1. Good Manufacturing Practice
& Quality Assurance :
GMP&QA
The GMP is enforced through Quality Management System (Q.M.S.)
The QMS starts with the concept of Quality Policy & Quality Manual

2. 3. QMS (Quality Management System)
This is an appropriate infrastructure of Quality System in the Organization Structure.
It ensures that the product will satisfy given requirements for Quality

3. Level I
Policy & Objectives
Level II
Quality Manual
SOP & Work Direction
Level III
Quality Records
Level IV

4. Def. of Good Manufacturing Practices (GMP)
As per WHO, GMP is that part of Quality
Assurance which ensures that the
products are consistently produced and
controlled to the quality standards
appropriate to their intended use and as
required by the market authorization.

5. Comments on GMP
The following points are very clear from
the above definition.
GMP is a part of Quality Assurance.
GMPs main objective is to produce Quality Product consistently.
GMP must meet the legal requirements of the country.

6. For meeting the expected. requirements GMP must deal with
For meeting the expected requirements GMP must deal with both production and Q.C. related issues.
GMP further talks about what
Precautions should be taken during storage and distribution of finished products.
Guideline to handle market and product complaints.

7. GMP is only a tool for manufacturing and distribution of Quality Pharmaceutical products for ailing human being. In GMP one basic rule is followed and that is “Do what you have written and write what you have done”. This means always follow only written document and always record what has been done.

8. Reason of failure of a product to be. used as data for improving the
Reason of failure of a product to be used as data for improving the quality of a product and the manufacturing system to he benefit of the Organization.
Def. of Quality Control (QC) :
Quality control is that part of GMP
concerned with sampling, specification
and testing documentation and release
procedure which ensures that necessary

9. and relevant tests are actually carried out and materials and not released for use nor products are released for sale and supply, until their quality has been judged to be satisfactory. Def. of Quality Assurance (QA) : It is the sum total of the organized arrangements made with the object of ensuring that the medical products are

10. of quality required for their ultimate use.
It is thus a wide ranging concept and
covers all matter affecting quality.
Comments on the definition of QA :
Quality Assurance deals with all matters
related to the quality of the product.

11. intended use or as required by the ultimate uses.
Quality of medicine must meet the
intended use or as required by the
ultimate uses.
Wide ranging concept covering many
aspects which are outside the scope
of QC/GM P.
Sum total of the arrangement for
producing a quality product.

12. Therefore, the key words about the
spirit of Q.A. :
Quality of the product
All matters/wide ranging concept
Ultimate user
Sum total of the total organized arrangements.

13. It is an accepted fact that products that meet the following 4 characteristics can be accepted as a quality product. Quality 1. Identify Characteristic 2. Strength or Quality Attributes 3. Purity 4. Safety

14. A product that meets all these four
attributes will definitely have desired
therapeutic efficacy
Identity : It may be considered as
product identity
2. Strength : It is mainly the strength of the Pharmaceutical unit dosage form as claimed on the label.

15. Purity : This means that the product
is free from Contamination / cross
contamination may be defined as presence of any undesired / unexpected material in the product.
In other words, this means that people,
material, equipment, place and
environment were all within control as
expected from the manufacturer of the
product.

16. Safety : The regulatory authorities refer it to the safety of the ultimate user i.e, patent. To consider this point at more basic level let us try to understand what should happen when a Pharmaceutical product is administered to a patient (suffering from some ailment and having a desire to get cured).

17. First : He gets no desired effect
First : He gets no desired effect. Second : He gets partial desired effect. Third : He gets unexpected, undesired effect (unknown side effect) plus desired effect. Fourth : He gets desired effect (i.e, known side effect + desired effect).

18. Fifth : He gets desired effect
Fifth : He gets desired effect. The product which gives 4th or only 5th Choice, may be considered as safe product. The manufacturing activity may be divided into three parts as below :

19. Pre production activities Related to
design and development of the
product / procurement of raw
materials, supplies of raw material
and P.M. (preventive maintenance)
packaging materials specifications
and contract manufacturing.

20. Production and Q.C. activities of the manufacturing premises.
Post production activities storage, transport (cold chain arrangement) of the pharmaceutical product outside the manufacturing premises.
Secondly, all matters should also
include all activities carried out by the
decision making people at various levels
which have an effect on the quality of the
product.

21. The third part is ultimate user The ultimate user of a pharmaceutical
product is the ailing patient who is
expected to be cured.
Patient’s interest what?
Effective medicine / Reliability of results.
Reasonable price.
Easy availability.

22. It is the responsibility of the manufacture to meet the expectation of the ultimate user. ‘Fitness for use’. Thus, any effort to meet this, should fall within the scope of Quality Assurance. The fourth part (4th) Sum total of the organized effort.

23. Efforts of the manufacturer through phases should contribute to the quality of the product. All activities should be value addition and not cost addition. There should not any scope of disorganized working or duplicating of the work.

24. All Pharmaceutical products are. released for sale after authorized
All Pharmaceutical products are released for sale after authorized person certified that the batch of drug so produced has been produced and control in accordance with market
authorization
Quality / Efficacy / Safety
The ultimate objective of Quality assurance
system of Pharmaceutical product has to be
ensured for intended use.

25. Quality Assurance may be considered as preventive measure to build quality. Now which practicing quality assurance system it has to be kept in mind that zero defect is our objective and I can be achieved through No error / No mix up / No contamination / Cross contamination

26. How to define quality. The most simple definition is fitness for use
How to define quality ? The most simple definition is fitness for use. If the user of the product is happy and delighted when using the products then it may be called as a Quality Product. USFDA has advocated the following concept of quality as;

27. Quality should be built into the product, and testing alone cannot be relied on to ensure product quality. The process of building quality into the product not only starts and ends in manufacturing premises.

28. But it starts from selection of
Site of manufacture
Water source
Layout of manufacturing unit
Purchase of equipment
Materials and
Hiring of right people.
Building quality into the product also
involves control at every stage of
manufacturing and not only terminal
control.

29. The stage wise control incorporates control on facilities equipment, materials process and testing etc. Quality concept goes beyond the manufacturing activities and also includes safe distribution of all products till the ultimate customer and getting feed back from them.

30. Hence, the concept of building quality into the product should become a way of life for manufacturing medicines. Consistent Quality that is dependent on (a) Defined (b) approved and (c) validated procedure SOP’s at critical steps.

31. Quality is achieved in QMS by Quality assurance and not by control of the Quality at the final stage and Inspection

32. PERCEPTION OF ‘QUALITY OF DRUG’
Patient/
Customer
Physician
Therapeutic efficacy
Lesser side effect
Regulatory affair
Compliance of
GCP
GMP
QA / QC
Manufacturer
Early relief from disease
Cost Factor
Attractive get up
PERCEPTION OF ‘QUALITY OF DRUG’
To improve
Quality
Efficacy
Safety

33. Contamination : Contamination : ----Wide range of different substances ---- It is a stuff in wrong place or where it should not be

34. Contamination Contd……. --- With ref
Contamination Contd……. --- With ref. to sterile product it means that sterile product got mixed with particulate viable (bacteria) non viable (particulate matter).

35. Contamination & Cross Contamination
Physical
Chemical
Microbes
Packing material
Facilities equipment
Environment
Human
Coughing
Sneezing
Hair & Skin
ii) Water
Starting material
Equipment

36. How contamination happens ?
Microbes
Product cleaning solution / residue
Unwanted materials
(i) Wire from sieves
(ii) Staple pin
(iii) Threads and fibres (from uniform)
(iv) Flaking paints as dust or
dirt
(v) Rodent and Insects

37. Control of contamination
Control through AHU / Pr. difference
Status labeling
Cleaning
Facility design
Hygiene practice & training
Cleaning and sanitation of manufactory area

38. A programme which provides a high degree of assurance that a specific
Validation
A programme which provides a high
degree of assurance that a specific
process will consistently produce
a product to meet its predetermined
specification of quality attributes.
Since last two decades the regulatory
authorities world wide started considering
process validation as one of the
Compliance in their inspections.

39. The following areas of validation are
considered necessary
Analytical method
Instrument calibration
Process utility services
Raw materials and packaging
materials
(v) Equipment

40. Facilities
Manufacturing operations
Product Design
Cleaning
Validation studies shall be an essential
part of Good Manufacturing process and
shall be conducted as per the pre
defined protocol.

41. Processes and procedures be established on the validation study and undergo periodic revalidation to ensure that they remain capable of achieving the intended results. Standard operating Procedure : Objectives : a) To perform the job properly.

42. To achieve consistency while doing

43. (b) Variations between
Factors leading to Quality and Integrity
of the product.
Exp. Quality variation in
four major sources
Materials (a) Variations between
supplies of the some substance
(b) Variations between
batches of the some
supplies

44. Exp. Contd…… (c) Variations within the batch 2
Exp. Contd…… (c) Variations within the batch 2. Machine (a) Variations of equipment of same process (b) Difference in adjustment of same

45. Exp. Contd…. 3. Method (a) In exact procedure (b) Inadequate procedure (c) Negligence by chance 4. Men (a) Inadequate training & understanding (b) In proper working condition

46. (d) Dishonesty, fatigue and carelessness
Exp.
Contd….
(c) Lack of interest
(d) Dishonesty, fatigue
and carelessness
These sources of quality variations need
to be controlled.

47. Preparation of SOP is a step in that direction
Preparation of SOP is a step in that direction. SOPs are usually created for critical process and are presented in a standard format that out lines responsibilities and procedure steps. Indeed, if there is change encountered in the process, the there is a separate SOP for change control.

48. SOPs are also used for training purpose of technical staff and fulfill important regulatory requirements. SOPs are a integral part of a successful quality system (a) To perform a job properly (b) Facilities consistency in the quality and integrity of a product.

49. Complaints, adverse reactions and recall
(Defective and sub standard drug)
All complaints concerning quality
shall be reviewed and records.
Each complaints shall be investigated evaluated by designated person of the company

50. Records of investigation and
remedial action shall be record and
maintained.
Reports of serious drug reaction with comments shall be sent to the concerned authority forthwith.
(e) Recall procedure according to SOP for defective drug.

51. Type of complaints (i) Originates from consumer due to
(a) Physical, Chemical and
Biological properties
(b) Condition of labeling and packaging

52. (2) Adverse drug reactions (from Physician) --- from medical person due to allergic reactions leading to near fatal / fatal situation --- Lack of efficacy and clinical response

53. Records of complaints should include Contents of complaints
name, dosage form and packing
date and place of occurrence
Handling of complaints
---- Written record should be
maintained

54. ---- Quality related problem should be forwarded to Q. C. department
---- Quality related problem should be forwarded to Q.C. department ADR and medical problem to be forwarded to Medical Advisor ---- Complainant sample should be tested with control Ref. sample ---- Defects, as revealed should be sent to concern department for rectification

55. ---- Possibility of counterfeit drug should be kept in mind during investigation Drug reprocessing as per SOP.