Post on 15-Feb-2017
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