GMP

1. GMP REQUIREMENTS
Dr. K. VENKATESWARA RAJU & Mr. SR PARTHASARATHY
SHRI VISHNU COLLEGE OF PHARMACY
mail4venkey@gmail.com

2. PERSONNEL
 GENERAL
 RESPONSIBILITIES OF HEAD OF PRODUCTION
 RESPONSIBILITIES OF HEAD OF THE QUALITY UNIT
 PERSONNEL RECORDS
TRAINING
HYGIENE
PREMISES- DESIGN, CONSTRUCTION AND LAYOUT
 LOCATION OF FACTORY
 BUILDINGS AND PREMISES
 PRODUCTION / AUXILIARY AREAS
 QUALITY CONTROL
MAINTAINANCE
SANITATION IN MANUFACTURING AREA
ENVIRONMENTAL CONTROL
UTILITIES
 PLUMBING
 DRAINAGE SYSTEMS
 GAS SYSTEMS
 WATER SYSTEM
 WATER SYSTEM- TYPES OF WATER
MAINTAINANCE OF STERILE AREAS
CONTROL OF CONTAMINATION
EQUIPMENT
RAW MATERIALS

3. 3
GMP and SCHEDULE-M
 The basic responsibility of a manufacturer is to ensure the
production of quality products
 These quality objectives can be achieved by GMP and hence they
were implemented as Schedule M in 1988.
 The Schedule M has again been amended in a major way by the
drugs and cosmetics act rules,2001

4. 4 PERSONNEL

5. 5
PERSONNEL - GENERAL
 The establishment and maintenance of a satisfactory system of QA and the correct
manufacture and control of pharmaceutical products and active ingredients rely upon
people.
 For this reason there must be sufficient qualified personnel to carry out all the tasks for
which the manufacturer is responsible.
 Individual responsibilities should be clearly defined and understood by the persons
concerned and recorded as written descriptions.
 The manufacturer should have an adequate number of personnel with the necessary
qualifications and practical experience. The responsibilities placed on any one individual
should not be so extensive as to present any risk to quality.
 Responsible staff should have its specific duties recorded in written descriptions and
adequate authority to carry out its responsibilities. Its duties may be delegated to designated
deputies with a satisfactory level of qualifications. There should be no gaps or unexplained
overlaps in the responsibilities of personnel concerned with the application of GMP. The
manufacturer should have an organization chart.
 All personnel should be aware of the principles of GMP that affect them and receive initial
and continuing training, including hygiene instruction, relevant to their needs. All personnel
should be motivated to support the establishment and maintenance of high quality
standards.
 Steps should be taken to prevent unauthorized people from entering production, storage
and QC areas. Personnel who do not work in these areas should not use them as a
passageway.

6. 6
PERSONNEL - GENERAL
 The company to have competent staff with experience and educational
qualifications
 The head of QC/ QA should be independent of production
 Approved technical staff to be available for testing
 Adequate staff to be provided for both quality assurance and control activities
 Job responsibilities have to be clearly laid down
 Sufficient QC personnel to carry out the work
 QC, Production, Store and other personnel to receive technical training in line
with their duties

7. 7
PERSONNEL - GENERAL
 Key personnel include the heads of production, the head(s) of quality unit(s)
and the authorized person. The quality unit(s) typically comprise the quality
assurance and quality control functions. In some cases, these could be
combined in one department. The authorized person may also be
responsible for one or more of these quality unit(s). Normally, key posts
should be occupied by full-time personnel. The heads of production and
quality unit(s) should be independent of each other. In large organizations,
it may be necessary to delegate some of the functions; however, the
responsibility cannot be delegated.
 Key personnel responsible for supervising the production and quality unit(s)
for pharmaceutical products should possess the qualifications of a scientific
education and practical experience required by national legislation
 They should also have adequate practical experience in the manufacture
and QA of pharmaceutical products. In order to gain such experience, a
preparatory period may be required, during which they should perform
their duties under professional guidance.

8. 8
PERSONNEL
THE HEAD OF PRODUCTION GENERALLY HAS THE FOLLOWING
RESPONSIBILITIES
 (a) to ensure that products are produced and stored in accordance with the
appropriate documentation in order to obtain the required quality;
 (b) to approve the instructions relating to production operations, including the in-
process controls, and to ensure their strict implementation;
 (c) to ensure that the production records are evaluated and signed by a
designated person;
 (d) to check the maintenance of the department, premises and equipment;
 (e) to ensure that the appropriate process validations and calibrations of control
equipment are performed and recorded and the reports made available;
 (f) to ensure that the required initial and continuing training of production
personnel is carried out and adapted according to need.

9. 9
PERSONNEL
THE HEAD OF QUALITY UNIT(S) GENERALLY HAVE THE FOLLOWING
RESPONSIBILITIES
 (a) to approve or reject starting materials, packaging materials, and intermediate, bulk
and finished products in relation to their specifications;
 (b) to evaluate batch records;
 (c) to ensure that all necessary testing is carried out;
 (d) to approve sampling instructions, specifications, test methods and other QC
procedures;
 (e) to approve and monitor analyses carried out under contract;
 (f) to check the maintenance of the department, premises and equipment;
 (g) to ensure that the appropriate validations, including those of analytical procedures,
and calibrations of control Equipment are carried out;
 (h) to ensure that the required initial and continuing training of quality unit personnel is
carried out and adapted according to need;
 (i) establishment, implementation and maintenance of the quality system;
 (j) supervision of the regular internal audits or self-inspections;
 (k) participation in external audit (vendor audit);
 (l) participation in validation programmes.

10. 10 PERSONNEL - PERSONNEL RECORDS
 The manufacturer must have an organization chart.
 People in responsible positions should have specific duties recorded in
written job descriptions and adequate authority to carry out their
responsibilities. Their duties may be delegated to designated deputies
of a satisfactory qualification level.
 Documents need to be designed, prepared and reviewed and
controlled
 Documents have to be such that they permit an audit trail
 All documents have to be prepared as per rules
 Documents need to be approved, signed and dated by authorized
personnel

11. 11 TRAINING

12. 12
TRAINING
 The manufacturer should provide training in accordance with a written programme for all
personnel whose duties take them into manufacturing areas or into control laboratories
(including the technical, maintenance and cleaning personnel) and for other personnel as
required.
 Besides basic training on the theory and practice of GMP, newly recruited personnel
should receive training appropriate to the duties assigned to them.
 Continuing training should also be given, and its practical effectiveness periodically
assessed. Approved training programmes should be available.
 Training records should be kept.
 Personnel working in areas where contamination is a hazard, e.g. clean areas or areas
where highly active, toxic, infectious or sensitizing materials are handled, should be given
specific training.
 The concept of QA and all the measures which aid its understanding and implementation
should be fully discussed during the training sessions.
 Visitors or untrained personnel should preferably not be taken into the production and
QC areas. If this is unavoidable, they should be given relevant information in advance
(particularly about personal hygiene) and the prescribed protective clothing. They should
be closely supervised.
 Consultant and contract staff should be qualified for the services they provide. Evidence
of this should be included in the training records.

13. 13
HYGIENE

14. 14
HYGIENE
 All personnel, prior to and during employment, as appropriate, should undergo health
examinations. Personnel conducting visual inspections should also undergo periodic eye
examinations.
 All personnel should be trained in the practices of personal hygiene. A high level of personal
hygiene should be observed by all those concerned with manufacturing processes. In particular,
personnel should be instructed to wash their hands before entering production areas. Signs to
this effect should be posted and instructions complied with.
 Any person shown at any time to have an apparent illness or open lesions that may adversely
affect the quality of products should not be allowed to handle starting materials, packaging
materials, in-process materials or medicines until the condition is no longer judged to be a risk.
 All employees should be instructed and encouraged to report to their immediate supervisor any
conditions (relating to plant, equipment or personnel) that they consider may adversely affect
the products.
 Direct contact should be avoided between the operator’s hands and starting materials, primary
packaging materials and intermediate or bulk product.
 To ensure protection of the product from contamination, personnel should wear clean body
coverings appropriate to the duties they perform, including appropriate hair covering. Used
clothes, if reusable, should be stored in separate closed containers until properly laundered and,
if necessary, disinfected or sterilized.
 Smoking, eating, drinking, chewing, and keeping plants, food, drink, smoking material and
personal medicines should not be permitted in production, laboratory and storage areas, or in
any other areas where they might adversely influence product quality.
 Personal hygiene procedures, including the wearing of protective clothing, should apply to all
persons entering production areas, whether they are temporary or full-time employees or non-
employees, e.g. contractors, employees, visitors, senior managers and inspectors

15. 15
PREMISES- DESIGN, CONSTRUCTION AND
LAYOUT

16. 16
PREMISES- DESIGN, CONSTRUCTION AND LAYOUT -
GENERAL
 Principle. Premises must be located, designed, constructed, adapted and maintained to suit the
operations to be carried out.
 The layout and design of premises 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.
 Where dust is generated (e.g. during sampling, weighing, mixing and processing operations, or
packaging of powder), measures should be taken to avoid cross-contamination and facilitate cleaning.
 Premises should be situated in an environment that, when considered together with measures to
protect the manufacturing process, presents minimum risk of causing any contamination of materials
or products.
 Premises used for the manufacture of finished products should be suitably designed and constructed
to facilitate good sanitation.
 Premises should be carefully maintained, and it should be ensured that repair and maintenance
operations do not present any hazard to the quality of products.
 Premises should be cleaned and, where applicable, disinfected according to detailed written
procedures. Records should be maintained.
 Electrical supply, lighting, temperature, humidity and ventilation should be appropriate and such that
they do not adversely affect, directly or indirectly, either the pharmaceutical products during their
manufacture and storage, or the accurate functioning of equipment.
 Premises should be designed and equipped so as to afford maximum protection against the entry of
insects, birds or other animals. There should be a procedure for rodent and pest control.
 Premises should be designed to ensure the logical flow of materials and personnel

17. 17
Location of factory
 No open sewers or public lavatory and drain in the proximity
 No factory producing soot or obnoxious odour / dust/ smoke and
biological emissions in the proximity
Buildings and premises
 Free from contamination because of other activities
 Adequate provision of working space
 Cross contamination and contamination avoided
 Adequate pest control measures taken
 Provided with Air conditioning, AHUs as applicable
 There has to be a comfort level for all those working in the area
 Drainages are constructed such that there is no Room for entry of insects
 Walls and floors to be free from cracks and open joints. All interior surfaces should
not shed any particles. No accumulation of waste can take place
 Floors and walls are smooth and impervious

18. 18 Warehouse

19. 19
Warehouse
 Space for storage of raw materials, packaging materials, intermediates, finished products,
products in quarantine, rejected materials, rejected products provided for
 Access to storage areas should be restricted to authorized personnel
 Storage conditions adequate
 Special conditions provided where required
 Records are maintained of storage conditions
 Satisfactory Storage area- House keeping to prevent any attack of pests
 Receiving and dispatch areas to be closed to protect materials
 Incoming materials to be cleaned prior to shifting to storage area
 Quarantine areas are well demarcated
 Sampling area provided for actives and excipients separately
 Segregated areas provided for storages for rejected, recalled and returned products
 Areas provided for narcotics, poisonous, hazardous substances etc
 Printed packaging materials stored under lock and key in a secure area
 All primary packaging materials are received in a closed condition to prevent
contamination during storage
 Dispensing areas separate for Beta lactum and Hormonal and other special products
under special conditions to prevent cross contamination
 Dispensing and sampling areas separate for sterile products under Class 100 conditions
(grade A )
 Adequate precautions to be taken to prevent breakage, spillage and leakage of
containers

20. 20 Production / Auxiliary areas

21. 21 Production areas
 Production area allows uni-directional flow of process
 Production of Penicillin and biological preparations to be
segregated
 Areas for potent products such as betalactum or sex hormones to
be separated from other areas
 Pipelines, electrical fittings and ventilation openings shall be
constructed to avoid creation of recesses
 Service lines to be identified by colour codes and flow directions
indicated

22. 22 Auxiliary areas
 Rest rooms to be separated from other areas. They cannot lead
directly to production area
 Change rooms and facilities therein to be commensurate with
number of workforce
 Maintenance workshops to be located away from main work areas
 Spares and tooling to be stored in production area have to be kept in
dedicated rooms or lockers
 Animal houses to be separated from other manufacturing areas and
shall be in line provisions on the Act

23. 23 Quality control

24. 24 Quality control
 QC laboratory to be independent of other production areas
 Provision to be made for chemical, instrumental, Microbiological and
radio isotope analysis
 Adequate steps to be taken to prevent cross contamination/
contamination during analysis
 A separate instrument room is to be provided with adequate facilities
 Sufficient area to be provided for storage of test samples, retained
samples, reagents etc
 Air locks and LAF benches to be provided for Microbiological
laboratory

25. 25
MAINTAINANACE
MAINTENANCE
Maintenance , literally means ‘The Process or Practice of keeping something in good condition’. I pharmaceutical industries as per
various regulatory bodies maintenance says - “Any building used in the manufacture, processing, packing, or holding of a drug
product shall be maintained in a good state of repair”.
DEFICIENCIES IN MAINTENANCE
The most important lacunas or illegibility or deficiencies that should be avoided in industries are :
1. Buildings under deterioration state
2. Cracks and holes on walls , floors and ceilings.
3. Deep floor cracks
4. Ingress of water from roof leaks
5. Holes in roofs or top of buildings
6. Damage to insulation or pipes
7. Light fittings
8. Improper building inspection and maintenance programs.
THE IMPACTS OF THESE DEFICIENCIES
The impacts of these deficiencies; Buildings under deterioration state: Deterioration of buildings not only presents a poor
image of the facility, it can also impact on product quality. Cracks and holes on walls, floors and ceilings: Cracks and holes in
walls, floors, or ceilings can provide access for insects, rodents, birds, dirt, or microorganisms. They can also hinder cleaning
and sanitation, thereby increasing the potential for cross contamination or microbial multiplication.
IMPORTANCE OF PROPER MAINTENANCE
Importance of proper maintenance Avoidance of contamination. Good product quality can be obtained. Accidents can be
avoided. Systematic and smooth functioning of the industry. Safety can be enhanced.

26. 26
MAINTAINANACE
Maintenance Classification
1. Corrective or Breakdown Maintenance
2. Scheduled Maintenance
3. Preventive Maintenance
4. Predictive Maintenance
1. Corrective Or Breakdown Maintenance
“Repairs that are made after the equipment is out of order and it cannot perform it’s normal function
any longer”
Eg: Electric Motor will not start
Used in small factories which get temporary Demand in excess of normal operating capacity
Causes For Equipment Breakdown
i. Failure to replace worn out parts
ii. Lack of Lubrication
iii. Neglected Cooling System
iv. External Factors
v. Indifference towards minor faults
vi. Indifference towards major faults
Advantages of Breakdown Maintenance
I. Lower Initial Costs
II. Requires Fewer Staff
III. No Planning Needed

27. 27
MAINTAINANACE
Disadvantages of Breakdown Maintenance
I. Reduction of Output
II. Faster Plant Deterioration
III. Increased Chances of Accidents
IV. More Spoilt Material
V. Direct Loss of Profit
VI. Breakdown at Inopportunate Times
VII. Plant Items Regulated by Statutory Provisions are not subject to breakdown
maintenance
2. Scheduled Maintenance
Aim: Avoiding Breakdown
Scheduled maintenance incorporates:
I. White washing of buildings
II. Overhauling of machines
III. Repair
IV. Cleaning Of Water & Other Tanks

28. 28
MAINTAINANACE
3. Preventive Maintenance
Principle: Prevention is better than cure
PM should not be done for the entire plant at once
It is better to tackle one department or machinery at a time
The entire PM programme hangs on inspections and their related duties of adjustments and
repairs
Aims at minimizing the problems of breakdown maintenance
Locates Weak Spots
Provides Regular inspection
Initiates minor repairs thereby reducing the risk of unanticipated breakdown
Minimizing the possibility of unanticipated production interruption.
4. Predictive Maintenance
1. New technique
2. Extends service life of equipment without failure
3. Makes use of human or other sensitive instruments like:
Pressure
Amplitude meters
Temperature
Audio Gauges

29. 29 SANITATION IN MANUFACTURING
AREA

30. 30
SANITATION IN MANUFACTURING AREA
Self contained facilities need to be provided for specific products
Manufacturing areas need to be cleaned and maintained and
should be free from debris, dust etc.
During manufacture of a product, the manufacturing area should
be used for the product manufactured only and not used as a
passage
There need to be a routine sanitation programme
There is a need for an SOP for the same giving all details
It has to specify the area to be cleaned and the frequency

31. 31 SANITATION IN MANUFACTURING AREA
The procedure has to specify the cleaning agent including
equipment and tools to be used along with frequency
The procedure has to assign the responsibility to a person for
cleaning
The production processes have to be logically placed to avoid
contamination between products
Provision has to be made for adequate Lighting in production
areas to be provided to carry out the activity, especially where
visual checks are carried out
Records need to be kept of cleaning and sanitation

32. 32 HEALTH, CLOTHES AND SANITATION

33. 33
HEALTH, CLOTHES AND SANITATION
 Personnel handling Betalactum products have to be tested for Penicillin
sensitivity
 Personnel handling potent and cytotoxic’s and sex hormones to be tested for
adverse effects periodically
 These personnel have to be rotated, as a health safeguard
 Personnel have to be examined at the time of employment for eyesight and
absence from TB.
 They have to be free from skin infections and other communicable diseases and
a record should be available of these aspects.
 A qualified physician is to be made available for assessing the health of
personnel
 Personnel have to be trained in Personal hygiene
 Instructions have to be displayed on personal hygiene

34. 34
HEALTH, CLOTHES AND SANITATION
 Employees to be told to report any apparent illness or skin lesions in order
to protect the products from any kind of risk
 Employees to be instructed to report any adverse change in their health
 Personnel have to wear protective clothing and such other gears to protect
the product from direct contact
 Employees in certain specific areas wear single suits where required
 Change rooms adequate in size have to be provided
 Change rooms should have independent cabinets to store their street as well
as factory dresses
 Facilities such as soap, disinfectants, dryers to be provided in these rooms
 Smoking, drinking, chewing is to be strictly prohibited in work areas and
restricted to identified areas

35. 35
ENVIRONMENTAL CONTROL
 Environmental control of pharmaceutical cleanrooms is essential to the
manufacture of a quality product.
 Control of such conditions as airborne particulate, microorganisms, temperature ,
humidity, differential pressure, airflow, air velocity and personnel is crucial to
protect the product from contamination.
 Therefore, the design, validation and ongoing monitoring of a cleanroom
 HVAC system are necessary to assure the quality and safety of the pharmaceutical
product.
 The manufacturing environment is critical for product quality and includes
1. Light
2. Temperature
3. Humidity
4. Air movement
5. Microbial contamination
6. Particulate contamination
 Uncontrolled environment can lead to product degradation
product contamination
loss of product and profit

36. 36
ENVIRONMENTAL CONTROL

37. 37
ENVIRONMENTAL CONTROL
 A Heating system (“H” in HVAC)
A Ventilating system (“V” in HVAC)
A Cooling system (“AC" in HVAC)
 HVAC systems can increase or decrease temperature, increase or reduce the
moisture or humidity in the air, decrease the level of particulate or gaseous
contaminants in the air. These abilities are employed for comfort and to
protect people and product.
 HVAC; Heating, Ventilation and Air conditioning – Validated Yearly by
external party
 Parameters:
1. Temperature
2. Air velocity
3. Air Changes
4. Filter integrity
5. Non-viable air borne particles
6. Viable air borne particles

38. 38
ENVIRONMENTAL CONTROL – CLEAN ROOMS CLASSIFICATION
Class >=0.5 µm >5 µm FED STD 209E equivalent
ISO 5 3,520 29 Class 100
ISO 6 35,200 293 Class 1,000
ISO 7 3,52,000 2,930 Class 10,000
ISO 8 35,20,000 29,300 Class 100,000

39. 39
ENVIRONMENTAL CONTROL

40. UTILITIES

41. UTILITIES
 Qualification of utilities that could impact on product quality
e.g. steam, gases, compressed air, HVAC,water
 Monitoring and action in case of OOL
 Drawings for these utility systems should be available
 Adequate ventilation, air filtration and exhaust systems and drainage
systems where appropriate
 Designed and constructed to minimize risks of contamination and
cross-contamination

42. UTILITIES - PLUMBING
 Potable water shall be supplied under continuous positive pressure in a plumbing
system free of defects that could contribute contamination to any drug product.
 The pipes and fittings must be of quality good enough to withstand the pressure
and heat conditions.
 Metals are often included in pharmaceutical facility waste water permitting
criteria but are not commonly a discharge issue. Compatibility of the materials of
construction with the characteristics of the waste water must be considered
during the design of the facility. For example: Copper plumbing should not be
used in drain line for acidic waste water because it might fail from corrosion but
also may result in waste water discharge above copper concentration limits.
 The pipes should be color coded according to the material it carries.
Grey ------------------------ Raw water
Orange ----------------- Distilled Water
Green --------------------Cooling water
Insulated----------------- Steam
White------------------------ Air

43. UTILITIES- DRAINAGE SYSTEMS
 They remove effluent from spaces, systems, or process.
 Drains shall be of adequate size and, where, connected directly to sewer, shall be
provided with an air break or other mechanical device to prevent back-siphon age.
 They should be easy to clean. And they must be cleaned at a proper interval. They must
be well closed and air tight.
 For biological waste, it should be treated in a proper manner before disposal to not to
harm the environment.
 Dissolved oxygen content in waste to be disposed in lake or river must be within limits
TYPES
- Sanitary waste system
- Laboratory waste system
- Process Waste System
- Hazardous Material Waste and Retention
- Storm Drainage System

44. 44
UTILITIES - GAS SYSTEMS
Many types of gases are utilized in the manufacturing process. The most prevalent of these include
compressed air use in process and controls, breathing air for hazardous environments, nitrogen,
vacuum, vacuum cleaning, natural gas, propane, and other process systems. All gases used in
manufacturing and processing operations, including the sterilization process, should be sterile
filtered at points of use to meet the requirements of the specific area. Gases to be used in sterilizers
after the sterilization or used at the filling line or microbiological testing area must also be sterile
filtered
All gases used in manufacturing and processing operations, including sterilization process
COMPRESSED AIR
 In general compressed air should be supplied by an “oil- free” type compressor and
 must be free of oil and oil vapour unless vented directly to a noncontrolled environment area.
 It should also be dehumidified to prevent condensation of water vapor.
BREATHING AIR
 Breathing air is generally provided for use to personnel working in hazardous environment.
 Provided centrally through a breathing air distribution system or at the local level with “backpack” type
breathing air units worn by each person.
NITROGEN
 Used for the purging of electrical equipment in volatile or explosive environments
VACUUM
 Vacuum is utilized in the encapsulation and tablet compression areas.
VACUUM CLEANING
 For dry particulate and powder pickup.

45. 45
UTILITIES - Water system
 Water is most widely used material in pharmaceutical manufacturing. A greater
volume of water is used in cleaning and rinsing processes than in formulation in
most facilities. Regardless of the water volume used in actual drug formulation ,
all pharmaceutical water is subject to cGMPs even when the water does not
remain in the finished product.
 Potable water available as per BIS
 Purified water produced should comply with IP
 Stored water adequately protected to prevent microbiological contamination
 Storage tanks are cleaned and records maintained
 Water purified has to be kept in circulation to prevent microbial buildup
 Demonstrate that water used is suitable for its intended use
 At minimum - WHO guidelines for drinking (potable) water quality
 Other chemical and/or microbiological water quality specifications can be used -
appropriate specifications for physical and chemical attributes, total microbial
counts, objectionable organisms and/or endotoxins established
 Validated water treatment process: water monitored with appropriate action
limits

46. 46
WATER SYSTEM- TYPES OF WATER
A) POTABLE WATER (drinking water) - being the source for obtaining various higher
qualities of water, adequate pretreatment are essential before it is used. It may be used for
synthesis of active ingredients and also used for cleaning of equipment's and facilities.
B) PURIFIED WATER - This water is used in preparation of non-parenteral dosage forms.
Bacteria should not be more than100 cfu/ml
C) WATER FOR INJECTION (WFI) - It is used in parenteral products. In bulk, this type of
water is also called Pyrogen free water or PFU and if it is sterilized, it is called sterile WFI.
Bacteria should not be more than10 cfu/100 ml. Storage time for all water must be less than
24 hrs. unless stored at 80°C.
D) SOFTENED WATER - which has its Calcium and Magnesium removed. Such a water can
be used e.g. for first washing steps. Certain processes require special well-defined qualities
of water.
E) CLEAN STEAM is a form of water that may be used for sterilization purpose and prepared
from deionized water.
F) WATER FOR FINAL RINSE is used for rinsing equipment after washing. It must be of the
same quality as the water used for manufacturing the product.
G) STERILE WATER FOR INJECTION water for injection which is sterilized within 12 hours
of collection and distributed in sterile containers. It is intended mainly for use as a solvent
for injectable preparations such as powders for injection that are distributed dry because of
limited stability of their solutions. It should be packaged only in single dose containers of
not larger than 1-litre size.
H) BACTERIOSTATIC WATER FOR INJECTION

47. 47
MAINTAINANCE OF STERILE AREAS
The production of sterile preparations should be carried out in clean areas, entry to which should be through
airlocks for personnel and/or for equipment and materials. Clean areas should be maintained to an
appropriate standard of cleanliness and supplied with air that has passed through filters of the required
efficiency.
The various operations of component preparation (such as those involving containers and closures), product
preparation, filling and sterilization should be carried out in separate areas within a manufacturing suite.
These areas are classified into four grades.
Manufacturing operations are divided here into two categories: first, those where the product is terminally
sterilized, and second, those which are conducted aseptically at some or all stages.
The sanitation of clean areas is particularly important. They should be cleaned frequently and thoroughly in
accordance with an approved written program. Monitoring should be regularly undertaken in order to
detect the contamination or the presence of an organism against which the cleaning procedure is ineffective.
In view of its limited effectiveness, ultraviolet light should not be used as a substitute for chemical
disinfection. Where disinfectants are used more than one type should be employed.
Disinfectants and detergents should be monitored for microbiological contamination; dilutions should be
kept in previously cleaned containers and should only be stored for defined periods unless sterilized.
Disinfectants and detergents used in grade A and B areas should be sterile before use.
A disinfectant program should also include a sporicidal agent since many common disinfectants are
ineffective against spores. Cleaning and disinfectant procedures should be validated.
In order to control the microbiological cleanliness of the cleanliness grades A-D in operation, the clean areas
should be monitored. Where aseptic operations are performed, monitoring should be frequent and methods
such as settle plates and volumetric air and surface sampling (e.g. swabs and contact plates) should be used.
The zones should not be contaminated through the sampling methods used in the operations. The results of
monitoring should be considered when batch documentation for release of the finished product is reviewed.
Both surfaces and personnel should be monitored after critical operations.
Levels (limits) of detection of microbiological contamination should be established for the purpose of
setting alert and action levels, and for monitoring the trends in environmental cleanliness in the facility.

48. 48
MAINTAINANCE OF STERILE AREAS
For the manufacture of sterile pharmaceutical preparations, four grades are
distinguished
here, as follows:
Grade A: The local zone for high-risk operations, e.g. filling and making aseptic
connections. Normally such conditions are achieved by using a unidirectional
airflow workstation
Grade B: In aseptic preparation and filling, the background environment for the
grade A zone.
Grades C and D: Clean areas for carrying out less critical stages in the manufacture
of sterile
products.
In order to reach the B, C and D air grades, the number of air changes should be
appropriate for the size of the room and the equipment and personnel present in
it.
HEPA filters should be subjected to installed filter leakage test in accordance with
ISO 14644-3 at least twice a year. The purpose of performing regular leak tests is
to ensure the filter media, filter frame, and filter seal are free from leaks. The
aerosol selected for HEPA leak testing should not support microbial growth and
should be composed of a sufficient number or mass of particles.

49. 49
MAINTAINANCE OF STERILE AREAS
Clean room and clean air device classification
Clean rooms and clean air devices should be classified in accordance with EN ISO
14644.
Maximum permitted airborne particle concentration for each grade is given
below.
Class >=0.5 µm >5 µm FED STD 209E equivalent
ISO 5 3,520 29 Class 100
ISO 6 35,200 293 Class 1,000
ISO 7 3,52,000 2,930 Class 10,000
ISO 8 35,20,000 29,300 Class 100,000

50. 50
CONTROL OF CONTAMINATION
 When dry materials and products are used in production, special precautions should be
taken to prevent the generation and dissemination of dust. Provision should be made
for proper air control (e.g. supply and extraction of air of suitable quality)
 Contamination of a starting material or of a product by another material or product
must be avoided. This risk of accidental cross-contamination arises from the
uncontrolled release of dust, gases, particles, vapours, sprays or organisms from
materials and products in process, from residues on equipment, from intruding insects,
and from operators’ clothing, skin, etc.
 The significance of this risk varies with the type of contaminant and of the product
being contaminated. Among the most hazardous contaminants are highly sensitizing
materials, biological preparations such as living organisms, certain hormones, cytotoxic
substances, and other highly active materials. Products in which contamination is likely
to be most significant are those administered by injection or applied to open wounds
and those given in large doses and/or over a long time.

51. 51
CONTROL OF CONTAMINATION
Cross-contamination should be avoided by taking appropriate technical or organizational measures, for
example:
 (a) carrying out production in dedicated and self-contained areas (which may be required for
products such as penicillin's, live vaccines, live bacterial preparations and certain other biologicals);
 (b) conducting campaign production (separation in time) followed by appropriate cleaning in
accordance with a validated cleaning procedure;
 (c) providing appropriately designed airlocks, pressure differentials, and air supply and extraction
systems;
 (d) minimizing the risk of contamination caused by recirculation or reentry of untreated or
insufficiently treated air;
 (e) wearing protective clothing where products or materials are handled;
 (f) using cleaning and decontamination procedures of known effectiveness;
 (g) using a “closed system” in production;
 (h) testing for residues;
 (i) using cleanliness stat
Measures to prevent cross-contamination and their effectiveness should be checked periodically
according to SOPs.
Production areas where susceptible products are processed should undergo periodic environmental
monitoring (e.g. for microbiological and particulate matter, where appropriate).us labels on equipment.

52. 52 EQUIPMENT

53. 53
EQUIPMENT
 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.
 Equipment should be installed in such a way as to minimize any risk of error or of contamination.
 Fixed pipework should be clearly labelled to indicate contents and, where applicable, the direction of flow.
 All service pipework and devices should be adequately marked and special attention paid to the provision of
non-interchangeable connections or adaptors for dangerous gases and liquids.
 Balances and other measuring equipment of an appropriate range and precision should be available for
production and control operations and should be calibrated according to a fixed schedule.
 Production equipment should be thoroughly cleaned according to a fixed schedule.
 Laboratory equipment and instruments should be suited to the testing procedures undertaken.
 Washing, cleaning and drying equipment should be chosen and used so as not to be a source of contamination.
 Production equipment should not present any hazard to the products.
 The parts of the production 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.
 Defective equipment should be removed from production and QC areas. If this is not possible, it should be
clearly labelled as defective to prevent use. Closed equipment should be used whenever appropriate. Where
open equipment is used or equipment is opened, precautions should be taken to minimize contamination.
 Non-dedicated equipment should be cleaned according to validated cleaning procedures between being used
for production of different pharmaceutical products to prevent cross-contamination.
 Current drawings of critical equipment and support systems should be maintained.
 Edible and food grade lubricants have to be used in equipment wherever required

54. 54 EQUIPMENT
 Equipment should be so designed so as to have suitable
maintenance and operations as per product requirements
 The layout should be suitable to facilitate effective cleaning
and maintenance in order to avoid cross contamination
 Balances and such other measuring devices to be available
in raw material stores and in-process areas

55. 55 EQUIPMENT
 These need to be calibrated as per SOP and records
maintained
 The material of construction of equipment should be such
that they do not react with the product to be manufactured
and do not contaminate the product
 Defective equipment have to be removed from the areas
where possible and labeled

56. 56 RAW MATERIALS

57. 57
RAW MATERIALS
 The purchase of starting materials is an important operation that should involve
staff who have a particular and thorough knowledge of the products and
suppliers.
 Starting materials should be purchased only from approved suppliers and,
where possible, directly from the producer. It is also recommended that the
specifications established by the manufacturer for the starting materials be
discussed with the suppliers. It is beneficial for all critical aspects of the
production and control of the starting material in question, including handling,
labelling and packaging requirements as well as complaints and rejection
procedures, to be contractually agreed between the manufacturer and the
supplier.
 For each consignment, at a minimum, the containers should be checked at least
for integrity of package and seal and for correspondence between the order, the
delivery note, and the supplier’s labels.
 All incoming materials should be checked to ensure that the consignment
corresponds to the order. Containers should be cleaned where necessary and
labelled, if required, with the prescribed information. Where additional labels
are attached to containers, the original information should not be lost.

58. 58
RAW MATERIALS
 Damage to containers and any other problem that might adversely affect the quality of a material
should be recorded and reported to the QC department and investigated.
 If one delivery of material is made up of different batches, each batch must be considered as
separate for sampling, testing and release.
 Starting materials in the storage area should be appropriately labelled.
 Labels should bear at least the following information:
(a) the designated name of the product and the internal code reference where applicable;
(b) the batch number given by the supplier and, on receipt, the control or batch number given by the
manufacturer, if any, documented so as to ensure traceability;
(c) the status of the contents (e.g. in quarantine, on test, released, rejected, returned, recalled);
(d) where appropriate, an expiry date or a date beyond which retesting is necessary. When fully
validated computerized storage systems are used, not all of the above information need be in a legible
form on the label.
 There should be appropriate procedures or measures to ensure the identity of the contents of
each container of starting material. Bulk containers from which samples have been drawn should
be identified.
 Only starting materials released by the QC 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.
 Materials dispensed for each batch of the final product should be kept together and conspicuously
labelled as such.

59. 59 RAW MATERIALS
Inventories of raw materials need to be kept and
records maintained as per Schedule “U” of D&C Act
Raw materials need to be quarantined upon receipt
Raw materials segregated and FIFO followed and
where applicable FEFO

60. 60 RAW MATERIALS
 All vouchers have to be made available for purchase of raw materials
and procured from approved vendors (for critical materials)
 The documents have to show whether the RAW materials are
purchased from manufacturers or suppliers
 Authorized personnel from QC need to examine all raw materials for
integrity of pack
 Damaged containers need to be segregated, identified and recorded
 If more than one batch is present in a consignment, it is to be
considered separately for testing and approval

61. 61 RAW MATERIALS
 Raw material containers have to be labeled for name of
product, any code reference, manufacturer’s name address,
supplier’s name address, batch number, status (quarantine,
under test and approved/ rejected), manufacturing date,
expiry date and re-test dates
 Areas have to be made available for “Quarantine”, “under
test”, “approved” & “rejected” segregated and partitioned in
order to have clear identity of status
 In case the quantity of raw material is too large, a mobile
system may be followed

62. 62 RAW MATERIALS
“Sampled ” containers need to be labeled
If there is any material accepted based on
manufacturer’s certificate of analysis, the
manufacturer needs to be audited and
documentation should be available justifying such
acceptance
All materials to be stored off the floor on pallet or
rack
It has to be ensured that the shelf life of product
does not exceed the shelf life of raw materials

63. Regulatory aspects
63 Complaints & adverse reactions

64. 64
Complaints & adverse reactions
 All complaints have to be carefully reviewed and recorded
 The complaint should be handled positively and give learnings for the future.
 Complaint should be carefully reviewed and should be considered as an important aspect.
 When the Drug Product company receives a complaint, it should acknowledge it with the person who had
given the complaint.
 Main responsibility for investigation of a complaint lies with the QA department.QA dept takes the help of
QC, Production, Maintenance, HRD etc.
 SOP’s are required for handling complaints & recalls.
 QA should go through documentation and batch records of respective batches.
 Any complaint when investigated should not be restricted to batch under question but should include the
pre and post batches in the entire production run.
 The lifecycle of complaint starts from the time product is designed till discontinuation, answering
complaints, retention of control samples, continuous stability monitoring, developing CAPA & Applying
CAPA to other product ranges.
 Each complaint has to be investigated and causes arrived at.
 Correct possible production defects before they lead to recall.
 A recall indicates GMP failure
 Related products are also investigated. Example if n excipient,/API is a causative factor of the complaint,
the products where these components are used also have to be investigated.
 Report on any adverse reactions has to be forwarded to drugs authorities
 If it is found on investigation, that the products remaining in the market can be injurious to the health of
the consuming public, the said product has to be recalled

65. Complaints Handling Principle
All complaints and other information concerning
potentially defective products must be carefully
reviewed according to written procedures:
Handle it positivelyCarefully reviewSee it as important
work
Managed by a senior
staff member
Thorough investigation
of the cause is essential
Correct possible production
defects before they lead to a
recall
Take necessary actions;
even a recall decision
A major source of
information & learning
65
Complaints and Recalls

66. Complaints Procedure - I
Designated responsible person
• Advise authorized person of results
• Sufficient support staff
• Access to records
Written procedure describing
action to be taken
Acknowledge and respond to
complainant within a
reasonable period
Record written and verbal
comments
66
Complaints and Recalls

67. Complaints Procedure - II
Investigate and
review
QA review
complaint
Appropriate
follow up actions
Review of trends
67
Complaints and Recalls

68. Records of Complaint Investigation
 Name of product
 Name of active substance (INN) if necessary
 Strength, dosage form
 Batch number
 Name of complainant and nature of complaint
 Records, retention sample investigated, other batches reviewed and staff
interviewed
 Result of investigation: “Justified” or “Not justified”
 If “justified”, actions taken to prevent reoccurrence
 Sign-off upon completion
68
Complaints and Recalls

69. Decision from a Complaint Investigation
Complaint justified
• Actions to prevent
reoccurrence
• Ongoing observation of
process
• Recall product may be
required
Complaint not justified
• Advise customer of findings
• Appropriate marketing
response
69
Complaints and Recalls

70. Other Issues
Inform competent authority of serious quality
problems
Regular review of trends required
Reoccurring problems Potential recall or withdrawal
70
Complaints and Recalls

71. Classification of Defects
Defects can be categorized as (but it is not a WHO guideline):
Critical defects Major defects Other defects
Once defect has been identified, company should be dealing with it in an
appropriate way, even recall
If complaint is justified, then there has been a failure of the quality system
71
Complaints and Recalls

72. Critical Defects
Those defects which can be life threatening and
require the company to take immediate action by
all reasonable means, whether in or out of
business hours
Examples
Product labelled with incorrect name or incorrect strength
Counterfeit or deliberately tampered-with product
Microbiological contamination of a sterile product
72
Complaints and Recalls

73. Major Defects
Those defects which may put the patient at some
risk but are not life threatening and will require
the batch recall or product withdrawal within a
few days
Examples
Any labelling/leaflet misinformation (or lack of information) which represents a significant
hazard to the patient
Microbial contamination of non-sterile products with some risk for patients
Non-compliance to specifications (e.g. active ingredient assay)
73
Complaints and Recalls

74. Other Defects
Those defects which present only a minor risk to
the patient - batch recall or product withdrawal
would normally be initiated within a few days
Examples
Readily visible isolated packaging/closure faults
Contamination which may cause spoilage or dirt and where there is minimal
risk to the patient
74
Complaints and Recalls

75. Regulatory aspects
75 Product recalls

76. Recall
Definition
Removal from the market
of specified batches of a
product
• May refer to one batch or all
batches of product
76
Complaints and Recalls

77. 77
Product recalls
 There should be SOPs governing recalls
 This SOP should describe in detail the method to inform the
Stockists, wholesalers, retailers and end users in a timely manner
about the recall
 The distribution records should be available to the person designated
to oversee the recall
 There should be a reconciliation done for the quantity distributed vis-
à-vis the quantity received
 The recalled product has to be segregated
 Recalled products should be identified and stored separately in a
secure area until a decision is taken on their fate. This decision should
be made as soon as possible.

78. Reasons for Recall
Customer complaint Detection of GMP failure
after release
Result from the ongoing
stability testing
Request by the national
authorities
Result of an inspection Known counterfeiting or
tampering
Adverse reaction
reporting
78
Complaints and Recalls

79. Detection of GMP failure
The photo shows an active tablet in the row of placebos in a bi-phasic
oral contraceptive blister pack.
79
Complaints and Recalls

80. WHO GMP Product Recall Principle
“There should be a system to recall from the
market promptly and effectively, products
known or suspected to be defective”
80
Complaints and Recalls

81. Designated Responsible Recall Person
May be authorized person
If not, must advise authorized person of results
Sufficient support staff for urgency of recall
Independent of sales and marketing
Access to records
81
Complaints and Recalls

82. SOP for Recall
Established, authorized
Actions to be taken
Regularly checked and updated
Capable of rapid operation to hospital and pharmacy level
Communication concept to national authorities and internationally
82
Complaints and Recalls

83. Distribution Records
Available to designated person
for recall purposes
Accurate
Include information on:
• Wholesalers
• Direct customers
• Batch numbers
• Quantities
83
Complaints and Recalls

84. Recall Progress
Written progress report and reconciliation
• Record progress as procedure followed
• Reconcile delivered with recovered products
• Issue final report
Effectiveness of procedures checked
• Test effectiveness from time to time
Secure segregated storage of returned goods
• Essential to keep returned goods away from other goods
84
Complaints and Recalls

85. HANDLING OF REJECTED, RECOVERED, REPROCESSED AND REWORKED MATERIALS,
RECALLED PRODUCTS, RETURNED GOODS, REAGENTS AND CULTURE MEDIA
Rejected, recovered, reprocessed and reworked materials:
 They should be clearly marked as such and stored separately in restricted areas.
 Action taken should be approved by authorized personnel and recorded.
 The reworking or recovery of rejected products is permitted only if the quality of the final
product is not affected and if specifications are met
Recalled products:
 Recalled products should be identified and stored separately in a secure area until a decision is
taken on their fate

86. Returned goods:
 They may be considered for resale or relabelling, or alternative action taken only after they
have been critically assessed by the QC function in accordance with a written procedure.
 Any doubt arises over the quality of the product, it should not be considered suitable for
reissue or reuse. Any action taken should be appropriately recorded
Reagents and culture media:
 There should be records for the receipt and preparation of reagents and culture media
 The label should indicate the concentration, standardization factor, shelf-life, the date when
restandardization is due, and the storage conditions. The label should be signed and dated
by the person preparing the reagent
HANDLING OF REJECTED, RECOVERED, REPROCESSED AND REWORKED MATERIALS,
RECALLED PRODUCTS, RETURNED GOODS, REAGENTS AND CULTURE MEDIA

87. 87
Disposal of waste
Waste disposal satisfies Pollution control board norms
All wastes awaiting disposal has to be kept protected
Provision for disposal of rejected drug products
Provision of storage space for hazardous chemicals,
flammable solvents, and their disposal
Toxic substances and flammable materials should be stored
in suitably designed, separate, enclosed cupboards, as
required by national legislation.
Waste material should not be allowed to accumulate.
 It should be collected in suitable receptacles for removal
to collection points outside the buildings and disposed of
safely and in a sanitary manner at regular and frequent
intervals.

88. 88
Batch production and processing records
Batch production and processing records should be available for all
products, batch and pack sizes
The batch processing records should represent the current master
formula
Line clearances need to be performed to get rid of all previous batch
identities for equipment and package lines and records maintained
The processing information need to contain name of product, batch
number, names of responsible personnel, date and time at which
significant steps have been carried out, initials of personnel who
have carried out and where relevant of supervisory personnel
Analytical report numbers have to be recorded in batch processing
records for all the raw materials used including water
Quantities of raw material dispensed need to be recorded
It has to list out the major equipment used
They have to give details of all in-process controls carried out and
the results thereof

89. 89 Batch production and processing records
 Yields need to be recorded at appropriate times
 Deviations need to be recorded with respect to yields and explanations
and comments have to made available
 If there are any deviations from master formula they need to be
explained
 Recoverable ’s added need to be recorded
 The stage at which recoverable ’s are added is to be recorded
 All additions of recoverable in a production batch is to be permitted by
master formula and the ratios to be added have to be fixed
 Batch packaging records need to be maintained
 Transcription errors need to be avoided (copying errors)
 Line clearances have to be carried out and records maintained

90. Regulatory aspects
90
Master formula records
A Master Formula Record should be available for each
product, batch and pack size

91. 91
Master formula records
This should have the following details:
1. Name of product, any reference code relating to the specifications
2. Patent & proprietary names along with generic name
3. Name, quantity, and reference codes for all materials including all materials which do not
form a part of final product(e.g. Solvents in coating)
4. Expected yield with acceptance limits
5. Location of processing and the principal equipment
6. Reference to SOPs for cleaning, assembling, calibrating and sterilizing(as applicable)
7. Stepwise manufacturing and processing instructions
8. Details of in-process controls and limits thereof
9. Storage conditions and any specific requirements as applicable
10. Any special precautions
11. Packing details and specimen labels/ cartons, foils

92. 92
Master formula records
Packaging details
There have to be authorized packaging instructions. They should have:
1. Name
2. Description of dosage form
3. Pack sizes – Number, Dose, Volume,
4. A total list of all packaging materials required for a standard batch size with reference to
the specifications of the packaging material
5. Specimens of all packaging materials
6. Line clearance instructions
7. Description of packaging operations
8. In-process controls
9. Reconciliation of materials, used, yield obtained, wastages and destroyed
10. Scope for investigation of any undue discrepancies

93. Regulatory aspects
93 Standard operating procedures and records

94. 94
Standard operating procedures and records
SOPs and associated records of actions taken or, where
appropriate, conclusions reached should be available for:
(a) equipment assembly and validation;
(b) analytical apparatus and calibration;
(c) maintenance, cleaning and sanitization;
(d) personnel matters including qualification, training, clothing and hygiene;
(e) environmental monitoring;
(f) pest control;
(g) complaints;
(h) recalls;
(i) returns

95. 95
Standard operating procedures and records
 There should be SOPs for the internal labelling, quarantine and storage of starting materials, packaging materials
and other materials, as appropriate.
 SOPs should be available for each instrument and piece of equipment (e.g. use, calibration, cleaning, maintenance) and
placed in close proximity to the equipment.
 There should be SOPs for sampling, which specify the person(s) authorized to take samples.
The sampling instructions should include:
(a) the method of sampling and the sampling plan;
(b) the equipment to be used;
(c) any precautions to be observed to avoid contamination of the material or any deterioration in its quality;
(d) the amount(s) of sample(s) to be taken;
(e) instructions for any required subdivision of the sample;
(f) the type of sample container(s) to be used, and whether they are for aseptic sampling or for normal
sampling, and labelling;
(g) any specific precautions to be observed, especially in regard to the sampling of sterile or noxious material.
 There should be an SOP describing the details of the batch (lot) numbering system, with the objective of ensuring that each
batch of intermediate, bulk or finished product is identified with a specific batch number.
 The SOPs for batch numbering that are applied to the processing stage and to the respective packaging stage should be
related to each other.
 The SOP for batch numbering should ensure that the same batch numbers will not be used repeatedly; this applies also to
reprocessing.
 Batch-number allocation should be immediately recorded, e.g. in a logbook. The record should include at least the date of
allocation, product identity and size of batch.

96. Regulatory aspects
96 Quality assurance / audit / control

97. Regulatory aspects
97 Quality assurance
 This is a wide ranging concept concerning all matters that individually and
collectively influence the quality of the product. It is the totality of the
arrangements made with the object of ensuring that products are of the
quality intended for their use
 Products need to be designed to meet the requirement of GXP
 Adequate arrangements need to be made for manufacture, supply and use
of correct starting and packaging materials
 Adequate controls exercised over starting materials, intermediate products
and bulk products
 In-process controls need to be carried out as per requirement

98. Regulatory aspects
98 Quality assurance
Calibrations carried out at pre-determined intervals
Processes have to be validated as per an approved
protocol
Products have to be manufactured as per established
procedures and tested
An authorized person before release for sale has to
certify the products
This person has to ensure that all the tests and checks
have been carried out before release

99. Regulatory aspects
99 Self inspection and quality audits
 There has to be a self inspection team to carry out quality
compliance audit and suggest various improvements
 The team members have to be independent, experienced
and qualified to carry out the same
 The auditors can either be in-house personnel or outsiders
who have the necessary expertise
 The audits need to be documented and recommendations
followed up for timely completion

100. Regulatory aspects
100 Self inspection and quality audits
 The programme should be focused to find out
shortcomings and it has to come out with
recommendations
 All recommended actions have to be followed through for
timely completion.
 The self inspection has to include all areas of materials
management, production, quality control and assurance,
HRD and Safety
 A compliance audit has to be conducted specifically after a
product recall, repeated complaints or before a regulatory
inspection

101. Regulatory aspects
101 Quality control system
 Quality control is concerned with sampling, specifications, testing,
documenting and release procedures such that the materials and
products meet pre-determined specifications prior to processing /
release
 There has to be a QC laboratory with adequately qualified and
experienced staff
 It is to be divided into Chemical, Instrumentation, Microbiological and
Biological testing sections
 Sufficient space and storage conditions need to be provided for
storing control samples

102. Regulatory aspects
102 Quality control system
 The QC lab has to store reference standard substances
 Detailed SOPs are required to carry out sampling,
inspection, testing of raw materials, in-process,
intermediates, bulk and finished products
 Authorized and dated specifications should be available for
materials, solvents and processes to assure their identity,
content, purity and quality

103. Regulatory aspects
103 Quality control system
 All specifications for raw materials, intermediates and
finished products have to be approved and maintained by
QC
 There has to be specifications for all grades of water used
in the process
 The products need to be tested and certified as per
specifications by authorized personnel before release
 Reference/ retained samples for each batch of product
need to be maintained

104. Regulatory aspects
104 Quality control system
 The quantity should be sufficient to carry out all the tests in duplicate
(except sterility and pyrogens)
 Retained samples have to filed in commercial pack
 Records pertaining to finished products have to be reviewed prior to
release
 It should include assessment of production conditions, results of in-
process testing, manufacturing and packaging documentation,
compliance of finished product with respect to specification and
examination of the finished pack

105. Regulatory aspects
105 Quality control system
 QC personnel should have free access to production areas
for sampling and investigating as appropriate
 Stability testing carried out to assign proper shelf life (as
per ICH guidelines)
 Records of such a study have to be maintained and
storage conditions recorded

106. Regulatory aspects
106 Quality control system
 All product complaints need to be investigated by QA in-
charge and records maintained
 All equipment to be calibrated and testing procedures need
to be validated
 Technical books like IP, reference standards, reference
spectra and working standards should be available in QC
lab

107. Regulatory aspects
107 Documentation and records

108. 108
Documentation and records
 Documents need to be designed, prepared and reviewed and controlled
 Documents have to be such that they permit an audit trail
 All documents have to be prepared as per these rules
 Documents need to be approved, signed and dated by authorized personnel
 The documents should be easily verifiable
 There has to be a title and purpose for every document
 All reproduced documents should be clear and legible
 Documents have to be regularly reviewed and kept up to date
 Records have to be updated when the activity is performed
 All records need to be maintained one year after expiry of product
 If data is computerized, they have to be handled by authorized personnel
 There need to be a “pass word” system in vogue to prevent any unauthorized change
 Hard copies should be available for documents which are filed and electronically
stored
 Backup data should be available for data electronically processed

109. Regulatory aspects
109 Distribution records

110. Distribution Records
Available to designated person
for recall purposes
Accurate
Include information on:
• Wholesalers
• Direct customers
• Batch numbers
• Quantities
110
Complaints and Recalls

111. Regulatory aspects
111 Distribution records
 Products to be distributed should be tested, approved and
released
 Pre-distribution checks have to be carried out at random
and compliance recorded
 Audits of warehouses carrying the stock should be
conducted and records maintained
 Distribution records should have traceability to identify
end user to facilitate complete recall if required