ወአገወአገxkyexjxyxjyetjextejxexeekyxdkyxe

1. Current Good Manufacturing Practices
1

2. Outline
2
 History of pharmaceutical quality
 Quality Management in pharmaceutical industry
 cGMP: Basic Principles
 Building and facilities
 Organization and personnel
 Material, packaging, labeling control
 Production and process controls
 Documentation

3. A History of Pharmaceutical Quality
3
 1937 – Massengil Company marketed
 “ELIXIR OF SULFANILAMIDE” formulated with diethyl glycol
 107 people died in the USA
 1948 WHO was established
 1957 - THALIDOMIDE (Contergan, Distaval) -antiemetic (morning
sickness) – sleeping aid
 1961 – association with malformation of newborn infants was
substantiated
 1962 –GMP becomes law and part of NDA in USA
 1967 – WHO prepared DRAFT GMP

4. History,…
4
 1990 – Ethylene glycol labelled as propylene glycol:
 109 infants died in Nigeria
 1991 – International Conference on Harmonization (ICH)
 1992 – WHO-GMP revised
 1996 – Haiti: Glycerol contaminated with diethyl glycol:
 62 infants died
 2003 – WHO-GMP revised

5. Introduction
 Good Manufacturing Practices (GMPs) are regulations that
describe the methods, equipment, facilities, and controls
required for producing:
human and veterinary products
 medical devices
 processed food
 Good Manufacturing Practice (GMP) ensures that quality is built
into the organization and processes involved in manufacture.
5

6. Introduction,…
 GMP covers all aspects of “manufacture” including collection,
transportation, processing, storage, quality control and delivery
of the finished product.
 GMPs are aimed primarily at diminishing the risks inherent in
any pharmaceutical production.
 GMP is part of quality assurance which ensures that products
are consistently produced and controlled to the quality standards
appropriate to their use.
6

7. Quality Management in pharmaceutical industry
 Quality management: the aspect of management function that
determines and implements “quality policy”,
 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.
 The QA unit monitors overall compliance with cGMPs.
7

8. Quality mgmt.,…
8
 Quality assurance establish control or check point to monitor
the quality of the product as it is processed and up on
completion of manufacture.
 It begins with
Raw material and component testing
In-process
Packaging
Labeling
Finished product testing and batch auditing and stability
monitoring are conducted

9. Quality mgmt.,…
9
 Manufacturers must ensure that pharmaceutical products
are fit for their intended use,
comply with the requirements of the marketing authorization
and
do not place patients at risk due to inadequate safety, quality
or efficacy.
 To achieve the quality objective, there must be a quality
assurance system incorporating GMP and Quality Control.

10. Quality Management,…
10
 The concepts of quality assurance, GMP and quality control
are interrelated aspects of quality management.
Quality Management
Quality Assurance
GMP
Production and Quality Control

11. Why GMP is important
11
 A poor quality medicine may contain toxic substances that have
been unintentionally added.
 A medicine that contains little or none of the claimed ingredient
will not have the intended therapeutic effect.
 Incorrect labels on containers, which could mean that patients
receive the wrong medicine.
 Insufficient or too much active ingredient, resulting in
ineffective treatment or adverse effects
 GMP helps boost pharmaceutical export opportunities.

12. cGMP (Current Good Manufacturing Practice)
 GMP should be “Designed” to be flexible to allow each
manufacturer to decide individually how to implement the
necessary controls by using scientific sound design, processing
methods and testing procedures
 The “C” in GMP means current – up to date technologies
 Overall concept:
Quality should be built into the product
Testing alone cannot be relied on to ensure product quality
A product that is ‘fit for its purpose”
12

13. Cont,…
cGMP Violations --Severe Consequences Product is
“adulterated
Shutdown of manufacturing facility
Seizure of product
Recall product
Competitive disadvantage
13

14. cGMP Principles
14
 Build QUALITY in.
 Have controls in place for each step of the process – increase
the likelihood the product produced in safe and fit for its
intended purpose
 Prevent the product from contamination and cross-
contamination and prevent mix-ups.
 Know what you are doing in advance and document what really
happened (document everything)
 Have an independent Quality Assurance Group.

15. Ten principles of GMP
15
 Design and construct the facilities and equipment properly
 Follow written procedures and Instructions
 Document work
 Validate work
 Monitor facilities and equipment
 Write step by step operating procedures and work on
instructions
 Design, develop and demonstrate job competence
 Protect against contamination
 Control components and product related processes
 Conduct planned and periodic audits

16. cGMP Requirements (as many regulations as GCP)
16
 A Quality System (change control, validation)
 Qualified and trained personnel
 Fit for use buildings and facilities to meet the purpose
 Equipment that is suitable, clean, maintained and calibrated
 Production and in-process controls for performance monitoring
and deviations
 Proper packaging and labeling – ID and Protection
 Laboratory controls – specifications , samples, testing

17. Building and facilities
 Premises must be located, designed, constructed, adapted, and
maintained to suit the operations to be carried out.
 Prevention of build-up of dirt and dust to avoid unnecessary
risks of contamination.
 There should be proper drains, air supply, dust extraction
systems
 Drains – prevent backflow
17

18. Cont,…
 Epoxy coated floors, walls
 Self closing doors
 Doors opening to the clean side
 Sufficient lighting
 Ventilation, air filtration, air
heating and cooling
 Plumbing
18

19. Ancillary areas
19
 Rest and refreshment rooms should be separate from
manufacturing and control areas.
 Facilities for changing and storing clothes and for washing
and toilet purposes should be easily accessible and
appropriate for the number of users.
 Toilets should not communicate directly with production or
storage areas.

20. Storage area
 Storage areas should be of sufficient capacity to allow orderly
storage of the various categories of materials and products with
proper separation and segregation: starting and packaging
materials, intermediates, bulk and finished products.
 They should be clean, dry, sufficiently lit and maintained within
acceptable temperature limits. Where special storage conditions
are required (e.g. temperature, humidity) these should be
provided, controlled, monitored and recorded where
appropriate.
20

21. Equipment
21
 Equipment must be located, designed, constructed, adapted,
and maintained to suit the operations to be carried out.
 The layout and design of equipment must aim to minimize the
risk of errors and permit effective cleaning and maintenance in
order to avoid cross-contamination, build-up of dust or dirt,
and, in general, any adverse effect on the quality of products.
 Defective equipment should be removed or clearly labelled
defective to prevent use from production and quality control
areas.

22. Equipment,…
22
 Production equipment should be thoroughly cleaned on a
scheduled basis.
 The parts of equipment that come into contact with the product
must not be reactive, additive, or absorptive to an extent that
would affect the quality of the product.
 Non-dedicated equipment should be cleaned according to
validated cleaning procedures between production of different
pharmaceutical products to prevent cross-contamination.

23. Materials, packaging, labelling control
23
 All incoming materials and finished products should be
quarantined immediately after receipt or processing, until they
are released for use or distribution.
 All materials and products should be stored under the
appropriate conditions established by the manufacturer and in an
orderly fashion to permit batch segregation and stock rotation by
a FIFO rule.
 Starting materials in the storage area should be appropriately
labelled.

24. Starting materials
24
 Starting materials should be purchased only from approved
suppliers.
 For each consignment, the containers should be checked for at
least integrity of package and seal and for correspondence
between the order, the delivery note, and the supplier’s labels.
 Starting materials in the storage area should be appropriately
labelled.

25. Starting materials,…
25
 Only starting materials released by the quality control
department and within their shelf-life should be used.
 Starting materials should be dispensed only by designated
persons, following a written procedure, to ensure that the
correct materials are accurately weighed or measured into clean
and properly labelled containers.
 Each dispensed material and its weight or volume should be
independently checked and the check recorded.

26. Finished products
26
 Finished products should be held in quarantine until their
final release, under conditions established by the
manufacturer.
 The evaluation of finished products and the documentation
necessary for release of a product for sale should be done by
QC.

27. Rejected, Reprocessed and Recall
27
 Rejected materials and products should be clearly marked as
such and stored separately in restricted areas.
 The need for additional testing of any finished product that has
been reprocessed should be considered by the quality control
department
 Recalled products should be identified and stored separately in a
secure area until a decision is taken on their fate.

28. GMP in Production
28
 Operations on different products should not be carried out
simultaneously in the same room unless there is no risk of
mix-up or cross-contamination.
 Avoidance in cross-contamination:
Segregated areas
 Ventilation systems
 Airlocks
 Clothing
 Closed processing systems
 Cleaning and decontamination

29. GMP in Quality Control
29
 Quality control laboratories should be separated from production
areas.
 Areas where biological, microbiological or radioisotope test
methods are employed should be separated from each other and
separate air-handling units.
 There should be adequate suitable storage space for samples,
reference standards (if necessary, with cooling), solvents, reagents
and records.

30. GMP in Quality Control,…
30
 Basic requirements for Quality Control
 Each manufacturer should have a QC Department
 Should be independent from production and other departments
 Should be under the authority of an appropriately qualified and
experienced person
 Resources:
Adequate facilities, Trained personnel,
Approved procedures

31. GMP in quality control,…
31
 Sampling
 Making records of sampled materials
 Test, records of tests made,
 Retain samples of starting materials and products
 Release of batches by authorized person
 Establish, validate and implement QC procedures
 Correct labelling of containers and materials and products
 Monitor stability of APIs and finished products

32. Documentation
32
 Good documentation is an essential part of QA system and,
should exist for all aspects of GMP.
 It define the specifications and procedures for all materials and
methods of manufacture and control;
 It ensure that all personnel concerned with manufacture know
what to do and when to do it;
 It ensure that authorized persons have all the information
necessary to decide whether or not to release a batch of a drug
for sale,

33. Types of documents
33
 Labels, specifications and master formulae
 Batch processing/manufacturing record (BMR)
 Batch packaging record (BPR)
 Standard operating procedures (SOPs)
 Standard analytical procedures (SAPs)
 Stock control and distribution records
 Water quality manual

34. Cont,…
34

35. Summary
35
o Regulations over product quality, patient safety, and efficacy
were born reactively from tragedies over the past 110 years and
becoming more proactive.
o Pharmaceutical industry should be regulated by GMP.
o Good Manufacturing Practices must be followed strictly.
o Quality should be built into the product.
o GMP ensures that drug products are safe, pure and effective.