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0510552 Pharmaceutical Quality

Control and Quality Assurance

Dr. Abdul Muttaleb Y. Jaber

Professor of Analytical

Chemistry

Philadelphia University

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Main Topics

• Quality in analytical Laboratories

• Instrumental Qualification and

Validation

• Analytical Method Validation

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PART ONE

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1. Quality in Chemical Laboratories

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1. Quality in Analytical Laboratories

• Quality, quality assurance, quality control

• Quality system

– Benefits of quality system

– Cost of quality system

• Quality manual

• Quality standards for laboratories

– Which quality standard to choose

– Assessing quality systems against quality standards

• Principles of GLP compliance

• Quality audit and quality system review

• Responsibility of laboratory staff for quality

The Process of Analysis

• Analytical chemistry is rarely a simple one-step process.

• The process of measurement often compares an unknown quantity with a known quantity.

• In chemistry the material embodying the known quantity is often presented to the measurement instrument first, in a step called calibration.

• Because of the complexity of matrices, an analyst is often uncertain – whether all the analyte is presented for analysis – or whether the instrument correctly responds to

it. • The measurement of a reference material can

establish the recovery or bias of a method, and this can be used to correct initial observations.

Steps and materials in an analysis.

Why quality

• too many mistakes can make analysis very costly due to expenses caused by wrong

decisions or

• repeating analysis of samples

• investigation of problems

• revision of procedures

• loss of good reputation

Quality in Analytical Measurements

• The Cost of Quality

• “if you think quality systems are expensive, look at the cost of not having them.”

• loss of life, loss of money through court, loss of business through loss of customer confidence

• It costs less to prevent a problem than it does to correct it’

• A formal quality system in the laboratory should prevent mistakes by means of: quality assurance measures

quality control of the analytical results

thorough documentation of the system

efficient maintenance of records

regular audits of all aspects of the system

The cost of quality. F = cost of failure, QS = cost of the quality system. The minimum in the combined graph is the optimum overall cost.

The cost of quality

• The combination of the costs and savings gives a point at which an optimum amount of money is being spent

• The cost of the quality system can be determined, but the cost of failures is less well known

• why bother with quality? The answer is “because it costs a lot to get it wrong.”

• There are many examples of failures in chemical analysis that have led to great material loss

• The false in cholesterol test was dropped from 18.5% in 1969 to 5.5–7.2% in 1994 when modern enzyme methods were being used

• with concomitant savings of $100 million per year.

• the quality of a product cannot be controlled until something is measured

• Once measurement data are available, statistics can be applied and decisions made concerning the future.

Some national metrology institutes

Definitions of Quality

• Delivering to a customer a product or service that

meets the specification agreed on with the customer,

and delivering it on time

• Satisfying customer requirements

• Fitness for purpose

• Getting it right the first time.

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Definition of Quality

• Quality can be interpreted as:

1."Conformance to specifications“. The difficulty with this is that the specifications may not be what the customer wants.

2."Fitness for use“. Fitness is defined by the customer.

3.A two-dimensional model: "must be quality" and "attractive quality". The former is

near to the "fitness for use" and the latter is what the customer would love, but has not yet thought about.

Supporters characterize this model more concisely as: “Products and Services that meet or exceed customers’ expectations".

4."Value to some person"

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ISO Definition of Quality

(ISO: International Organization for Standardization)

Quality: The totality of features and characteristics of a product or service that bear on its ability to satisfy stated or implied needs (ISO 1994).

Quality: Degree to which a set of inherent characteristics

fulfils requirements where “characteristics” are

distinguishing features, and “requirements” are need or expectation that is stated, generally implied, or obligatory. (ISO 2005),

(Quality of a result is equivalent to its accuracy)

Quality is providing results which:

– meet the specific needs of the customer

– attract the confidence of the customer

– represent value for money

Quality is not immediate; it is only achieved if an extensive set of (a priori, pre-supposed by experience) measures are taken and complied with.

QM, QC and QA

• Quality management system: Management system to direct and control an organization with regard to quality

(AOAC International 2006)

• Quality control: Part of quality management focused on fulfilling quality requirements (AOAC International

2006)

• Quality assurance: Part of quality management focused on providing confidence that quality requirements will

be fulfilled (AOAC International 2006).

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QA and QC

• Quality Assurance (QA) – Activities that ensure that data collected are of adequate

quality

– Quality Assurance consists of two separate but interrelated activities: Quality Control (QC); and Quality Assessment.

• Quality control

Technical activities employed to ensure that the data collected are adequate

• Quality Assessment

Activities implemented to quantify the effectiveness of the quality control procedures.

Quality Assurance vs. Quality Control

Quality Assurance

An overall

management plan to

guarantee the

integrity of data

(The “system”)

Quality Control

A series of

analytical

measurements used

to assess the

quality of the

analytical data

(The “tools”)

QA Systems

Quality Assurance measures apply to the

laboratory analytical work overall, which

includes:

• identifying the person having the overall

responsibility for quality

• having laboratory equipment calibrated to

recognized standards

• using reference materials

• joining proficiency testing schemes with

other laboratories doing similar tests

QC systems

• reagent blanks

• verified standard

solutions

• check samples (from

both within the lab

and from outside)

• blind samples

• replicate analyses;

• control charts

Quality control measures apply to each analytical tests

in the laboratory by use of:

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Quality Assurance QA as applied to laboratory operation:

• Laboratory operations undertaken to achieve the following objectives of documentation:

1. Quality control procedures are indeed being

implemented in the laboratory.

– An example is

– quality control requires that all pH meters be calibrated before use.

– Quality assurance requires that the fact that the meter was calibrated, and the results obtained, shall be recorded.

2. Assure that the "Accountability" (responsibility)

of the data is maintained.

• "Accountability" means that the data reported do reflect the sample as it was received in the lab., that is, that sample mix-up was avoided and the sample was properly preserved prior to analysis.'

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3. Facilitate traceability of an analytical

results.

– Every result reported should be traceable to the

date of analysis,

• The analysts who ran the sample, the method

used, the instruments used and its (their)

condition, and the status of the analytical

system at the time of analysis.

4. Ensure that reasonable precautions are

taken to protect the raw data against loss,

damage, theft, or tampering (missing

about, altering)

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Official definitions of Quality Assurance and

Quality Control

• Quality Assurance (QA)

Planned activities designed to ensure that the quality control activities are being properly implemented, (AOAC )

• All planned and systematic actions necessary to provide adequate confidence that a product, or process or service will satisfy given quality requirements.

(Definition by ISO :International Organization for standardization)

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Quality Control (QC)

The operational techniques and activities that

are used to fulfill requirements for quality (Data

generated by the lab are of known accuracy to

some stated quantitative degree of probability)

• Quality control: Planned activities designed to

provide a quality product

(AOAC, Association of official analytical chemists)

• QA and QC are components of the quality

system.

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Quality Control

• QC’s are those laboratory operations whose objective is to ensure that the data generated by the lab are of known accuracy to some stated, quantitative degree of probability. – the laboratory should be able to attach to every result

reported a range within which the true value of the analyte can be stated to lie with a certain degree of confidence in the probability of being correct (the confidence limits of the analysis).

• This does not mean that the confidence limit or precision of the analysis must be reported with the result (although this might be a good idea), but rather that the laboratory should be able to make this statement, if required.

• The kinds of operations referred to in this definition are those that are generally applied as good scientific practice: instrument calibration, personnel training, use of pure reagents, use of standards and reference materials, and so on.

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Quality Policy

The overall quality intentions and directions of an organization regarding quality as formally expressed by the top management

Quality Management

The aspects of the overall management function that determines and implements the quality policy

Quality System:

The organizational structure, responsibilities, procedures and resources set by company for implementing quality management (it is QA, QC and QM)

(It is a set of procedures and responsibilities which a company puts in force to make sure that the analytical chemist has the facilities and recourses to carry out measurements that satisfy customers)

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Quality Systems in Chemical Laboratories

• A laboratory's Quality System is the formal structure

set up to include all aspects of quality in the

laboratory.

• This system is the common sense procedures

adopted by the laboratory, written down on paper.

• This system should cover everything

– from the laboratory management's statement of

their policy towards quality through

– to the detailed procedures used by the staff at the

bench to ensure quality in each and every

analysis that they carry out.

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Benefits of a quality system

• Mistakes in operating procedures will be reduced.

• The time required for extra work to put things right

after an error has occurred is minimized.

• Achieving major advantage over competitive

organizations whose products, however impressive

but are considered to be unreliable.

• The customers are increasingly asking for evidence

of the reliability of results

• the laboratory can use the recognition of their

standards as a positive advertisement for its

services.

• Customers are increasingly seeking reputable

laboratories to undertake their work.

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The cost of a quality system

• Involving some of the manpower resources in quality activities rather than working for customers.

• Extra cost should be paid to keep the Quality System up-to-date. e.g., – the costs of having a Quality Manager for the

laboratory to run the Quality System

– The cost of carrying out periodic checks “Quality Audits” on how the Quality System is working.

– The cost of putting right problems identified by the audit.

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• Extra costs of running internal system of quality assurance such as:

– Quality assurance trials (both internal blind trials and participation in external proficiency testing schemes)

– Replicate testing

– Control charting

– validating methods

– Qualifying instruments

– obtaining and using suitable reference materials and the regular analysis of blanks and standards.

• Fees for accreditation if the lab seeks it.

• This cost is justified by the combination of the savings due to error reductions, a simplified operational structure which is easier to manage and the benefits of a better image of the laboratory to its existing and potential customers.

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Quality Manual

• The details of the laboratory's Quality

System are written down so that everyone in

the laboratory can see what the system is

and what is expected.

• Quality manual is required for Laboratories

seeking government contracts, or complying

with the governmental regulations or seeking

accreditation by accreditation agency

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Quality Manual: Outline

• Introduction: Title page, table of contents

– Quality assurance policy: Objectives, resources, QA management

• Overview of the manual: – Definition of terms, scope, fields of testing

covered by the manual, management of QA manual

– Description of lab: Identification, fields of activity, organizational structure, responsibility for QA program, technical management responsibility, SOP’s, deputy assignments, statements of policy on confidentiality of information

– Staff: job description, personnel records, supervision, other relevant documents

– Testing and measuring equipment: Inventory, maintenance, calibration

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• Environment: physical facilities, heating, ventilation, Ac systems, special environmental facilities (sample storage, handling, waste storage and disposal, archive..)

• Test methods and procedures: list of standard analytical procedures (SOP’s), methods of validating nonstandard procedures, methods of maintaining historical file of methods, procedure for authorizing analytical methods

• Updating and control of QA documents

• Sample and test item handling: system for sample receipt, log-in and storage, sample security (avoid sample mix up), sample preservation

• Verification of results: system for verifying calculation and data transfer, software of QA for computerized data software

• Test reports: Report format, report revision

• Diagnostic and corrective actions: feedback, proficiency testing, inter-lab comparison programs, use of reference materials, quality system audits

• Records: record maintenance, confidentiality and security, historical file records

• Subcontracting: describe system for evaluating quality program of a lab to which work is subcontracted and policy of reporting subcontracted work to clients.

Laboratory Quality System Admin 1.5.1.

Quality Manual

Amiable Laboratory Page 1 of 1

Issue No.

Title of Section

Issue Date

Title Page Issued by

QUALITY MANUAL for

Amiable Laboratory

Benevolent Department

Well-intentioned Organisation

Usual Location

This Manual is issued under the authority of

............................................................

A Person

Head of Laboratory

Issue Date

Issue No. 3

Copy No.

Holder

Quality

Manual

Quality Manual - cover page

A quality manual

defines the quality

system under

which the

laboratory operates

Laboratory Quality System - Quality manual Admin 1.5.1.

Index

Amiable Laboratory Page 1 of 2

Benevolent Department

Well-intentioned Organisation Issue No. 3

Copy No.

Title of Section Issue Date

Index of Contents Issued by

Section Para.

No.

Content

1 QUALITY POLICY

2 QUALITY SYSTEM

2.1 Aims and Form of Quality System

2.2 Quality Manual

2.3 Quality Management

2.4 Documentation

3 ORGANISATION AND MANAGEMENT

3.1 Organisation

3.2 Organisational Chart

3.3 Staff - Qualifications and Training

Quality Manual -

contents

Section Para.

No.

Content

4 QUALITY AUDIT AND QUALITY SYSTEM

REVIEW

4.1 Purpose

4.2 Responsibility

4.3 Implementation

5 EQUIPMENT

5.1 Calibration and Testing Equipment

5.2 Operation and Maintenance of Equipment

5.3 Equipment Records

6 MEASUREMENT TRACEABILITY AND

CALIBRATION

6.1 Policy

6.2 Uncertainty of Measurement

6.3 Calibration

7 METHODS AND PROCEDURES FOR TESTS

7.1 Policy and Scope

7.3 Documentation of Methods and Procedures

7.4 Integrity of Data

7.5 Uncertainty of Results

Quality Manual

contents

-

Section Para

No.

Content

8 LABORATORY ACCOMMODATION AND

ENVIRONMENT

9 HANDLING OF TEST ITEMS

9.1 Receipt and Handling of Items

9.2 Identification of Items

10 RECORDS

11 TEST REPORTS

11.1 Use of the UKAS Accreditation Mark

11.2 Validity of Reports

12 HANDLING COMPLAINTS AND ANOMALIES

12.1 Policy

12.2 Procedures

13 SUB-CONTRACTING OF TESTS

13.1 Policy

13.2 Register

14 OUTSIDE SUPPORT SERVICES AND

SUPPLIES

14.1 Policy

14.2 Records

15 SITE SECURITY

15.1 Security of Laboratory Premises

Quality Manual

contents

1. Admin Audit reports

System reviews Blank forms Memos Notices Quality Manual Record of anomalies

Preventive actions 1.2.1.(index) General contract

2. Validation Fibre Milk Proficiency test

3. Equipment 3.01 Equip records 3.02 Operating procedures

3.2.1. balance 3.2.2. ovens 3.2.3. muffles 3.2.4. thermometers 3.2.5. pH meters

List of General Procedures

4. Procedures

4.06 Quality control records

4.07 Reference standards

4.08 Result acceptability

4.09 Result reporting

4.10 Result uncertainties

4.11 Sample disposal

4.12 Sample reception

4.13 Sample registration

4.14 Staff records

4.15 System reviews

4.16 Training and competence

4.17 Recording and storing data

4.18 Document control

4.01 Calibration records

4.02 Complaints and anomalies

4.03 Equipment records

4.04 Method validation

4.05 Quality audits

5. Quality Control

5.01 Fibre analysis 5.02 Milk analysis 5.03 Feed analysis 5.04 N by combustion 5.05 Q.C. limits 5.06 Test reports & log

6. Staff Records Job descriptions

7. Standard Methods ADF Dry matters Fat, protein & lactose in milk NDF

Quality system files: Just an example

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Quality Standards For Laboratories

• A number of organizations have already developed

and published standards for Quality Systems which

are relevant to laboratories.

• These standards can therefore be `taken off the shelf'

and referred to by laboratories and by their customers.

• There are few groups which have published standards

for Quality Systems relevant to analytical chemistry

laboratories. These are:

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1. International and national standards organizations: The International Organization for Standardization (ISO) has produced a range of standards and guidance relevant to laboratories. The most relevant of these are the ISO 9000 series of quality standards, ISO Guide 25 `General requirements for the competence of calibration and testing laboratories' and ISO Guide 49 `Guidelines for development of a quality manual for testing laboratories'.

a. In Europe, The European Committee for Standardization (CEN) has produced its own range of standards concerning quality, including the EN 29000 series and the EN 45000 series. These are closely based on the ISO 9000 series and ISO Guide 25, respectively.

2. The Organization for Economic Co-operation and Development (OECD), which has developed the Good Laboratory Practice standard, often referred to as `GLP'.

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3. In Britain, the British Standards Institution (BSI) has also produced the BS 5750 Quality Standard, which is equivalent to ISO 9000 and, therefore, the EN 29000 series of European Standards. • In addition, BSI has also adopted the EN

45000 series of standards and has issued them as the BS 7500 series.

4. National laboratory accreditation bodies produce more detailed quality requirements for laboratories, usually based on the general criteria set out in ISO, EN and any appropriate national standards. They then offer to assess laboratories against these quality requirements. In the United Kingdom, the National Measurement Accreditation Service (NAMAS) is the major accreditation body for laboratories.

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Which quality standard should we choose?

• Management of a laboratory will look at all possibilities, decide on the Quality Standard which best suits their organization and then design its own Quality System to meet the standard's requirements.

• For analytical chemistry a quality standard based around the recommendations of ISO Guide 25 would be appropriate.

• If some of the work is involved with registration then GLP will be required for work.

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Quality Standards for Laboratories

ISO-9000

• Definition:

– A series of voluntary quality systems which

describes the process, organizational

structure, procedures and resources that

manufacturers and suppliers use to produce

a product of consistent quality, which meets

defined specifications.

• Goals:

– Product quality

– Harmonization of international trade

– Provide consistent terminology

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Assessing quality systems against quality standards

• An independent assessor - sometimes referred to as a `third party audit' - has to inspect to ensure that the requirements of the standard are being achieved.

• Assessors will not tell a laboratory exactly how it must operate, but will instead identify any aspects of the Quality System which do not meet the requirements of the Quality Standard.

• It is then up to the laboratory to decide what action it would prefer to take to rectify the situation

• Regular re-assessments are carried out to ensure that the Quality System remains operational and appropriate, and that the normal commercial pressures on the laboratory have not caused them to compromise the required standards of quality.

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Principles of GLP compliance

• Management

• Quality assurance program

• Facilities

• Equipment

• Test facility working procedures (SOP’s)

• Planning and conduct of study

• Final report

• Storage of data

GLP scheme is an international scheme intended

primarily for laboratories carrying out analyses and

evaluations of substances for regulatory purposes.

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Quality Audit (QA)

QA is a continuing process of testing the Quality Systems in use in the laboratory to check if the systems are effective, documented, and being adhered to by the working staff.

• From the lab point of view, a quality audit will check that the lab has been carrying out its job as set down in the laboratory's written procedures.

– Quality Audit is the responsibility of the Quality Manager

Quality System Review (QSR)

QSR is the periodic re-examination of the laboratory's Quality Systems to check if the systems are still appropriate.

– QSR is the responsibility of the laboratory management.

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Internal versus External Audits

• No laboratory should rely solely on periodic

assessments by an external body to ensure that

standards of quality are continuously maintained

• Although external assessments offer a valuable insight

into a laboratory's procedures, and an independent

recognition of the quality of operations, they cannot by

themselves ensure continuing quality within the

laboratory.

• For the laboratory to maintain and improve its quality

of operation, it must continually test and reexamine its

own Quality System (Internal auditing).

• A systematic and regular process of internal Quality

Audit and Quality System Review offers a structured

route to achieve this.

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Responsibility for Internal Quality Audits, IQA

• IQA is the responsibility of the Quality Manager, who must have direct access to senior management to report his findings and recommendations.

• As some of the recommendations from the audit may be difficult or costly to implement, the Quality Manager must also be of sufficient standing within the organization to ensure that any actions necessary to protect the quality standard of the laboratory are carried out.

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Responsibility for Internal Quality Audits/cont.

• In a small laboratory, the Quality Manager may be able to carry out the Quality Audit himself.

• When it is impractical to use internal auditors, a laboratory can employ external auditors to carry out internal Quality Audits.

• It is the responsibility of the Quality Manager to ensure that any non-compliances identified during the audit are satisfactorily cleared and to forward the results of the Quality Audit to the laboratory's management team for consideration as part of their Quality System Review

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Planning of Internal Quality Audits

The audit program can be of two types

1. A rolling program, organized so that different activities within the laboratory are audited each month in a series of visits.

2. A complete audit, covering all activities of the laboratory in one visit

– A laboratory is free to decide which scheme is most appropriate for its own circumstances.

– Laboratories entering the audit process for the first time may prefer to carry out an initial complete audit to establish if problems exist, followed, after an appropriate interval, by a rolling program to maintain standards.

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Training of Quality Auditors • Some members of the staff of the laboratory may be

trained as assessors by one of the accreditation bodies

• The auditors may be trained and instructed by the Quality Manager as to how they should go about their task

• Instructions should include aspects to be examined against quality standards and how to approach the audit process.

• Encouraging open discussion and constructive suggestions should be the rule, rather than negative criticism.

• The personality and presentational skills of the staff selected to be auditors will therefore be extremely important, as well as their technical knowledge

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Conduct of Internal Quality Audits • Each auditing officer should be accompanied

by a member of that part of the laboratory which is being audited, who can explain the relevant procedures to the auditor

• A record of what has been examined should be prepared in the form of the Audit report

• Audit report will include:

– Details of what has been examined

– Reporting the non-compliance

– Defining the corrective actions

– Indicating the auditor responsible for the follow up and the date

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Main Areas which should be verified in an internal audit 1. Staff • Staff have the appropriate blend of background, academic or

vocational qualifications, experience and on-the-job training for the work they do.

• On-the-job training is carried out against established criteria, which wherever possible are objective. Up-to-date records of the training are maintained.

• Tests are only carried out by authorized analysts.

• The performance of staff carrying out analyses is observed by the auditor.

2. Environment • The laboratory environment is suitable for the work carried out.

• The laboratory services and facilities are adequate for the work carried out.

• There is adequate separation of high-level and low-level work.

• The laboratory areas are sufficiently clean and tidy to ensure the quality of the work carried out is not compromised.

• There is adequate separation of sample reception, preparation, clean-up, and measurement areas, to ensure the quality of the work carried out is not compromised.

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3. Equipment • The equipment in use is suited to its purpose.

• Major instruments are correctly maintained and records of this maintenance are kept.

• Appropriate instructions for use of equipment are available.

• Traceable equipment, e.g. balances, thermometers, glassware, timepieces, pipettes, etc are appropriately calibrated and the corresponding certificates or other records demonstrating traceability to national standards are available.

• Calibrated equipment is appropriately labeled or otherwise identified to ensure that it is not confused with uncelebrated equipment and to ensure that its calibration status is clear to the user.

• Instrument performance checks and calibration procedures are carried out at appropriate intervals and show that calibration is maintained and day-to-day performance is acceptable. Appropriate corrective action is taken where necessary.

• Records of calibration, performance checks and corrective action are maintained.

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4. Methods and Procedures

• In-house methods are fully documented,

appropriately validated and authorized for use.

• Alterations to methods are appropriately authorized.

• Copies of any relevant published and official

methods are available.

• The most up-to-date version of the method is

available to the analyst.

• Analyses are (observed to be) following the methods

specified.

• Methods have an appropriate level of advice on

calibration and quality control.

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5. Chemical and Physical Standards, Calibrants, Certified Reference Materials and Reagents

• The standards required for the tests are readily available.

• The standards are certified or are the `best' available.

• The preparation of working standards and reagents is documented.

• Standards, reference materials and reagents are properly labeled and correctly stored.

• New batches of standards, and reagents critical to the performance of the method are compared against old batches before use.

• The correct grade of materials is being used in the tests.

• Where standards, calibrants, or reference materials are certified, copies of the certificate are available for inspection.

Reference materials & check samples

CERTIFIED REFERENCE

MATERIALS (CRMs)

INTERNAL

QC SAMPLES

SAMPLES

SUPPLIED FOR

PROFICIENCY

TESTING

Internal QC samples

are prepared and

quantity values of

target components

are checked against

CRMs

An accredited

laboratory has to prove

its performance by

routinely analysing

samples supplied by

an independent

laboratory

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6. Quality Control

• There is an appropriate level of QC for each test.

• Where control charts are used, performance has been maintained within acceptable criteria.

• QC check samples are being tested by the defined procedures, at the required frequency, and there is an up-to-date record of the results and actions taken where results have exceeded action limits.

• Results from the random re-analysis of samples show an acceptable measure of the agreement with the original analyses.

• Where appropriate, performance in proficiency testing schemes and/or inter-laboratory comparisons is satisfactory and has not highlighted any problems or potential problems. Where performance has been unsatisfactory, corrective action has been taken.

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7. Sample Management

• There is an effective documented system for receiving samples, identifying samples against requests for analysis, showing progress of analysis, issue of report, and fate of sample.

• Samples are properly labeled and stored.

8. Records

• Notebooks/worksheets or other records show the date of test, analyte, sample details, test observations, quality control, all rough calculations, any relevant instrument traces, and relevant calibration data.

• Notebooks/worksheets are completed in ink and the records are signed or initialed by the analysts.

• Mistakes are crossed out rather than erased or obliterated. Where a mistake is corrected the alteration is signed or initialed by the person making the correction.

• The laboratory's procedures for checking data transfers and calculations are being complied with.

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9. Test Reports

• The information given in reports is consistent with the requirements of the relevant Quality Standard, and reflects any provisions made in the documented method.

10. Miscellaneous

• There are documented procedures in operation for handling queries and complaints and system failures.

• The Laboratory Quality Manual is up-to-date and is accessible to all relevant staff.

• There are documented procedures for

sub-contracting work.

• Vertical audits on random samples (i.e. checks made on a sample, examining all procedures associated with testing from receipt through to the issue of a report) have not highlighted any problems.

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Quality System Reviews, QSR

• Internal Quality System Review is the responsibility

of the laboratory management team, supported by

the Quality Manager.

• The Quality Manager then has the responsibility of

recording the outcome of the review, including

recommended actions, and ensuring that these

actions are put into effect within the agreed

time-scale

• ISO Guide 25 requires that internal Quality System

Reviews should be held annually.

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Information to be examined in the QSR

• Results of internal quality audits

• Findings of external assessments

• Results from quality control schemes

• Results from proficiency testing schemes (both in-house and interlaboratory)

• Results from the use of certified reference materials

• Replicate testing results

• Calibration and training needs

• Customer complaints or comments that have been

received;

• Changes in the operation of the laboratory.

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Responsibilities of Laboratory Staff for Quality

1. Laboratory Management's Responsibilities for Quality • The management of a laboratory has the initial responsibility of

deciding on the laboratory's Quality Policy and selecting the appropriate Quality Standard (or Standards) for their laboratory to adopt.

• They must make available the resources that will be necessary to put the Standard into practice, including appointing an appropriate person to be the laboratory's Quality Manager.

• The laboratory's Quality System will then be drawn up in the form of a Quality Manual,

• The management will be required to approve the Manual as the written detail of how their Quality Policy is put into practice

• The management then has a continuing responsibility periodically to re-examine the laboratory's Quality System to see if it is still appropriate to the needs of the laboratory's work program.

• This is usually carried out by means of the Quality System Review Meeting.

• Management's final responsibility is to supply the resources necessary to maintain the Quality System at the required level.

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2. The Quality Manager's Responsibilities • The Quality Manager is responsible for ensuring laboratory

staff are familiar with the requirements of the relevant Quality Standard(s).

• He is also responsible for drawing up, and maintaining, the Quality Manual, which sets out how the laboratory's Quality System is operated in practice.

• The Quality Manager has to organize the laboratory's system of Quality Audits of the Quality System, and to ensure that any problems identified by the audits are corrected within an agreed timescale.

• The Quality Manager then prepares all the relevant material for consideration at the Quality System Review Meeting, and ensures that the decisions reached at this meeting are carried out.

• In a laboratory which is accredited by an independent accreditation body, the Quality Manager will also be responsible for liaising with the accreditation body and for making the necessary arrangements for their periodic assessment visits to the laboratory.

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3. Responsibilities of Individual Members of Staff • All members of staff of the laboratory are responsible for

ensuring that they are familiar with the Quality System, as set out in the Quality Manual, and any supporting documentation.

• They are then expected to follow the procedures set out in the Quality Manual. However, this does not mean that they should merely become robots, with no freedom of choice or expression in their work. They should instead be using their practical expertise and experience to suggest improvements which could be made to the laboratory's systems to reflect changes in customers' requirements, improvements in technical equipment and all the other changes which continually occur in analytical work.

• It should always be borne in mind that Quality Standards are not intended to prevent change, but they do require that changes are handled in a structured way. Change is a constant requirement of any dynamic system but, if introduced in a haphazard manner, can cause confusion and error.

• Any Quality System has to be able to accommodate changes which will improve the way the laboratory operates, but must ensure that the changes are considered, approved, documented and introduced in a controlled manner.

Validation of analytical measurements

Principles of making reliable analytical measurements:

1. Analytical measurements should be made to satisfy an

agreed requirement.

2. Analytical measurements should be made using methods

and equipment that have been tested to ensure they are fit

for purpose.

3. Staff making analytical measurements should be both

qualified and competent to undertake the task.

4. There should be a regular independent assessment of the

technical performance of a laboratory.

5. Analytical measurements made in one location should be

consistent with those elsewhere.

6. Organizations making analytical measurements should have

well defined quality control and quality assurance

procedures.

Quality Management, QM

• QM is managing all aspects of the organization in order to

excel in all dimensions that are important to “customers

• is the assembly and management of all activities

aimed at the production of quality by organizations

of various kinds.

• In a case like soil and plant laboratories this implies

the introduction and proper running of a "Quality

System" in laboratories.

– A statement of objectives and policy to produce quality

should be made for the organization or department

concerned (by the institute's directorate).

– This statement also identifies the internal organization and

responsibilities for the effective operation of the Quality

System.

71

A Quality Management System

It is:

• A belief in the employee’s ability to solve problems

• A belief that people doing the work are best able to improve it

• A belief that everyone is responsible for quality

TQM is a management philosophy:

• continuous improvement

• leadership development

• partnership development

Total Quality Management

• TQM approach involves concepts such as the driver of

customer satisfaction, a correct policy and strategy in the

organization, accountability of individuals, and

continuous improvement.

• TQM comprises all the methods of monitoring and

testing and puts them together in a system that operates

enterprise wide

– Absolute commitment by the highest management that

the organization will actively accept the philosophy

of TQM and commit resources to its implementation.

– Each member of the organization is involved in

rounds of continuous improvement, with a structured

program in which the product and processes are

studied, improvements are planned, changes are

implemented, and so on

73

Total Quality Management

• The traditional TQM concerns manufacturing

industry where a goal is “zero defects”

• According to analytical laboratories:

– TQM involves validation of methods,

measurement uncertainty and traceability, and

perhaps monitoring by participation in

interlaboratory trials and the use of control

charts.

– TQM can be more productive than peer review or

benchmarking, in which the personnel can feel

they are being judged and so might hide improper

practices. 74

History of Quality Management

• Deming and Juran outlined the principles of Quality

Management.

• Tai-ichi Ohno applies them in Toyota Motors Corp.

• Japan has its National Quality Award (1951).

• U.S. and European firms begin to implement Quality

Management programs (1980’s).

• U.S. establishes the Malcolm Baldridge National Quality

Award (1987).

• Today, quality is an imperative for any business.

Deming’s 14 Points

1. Create constancy of purpose for improvement

2. Adopt a new philosophy

3. Cease dependence on mass inspection

4. Do not award business on price alone

5. Work continually on the system of production and service

6. Institute modern methods of training

7. Institute modern methods of supervision of workers

8. Drive out fear

9. Break down barriers between departments

10. Eliminate slogans, urging, and targets for the work force

11. Eliminate numerical quotas

12. Remove barriers preventing pride of workmanship

13. Institute a vigorous program of education and retraining

14. Take action to accomplish the transformation

History of Quality Management

Components of Total Quality Management

TQM is a management philosophy:

• continuous improvement

• leadership development

• partnership development

From

Motivation through fear and loyalty

To

Motivation through shared vision

Attitude: “It’s their problem” Ownership of every problem

affecting the customer

Attitude: “the way we’ve always done

it”

Continuous improvement

Decisions based on assumptions/ judgment calls

Decisions based on data and facts

Everything begins and ends with

management

Everything begins and ends with

customers

Crisis management and recovery Doing it right the first time

Choosing participative OR scientific management

Choosing scientific AND participative management

TQ: is transforming an Organization

What is Six Sigma?

• It was introduced by Motorolla in 1986

• A goal of near perfection in meeting customer requirements

• A sweeping culture change effort to position a company for

greater customer satisfaction, profitability and competitiveness

• A comprehensive and flexible system for achieving,

sustaining and maximizing business success; uniquely driven

by close understanding of customer needs, disciplined use of

facts, data, and statistical analysis, and diligent attention to

managing, improving and reinventing business processes

(Source:The Six Sigma Way by Pande, Neuman and Cavanagh)

Six Sigma

• Six sigma is named after a tolerance spread T of ± 6σ which,

after allowance for ±1.5σ for random effects, leads to a

calculation of 3.4 defects per million

• the analyst should achieve a target measurement uncertainty

that complies with T = 6σ.

• The basic sequence of events associated with six sigma is

recognize–define–measure–analyze–improve–control

• These events are discussed in two scenarios

– One in which an existing product is found in need of

improvement after customer concerns. It makes use of

of acronym DMAIC (define–measure–analyze–improve–

control)

• .

• Six Sigma is a relatively new program, and was only

started in 1986. It was first put into implementation at

Motorola, but is now in use by most large corporations.

• The Six Sigma program is in place to eliminate any

abnormalities, failures, or defects that occur within a

given process

• Six Sigma is also used in developing new processes.

• Six Sigma quality is a term generally used to indicate a

process is well controlled (within process limits ±3s

from the center line in a control chart, and

requirements/tolerance limits ±6s from the center line).

• In simple terms, Six Sigma quality performance means

3.4 defects per million opportunities (accounting for a

1.5-sigma shift in the mean).

• therefore, when one hears about Six Sigma, inherent in

that statement is that the short term capability of the

process is 6, the long term capability is 4.5 (3.4 DPMO

– what the customer sees) with an assumed shift of 1.5

• The Six Sigma program strives to achieve six standard

deviations between the mean and the closest

specification limit on a short term study.

• This shift of the mean is by 1.5 standard deviations for

long term studies

• the goal for the Six Sigma program is to have fewer

than 3.4 failures per one million opportunities when the

data is evaluated to include the shifted mean from

process variability (6 standard deviations - 1.5

standard deviations = 4.5 standard deviations).

• 3.4 failures per one million opportunities represents 4.5

standard deviations (sigma) away from the median

value, either up or down, under a bell curve.

• A method that provides organizations tools to improve

the capability of their business processes.

• This increase in performance and decrease in process

variation lead to defect reduction and improvement in

profits, employee morale, and quality of products or

services.

• Six Sigma quality is a term generally used to indicate a

process is well controlled (within process limits ±3s

from the center line in a control chart, and

requirements/tolerance limits ±6s from the center line).

• In simple terms, Six Sigma quality performance means

3.4 defects per million opportunities (accounting for a

1.5-sigma shift in the mean).

Six Sigma

• The second scenario is used for

developments of new products. It uses

DMADV (define–measure–analyze–

design–verify)

Six Sigma Quality

• A philosophy and set of methods companies use to

eliminate defects in their products and processes

• Seeks to reduce variation in the processes that lead

to product defects

• The name “six sigma” refers to the variation that

exists within plus or minus six standard deviations

of the process outputs

6

Six Sigma

Six Sigma Roadmap (DMAIC)

Next Project Define Customers, Value, Problem Statement

Scope, Timeline, Team

Primary/Secondary & OpEx Metrics

Current Value Stream Map

Voice Of Customer (QFD) Measure

Assess specification / Demand

Measurement Capability (Gage R&R)

Correct the measurement system

Process map, Spaghetti, Time obs.

Measure OVs & IVs / Queues

Analyze (and fix the obvious) Root Cause (Pareto, C&E, brainstorm)

Find all KPOVs & KPIVs

FMEA, DOE, critical Xs, VA/NVA

Graphical Analysis, ANOVA

Future Value Stream Map

Improve Optimize KPOVs & test the KPIVs

Redesign process, set pacemaker

5S, Cell design, MRS

Visual controls

Value Stream Plan

Control Document process (WIs, Std Work)

Mistake proof, TT sheet, CI List

Analyze change in metrics

Value Stream Review

Prepare final report

Validate

Project $

Validate

Project $

Validate

Project $

Validate

Project $

Celebrate

Project $

Is 99% Quality Good Enough?

• 22,000 checks will be deducted from the wrong bank accounts in the next 60 minutes.

• 20,000 incorrect drug prescriptions will be written in the next 12 months.

• 12 babies will be given to the wrong parents each day.

Six Sigma Quality

The objective of Six Sigma quality is 3.4 defects per million opportunities!

(Number of Standard Deviations) 3 Sigma 4 Sigma 5 Sigma 6 Sigma

0.0 2700 63 0.57 0.002

0.5 6440 236 3.4 0.019

1.0 22832 1350 32 0.019

1.5 66803 6200 233 3.4

2.0 158,700 22800 1300 32

But is Six Sigma Realistic?

·

1

11

21

31

41

3 4 5 6 7

10

1

100

1K

10K

100K

7 6 5 4 3 2

(66810 ppm) · IRS – Tax Advice (phone-in)

Best in Class

(3.4 ppm)

Domestic Airline Flight Fatality Rate

(0.43 ppm)

· (233 ppm)

Average Company

Purchased Material Lot Reject Rate

Air Line Baggage Handling

Wire Transfers

Journal Vouchers Order Write-up

Payroll Processing

Doctor Prescription Writing

Restaurant Bills

· · · · · · ·

De

fects

Pe

r M

illi

on

Op

po

rtu

nit

ies (

DP

MO

)

SIGMA

Six Sigma Improvement Methods DMAIC vs. DMADV

Define

Measure

Analyze

Design

Validate

Improve

Control

Continuous Improvement Reengineering

Six Sigma DMAIC Process

Measure

Control

Define

Analyze

Improve

Define: Define who your customers are, and what their requirements are for your products and services – Their expectations. Define your team goals, project boundaries, what you will focus on and what you won’t. Define the process you are striving to improve by mapping the process.

Six Sigma DMAIC Process

Measure

Control

Define

Analyze

Improve

Measure: Eliminate guesswork and assumptions about what customers need and expect and how well processes are working. Collect data from many sources to determine speed in responding to customer requests, defect types and how frequently they occur, client feedback on how processes fit their needs, how clients rate us over time, etc. The data collection may suggest Charter revision.

Six Sigma DMAIC Process

Measure

Control

Define

Analyze

Improve

Analyze: Grounded in the context of the customer and competitive environment, analyze is used to organize data and look for process problems and opportunities. This step helps to identify gaps between current and goal performance, prioritize opportunities to improve, identify sources of variation and root causes of problems in the process.

Six Sigma DMAIC Process

Measure

Control

Define

Analyze

Improve Improve: Generate both obvious and creative solutions to fix and prevent problems. Finding creative solutions by correcting root causes requires innovation, technology and discipline.

Six Sigma DMAIC Process

Measure

Control

Define

Analyze

Improve

Control: Insure that the process improvements, once implemented, will “hold the gains” rather than revert to the same problems again. Various control tools such as statistical process control can be used. Other tools such as procedure documentation helps institutionalize the improvementl.

Six Sigma DMADV Process

Measure

Validate

Define

Analyze

Design

Design: Develop detailed design for new process. Determine and evaluate enabling elements. Create control and testing plan for new design. Use tools such as simulation, benchmarking, DOE, Quality Function Deployment (QFD), FMECA analysis, and cost/benefit analysis.

Six Sigma DMADV Process

Measure

Validate

Define

Analyze

Design

Validate: Test detailed design with a pilot implementation. If successful, develop and execute a full-scale implementation. Tools in this step include: planning tools, flowcharts/other process management techniques, and work documentation.