quality assurance and quality control

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QUALITY ASSURANCEPREPARED BY: B.PUNITHA M.SUGANESWARI H.KALAIVANI S.SASIKALA L.SINDHUJA M.SHANMUGA PRIYA S.THILAGAM

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INTERNATIONAL STANDARDS OF ORGANISATION (ISO)

INTRODUCTION In the 1970’s many organizations

published their own quality management Standards(e.g. Ford’s Q101,the ministry of Defence’s 05-20 series,etc.)

This introduced the idea that confidence

in a product could be gained from an approved quality management system and quality manuals.

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INTERNATIONAL STANDARDS OF ORGANISATION (ISO) By the late 70’s it was decided that, there

would be a national standard on what constituted a quality system.

They promote the development of standard of standardization and related activities in the world to facilitating international exchange of goods and services and to develop co-operation in the sphere of intellectual,scientific, technological and economic activity.

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IMPORTANCE OF STANDARD: Zero defects states

Responsible for long term benefits

Essential requirement for business and helps promoting products to foreign markets

Viewed as position of strength during product litigation

GMP’s are automatically implemented

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ISO 9000 It is a family of standards for quality

management and quality assurance systems

The ISO 9000 is an international set of documents written by members of a world wide delegation known as the ISO/ tech committee 176

Members from America ,Canada, and Western Europe were the first to prepare the ISO standards

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ISO 9000 It was first published in 1987 and updated

every 5 years

It defines the principle quality concept and provides guidance for selecting appropriate standards.

This calls for a quality policy statement from top management.

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QUALITY POLICY: it provides overall quality objectives and

direction of organization pertaining to key elements of quality (e.g. For use, performance safety)

QUALITY MANAGEMENT: A function that establishes

and implements quality policy.

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QUALITY SYSTEM: The organizational structure responsibility,

procedures, process and resources used for implementing quality management.

it also includes: A set of procedures that cover all key

processes in the business. Monitoring the processes to ensure they are

effective. Keeping adequate records.

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QUALITY SYSTEM: Checking output for defects with appropriate

and corrective actions where necessary. Facilitating continual improvement. A company or organization that

has been independently audited and certified to be in conformance with ISO 9001 may publicity state that it is “ISO 9001 certified” or “ ISO 9001 registered.

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QUALITY SYSTEM: certification to an ISO 9001

standard does not guarantee any quality of end products and services; rather, it certifies that formalized business processes are being applied.

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ISO 9001: ISO 9001:2008 Quality management

systems- requirements is a document of approximately 30 pages which is available from the national standards organization in each country.

Outline contents of ISO 9001 are as follows:

Quality systems –Modal for quality assurance in design/ development, production, installation and servicing.

It calls for the management to define document, implement and maintain a quality policy.

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ISO 9001 The standard specifies six compulsory

documents : (1) control of documents (2) control of records (3) internal audits (4) control of non-conforming

products / service (5) corrective action (6) preventive action

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ISO 9002: Quality systems-Model for quality

assurance in production and installation.

ISO 9003: Quality systems-Model for quality

assurance in final inspection and test.

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ISO 9004:

Quality management and quality system eliminate guidelines.

this provides quality guidelines for quality management as a way to prevent reduce or eliminate quality deficiency.

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CERTIFICATION PROCESS: initial contact with certifying body(ISO)

enter into the contract

manual revenue

Acceptable non-acceptable

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CERTIFICATION PROCESS acceptable

pre-registration audit

assessment

acceptable non-acceptable

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CERTIFICATION PROCESS acceptable

certification

surveillance audit acceptable non-

acceptable(warning) (3 yrs renewal)

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STEPS OF IMPLEMENTATION: approval from the top management Training to all key persons for the

implementation Establish policy objective Form resource group Evaluate and improve Provide training at all levels Commence writing the documents Implement system at work place conduct internal audit-improve compliance Get audited by external energy

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CLAUSES OF ISO 9000 SERIES:DESIGN CONTROL: identification of responsibility for

each design and development and activity. these activities are performed by

qualified staffs equipped with adequate resources.

it requires that the organizational and technical interfaces between different groups are identified.

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CLAUSES OF ISO 9000 SERIES:DOCUMENT CONTROL: CGMP stresses on the master

production and control records for every drug.

ISO requires identification, documentation and appropriate review and approval of all designs, changes and modification.

these changes must be received and approved by same organization that performs original review.

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CLAUSES OF ISO 9000 SERIES: PURCHASE LEVEL: ISO requires the firm to evaluate

suppliers quality system and select suppliers on the ability to meet the firm’s quality requirements.

PRODUCT IDENTIFICATION AND

TRACEABILITY: ISO requires that the product be

identified through out all stages of production, delivery and installation.

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CLAUSES OF ISO 9000 SERIES:PROCESS CONTROL: ISO requires identification and

planning of all the productions that has direct bearing on the quality.

Prospective validation of process equipments involves:

(a)installation qualification: This ensures documented

verification that all key aspects of installation adhere to manufacturer’s recommendation.

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CLAUSES OF ISO 9000 SREIES: (b)Operational qualification: -Known as performance

qualification -This ensures documented

verification that the system/sub-systems perform as intended throughout all specified operating ranges.

(c)Calibration: Demonstrating that a measuring

device produces results with in specified limits of those produce by a reference standard device over an appropriate range of measurements.

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CLAUSES OF ISO 9000 SERIES:INSPECTION AND TESTING: CGMP requires laboratory control

written procedures in the form of specification and standards, sampling plants and test procedures, which are used in lab for controlling components and finished products.

ISO provides checking whether purchased product need urgent release for production purpose is being documented and recorded.

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CLAUSES OF ISO 9000 SERIES: INSPECTION, MEASURING AND TEST

EQUIPEMENT: ISO requires that precision and

accuracy of all measuring and testing equipment be determined.

INSPECTION TEST STATES: ISO requires marking, stamps or tags

indicating the stage of the product. (e.g. Under test, pass, rejected)

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CLAUSES OF ISO 9000 SERIES: CONTROL ON NON-CONFORMING PRODUCT: ISO like CGMP regulation requires the

isolation of non-conforming products. ISO requires that the causes of non-

conformation of products are investigated under corrective actions needed to prevent re-currence be taken.

HANDLING, STORAGE, PACKING AND DELIVERY:

CGMP has regulation regarding sanitary inspections.

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CLAUSES OF ISO 9000 SERIES: CGMP and ISO stresses on

maintenance and conformation to procedures regarding handling, storage and packaging of pharmaceuticals.

ISO concerned with delivery of products up to the consumer and acting on the feed back received from the customer.

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QUALITY RECORDS: ISO requires establishment and

maintenance procedure of identification, collection, indexing, filling, storage, maintenance and disposition of quality records.

QUALITY AUDITS: Internal audit to ensure compliance. External audit carried out to analyze the firm’s own quality performance. Two types—system audit & product audit.

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CLAUSES OF ISO 9000 SERIES:TRAINING: ISO requires procedures for identifying

the training need of all personnel performing activities affecting quality.

INDIAN CORRESPONDENCE: Bureau of Indian standards (BIS) has

adopted ISO 9000 series and have brought about the IS 14000 series (IS 14001, IS 14002, IS 14003 and IS 14004)

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SPECIAL PRODUCTS: ISO have 2 magazines: 1.ISO Focus-an overview of ISO’s

activities 2.ISO management systems

published 6 times a year.

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TOTAL QUALITY MANAGEMENT(TQM)INTRODUCTION: TQM is relatively new concept of quality

control. It is basically, management function involving the direction of top management and co-ordination of all quality related activities throughout the company to achieve Zero defects and customer satisfaction.

The topic is of contemporary interest to industrial pharmacist, community pharmacist and to all those who are conscious about quality.

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INTRODUCTION: Since quality is a measure of the users

satisfaction provided by the product, it should include-

(i)Functional efficiency (ii) Appearance (iii) Ease of installation and operation (iv) safety (v) Reliability (vi)Maintainability (vii)Running and maintenance cost

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INTRODUCTION: In this quality awareness begins at the very

continues during the various stages of its development and manufacture and even its usage to provide feedback from the users which is so essential for quality improvement.

CONCEPT IN TQM: it refers to the goal of an organisation which

can be achieved, 1.it requires the commitment of senior level

management and supervision of all departments, operators, supplies and customers.

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CONCEPT OF TQM: * When every individual is associated

with the organisation directly committed to the quality performance and activities in the organisation should be of desired quality.

* Concept of this TQM is developed from Inspection

Quality control Quality assurance

Quality circle

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CONCEPT OF TQM(a) Inspection:

Ascertaining earlier, whether a product confirms to the specification.

it uses the measurement of the post production activity in the business organisation.

(b)Quality control It is post production activity.It is done to notify whether every manufacturing activity is performed according to the predetermined standard and instructions.

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CONCEPT OF TQM it is carried out the structural, for al pack of information consisting of specification for

- starting material -the packaging materials -finished product(c)Quality assurance: it is a III evolutionary phase it is a wide ranging concept covering all matters that individually or collectively influences the quality of a product.

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CONCEPT OF TQM it is a totally of arrangements made that the object of ensuring that the pharmaceutical products are of the quality required for their interest.

It is an online action having the system of appraisal(judging the value of the product) prevention and measurement activity with management status.

In QA there is auditing by III party E.g. Government or any other agency

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CONCEPT OF TQM (d) Quality circle:

• it is a small group of employees (i) in same working area (ii) Undergoing similar type of work

• In this on regular basis they directly involved in the production process to discuss and make improvements to the production process.

• it is to improve the quality and minimising the cost.

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ELEMENTS OF TQM Total quality is a description of

culture, attitude and organisation of a company that strives to provide customers product and services that satisfy their needs.

successful implementing TQM an organisation must concentrate on 8 key elements are:

(i) ethics (ii) integrity (iii) trust (iv) training (v) team work (vi)

leadership (vii) recognitions (viii) communications

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ELEMENTS OF TQM These elements have been coined to

describe a philosophy that makes quality the driving faces and leadership design, planning and improvement initiatives.

BENEFITS OF TQM: Advantages unique to TQM: 1. it makes company a leader 2. it makes fosters team work 3. it makes the company more sensitive

to customer needs 4. it makes the company adapt more

readily to change.

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BENEFITS OF TQM BENEFITS FOR THE CUSTOMER: 1.Fewer problems with the product

(or) service. 2. better customer care 3. greater satisfaction.BENEFITS FOR THE STAFF: 1. Empowerment 2. More training and more skills 3. More recognisation.

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BENEFITS OF TQM

BENEFITS FOR THE COMPANY: 1. Quality improves 2. Staff are more motivated 3. Productivity increases 4. Cost reduced 5. Zero defects 6. Problems resolved faster

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ORGANISATION OF TQM Organisation is one of the most

important elements of TQM in any field of human activity. Team working co-operative relationships are of great importance in TQM.

The main quality functions can be considered into two distinct groups namely

(a) Quality engineering & (b) Quality control

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ORGANISATION FOR TQMQUALITY ENGINEERING: These compromises of the specialist

staff functions as well as activities connected with development. Its main work elements are

a). Advice to the management on the quality policy of the company.

b). Analysis of the customers quality requirements.

c). The review and evaluation of the product design.

d). Defining quality standards and preparation of product specifications.

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ORGANISATION FOR TQMQUALITY ENGINEERING: e). Development of quality control

techniques and inspection methods. f). Conducting process capability g). Analysis of quality costs h). Quality audit of the companyQUALITY CONTROL: It concerned with the interpretation and

quality plants. It comprises of in process and post production testing. The main work elements are,

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ORGANISATION FOR TQM a). Assistance in establishing quality control b). Maintenance and calibration of process

control equipment. c). Investigation of defects and quality

problems d). Implementation of quality control

measures for incoming materials and stores e). Arranging final inspection to assess the

quality of the end product f). Checking the quality of the packaging

products. g). Feed back to defect data and customer

complaint.

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FUNCTIONS OF MANAGERS IN TQM 1.PLANNING: Planning involves a rotational and

orderly thinking of ways and means with the help of which goals are desired to be achieved. In other words it involves

(a) Diagnosis of the problem (b) Development of alternatives. (c) Evaluation of alternatives. (d) Selection of the best course of

action.

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FUNCTIONS OF MANAGERS IN TQM 2. ORGANISATION: Organisation is a tool for achieving

the objections in a systematic and scientific manner. It provides an integrated apparatus for attainment of set goals.

3. DIRECTION: Direction embraces and includes the

functions of (i) supervision, (ii) leadership,

(iii) motivation, (iv) communication.

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FUNCTIONS OF MANAGERS IN TQM 4. CONTROL: Control is a process of evaluation of

the work assigned to individuals and various departments with a view to achieve the set goals.

5.MOTIVATION: Management is concerned with the

motivation of people for the realisation of the pre-determined objectives of the organisation. Motivation is the process of providing the personnel an inspiration to get the work done.

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FUNCTIONS OF MANAGERS IN TQM 6. CO-ORDINATION: Co-ordination is the essence of any

management process. It achieves the commonness of the purpose.

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PROCESS VALIDATIONGENERAL: The requirements and principles outlined in

this chapter are applicable to the manufacture of pharmaceutical dosage forms.

They cover the initial validation of new processes, subsequent validation of modified processes and revalidation.

Process validation should normally be completed prior to the distribution and sale of the medicinal product(prospective validation)

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PROCESS VALIDATION GENERAL: In exceptional circumstances, where this is

not possible it may be necessary to validate processes during routine production(concurrent validation)

facilities, systems and equipments to be used should have been qualified and analytical testing methods should be validated.

Facilities, systems, equipments and processes should be periodically evaluated to verify that they are still operating in a valid manner.

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PROSPECTIVE VALIDATION 1. Prospective validation should

include, but not be limited to the following: Short description of the process Summary of the critical processing steps

to be investigated. List of the equipments/ facilities to be used

together its calibration status. Finished product specification for release List of analytical methods as appropriate Proposed in process controls with

acceptance criteria.

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PROSPECTIVE VALIDATIONAdditional testing to be carried out, with acceptance criteria and analytical validation, as appropriate

sampling plan methods for recording and evaluating results

functions and responsibilities proposed timetable

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PROSPECTIVE VALIDATION 2. Using this designs process a series

of batches of the final product may be produced under routine conditions.

The number of process runs carried out and observations made should sufficient to allow the normal extent of variation and trends to be established and to provide sufficient data for evaluation.

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PROSPECTIVE VALIDATION 3. Batches made for process validation

should be the same size as the intended industrial scale batches

4. If it is intended that validation batches be scald or supplied. The conditions under which they are produced should comply fully with the requirements of good manufacturing practice. Including the satisfactory outcome of the validation exercise and marketing authorisation.

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CONCURRENT VALIDATION In exceptional circumstances it may

be acceptable not to complete a validation programme before routine production starts.

The decision to carry out concurrent validation must be justified, document and approved by authorised personnel.

Documentation requirements for concurrent are the same as specified for prospective validation.

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RETROSPECTIVE VALIDATION Retrospective validation is only

acceptable for well-established processes and will be inappropriate where there have been recent changes in the composition of the product. Operating procedures (or) equipment.

validation of such processes should be based on historical data. The steps involved require the preparation of a specific protocol and the reporting of the results of the data. Review, leading to a conclusion and a recommendation.

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RETROSPECTIVE VALIDATION The sources of data for this validation

should include, but not be limited to batch processing and packaging records, process control charts, maintenance log books, records of personnel changes, process capability studies, finished product data, including trend cards and storage stability results.

batches selected for retrospective validation should be representative of all batches made during the review period, including any batches that failed to meet specifications, and should be sufficient in number to demonstrate process consistency.

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RETROSPECTIVE VALIDATION For retrospective validation,

generally data from ten to thirty consecutive batches should be examined to assess process consistency but fewer batches may be examined if justified.

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PROCESSPROCESS VALIDATION: This section will explaw the implication of

validation in the over all manufacturing process.PROCESS DECRIPTION FOR DRY PRODUCTION FACILITY

PROCESS FLOW

CONTROL VARIABLES

MEASURED RESPONCES

Addition of raw materials active excipients

Sizing mill/sieve Screen typeScreen size

Granules size distribution

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PROCESSPROCESS FLOW CONTROL

VARIABLES MEASURED RESPONCES

Action of raw materials lubricants disintegrates BlendingBlender

Load sizeBlending time

Blend uniformityFlow characteristics

Tabulating high-speed rotary machine

Compression rateGranules feed rateFill-o-matic speed

Weight validation Friability Hardnessdissolution thickness

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PROCESSPROCESS FLOW, VARIABLES& RESPONCES:

POWDER FOR SUSPENSIONS PROCESS FLOW CONTROL

VARIABLES MEASURED RESPONCES

Addition of raw materials active excipientsSizingMill/ sieve

Screen typeScreen size

Granules size distribution

Blending blender Load size Blending time

Blend uniformityMoisture content

Filling automatic powder filling machine

Filling machine speedFlow characteristics

Weight variation

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PROCESSPROCESS FLOW, VARIABLES AND RESPONCES:

SYRUP,SUSPENSIONS AND PRODUCTSPROCESS FLOW CONTROL

VARIABLESMEASURED RESPONSES

Addition of raw materials active excipientsMixing jacketed vessel with variable speed mixer

Mixing timeTemperatureFinal volume

ClarityViscosityAssay

Filtration filter press/ cartridge filter/ nylon filter

Mesh sizeFilter integrity

Clarity

Filling automatic filling machine

Filling machine speed

volume

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PROCESS FLOW, VARIABLES AND RESPONSES: CAPSULES

PROCESS FLOW CONTROL VARIABLES

MEASURED RESPONCES

Addition of raw materials active excipientsMixingMixer

Load sizeMixing time

Mixing uniformity

Addition of raw materials lubricating disintegratesBlendingBlender

Load sizeBlending time

Blend uniformityFlow characteristics

Capsulating high-speed capsulation machine

Capsulation speedPowder speed rate

Weight variationDisintegration timeLouring

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PROCESSProcess flow, variables and responses: cream,

ointments and suppository products PROCESS FLOW CONTROL

VARIABLESMEASURED RESPONSES

Action of raw materials active excipientsMixing jacketed vessel with variables Speed mixer

Mixing timeTemperatureRpmAmount of stiffening agentFinal volume

ClarityViscosityAssay

Filling automatic filling machine

Filling machine speed

Volume variation

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PROCESSProcess flow, variables and responses: Aseptic

fill products:PROCESS FLOW CONTROL

VARIABLESMEASURED RESPONSES

Issurance of flow and packing materialAddition of raw material activeNon-activeMedium Water for injection

Temperature PhConductivityAMC

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PROCESSPROCESS FLOW CONTROL

VARIABLESMEASURED RESPONSES

Steam sterilisation pressure vessel/ filling and filtration assembly/ stopper stand seals/ gowning

Time and temperature of steam sterilizer

Time & temperaturePrintout or graph

Mixing pressure vessel

Mixing timeRPMTemperatureFinal volume

Ph clarity

Ampoules/ vialsWashing

TemperaturePressureWashing cycle

Ampoules/ vialsHot air sterilisation

Time& temperature of dry heat sterilizer

Time & temperature printout or graph

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PROCESSPROCESS FLOW CONTROL

VARIABLESMEASURED RESPONSES

FiltrationFiltration assembly and 0.22 micro filter

Pressure Filter integrity test

Aspticing automatic filling & sealing machine in line- filtration casing

Machine speedPressureFlow nature

Filter integrity testIn process check Environmental monitoring Air sampling& gloves print for microbial counts

Leak test TemperaturePressureVacuum

Inspection of filled ampoules or vials

Chemical & micro biological analysis In process checks

Labelling/packing

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