastructure needed to achieve conformity to product requirements has been determined and provided and maintained according to the repairs and maintenance procedure. These infrastructures may include, but not be limited to:

- Buildings, workspace and associated utilities (such as cleanrooms, HVAC3

system, water systems, etc)

3 Heating, Ventilation and Air Conditioning

of 19

- Process equipment, (including production and laboratory equipment, reference standards used for calibration, the software used to production and laboratory , etc)

- Supporting services (such as computers, computer networks, lift trucks, etc)All the requirements related to the repair and maintenance activities including maintenance activities frequencies are described in the repairs and maintenance procedure.

6-4- Work Environment

Work environmental conditions at different working areas including temperature, humidity, differential pressure, other relevant parameters and also safety relevant issues that affect product quality (such as personnel clothes, entering into and exiting from cleanrooms, etc) have been determined in production and laboratory environments according to the regulatory requirements related to the products as follows:

- Requirements related to health, cleanliness and clothing of personnel if contact between such personnel and the product or work environment could adversely affect the quality of the products.

- Requirements of environment conditions when these conditions can have an adverse effect on product quality.

- Providing special trainings for all personnel who are required to work temporarily under special environmental conditions.

- Special arrangements for the control of cross contaminationAll above requirements have been established in production SOPs and test methods. Monitoring and controlling environmental conditions methods have been also identified in these instructions.

References of Clause 6

- Training procedure No. SP/TR-GE-001- Repair and maintenance procedure No. ……………………- Management review procedure No. ………………..- Personnel job descriptions- Production SOPs- Test methods

of 19

7- Product Realization

7-1- Planning of Product Realization

The processes needed for product realization are planned and developed, and the interaction between these processes and other processes of the quality management system is also defined. In planning product realization, the following has been taken into consideration:

- Determination of required documents, sub-processes and resources needed to realize these processes

- Verification, validation, inspection and test activities of row materials, packaging material, semi-finished and finished products and their conformance to products acceptance criteria

- Records needed to provide evidence that the realization processes and resulting product meet requirements

All above requirements have been prepared in Drug Master File (DMF) format for all products. SIPOC tables have also been prepared for realization processes at all required levels.

7-2- Customer Related Processes

7-2-1- Determination of Requirements Related to the Product

Requirements related to the product have been determined by the organization, including:- Requirements specified by customers (distribution companies), including the

requirements for products type and quantity and delivery time - Requirements not stated by the customer but necessary for intended use of the

products such as requirements for packaging and information accompanying product

- Statutory and regulatory requirements related to the product including the requirement stated in pharmacopeias or determined by Ministry of Health

- Organizational requirements and requirements stated by commercial partnersThe method for defining these requirements has been described in sales procedure.

7-2-2- Review of Requirements Related to the Product

Requirements related to the product are reviewed. This review is conducted prior to committing to supply a product to customers. These reviews are conducted annually by sales manager according to received information from production planning, marketing and statistics about sales quantity in previous years, production lines capacity and other constraints. Review output is reported to Ministry of Health by managing director. The review of distribution companies’ requirements is also conducted through out the year by sales manager. The intent of these reviews is to ensure that:

- Product requirements (including requirements related to delivery and post-delivery activities) are defined

- Contract or order requirements differing from those previously expressed are resolved

- Records of the results of review and actions arising from this review are maintained

of 19

- When product requirements are changed, relevant documents are amended and the relevant personnel are made aware of the changed requirements.

The detailed information is described in sales procedure.

7-2-3- Customer Communication

Required arrangements for communication with customers relating to the followings are determined and implemented:

- Product information according to the customer communication procedure- Enquiries, contracts or order handling, according to the sales procedure- Customer feedback, according to the customer communication procedure and

when receiving complaints from customer according to the complaints follow-up procedure and when product recall is necessary, this process will be handled according to the product recall procedure

7-3- Design and Development

7-3-1- Design and Development Planning

Planning of R&D4 projects (products design) is being done by R&D manager. R&D manager is responsible for establishing time schedule for each project. During the projects planning, the followings are determined:

- The project stages- Review, verification and validation appropriate to each stage- Responsibilities and authorities

The method for managing the interfaces between different groups involved in R&D projects to ensure effective communication and clear assignment of responsibility has been described in research and development procedure.Time schedule for each project will be updated along with project completion.

7-3-2- Design and Development Inputs

Design and development Inputs are defined according to research and development procedure and records of theses inputs are maintained. These inputs include:

- Functional, performance and safety requirements, according to the intended use (including physical, chemical and other specifications)

- Applicable statutory and regulatory requirements (according to pharmacopoeia requirements)

- Applicable information derived from previous similar designs- Other requirements essential for design and development

All design inputs shall be reviewed and approved for adequacy according to design and development procedure. Requirements are complete, unambiguous, and not in conflict with each other.

7-3-3- Design and Development Outputs

The outputs of design and development are provided in a form that enables verification against the design and development input, and are approved prior to release according to research and development procedure. Design and development outputs:

- Meet the input requirements for design and development

4 Research & Development

of 19

- Provide appropriate information for purchasing and production (including required APIs5 and other raw materials, primary formulation, etc)

- Contain products acceptance criteria- Specify the characteristics of the product that are essential for safe and proper use

(including brochure and drug use instruction)

7-3-4- Design and Development Review

Reviews of design and development are performed according to research and development procedure in accordance with the nature of projects and planned arrangements. These reviews are conducted to:

- Evaluate the ability of the results of design and development to meet requirements- Identify any problems and propose necessary actions

Participants in design and development review include representatives of functions concerned with the design and development stage being reviewed. Records of the results of the reviews are maintained.

7-3-5- Design and Development Verification

Verification of design and development is performed in accordance with planned arrangements determined in research and development procedure and project time schedule to ensure that the design and development outputs have met the design and development input requirements. Design and development verification is conducted in accordance with the results of tests performed on the primary formulation. Records of the results of the verification are maintained.

7-3-6- Design and Development Validation

Design and development validation is performed in accordance with research and development procedure and project time schedule to ensure that the resulting product is capable of meeting the requirements for the specified application or intended use. Validation is performed in accordance with the results of trial production and product stability test results.

7-3-7- Control of Design and Development Changes

All design and development changes are identified and analyzed according to research and development procedure. The changes are reviewed, verified and validated as appropriate. The review of design and development changes includes evaluation of the effect of the changes on products.

7-4- Purchasing

7-4-1- Purchasing Process

Purchasing procedure in Sobhan Chemotherapeutical Company is divided to internal purchasing and external purchasing. Purchasing process depends on the type of purchased products (supplied internally or externally) and is being done according to internal and external purchasing procedures.Purchasing processes are controlled to ensure purchased product conforms to specified purchase requirements. This control is applied to purchased items, goods, equipment and

5 Active Pharmaceutical Ingredients

of 19

services that affect product quality. Suppliers are evaluated and selected based on criteria defined in suppliers’ evaluation procedure.7-4-2- Purchasing informationPurchasing information is defined according to internal or external procedures. Purchasing information describes the product to be purchased, including where appropriate:

- requirements for approval of product, procedures, processes and equipment,- requirements for qualification of personnel, and- Quality management system requirements.

Purchasing information adequacy is reviewed prior to stating the specified requirements to suppliers according to internal or external procedure.Purchasing information including relevant documents and records are maintained in order to provide product traceability.

7-4-3- Verification of Purchased Product:

Inspection and testing activities are performed according to raw materials and packaging items quality control procedure to ensure that purchased products meet specified requirements.For other items and equipment which affect the quality, inspection and testing activities are performed according to internal or external purchase procedure.Where verification of purchased product is intended at suppliers’ premises, verification includes comparing products with specified specifications via testing and inspection at supplier’s premises or supervision on testing process and examining results and measuring equipment accuracy.

7-5- Production

7-5-1- Control of Production

All products production process is planned. Production and material planning is performed according to production planning procedure. The following activities are carried out by Sobhan Chemotherapeutical Company to control production process:

- The availability of information that describes the characteristics of the product (including DMF for all products)

- The availability of documented procedures (to describe production processes and equipment usage), documented requirements, work instructions, reference materials and reference measurement procedures

- The use of suitable equipment according to the world latest technologies- The availability and use of monitoring and measuring devices (such as balances,

thermometers and humidity meters)- The implementation of monitoring and measurement by control laboratories at

different stages of production process such as raw materials, semi-finished products and final products

- The implementation of release, delivery, and post-delivery activities- The implementation of defined operations for labeling an packaging

Sobhan Chemotherapeutical Company establishes and maintains a record for each batch of its products (batch record) to provide traceability and identify amount manufactured

of 19

and amount approved for distribution. Batch record is verified and approved by quality assurance manager.

7-5-2- Validation of Processes for Production

All of production sub-processes where their resulting output cannot be verified by subsequent monitoring or measurement are validated. The validation of these processes is being done according to defined procedures to prove the ability of theses processes for reaching planned results.The following items are considered in preparing validation procedures and checklists:

- Defined criteria for review and approval of the processes (such as necessary environmental conditions, time…)

- Approval of equipment and qualification of personnel- Use of specific methods and procedures- Requirements for records- Revalidation in defined intervals or while changes occur in process

7-5-3-Identification and Traceability

All products of Sobhan Chemotherapeutical Company are identified according to identification and traceability procedure from the primary stages of production to packaging.Recalled products are also identified according to product recall procedure and conforming products are segregated from the non-conforming ones.Traceability is established for all products according to identification and traceability procedure. Batch record indicates traceability for all products. Organization controls and records product unique identification throughout the production process.The records of all product components (including test results), materials and work environment conditions are considered in batch record to demonstrate the tractability.Products status is identified with respect to monitoring and measurement requirements by sticking labels defined in quality control procedures.

7-5-4- Customer Property

Regarding to explanations in clause 2-3, requirements of this clause are not applicable in Sobhan Chemotherapeutical Company.

7-5-5- Preservation of Product

Preservation includes identification, handling, packaging, storage and protection. Preservation is also applied to the constituent parts of a product.Identification of all products is carried out according to clause 7-5-3.Handling and preservation of products throughout internal processing is performed according to production procedures.Packaging of products is carried out according to packaging procedures.Storage of products is carried out according to storage procedure.

7-6- Control of Measuring and Monitoring Devices

All requirements necessary for calibrating measuring and monitoring devices are described in calibration procedure. All measuring and monitoring devices in Sobhan Chemotherapeutical Company are:

of 19

- Calibrated at specified intervals, or prior to use, against measurement standards traceable to international or national measurement standards; where no such standards exist, the basis used for calibration is recorded

- Adjusted or re-adjusted as necessary- Identified according to repair and maintenance procedure to enable the calibration

status to be determined- Safeguarded from adjustments that would invalidate the measurement result; and,- Protected from damage and deterioration during handling, maintenance and

storage according to equipment technical instructionsThe equipment is sent for calibration before the specified time when it is found not to conform to requirements. If necessary, the parameters measured by the nonconforming device are measured again according to calibration procedure.The computer software used for measurement and monitoring are validated according to computer systems validation protocol and their ability to meet the requirements is confirmed.

Reference of Clause 7

- Drug Master Files (DMFs)- Sales procedure No. ………- Customer communication procedure No. ………- Complaints follow-up procedure No. ………- Product recall procedure No. ………- Research and development procedure No. ………….- Internal purchasing procedure, No. SP/PU-GE-001- External purchasing procedure No. ………….- Suppliers’ evaluation procedure No. ………….- Raw materials and packaging items procedure No. ………- Production Planning procedure No. …………- Validation procedures- Product identification and tractability procedure No. ………- Quality control procedures- Production procedures- Packaging procedures- Storage procedure No. ………- Calibration procedure, SP/EN-GE-001- Repair and maintenance procedure No. ………- Computer systems validation protocols

of 19

8- Measurement, Analysis and Improvement

8-1- General Requirements

Sobhan Chemotherapeutical company plans and implements required processes for monitoring, measurement, analysis and improvement in order to demonstrate product conformity, ensure quality management system compliance and continual improvement of quality management system effectiveness. In this regard, specific methods are defined for use of statistical techniques including control charts, analysis using histograms, Pareto, cause and effect diagrams and other statistical tools.

8-2- Monitoring and Measurement

8-2-1- Customer Satisfaction

Sobhan Chemotherapeutical Company monitors and measures information related to customers’ (doctors, distributing companies and patients) perception at defined intervals as to whether the organization has met customers’ needs and expectations according to customer communication procedure.

8-2-2- Internal Audit

Periodic internal audits are conducted at planned intervals according to internal audit procedure in order to:

- Evaluate quality management system compliance with the requirements of ISO 9001:2000 International Standard and

- Evaluate the effectiveness and deployment of quality management system Audit plan is prepared with respect to the status and importance of quality management system processes, according to internal audit procedure. This plan includes audit schedule, audit criteria, scope and audit team.In selecting audit team members it is noted that auditors should be qualified. Auditors should be independent from the process being audited and do not audit their own work.The responsibilities and requirements for planning and conducting audits, audit report preparation, records maintenance and nonconformities follow-up are described in internal audit procedure.

8-2-3- Monitoring and Measurement of Processes

As mentioned in clause 4, monitoring and measurement of processes is carried out with respect to key performance indicators (KPIs) using methods and criteria defined in process indicator determination form.The ability of the processes to achieve planned results is checked regarding monitoring and measurement results (KPIs status). When planned results are not achieved, correction and corrective action are taken, as defined in corrective action and preventive action procedures.

8-2-4- Monitoring and Measurement of Product:

The characteristics of the product are monitored and measured at different stages of production according to quality control procedures and testing instructions through physical, chemical, microbial and biological tests to verify that product requirements are fulfilled.

of 19

Evidence of conformity with the acceptance criteria (test results) is maintained. Theses records compose part of the batch record. Product release does not proceed until the batch records are checked by quality assurance managerThe identity of persons performing any kind of inspections and tests is recorded in related forms.

8-3- Control of Nonconforming Product

In order to ensure that nonconforming products are not used unintentionally, these products are segregated from other products according to control of nonconforming product procedure. Controls, related responsibilities and authorities for dealing with nonconforming product and disposition of these products are defined in control of nonconforming product procedure.Nonconforming product is managed by one or more of the following methods:

- Taking action to eliminate the detected nonconformity and performing required corrections

- Authorizing its use, release or acceptance under concession where regulatory requirements are met.

- Taking action to preclude product use or application.Records of the nature of nonconformities and any subsequent actions taken, including concessions obtained, are maintained according to control of nonconforming product procedure.When nonconforming product is corrected, it is subject to re-verification to demonstrate conformity to the requirements.

8-4- Analysis of Data

Determination, collection, and analysis of appropriate data to demonstrate the suitability and effectiveness of the quality management system, and to evaluate where continual improvement of the quality management system can be made is described in data analysis procedure.This includes data generated as a result of monitoring and measurement (customer feedback, monitoring sand measurement of processes, monitoring and measurement of product, etc) and from other relevant sources.The analysis of data provides information relating to:

- Customer feedback- Conformance to product requirements- Characteristics and trends of processes and products including opportunities for

preventive action- Suppliers.

Records of data analysis are maintained according to data analysis procedure.

8-5- Improvement

8-5-1- General

Sobhan Chemotherapeutical Company continually improves its quality management system efficiency through the use of quality policy, quality objectives, audit results, analysis of data, corrective and preventive actions and management review according to continual improvement procedure and defining improvement projects.

of 19

8-5-2- Corrective Action

Corrective actions are taken to eliminate the cause of nonconformities in order to prevent recurrence according to corrective action procedure. Determining and implementing of corrective action includes the following stages:

- Reviewing nonconformities- Determining the causes of nonconformities- Evaluating the need for action to ensure that nonconformities do not recur- Determining and implementing action needed- Records of the results of actions taken- Reviewing corrective action taken.

8-5-3- Preventive Action

Preventive actions are determined to eliminate the causes of potential nonconformities in order to prevent occurrence according to preventive action procedure. Determining and implementing preventive action includes the following stages:

- Determining potential nonconformities and their causes- Evaluating the need for action to prevent occurrence of nonconformities- Determining and implementing action needed- Records of results of action taken; and- Reviewing preventive action taken.

Reference of Clause 8

- Customer communication procedure No. ………- Internal audit procedure No. ………- Quality control procedures- Control of nonconforming product procedure No. ………….- Data analysis procedure, No. ……………………- Continual improvement procedure No. ………….- Corrective action procedure No. ………- Preventive action procedure No. …………

of 19