Total Quality Management

Sangam B. KanthaleSCHOOL OF PHARMACY

SWAMI RAMANAND TEERTH MARATHWADA UNIVERSITY, NANDED

How can we maintain the quality

“Quality should be built into the product”- Starting to end process - It start from the purchase of materials,

equipment & hiring right people - Beyond manufacturing activities

- safe distribution of the product till the ultimate customers

- getting feedback to improve quality of product- for maintaining quality it requires control on facilities,

equipment, materials, processes and testing

QUALITY Grade of excellence

Meeting the requirements of the customer

A state of being free from defects, deficiencies and significant variations

The totality of features and characteristics of a product or service that bears its ability to satisfy stated needs

A pharmaceutical product which meet the following 5 characteristics-

i) Identity (name and contents of product)

ii) Strength (complete strength statement )

iii) Safety (safety of ultimate users or patient)

iv) Purity (free from any cross contamination)

v) Efficacy (getting desired effect)

Higher quality enables company to

Increase customer satisfaction Make products salable Meet competition Increase market share Provide sales income

Objectives of Quality Management

Provide high quality drug product to patientsReduce number of recalls, returned & defective product

entering the market placeHarmonize the c GMPTo handle many types of changes to facilitate,

equipment and processes To help in getting quality by designTo achieve success in business improving risk

management and thus increases profitability

Quality Management System Quality Quality by design and Product development Risk management and risk assessment -RM(establishing specification & process parameters) -RA(need for investigation & taking necessary corrective action) Corrective and preventive action (CAPA) - correcting discrepancies and attempting to prevent recurrence Change control -focusing on managing change & preventing unintended

consequences The quality unit

»Quality Assurance (testing)»Quality Control (review-approval-maintance)

Six system inspection modelsThe FDA’s Drug Manufacturing Inspection

Compliance programme is system based and it carries evaluation of 6 quality systems– Production– Facilities and equipment–Materials– Packaging and labeling– Laboratory control– Overall quality system• System based(it assess whether each of the system

is in a state of control)

QMS

COMPONENTS OF Q.M.S.W.H.O. guidelines of GMP define quality management

as- “The aspect of management function that determine and

implements the Quality Policy” 1) An appropriate infrastructure of ‘quality system’

considering organizational structure, procedure and recourses

2) Systematic action necessary to check product.

Code of Federal Regulations (CFR)

The Code of Federal Regulations (CFR) is the codification of the general and permanent rules and regulations (sometimes called administrative law) published in the Federal Register by the executive departments and agencies of the federal government of the United States.

QUALITY ASSURANCE

Quality assurance is a wide ranging concept covering all matters that individually or collectively influence the quality of a product.

It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use.QA is the heart and soul of quality control QA = QC + GMP /Other Quality Systems Quality

Raw material Top Management

Customer Customer Complaints

According to QA, products are designed and developed in a way that takes account of the requirements of GMP and other associated codes such as those of good laboratory practice (GLP) and good clinical practice (GCP).

Product and control operations are clearly specified in a written form and GMP requirements are adopted.

Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials.

All necessary controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations, and validations are carried out

The finished products is correctly processed and checked according to the defined procedures.

Products are not sold or supplied before the authorized persons have certified that each production batch has been produced and controlled in accordance with the requirements of the marketing authorization and any other regulations relevant to the production, control and release of products.

Satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical products are stored by the manufacturer, distributed and subsequently handled so that quality is maintained throughout their shelf- life.

There is a procedure for self-inspection and/or quality audit that regularly appraises the effectiveness and applicability of the quality assurance system.

Regular evaluations of the quality of pharmaceutical products should be conducted with the objective of verifying the consistency of the process and ensuring its continuous improvement.

Evaluation and Analysis of the Deviations, Out of Specification results and Change Controls during the Manufacturing.

Complaint handling.Documentation of the process from staring material

to the end user and its storage.Stability studies

QC

GMP

QA

QC

Quality relationships

Quality Management

Quality Assurance

GMP

Quality Control

Quality control (QC)Quality control (QC) includes the activities from the

suppliers, through production, and to the customers. Incoming materials are examined to make sure they

meet the appropriate specifications.The quality of partially completed products are

analyzed to determine if production processes are functioning properly.

Finished goods and services are studied to determine if they meet customer expectations.

QC Throughout Production Systems

Raw Materials,Parts, andSupplies

ProductionProcesses

Products andServices

Inputs Conversion Outputs

Control Chartsand

Acceptance Tests

Control Chartsand

Acceptance TestsControl Charts

Quality ofInputs

Quality ofOutputs

Quality ofPartially Completed

Products

Definition by WHO:Q.C. is the part of GMP concerned with sampling,

specification, testing, with the organization, documentation and release procedures which ensures that necessary and relevant test are actually carried out and that materials are neither release for use.

Definition by MCC South Africa:Q.C. is the part of GMP concerned which is concerned with

the organization, documentation and release procedures which ensure that necessary and relevant test are actually carried out that materials are not release for use, not product release for sale or supply, until their quality has been judged to be satisfactory.

Components of Quality Control:The independence of Q.C. from production.Adequate facilities, trained personnel and approved

procedures must be available for sampling, inspection and testing of starting material.

Q.C. Lab should have- testing lab should have chemical, glassware, reagent- instruments like HPLC,GC,FTIR- provision for stability sample- documentation room- various books like pharmacopeias, microbiology, analytical chemistry

Q.C. lab should have trained personnel'sQ.C. lab should have SOP related sampling and

testing, instrumental analysis- do as you have written (SOP)- write you have done (records)

The method must be validatedSufficient sample of starting materials and products

must be kept as retained to permit further examination of the product if necessary.

Goal of QCTo detect significant errors rapidlyReport out good results in a timely mannerBe cost effective and simple to use If there is an error, identify the source of the error

GOOD MANUFACTURING PRACTICEDef by WHO “GMP is the part of quality assurance that products are

consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization”

Def by MCC South Africa “GMP is the part of quality assurance that products

are consistently produced and controlled to the quality standards appropriate to their intended use and the legal requirement. It is concerned with both production and quality control matters”

Various Aspects of GMP

Personnel

Buildings and facilities

Raw materials

Equipment

Storage

Waste disposal.

Comments:

GMP is a part of QAGMP’s main function is to produce quality product

consistentlyGMP must meet legal requirement of the countryGMP must deal with both production and QC related

issues Mainly GMP diminish the risk of mixups and

contamination

Components of GMP All manufacturing processes should be clearly defined Critical steps of manufacturing processes and any significant

changes made to the process validated All necessary facilities are provided including

- qualified trained personnel's- adequate premises and space- suitable equipment and services- correct materials, containers and label- approved procedures and instruction- suitable storage and transport

Operators are trained to carry out procedures correctly Records are made during manufacturer to show that all the steps The proper storage and distribution of the product minimizes any

risk of their quality.

Sampling One can not always non destructively analyze the materials

and hence small sample/population of the material is collected as representative samples and tested for its quality.

If not………. Hence the entire sampling activities get lots of attention of all

the regulatory bodies. Various points covered include-– Sampling area– Sampling of sterile products– Sampling procedures– Reference sample– Sampling of IPQC materials– Sampling of finished and packed material

Sampling area

There should be separate area for-

–API, Excipients, sterile materials

–Liquids, hazardous, poisonous and explosive

materials

–In process, bulk, finished and bulk

–Primary, secondary and tertiary packaging

materials

Sampling of sterile productShall be conducted in aseptic conditionsSterile equipment, sterile product and aseptic sampling

shall be used.Sampling procedureCFR 211.210To avoid contamination or others adverse effects on

qualityFollowing procedures are followed for samplingContainers should be cleaned Containers shall be opened, sampled and resealedSterile equipment, aseptic sampling techniquesContainers from which samples have been taken shall be

marked

Reference sample It is a representative sample of a substance used in

manufacturer of a pharmaceutical product as also the sample of the finished pharmaceutical product.

Sampling of IPQC materials USFDA gives specific guideline on IPQC sampling and

testing in CFR 211.11. Purpose: to assure batch uniformity and integrity of the drug

product. For tab: weight variation, dissolution time, disintegration

time For liquid: clarity, pH Semi solid: viscosity

Specification of finished bulk and packed finished product

Testing • Testing of material is one of the main activity in QC

department which involve testing of following materials namely,– Active and inactive pharmaceutical ingredients– 1° ,2 ° and other packaging materials– In process materials– Finished bulk product– Finished packed product

Regulatory guidelines are available for following areas:

Analytical method validationLaboratory reagent used in testingCalculation verificationUse of laboratory animalSpecial testing requirementTest recordRelease of finished productLegal requirement

Analytical method validationThese procedure includes stability studies must be

validated to demonstrate their reliability Revalidation of analytical method becomes necessary

in-– Change in synthesis of a drug substance– Change in the composition of a finished products– Change in the analytical procedureTypical validation characters which should be

considered are- accuracy, precision, specificity, LOD, LOQ, Linearity and range

Laboratory reagent used in testingEvery lab should have sufficient quantity of all

reagents required for testing.Results of testing depends upon quality of reagentsSOP should be available for making and

standardizing reagents.Records of such preparation and standardization be

kept in a register.Prepared reagents must be properly labeled– Name and strength– Shelf life and date of preparation– Storage condition

Calculation verificationAll analytical calculations carried out by analyst must

be checked and verified by a competent person before the report is accepted

Use of laboratory animal Animal used in testing shall be maintained and

controlled They must be identified and records must be maintainedThey must be appropriately quarantined before use

Special testing requirement

• SOP should be available for following test

– Pyrogen testing

– Sterility testing

– Bacterial endotoxin test

– Test for foreign particles

Self inspection and quality audits1) Self inspection evaluate the manufacturer compliance with GMP detect any short coming in the implementation can be performed routinely may be inhouse or carried out by local regulatory authoritiesFor self inspection SOP should cover the

-items for self inspection-self inspection team-frequency of self inspection -self inspection report-follow up action

Quality AuditExamination and assessment of all parts of a quality

system with a specific purpose of improving itConducted by outside or independent specialist or a

team designated by the management for this purpose.

THANK YOU