This contains all about Quality Management System

1. Total Quality Management

2. 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

3. 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)

4. Higher quality enables company to
 Increase customer satisfaction
 Make products salable
 Meet competition
 Increase market share
 Provide sales income

5. Objectives of Quality Management
 Provide high quality drug product to patients
 Reduce number of recalls, returned & defective product
entering the market place
 Harmonize the c GMP
 To handle many types of changes to facilitate,
equipment and processes
 To help in getting quality by design
 To achieve success in business improving risk
management and thus increases profitability

6. 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)

7. Six system inspection models
 The 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)

8. QMS
EVALUATION
ACTIVITIES
RESOURCES
MANUFACTURING
OPERATION
MANAGEMENT
RESPOSIBILITIES

9. 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.

10. 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.

14. QUALITYASSURANCE
 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

15. Raw material Top Management
Customer Customer Complaints

16.  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

17.  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.

18.  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

19. QC
GMP
QA
QC

20. Quality relationships
Quality Management
Quality Assurance
GMP
Quality Control

21. 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.

22. QC Throughout Production Systems
Raw Materials,
Parts, and
Supplies
Production
Processes
Products and
Services
Inputs Conversion Outputs
Control Charts
and
Acceptance Tests
Control Charts
and
Acceptance Tests
Control Charts
Quality of
Inputs
Quality of
Outputs
Quality of
Partially Completed
Products

23. 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.

24. 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

25.  Q.C. lab should have trained personnel's
 Q.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 validated
 Sufficient sample of starting materials and products
must be kept as retained to permit further
examination of the product if necessary.

26. Goal of QC
 To detect significant errors rapidly
 Report out good results in a timely manner
 Be cost effective and simple to use
 If there is an error, identify the source of the error

27. GOOD MANUFACTURING PRACTICE
 Def 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”

28. Various Aspects of GMP
 Personnel
 Buildings and facilities
 Raw materials
 Equipment
 Storage
 Waste disposal.

29. Comments:
 GMP is a part of QA
 GMP’s main function is to produce quality product
consistently
 GMP must meet legal requirement of the country
 GMP must deal with both production and QC related
issues
 Mainly GMP diminish the risk of mixups and
contamination

30. 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.

31. 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

32. 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

33. Sampling of sterile product
 Shall be conducted in aseptic conditions
 Sterile equipment, sterile product and aseptic
sampling shall be used.
Sampling procedure
 CFR 211.210
 To avoid contamination or others adverse effects on
quality
Following procedures are followed for sampling
 Containers should be cleaned
 Containers shall be opened, sampled and resealed
 Sterile equipment, aseptic sampling techniques
 Containers from which samples have been taken shall
be marked

35. 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

36. Specification of finished bulk and packed
finished product

37. 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

38. Regulatory guidelines are available for following
areas:
 Analytical method validation
 Laboratory reagent used in testing
 Calculation verification
 Use of laboratory animal
 Special testing requirement
 Test record
 Release of finished product
 Legal requirement

39. Analytical method validation
 These 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 procedure
Typical validation characters which should be
considered are- accuracy, precision, specificity,
LOD, LOQ, Linearity and range

40. Laboratory reagent used in testing
 Every lab should have sufficient quantity of all
reagents required for testing.
 Results of testing depends upon quality of reagents
 SOP 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

41. Calculation verification
 All 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
maintained
 They must be appropriately quarantined before use

42. Special testing requirement
• SOP should be available for following test
– Pyrogen testing
– Sterility testing
– Bacterial endotoxin test
– Test for foreign particles

43. Self inspection and quality audits
1) 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 authorities
For self inspection SOP should cover the
-items for self inspection
-self inspection team
-frequency of self inspection
-self inspection report
-follow up action

44. Quality Audit
 Examination and assessment of all parts of a quality
system with a specific purpose of improving it
 Conducted by outside or independent specialist or a
team designated by the management for this purpose.