Monday, July 25, 2016


1. What is Safety ?

It is a condition which gives you freedom from hazard, risk, accident which may cause injury, damage and loss to material or property damage and even death.
Safety is defined as freedom from those condition that can cause injury to persons including death or damage to property or environment.

2. What is accident ?
It is an unexpected or unplanned event which may or may not result in injury or damage or property loss or death.

3. What is injury ?
It is defined as a harmful condition sustained by the body as a result of an accident.

4. What is hazard ?
Inherent property of a substance or an occurrence which has potential to cause loss or damage property, person or environment.

5. What is risk ?
In probability of the realization of potential for loss or damage or injury.

6. What is incident?
It is an event which represents deviation from the intended sequence of designed steps.

7. What is safety policy?
Any company has a social and legal obligation to provide a safe and health working environment to all his improvement to all his employees.

8. What is safety audit?
The safety audit is the process that identifies un-safe conditions and unsafe acts the plant and recommended safety improvement.
Walk through It evaluates the unsafe condition notice able to naked eye during work through the plant. ( Stores, civil work, erection work)
Inter mediate-more details study and review of plant design and plant operation.
Comprehensive –It evaluates the safety factors in the plant on the base engineering, analysis, testing, measurement.

9. What is safety tag?
Safety tag can be defined a surface made of card board or paper board on which English local languages letters written for warning safety instructions to employees.

10. What is safety programme?
Safety programme can be defined as five methods by which accident can be prevent easily they are engineering, education, enforcement, enthusiasm and example safety programmes are plain spoken and carry out certain legal steps.

11. What is attitude?
Attitude may be described as continuous behavior . if man’s behavior is good, then his action will be either correct or safe.

12. what is emergency planning?
Emergency planning can defined as a control measurer. It can control the accidents safe guard people and provide information to media.

13. What is work permit system?
Work permit system is a “ written documents” for permission to undertake a job by area in charge or it is written document issued by the area in charge to the performer to under take the specific job.

14. What is work at height?
Any work above 2 meters from ground is caused work at height.

15. What is confined space?
An area which is small and enclosed or an area where one entry and exits or where a man cannot work comfortable in any location is caused confined space.

16. What is excavation?
Marking a hole or tunnel by digging the ground by man or machine is called excavation.

17. What is scaffolding?
It is a temporary platform constructed for supporting both men and materials
and working safety at a construction site.

18. What is welding?
The process of joining of metals either by electrical or by gas is called welding.

19. What is gas cutting ?
The process of joining of cutting metals by using oxygen and combustible gas is called gas cutting.

20. What is sand blasting?
The process of removing rust dust, dirt, scales and old prints from the old surface using compressed air is called sand blasting.

21. What is painting?
The process after sand blasting is called painting .

22. What is LEL?
The minimum concentration of vapour, gasses and dust in air below which propagation of flame does not occur on contact with a source of ignition is called LEL.

23. What is UEL?
The maximum proporation of vapour, gasses and dust in air above which proposal the flame does not occur on contact with a source of ignition is called UEL.

24. What is manual handing?
The process of lifting, carrying and stacking materials by men is called manual handing.

25. What is house keeping?
House keeping means not only cleanness but also orderly arrangement of operations, tools, equipments storage facilities and suppliers.

26. What is personal protective equipment?
It is an equipments used to project the person from hazards such dust, dirt, fumes and sparks etc. It is the barrier between hazard and person.

27. What is grinding?
Grinder is a portable machine with a wheel guard in position to reduced the danger.

28. What is Crane?
A tall machine used for moving heavy objects by suspending them from a projecting arm with hook.

29. What is fork lift truck?
Fork lift truck are designed to handle heavy loads.

30. What is JSA?
The procedure of analyzing job for the specific purpose of finding the hazards and developing .

31. What are the duties of a safety officer?
Prepare tool box talk
Prepare monthly statistics
Prepare the checklist
Accident reports
Management meetings
Arrange the safety classes/training
Arrange monthly safety bulletin
Inspection of fire extinguisher
Arrange first aid training classes
Arrange safety competitions like quiz, slogan, poster competitions exhibition etc.

32. What are the duties of a supervisor?
He has to instruct this workers about the work methods and procedures.
He has to maintain discipline among the workers
He has to supply necessary materials
He has to control quality and cost of the job
He has to guide has workers in doing a job in the correct and safe way
He has to supply suitable personal protective equipment to his workers
He should conduct periodical safety meetings.
He should conduct safety inspection of his working area
He should know about the fire fight equipments
He should know investigate the accident and find out the cause of accident

33. What are the pre cautions for welding?
1. Remove all combustion material from the place of welding
2. Clear the work area and cover wooden floor with fire proof mats. ( Welding mechanic should be kept with in the visibility of the welders.
3. Erect fire resistance screen around the work
4. All welding cables should be fully insulted
5. All welding mics shall be double earthed
6. Welding area should be dry and free from water
7. Keep the fire extinguisher / sand really
8. Use leather hand gloves, goggles and helmets
9. Switch off the power when welding is stopped
10. Do not allow the helper to do welding
11. Do not shift he welding cable unless the electric power is switched off.
12. Do not allow the helper to carry the welding. Terminal of the welding cables should be provided 3-cable with lugs and kept tight.
13. Oxygen hose in black and Acetylene hose in red in color as per standard
14. NRV of the blow torches should be maintained properly avoid back fire
15. Welders should be trained properly
16. Cylinders should be stored in a cold dry place away bottom heat and direct sunlight.
17. Proper house keeping, good ventilation in the working area
18. Smoking should be avoided from welding area
19. Hose connection should be proper made
20. Barricade the work area and put a sign board
21. Rolling of cylinders should be avoided
22. Flash back arrestor should be attached in each cylinders
23. Any leakage of cylinder should be kept separately

34. What is the precaution for gas cutting?
1. Keep fire extinguisher nearby
2. Keep fire watch near by
3. Remove all combustible from work area
4. Use all necessary PPE
5. Never put welding gas cylinder in side a confined space
6. Hoses shall not be laid in path ways
7. Gas cutting torch should have flash back arrestors
8. Gas test to be done to check for presence of flammable gas in site.
9. Good house keeping and ventilation necessary in working area.
10. Hose connections should be made properly

35. What are the precaution for “sandblasting”?
1. Compressed airline, hoses and other fitting must installment firmly with out leaks the hose.
2. Mis use compress are should be avoided
3. A fresh air hood or mask must be worn
4. House keeping can be done period cally
5. Fire extinguish her shall be kept near by
6. Dust mask ear plugs / muffs should be used
7. No sand blasting shall be done on top of floating roof tank in service.
8. Use goggles & face shield
9. Sand blasting operation must be gas free

36. What are the precaution for “painting”?
1. All flammable material should be cleared from the work area
2. The required protective clothing and equipment must be worn
3. Cartridge respirators shall always be worn
4. Adequate ventilation is necessary
5. Adequate washing facilities must be readily available
6. Barrier cream should be applied to the skin

37. What are the hazards in welding?
Eye injury
Burn injury Arc realization
Electrical shock Light arc radiation
Heat, light and radiation effect Heat fume
Poisonous gases Chipped price of weld metal
Explosion Scattering
Noise Sparking
Flying sand

38. What are hazards and injuries in manual handing?
1. Cutting fingers due to sharp edges
2. Burns due to handing of hot articles
3. Foot injuries due to dropped articles
4. Slipped disc due to improper posture in lifting on object
5. Strains to wrist or fingers
6. Sprains, wounds hernias, fractures

39. Cause of accidents in manual handling?
1. Improper lifting
2. Carrying too heavy loads
3. Improper gripping
4. Failure to use PPE
5. Lifting greasy, oily and irregular objects
6. Poor physique

40. What precautions are need to avoid accident in manhandling?
1. Stand at safe distance from the load
2. Sharp edge and burns are removed before lifting a material.
3. PPE such as safety gloves and safety shoes are to be used.
4. If the weight is too heavy for one person to lift, then he has to seek the assistance.
5. The pathway is not blocked by obstacles while carrying the load.
6. The different actions, movements and forces necessary while carrying the load.
7. Modify the task by using hooks and crow bars.
8. Mechanical equipments like cranes shall be used.
9. Modify the objects
10. Change the way things are used.

41. Tips for manuals handling?
1. Plan
2. Clear the path
3. Move in close to the load
4. Secure your grip
5. Hold your head upright
6. Maintain normal curves of the spine
7. Power the lift with legs and body weight
8. Don’t twist

42 Cause of accidents in mechanical handling?
1. The sudden failure of wire rope or a chain
2. Slipping of the load from the sling
3. Swinging of the load at the time of lifting
4. The load sometimes hits the man

43. What are the accidents in “poor house keeping”?
1. Men getting hit by failing from overhead
2. Men slipping as greasy, wet or dirty floor
3. Men failing in open tank without cover in level floor
4. Accidents due to poor lighting
5. Fire accidents due to faulty electrical wires

44. What are the advantages in good house keeping?
1. It helps in the reduction of accidents including fire accidents
2. It saves the property damages
3. It improves employee moral
4. Better productivity
5. Working area be-comes presentable
6. Human energy is conserved
7. Visitors are very much satisfied
8. The burden of supervisor is reduced

45. How to care and maintenance of hand tools?
1. Tools must be kept clean and free from corrosion
2. Keep metal parts lightly oiled
3. Remove burrs from edges of tools and heads of chisels.
4. Tools which are not in used must be stored separately
5. A good worker regularly inspects his tools
6. Do not use tools without handles

46. How to prevent accidents of “power tools”?
1. The operators should wear face shields or safety glasses
2. Power tools should be placed in the store room after use
3. power tools should have protected by guards
4. Pneumatic hoses or electric cables of power tools should not pass through passage ways.
5. The electrical power tools should be properly earthed
6. Never horse play with hose of pneumatic tools
7. Power tools machines should be maintained and operated properly.

47. What are the causes of accidents of “hard tools”?
1. Due to wrong way using of tools.
2. Due to defective condition of tools
3. Due to failure of using right tools for right job
4. Due to wrong way of carrying tools
5. Due to strong of tools un safety

48 What precautions are necessary in electrical work?
1. All electrical installations shall be as per Indian electricity rules
2. Only competent persons should handle the electrical equipments
3. The equipments should be earthed properly
4. All temporary electric lines should be drawn at least above man’s height
5. Cable should be completely insulted
6. Cable should not have any joints
7. Only connection for one point
8. Good house keeping on the area
9. Fire protection equipment to be kept near by
10. Use rubber gloves and rubber boots
11. Use good quality of wire
12. Power isolation close to the job
13. Use three pin plug instead of loose wire
14. Never operate any electrical equipment with wet hands
15. Never stand wet surface while working electrical equipments
16. During thunder storm do not stand under tree
17. Proper sign board is necessary
18. No person shall work on any live electrical conductor
19. The switch shall only be put on by person who switched it off

49. What are the hazards in construction?
1. Fall of person from top and getting injured
2. Fall of objects from top and below person injury
3. Fall of materials from top and damaged
4. Person fall into excavated pit
5. Collapse of soil and below person get injury or may
6. Damage of UG cables and sewage pipe
7. Collapse of scaffolding and person fall from height, get injury
8. Electrical shock
9. Fire and explosion
10. Burn injury
11. Health and lung problems
12. Snakes bite
13. Poisonous gas
14. Foreign body in eye

50. Cause of accident in construction?
1. Erection equipment failure
2. Falling of persons from height
3. Electrical shocks
4. Improper lighting
5. Non stop working by worker
6. Up safe work methods
7. Collapsing of earth during trench excavation
8. Failure of use safety equipment
9. Working a height without safety belt

51 General safety precautions in construction?
1. Adequate first aid equipment should be kept ready
2. Adequate fire fighting equipment should be available
3. All general electrical rules should be followed
4. suitable lighting arrangements should be necessary at night work
5. Work men at height should be wear safety belts
6. Work men handling cement should be provided with goggles, rubber gloves and rubber boots by nose mask.
7. The moving parts of grinding machines used construction site should be covered with guards
8. The moving parts of grinding machines used construction site should be covered with guards
9. Excavated material should not kept near the excavated
10. Very short duration of work red flags must be hoisted and more duration red banners must be stretched
11. Defective tools should not be used
12. The worker should not carry tools in his hands when climbing a ladder
13. Excavation should be guarded by suitable fencing

52. How to erect scaffolding?
1. It should be erected on levels firm ground
2. It erected by trained / skilled person
3. It is constructed using metal pipes and wooden boards
4. It should be design and constructed from good and sound material
5. Not to be erected on loose earth
6. Clamps should fixed
7. Properly bracing
8. Sole plate is necessary the base of vertical pipe

53. Safety precaution of scaffold?
1. Wooden board not be painted
2. Wooden board should not to any cracks
3. Check for rust in pipes / clamps
4. Clamps should fixed and good quality
5. Boards thickness should be 3.4 cms and no bending
6. The construction must be rigid, properly based
7. Use of good and sound materials
8. The wooden bellies has not joints
9. Vertical poles should not be more than 6 feet
10. Chains, ropes used for the suspension of scaffoldings
11. Never throw any materials from height
12. Use safety harness while working at above 6 feet
13. Properly ties to be arrangement

54 What control measures area necessary in confined space?
1. Enter with air line BA sets
2. Use 24v flame proof hand lamps
3. A hole watch to be kept near man hole
4. Keep fire fighting equipment ready
5. Gas test to be done to check for oxygen level
6. Provide blowers
7. Don’t smoke in confined space
8. Use ropes and harness
9. The spaces clean before entry
10. Use non sparking tools it there is any risk of flammable vapors being present.

55. Safety rules when using ladders?
1. The foot wear is not greasy, oily and muddy and has a good grip on the rungs.
2. When climbing or coming down a ladder should be face the ladder side and had on with both hand.
3. Carry light tools in pockets in a shoulder bag.
4. Hold on with at least new hand if use of both hands then, use safety belt
5. Never climb higher than the third rung from the top on straight or second tired from the top on extension ladder.
6. Step ladder must be fully open and the divider locked
7. Metal ladder shall not be used near electrical equipments.
8. Metal ladder shall not be place on firm footing and at angle of 75
9. Any ladder found defect in any way should be marked do not use
10. Ladder shall not be placed on a box or drum.
11. Rubber protection on head and heel of a ladder is necessary.

56. Safety rules insuring oxygen cylinders?
1. Oxygen cylinders should not be kept near combustible materials.
2. Oxygen cylinders should not be handled with grassy hands or gloves.
3. Oxygen cylinders and their fittings should not be tested with oil based soap solution.
4. Oxygen cylinders and other combustible gas cylinders should not be stored together.
5. The top cover of the cylinder should be kept in position and screwed safety when not in use.
6. Cylinders should not be used as rollers for moving materials
7. Oxygen must not be use for ventilating confined spaces.

57. Safety rules in using compressed air?
1. Only authorized persons should used compressed air.
2. The body or clothes should not be cleaned with compressed air.
3. Compressed air hose pipes should not be placed across passage ways
4. Leakage of compressed air should not be tested with hands.
5. While working with tools run by compressed air safety shoes are to be used.
6. The tools should not be kept on position when not in use.

58. Handling of compressed gas cylinders?
1. They are not to be dragged or dropped
2. They should be stored in dry and well ventilated places
3. Chins and slings should not be used for lifting cylinders.
4. the caps of the cylinders should not be removed when they are not the use.
5. Cylinders should not be stored near hot sources
6. Acetylene cylinders should not be stored horizontally
7. Empty cylinders and fully cylinders should be stored separately
8. Leakage cylinders removed to open space and release the gas without getting ignited.

59. Storage of gas cylinders.
1. Cylinders should stored in a safe, dry and well ventilated store
2. Oxygen cylinders should be stored horizontally and acetylene cylinders shall be stored vertically.
3. The standing cylinders should be secured properly avoid falling.
4. Flammable gas shall be stored at least 50 feet away from another building
5. Oxygen cylinder shall never be stored necessary flammable gas cylinder
6. Empty cylinder shall be identified by marking with a chalk (MT) and checked for damage before returning to suppliers.
7. Cylinders should not be kept as supports.

60. Give a brief note about crane and LE?
1. Only authorized and competent person should operated cranes
2. The correct sling must be used for the load to be lifts
3. Lifting equipment must be certified from competent authority and mark with its SWL
4. Never be used for loads excess of its SWL
5. Cables and slings must be padded when passing over sharp edges of equipments
6. Check the condition of the ground before parking the crane and use out riggers
7. All moving parts must be guarded
8. Uncertified chains, ropes, slings and hooks should not be use
9. All slings to be inspected by third party inspectors
10. Never stand or work under a suspended load
11. Place the out riggers on firms ground
12. Guide ropes shall be used to control swing of lifted material
13. Never operate the crane at the time of speed wing
14. Lifting over live equipment should not be encouraged
15. The crane should under go periodical maintenance as per manufactures

61 Give brief note about fork lift truck?
1. Check breaks, lift tilt and tires.
2. Check the stability of load before moving it
3. Never leave your fork lift truck un-attend with motor running
4. Never park fork lift truck on passage way
5. Never drive with wet or greasy hands
6. Always drive with a safe speed and slow down at turning point
7. When driving without load forks about 6 inches above the floor or ground
8. Never operate trunk in gaseous area
9. Never carry a load so high that you can not head, If necessary operate truck in reverse
10. Avoid carrying lose materials on forks
11. Never allow one to go under elevated loads
12. Warn other employees to stand clear when staking or removing materials
13. Exhaust pipe should have flame arrestor
14. Fork should be lowered to the floor when the truck is unattended
15. Stay alert t all times

62 Give a brief about grinding?
1. Proper wheel shall be used a per the grinding M/c’s specification
2. All the grinding M/c’s shall be used with wheel guard
3. Grinding cables shall not mingle with welding cables
4. All the cables shall be protected from damage
5. Provide face shield with safety helmet
6. Never use fracture wheel
7. Excessive tighting of maintaining is dangerous
8. All guards should be in position before the machine operated
9. The speed of the grinding should match in the speeds of the grinding machines
10. Only skill person should be handle this work
11. Testing of wheel is necessary

63 Describe about vehicles and plants?
1. All vehicles requiring security vehicles pass
2. All drivers should have valid driving licence
3. Drivers should not use fork lift trucks for carrying passengers
4. All traffic regulations and speed limit should be strictly followed in side the plant area
5. All vehicles area in a road worthy condition
6. Vehicles park in the operation area must always unlocked with in ignition key in position

64 Precaution of excavation?
1. Excavation area should be suitable barricade
2. Put sign boards lights and flags
3. Avoid heavy vehicle coming near the sides
4. PPE like helmet, safety shoes should be used
5. Keep the excavated soil at least 5 feet distance
6. Excavated sides should be sloped bake to a safe angle
7. Hand excavation should be done at the present of UG pipes or cables place
8. Cutting shall be done from top to bottom
9. All narrow trenches 4 feet or more deep shall be supplied at least one ladder
10. While excavating on the slope on the slope whose height is over 10 feet men should use safety belts

65 What are advantages of JSA? ( Job safety Analysis)
1. It helps to identify hazards and prevent accident
2. It helps to establish safe work method, working conditions and suitable plant safety rules
3. It helps to asses the safety training four heading can be used for JSA.
4. It helps to inspection the plant
a) Name of operation for JSA
b) Description of the operation
c) Hazards
d) Precautions

66 What is tool box talk?
1. Job related safety aspects
2. Job related hazards / risk
3. Control / preventive measure
4. Adequacy of PPE’s / condition
5. Following safety rules / procedures
6. Safe work procedures / methods

67 Describe different types of hazards?
1. Mechanical hazards — in adequately guarded machines parts
2. Chemical hazards — of toxemic gasses, vapours, fumes, smoke in dust.
3. Electrical hazards : in adequately insulated line wires
4. Fire hazards – chemical reaction, electrical Arcs
5. Radiation hazards – dazzing light in fraved rays ultra violet rays
6. Pollution — water pollution & noise pollution

68 What is inspection?
1. Inspection means to fin out hazards according to checklist prepared with reference to the department operations by the people who are familiar with the plant.

69 Plant safety inspection by whom?
Safety officer
By line management personal
By senior management personnel
First line supervisor
By maintenance engineers
By workers
By safety committee
By statutory authorites

70 How many types inspection?
There are 5 types inspection ; pressures of boilers( supervisor)
1. Continuous inspection – select employees / operator
2. Periodical Inspection – material storage, fire fighting equipments, handling equipments
3. Intermittent inspection – un announced inspection done by safety officer, safety committee. ( Particular work spot)
4. Statutory inspection – storage area, location at height ( cranes, ropes, chains, it my tackles inspection)
5. Special inspection – accident investigation
Inspection of new building, general lighting, use of PPE’s etc. construction work.

71 What is safety management?
Safety management is an act and science of setting safety objectives of the industrial company.

72 What is accident investigation?
Accident investigation means to carried out immediately the occurrence of accident to find out real facts to avoid the future accident.

73 What is accident statistics?
It means to maintenance of accident details

74 How to investigate an accidents?
Injured persons name, address, designation age
Exact place and types of hazards
Date, shift, time
To find out the causes/ reasons
To take correction action
Fact finding not fault finding

75 How to report an accident?
1. Date and time
2. Activity
3. What happened
4. Person involved
5. What went wrong
6. Causes
7. Corrective action suggested
8. Signature
9. Safety officer
10. Safety in charge
11. Project manager

76 What is accident prevention?
Accident prevention may be defined as an integrated programme and directed to control un safe mechanical or physical condition.

77 Role of management in industrial safety?
1. A written safety policy be issued by the management’s towards men, material and machines.
2. The safety policy should bring out the management’s towards men, material machine.3
3. The safety policy should be circulated to top, middle and to workers
4. Management meeting should be in a position
5. Management should arrange for safety inspection ( once in 3 months ) and safety audit ( once in year) to be carried out.

78 Give a brief note about safety policy ?
1. The safety and heath of all employees is one of prime concerned of the company.
2. Every company will be require to the policy both in letter and in spirit.
3. the company shall comply straightly with act, laws, rules and regulations
4. The company shall impart raining in health safety and occupational health to all employees.
5. The company will adopt own safety and health standards where laws may not be available.

79 Safety in the use of hand trucks?
1. the truck should be inspected
2. The axles should be greased well
3. Safety shoes should be work by the operators.
4. The load should be balanced and the weight of the load should not fall on the axle
5. The hard cart should not be wider than the width of the hand truck.
6. The hard cart should be pushed and not pulled
7. The truck should not be placed on path ways.

80 How many types of safety?
There are three types of safety.
a. Plant safety b. Workers safety 3. Consumer safety

81. Human factors causing accidents?
1. Carelessness
2. Fooling bout it
3. Hurrying to increase production
4. Laziness in house keeping
5. Hurrying in Lunchtime
6. Lack of attention due to worry
7. Alcohol and drugs
8. Lack of skill and experience
9. Not using PPE

82. How many steps in safety?
There are 4 steps in safety
1. Policy
2. Implementation
3. Take advantages of factory act
4. Safe working conditions.

83. Write causes of accidents ?
Direct cause: Unsafe act and unsafe condition.
Indirect Cause: 1. Lack of knowledge or skill
2. Improper attitude
3. Physical or mental deficiency

84. Give some examples about unsafe act?
1. Operating any equipment without properly authority
2. Failure to warning
3. Operating at unsafe speed
4. Failure to use PPE
5. Using hands instead of tools and equipment
6. Unsafe loading or placing or stacking
7. Unsafe position/ posture
8. Working on moving equipments
9. Wearing loose clothes while working on running machine
10. Working at height without safety belt

85. Give some examples about un safe conditions?
1. Un guarded machine/ equipment
2. Poor lighting
3. Narrow road
4. Improper stacking
5. Oil on floor
6. Unsafe ventilation
7. Unsafe defective construction
8. Defective condition of tools and equipment
9. Unsafe method or procedure
10. Bad housekeeping

86. Write about accident sequence?
A personal injury occurs only as the result of an accidents
An accident occurs only as the result of a unsafe action or un safe mechanical or physical conditions or both.
Unsafe action or unsafe condition or mechanical or physical condition exist only because of faulting the part of persons.
Fault of persons acquires from the environment and the causes for lack of knowledge or skills or improper attitude.

87. Write a brief about classification of fire?
They are mainly five types of fire.
Class A Fire : Wood, paper, clothes, rubbers etc.
Class B Fire : Oil, grease, paint, petroleum etc.
Class C Fire : Acetylene, ethane, methane etc.
Class D Fire : Sodium, magnesium, potassium etc.
Class E Fire : Electrical equipment etc.

88. Write uses of extinguisher for purpose ?
1. Water type extinguisher – Class A fire (not be B & E)
2. Foam type extinguisher – Class B fire (S.B + A.S.= Co2)
3. Carbon dioxide extinguisher Class C Fire
4. DCP Extinguisher – Class C, D or E

89. What precaution are necessary for protect of fires ?
1. Buildings and plants shall be so laid out and roads, passage ways etc.
2. Doors and windows shall be located in suitable positions on all external walls of the building.
3. Smoking lighting or carrying matches are to be prohibited
4. Gas cylinders should not be stored near high flammable substances
5. Flammable liquids shall be stored in suitable containers with close fitting covers.
6. In every factory has to suitable fire fighting equipment
7. All fire fighting equipment shall be subjected to routine maintenance inspection and testing by proper trained persons.
8. Sufficient number of persons shall be trained in the proper handling of fire fighting equipment.

90. Precaution for burn person?
1. It fire catches a single person’s cloth; he should immediately roll on the floor.
2. No lotion of any kind should be applied on the burn area
3. In case of burns due to corrosive chemicals, the burn parts should be flooded with water
4. The burn area should be covered with dry sterile dressing
5. Physical shock of the person is treated by giving him weak tea or coffee
6. In major cases the patient should be sent to hospital as quickly as possible

91. Factory act?
Sec.’6’ Registration of a factory
Sec.’11’ Cleanliness
Sec.’13’ Ventilation and temperature
Sec.’17’ Lighting
Sec.’18,19’ Drinking water and sanitary
Sec.’23’ Employment of young person on dangerous mechanical
Sec.’28’ Hoist and lifts
Sec.’29’ Lifting machines and tackles
Sec.35’ protection of eyes
Sec.’36’ Precaution against danger furmes
Sec.’36(A)’ Use of portable electric light
Sec.’38’ Protection in case of fire
Sec.’40(A)’ Maintenance of building
Sec.40(B)’ Safety officers duty
Sec.’45’ First aid boxes
Sec.’111’ Obligation of workers

92. Personal protective equipments? P.P.E
1. Head protection – Hard hat, cap, and helmet
Made – aluminum, PVC, fiber glass, Plastic
Protect – heal, spark, danger materials
2. Face and eye protection – Spectacles, Welding goggles, face shield
Protect – flying particles, radation
3. Hand protection – Gloves, hand pads
Made – leather, rubber, PVC, asbestos
Protect – acid, oil grease, pure Alex rubber gloves electrical
4. Foot and leg protection – Safety shoes, gum boots, foot leg guard
Made – Metal, leather, rubber
Project – falling materials and electrical work
5. Body protection – Apron, hood, coverall, jacket
Made rubber, leather canvas, lead, PVC asbestos
Asbestos hood – Fire fighting
Rubber, PVC full suit – ( Corrosively liquid, fumes, vapour
Safety belts – work exceeds 3 mts
6. Ear production – earmuff – noise – 30 – 135DB
7. Ear plug – 115 – 120 DB

93. What is safety management?
Safety management is an art and science of setting safety objectives of the Industrial company and related activities of planning, administration, Improving, Various functions to achieve the safety objectives.

94. What are the objectives of safety management?
1. Taking care of workers and staff in the event of an accident
2. Providing health full environment and surrounding
3. Welfare
4. Continuous vigil and improvement

95. How many types of PPE?
There are two types of PPE
1. Respiratory 2. Non respiratory
Respiratory — Air supplied
— Air purified
Air supplied — Compressed air breathing apparatus set
Air purified — Cannisters gas mask
—- Chemical cartridges respirator
——– Surgical cotton mask
Dust filter mask (dust respirator)

96. How many types work permit?
There are two types of work permit
1. Cold work permit
2. Hot work permit
The hot work permit further classified into 3 types
Normal hot work permit
Blanket hot work permit
Delegate hot work permit

97. What is blanket permit?
A blanket permit is a permit issued on the basis of location where the multiple jobs are to be carried out at safe location.

98. What is delegated work permit?
Delegated work permit used for areas requiring light control. Ex : Fabrication, yards – valid – 30 days

99. How many types of accidents?
There are 4 types of accidents
1. Near miss accident – escape
2. No lost time reported 48hrs. before
3. Los time – reported 48hrs. after
4. Fated – Death

100. Heinrich accident ratio?
Major injury
Minor injury
No injury

Bird accident ratio?
Property damage
No visible injury

101. How to control risk?
The risk is control by following process they are eliminate, replace, reduce, control and PPE.

102. What are the hazards in chemical safety?
1. Danger due to fire/ explosion
2. Danger due to toxicity

103. How to control the chemical hazards?
The chemical hazards are control by engineering method, administrative method and PPE.

104. Give a brief note about act related with session?
The factory Act – 1948 Petroleum Act – 1934
The mines Act – 1952 Water Act – 1974
Automatic energy Act – 1962 Air Act – 1948
Railways Act – 1890
Indian electricity Act – 1910
Indian boilers Act – 1884
Workmen compensation Act – 1948
Employee’s state insurance Act – 1948

105. What is first aid?
Firs aid is temporary and immediate care given to the victim of an accident.

106. What are the hazards in petroleum industry?
1. Fire, 2. Explosion, 3. General hazards, 4. Frostbite

107. How to control the petroleum hazards
1. Proper design, operation and maintenance
2. Avoid leakage
3. Steel pressure cylinder
4. Vapor release is to be directed away from heat sources
5. Wear goggles and SCBA sets

108. What are the causes of industrial accidents?
1. Inadequate skill, improper supervision etc.
2. Rapid industrialization
3. Expansion of exiting factories
4. Setting up new industries involving hazards not known earlier

109. What are the responsibility for workers for safety?
1. Report unsafe condition to supervisor
2. Do not operate the machine without knowing the operation
3. Before starting the machine, whether the machine is in condition not
4. Use correct tools
5. Follow the safety rules
6. Always do not horse play
7. Do not lift over load
8. Do not chit on at with others

110. What general precautions are necessary while driving?
1. Follow all traffic rules, signs and signals
2. Do not exceed the speed limit
3. Take ten minute break after every 2 hours on long driving
4. Drive in correct gear
5. Keep both hand on steering wheel
6. Do not drive if you are not filling well or feting sleep
7. Slow down while passing junctions, corners, crowded places and parking

111. What are cause of road accident?
1. Not following defensive arriving techniques
2. Not observing lane displine
3. Overtaking on turns or from wrong side
4. Not obey traffic signals
5. Poor road condition
6. Poor maintained vehicle

112. What are belongs to road safety?
1. The speed limits displayed along the road should be strictly
2. Short cuts and cutting across the corners should be avoid
3. No body should try to cross the level crossing when drop gates are closed
4. Signal given blocking the road ‘ stop’ look, listen and proceed should be followed.

113. What is factory act?
The factory act is a social enactment to achieve social reform and given liberal construction to achieve legislative.

114. What are main provision in the factory act?
Health, safety, welfare, hours of work, employment, person, occupational disease, special provision and penalties and procedures.

115. What the advantages of ventilation
1. It helps to reduce the chances of fire or explosion
2. It protects the occupational diseases
3. It provides comfort to the workmen

116. What the role of government in industrial safety?
The Govt. responsible for protection workers, consumers from dangers at work, on the road, in the air in the water, from air and water pollution etc.

117. How does the workers health influence ?
The workers health influences by occupational factors – physical, chemical, biological, social.
Non occupational factors – food, cloth, water, housing, smoking & alcohol etc.

118. How is audit conducted?
1. Preliminary visit and understanding the factory
2. Identify the audit element
3. Prepare the questionnaire
4. Get the reply from the company
5. Discussion with management, executives & workers.
6. Cross Verification at site
7. Preparation of report.

119 What are the procedures for work permit?
3 copies of the permit
At the work site.
In the permit file
On the permit board.

120. How many types of appliance
1. Safety appliance for PPE
2. Safety appliance for general protection
121. What are causes of accident of working at height (Personal)?
a. Lack of knowledge and skill
b. over work
c. Feeling of dizziness
d. Non usage of PPEs like safety belt cygnet
e. Unsafe platform (Not covered having floor openings)
f. Improper erecting
g. Unlearning work at height?

122. Control measure of work at height ?
i. Use safety belt with proper anchoring above head.
ii. Special training must be given before starting the job.
iii. All scaffolds must be erected by skill persons.
iv. No work after sun set
v. Every platform should free from unnecessary obstruction
vi. Grease, mud, paint removed from working platform

123. What is earthling?
Earthling means connecting the natural point of the supply system to the general mass of the earth by line.

124. What is ELCB?
It is protection of living beings under electro charging by fast isolation from the live conductor to avoid permanent disability or death.

125. Precaution for electric shock
Use dry hard gloves & rubber sole, safety boots, gum boots
The electric holder must be fully insulted
Proper protection for the body
During chipping of slag use white goggles

126. What is term card
It is legal requirements in case of emergency in violin vehicles carrying hazards substance.

127. What are audit elements
OS & H policy, educational training, safety manual and rules, new equipments, safety inspection, machine guarding, material handling safe operating procedures noise.

128. What are five rules of forth job
1. Select the right ladders forth job
2. Inspect ladder before you see it
3. Setup the ladder with care
4. Climb in carefully
5. Use safe practices

129. What are 4 Ps
Procedure – Rules, regulation
Protective gear – PPE
Promotional aspects – Competitions, rewards
Publicity – Bulleting, posters

130. How many types of sign boards
Fire or explosion

131. What is TWA ? – for 8 Hrs. exposure perday
It is define as the limit of air bone concentration of substances under which personnel may be exposed for 8 hrs. per day without any adverse effect.

132. What is STEL 0 for 15 minutes continuous exposure
It is considered as maximum allowable concentration not to be exceeded at any time during 15 minutes continuous expose period.
It is a maximum on concentration to which works or can be exposed to a period of to15 minutes continuously without suffering from irritation.

133. What are the duties of a factory inspector ?
He takes up the license and registration of factories
He also verify the documents related to factory workers
He suggests suitable and welfare measures

134. What are welfare measures of factory act ?
Adequate and suitable washing facilities should be provided
Facilities for sitting during rest hours should be provided
If more than 250 workers are employed in a factory a canteen facility shall be provided.
Shelters rest rooms and drinking water shall be provided.
Welfare officer shall be employed where than 50 workers are working.

135. What is safety inventory system ?
It is a safety date collecting technique and carried out to promote full employee co-operation condition in the implementation of the company’s safety surveys.

136. What is safety surveys ?
Safety surveys are made to have detailed observations of all types of unsafe physical and environment conditions as well as unsafe practices committed the health and comfort or workers.

137. what is industrial hygiene ?
Industrial hygiene is defined as the art and science of the presentation and improvement of the health and comfort of workers.

138. What are belongs to un hygienic working environment ?
Presence of toxic,
High temp.
Excessive noise
Emission of radiation
Improper lighting
Improper ventilation
Process involving handling of poisonous.

139. What is ingestion ?
Entry of harmful materials through mouth is called ingestion

140. What is inhalation ?
Entry of harm full materials through mouth is called ingestion

141. What are of four legs of fire safety ?
Fire protection
Fire prevention
Quantity control
Preventive Maintenance

142. What are the important points to be observed for fire prevention ?
Good house keeping
No smoking
Use of fire resistant paint
Electrical safety
Fire check doors
Noked flame safety
Separate storage of hazardous chemicals

143. Safety Triangle – Green ?
Safety day – 4th March
Fire Day – 14th April
Hot Work – Red or pink
Cold Work – Green
Confined – Blue
Radiography – Yellow
Water type extinguisher – Red
Foam type extinguisher – Cream (green)
Co2 extinguisher Black
DCR extinguisher Blue

144. What is lathe ?
Lathe is an equipment use for cutting, threading, millingor facing etc.

145. What is Noise ?
Up wanted sound which causes irritation to the ears caused by mechanical movement.

146. What is respiration ?
The process of inhaling fresh hair and exhaling, to entering a confined place is called respiration.

147. What is hot work permit ?
Any work which involves spark flame, temperature is called HWP

148. What is cold work permit ?
Any work which does not involved production of spark flame, heat, temp. is called

149. What
A form on energy resulting from the existence of charged parites by dynamically as a current.
It requires for worker on electrical equipments, machinery, cables, switch boards, pumps and other distribution boards.

150. What is radiography ?
It is conducted to check the welding joints for any blow holes defects through x-ray.

151. What is vehicles / Mobile permit ?
The permit is required for taking any vehicle are mobile equipments having a diesel equipment having a diesel or petrol operated engine in to hazardous area.

152. What are risks in vehicle permit ?
1. Sparks, 2. Accidents 3. Pollution

153. Control measures of vehicles permit ?
Fitted spark arrester
Speed 30 km./hours
Proper warring lights
No over load
Correct parking
Pollution check
3rd party inspection

154. Control measures of radiography?
Barricade the area
Remove all un-necessary persons away from site
Check radiation level with dosimeter
Use lead shields
Put a sign board
Risk tissue damaged
Use special filter glass
Use lead coated aprons

Saturday, July 9, 2016

Corrective and preventive action (CAPA)

Corrective and preventive action (CAPA, also called corrective action / preventive action, or simply corrective action) are improvements to an organization's processes taken to eliminate causes of non-conformities or other undesirable situations.[1] CAPA is a concept within good manufacturing practice (GMP), and numerous ISO business standards. It focuses on the systematic investigation of the root causes of identified problems or identified risks in an attempt to prevent their recurrence (for corrective action) or to prevent occurrence (for preventive action).

Corrective actions are implemented in response to customer complaints, unacceptable levels of product non-conformance, issues identified during an internal audit, or adverse or unstable trends in product and process monitoring such as would be identified by statistical process control (SPC). Preventive actions are implemented in response to the identification of potential sources of non-conformity.

To ensure that corrective and preventive actions are effective, the systematic investigation of the root causes of failure is pivotal. CAPA is part of the overall quality management system (QMS).


Clearly identified sources of data which identify problems that will be investigated. Root cause analysis to identify the cause of a discrepancy or deviation and suggest corrective actions of a problem which is identified.
A common misconception is that the purpose of preventive action is to avert the occurrence of a similar potential problem. This process is all part of corrective action, because it is a process of determining such similarities that should take place in the event of a discrepancy.

The PDCA cycle[2]
Preventive action is any proactive methodology used to determine potential discrepancies before they occur and to ensure that they do not happen (thereby including, for example, preventive maintenance, management review or other common forms of risk avoidance). Corrective and preventive actions both include investigation, action, review, and further action if so required. It can be seen that both fit into the PDCA (plan-do-check-act) philosophy as determined by the Deming-Shewhart cycle.

Investigations to root cause may conclude that no corrective or preventive actions are required, and additionally may suggest simple corrections to a problem with no identified systemic root cause. When multiple investigations end in no corrective action, a new problem statement with expanded scope may be generated, and a more thorough investigation to root cause performed.

Implementation of corrective and preventive actions is the path towards improvement and effectiveness of Quality Management Systems. Corrective actions is nothing but the action/s based on the problem identification. The problem or a non-conformance can be identified internally through staff suggestions, management reviews, document reviews or internal audits. Customer complaints / suggestions, customer rejections, non-conformities raised in customer / third party audits and recommendations by the auditors are the external sources which lead to find the root cause of the problem.

Root cause is the identification of the source of the problem where the person(s), system, process or external factor is identified as the cause of the non conformity.

Corrective action is the re-work / rectification activity of the non conforming products as per ISO 9001:2008 (8.5.2).

Preventive action is prediction of problem and trying to avoid the occurrence (fail safe) through self initiated actions and analysis related with processes/products. This can be initiated with the help of active participation of staff members/workers through improvement teams, improvement meetings, opportunities for improvement during internal audits, management review, customer feedback and deciding own goals quantized in terms of business growth, reducing rejections, utilizing the equipment effectively, etc.

Medical Devices and FDA Compliance

In order comply with FDA 21 CFR 820.100[3] medical device companies need to establish a CAPA process within their QMS. This part of the system may be paper or digital, but it is something that is looked for during an FDA visit. In 2015 there were over 450 issues found with the CAPA systems for medical device companies. To have an FDA complaint QMS system required the ability to capture, review, approve, control, and retrieve closed-loop processes.[4]

Examples of corrective actions

Error Proofing Visible or Audible Alarms Process Redesign Product Redesign Training or enhancement/ modification of existing training programmes Improvements to maintenance schedules Improvements to material handling or storage
In some cases a combination of such actions may be necessary to fully correct the problem.

ICH Q8, Q9, and Q10 - Questions and Answers?

Q. Is the minimal approach accepted by regulators?

Ans: Yes. The minimal approach as defined in Q8(R2) (sometime also called “baseline” or “traditional” approach) is the expectation that is to be achieved for a fully acceptable submission. However, the “enhanced” approach as described in ICH Q8(R2) is encouraged.

Q. What is an appropriate approach for process validation using ICH Q8, Q9, and Q10?

Ans: The objectives of process validation are unchanged when using ICH Q8, Q9, and Q10. The main objective of process validation remains that a process design yields a product meeting its predefined quality criteria. ICH Q8, Q9, and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process, and the control strategy. This information can be used to identify the type and focus of studies to be performed prior to and on initial commercial production batches. As an alternative to the traditional process validation, continuous process verification can be utilized in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product life-cycle.

Q. How can information from risk management and continuous process verification provide for a robust continual improvement approach under ICH Q8, Q9 and Q10?

Ans: Like the product itself, process validation also has a lifecycle (process design, process qualification and ongoing process verification). A risk assessment conducted prior to initial commercial validation batches can highlight the areas where particular focus and data collection could demonstrate the desired high level of assurance of commercial process robustness. Continual monitoring (e.g., via continuous process verification) can further demonstrate the actual level of assurance of process consistency and provide the basis for continual improvement of the product. Quality Risk Management methodologies of ICH Q9 can be applied throughout the product lifecycle to maintain a state of process control.

Quality by Design (QbD):

Q. Is it always necessary to have a design space (DS) or real-time release (RTR) testing to implement QbD?

Ans:  Under Quality by Design, establishing a design space or using real-time release testing is not necessarily expected.

Q. Is it necessary to study multivariate interactions of all parameters to develop a design space?

Ans:  No, the applicant should justify the choice of material attributes and parameters for multivariate experimentation based on risk assessment and desired operational flexibility.

Q. Can a design space be applicable to a site change?

Ans:  Yes, it is possible to justify a site change using a site independent design space based on a demonstrated understanding of the robustness of the process and an in depth consideration of site specific factors (e.g., equipment, personnel, utilities, manufacturing environment, and equipment). There are region specific regulatory requirements associated with site changes that need to be followed.

Q. Can a design space be developed for single and/or multiple unit operations?

Ans: Yes, it is possible to develop a design space for single unit operations or across a series of unit operations.

Q. Is it possible to develop a design space for existing products?

Ans: Yes, it is possible. Manufacturing data and process knowledge can be used to support a design space for existing products. Relevant information should be utilized from e.g., commercial scale manufacturing, process improvement, corrective and preventive action (CAPA), and development data. For manufacturing operations run under narrow operational ranges in fixed equipment, an expanded region of operation and an understanding of multiparameter interactions may not be achievable from existing manufacturing data alone and additional studies may provide the information to develop a design space. Sufficient knowledge should be demonstrated, and the design space should be supported experimentally to investigate interactions and establish parameter/attribute ranges.

Q. Is there a regulatory expectation to develop a design space for an existing product?

Ans: No, development of design space for existing products is not necessary unless the applicant has a specific need and desires to use a design space as a means to achieve a higher degree of product and process understanding. This may increase manufacturing flexibility and/or robustness.

Q. Can a design space be applicable to formulation?

Ans: Yes, it may be possible to develop formulation (not component but rather composition) design space consisting of the ranges of excipient amount and its physicochemical properties (e.g., particle size distribution, substitution degree of polymer) based on an enhanced knowledge over a wider range of material attributes. The applicant should justify the rationale for establishing the design space with respect to quality attributes such as bioequivalence, stability, manufacturing robustness etc. Formulation adjustment within the design space depending on material attributes does not need a submission in a regulatory post-approval change.

Q. Does a set of proven acceptable ranges alone constitute a design space?

Ans: No, a combination of proven acceptable ranges (PARs) developed from univariate experimentation does not constitute a design space. Proven acceptable ranges from only univariate experimentation may lack an understanding of interactions between the process parameters and/or material attributes. However proven acceptable ranges continue to be acceptable from the regulatory perspective but are not considered a design space.

Q. Should the outer limits of the design space be evaluated during process validation studies at the commercial scale?

Ans: No. There is no need to run the qualification batches at the outer limits of the design space during process validation studies at commercial scale. The design space should be sufficiently explored earlier during development studies.

Q. How is batch release affected by employing real-time release testing?

Ans: Batch release is the final decision to release the product to the market regardless of whether RTR testing or end-product testing is employed. End-product testing involves performance of specific analytical procedures on a defined sample size of the final product after completion of all processing for a given batch of that product. Results of real-time release testing are handled in the same manner as end-product testing results in the batch release decision. Batch release involves an independent review of batch conformance to predefined criteria through review of testing results and manufacturing records together with appropriate good manufacturing practice (GMP) compliance and quality system, regardless of which approach is used.

Q. Does real-time release testing mean elimination of end-product testing?

Ans: Real-time release testing does not necessarily eliminate all end-product testing. For example, an applicant can propose RTR testing for some attributes only or not all. If all critical quality attributes (CQAs) (relevant for real-time release testing) are assured by in-process monitoring of parameters and/or testing of materials, then end-product testing might not be needed for batch release. Some product testing will be expected for certain regulatory processes such as stability studies or regional requirements.

Q. Is a product specification still necessary in the case of RTR testing?

 Ans: Yes, product specifications still need to be established and met, when tested.

Q. When using RTR testing, is there a need for stability test methods?

Ans: Even where RTR testing is applied, a stability monitoring protocol that uses stability indicating methods is required4 for all products regardless of the means of release testing.

Q. What is the relationship between control strategy and RTR testing?

Ans: RTR testing, if utilized, is an element of the control strategy in which tests and/or monitoring can be performed as in-process testing (in-line, on-line, at-line) rather than tested on the end product.

Q. Do traditional sampling approaches apply to RTR testing?

Ans: No, traditional sampling plans for in-process and end-product testing involve a discrete sample size that represents the minimal sampling expectations. Generally, the use of RTR testing will include more extensive on-line/in-line measurement. A scientifically sound sampling approach should be developed, justified, and implemented.

Q. If RTR testing results fail or trending toward failure, can end-product testing be used to release the batch?

Ans: No, in principle the RTR testing results should be routinely used for the batch release decisions and not be substituted by end-product testing. Any failure should be investigated and trending should be followed up appropriately. However, batch release decisions should be made based on the results of the investigations. In the case of failure of the testing equipment, please refer to the previous question. The batch release decision should comply with the content of the marketing authorization and GMP compliance.

Q. What is the relationship between in-process testing and RTR testing?

Ans: In-process testing includes any testing that occurs during the manufacturing process of drug substance and/or finished product. Real-time release testing includes those in-process tests that have a direct impact on the decision for batch release through evaluation of critical quality attributes.

Q. What is the difference between “real time release” and “real-time release testing”?

Ans: The definition of real-time release testing in Q8(R2) is “the ability to evaluate and ensure the acceptable quality of in-process and/or final product based on process data, which typically includes a valid combination of measured material attributes and process controls.” The term real time release in the Q8(R2), step 2 document was revised to “realtime release testing” in the final Q8(R2) Annex to fit the definition more accurately and thus avoid confusion with batch release.

Q. Can surrogate measurement be used for RTR testing?

Ans: Yes, RTR testing can be based on measurement of a surrogate (e.g., process parameter, material attribute) that has been demonstrated to correlate with an in-process or end-product specification.

Q. What is the relationship between RTR testing and parametric release?

Ans: Parametric release is one type of RTR testing. Parametric release is based on process data (e.g., temperature, pressure, time for terminal sterilization, physicochemical indicator) rather than the testing of material and/or a sample for a specific attribute.

Q. What is the difference in a control strategy for products developed using the minimal approach vs. “quality-by-design” approach?

Ans: Control strategies are expected irrespective of the development approach. Control strategy includes different types of control proposed by the applicant to assure product quality such as in-process testing and end-product testing. For products developed following the minimal approach, the control strategy is usually derived empirically and typically relies more on discrete sampling and end-product testing. Under QbD, the control strategy is derived using a systematic science and risk-based approach. Testing, monitoring, or controlling is often shifted earlier into the process and conducted in-line, online, or at-line testing.

Q. Are GMP requirements different for batch release under QbD?

Ans: No, the same GMP requirements apply for batch release under minimal and QbD approaches.

Q. What is the relationship between a design space and a control strategy?

Ans: A control strategy is required for all products. If a design space is developed and approved, the control strategy provides the mechanism to ensure that the manufacturing process is maintained within the boundaries described by the design space.

Q. What approaches can be taken in the event of on-line/in-line/at-line testing or monitoring equipment breakdown?

Ans: The control strategy provided in the application should include a proposal for use of alternative testing or monitoring approaches in cases of equipment failure. The alternative approach could involve use of end-product testing or other options, while maintaining an acceptable level of quality. Testing or monitoring equipment breakdown should be managed in the context of a deviation under the quality system and can be covered by GMP inspection.

Q. Are product specifications different for minimal versus QbD approaches?

Ans: In principle no, product specifications are the same for minimal and QbD approaches. For a QbD approach, the control strategy can facilitate achieving the end product specifications via real time release testing approaches. Product must meet specification, when tested.

Pharmaceutical Quality System

Q. What are the benefits of implementing a pharmaceutical quality system (PQS) (in accordance with ICH Q10)?

Ans:  The benefits are:

Facilitated robustness of the manufacturing process, through facilitation of continual improvement through science and risk-based post-approval change processesConsistency in the global pharmaceutical environment across regionsEnable transparency of systems, processes, and organizational and management responsibilityClearer understanding of the application of a quality system throughout product lifecycleFurther reducing risk of product failure and incidence of complaints and recalls, thereby providing greater assurance of pharmaceutical product consistency and availability (supply) to the patientBetter process performanceOpportunity to increase understanding between industry and regulators and more optimal use of industry and regulatory resources; enhance manufacturer’s and regulators’ confidence in product qualityIncreased compliance with GMPs, which builds confidence in the regulators and may result in shorter inspections

Q. How does a company demonstrate implementation of PQS in accordance with ICH Q10?

Ans: When implemented, a company will demonstrate the use of an effective PQS through its documentation (e.g., policies, standards), its processes, its training/qualification, its management, its continual improvement efforts, and its performance against pre-defined key performance indicators. A mechanism should be established to demonstrate at a site how the PQS operates across the product lifecycle, in an easily understandable way for management, staff, and regulatory inspectors, e.g., a quality manual, documentation, flowcharts, procedures. Companies can implement a program in which the PQS is routinely audited in-house (i.e., internal audit program) to ensure that the system is functioning at a high level.

Q. Is it necessary to describe the PQS in a regulatory submission?

Ans: No, however relevant elements of the PQS (such as quality monitoring system, change control, and deviation management) can be referenced as part of the control strategy as supporting information.

Q. Will there be certification that the PQS is in accordance with ICH Q10?

Ans: No. There will not be a specific ICH Q10 certification program.

Q. How should the implementation of the design space be evaluated during inspection of the manufacturing site?

Ans: Inspection should verify/assess that manufacturing operations are appropriately carried out within the design space. The inspector in collaboration with the assessor, where appropriate, should also verify successful manufacturing operations under the design space and that movement within the design space is managed within the company’s change management system

Q. What should be done if manufacturing operations run inadvertently outside of the design space?

Ans: This should be handled as a deviation under GMP. For example, unplanned “oneoff” excursions occurring as a result of unexpected events, such as operator error or equipment failure, would be investigated, documented, and dealt with as a deviation in the usual way. The results of the investigation could contribute to the process knowledge, preventive actions, and continual improvement of the product.

Q. What information and documentation of the development studies should be available at a manufacturing site?

Ans: Pharmaceutical development information (e.g., supporting information on design space, chemo-metric model, risk management) is available at the development site. Pharmaceutical development information that is useful to ensure the understanding of the basis for the manufacturing process and control strategy, including the rationale for selection of critical process parameters and critical quality attributes, should be available at the manufacturing site. Scientific collaboration and knowledge sharing between pharmaceutical development and manufacturing is essential to ensure the successful transfer to production.

Q. Can process parameters be adjusted throughout the product lifecycle?

Ans: Process parameters are studied and selected during pharmaceutical development and monitored during commercial manufacturing. Knowledge gained could be utilized for adjustment of the parameters as part of continual improvement of the process throughout the lifecycle of the drug product.

Q. How will product-related inspections differ in an ICH Q8, Q9 and Q10 environment?

Ans: In the case of product-related inspection (in particular, preauthorization) depending on the complexity of the product and/or process, greater collaboration between inspectors and assessors could be helpful (for example, for the assessment of development data). The inspection would normally occur at the proposed commercial manufacturing site, and there is likely to be greater focus on enhanced process understanding and understanding relationships, e.g., critical quality attributes (CQAs), critical process parameters (CPPs). The inspection might also focus on the application and implementation of quality risk management principles, as supported by the pharmaceutical quality system (PQS).

Q. How will system-related inspections differ in an ICH Q8, Q9, and Q10 environment?

Ans: The inspection process will remain similar. However, upon the implementation of ICH Q8, Q9, and Q10, inspections will have greater focus on (but not only focus on) how the PQS facilitates the use of e.g., quality risk management methods, implementation of design space, and change management.

Q. How is control strategy approved in the application and evaluated during inspection?

Ans: Elements of control strategy submitted in the application will be reviewed and approved by the regulatory agency. However, additional elements are subject to inspection.

Knowledge Management

Q. How has the implementation of ICH Q8, Q9, and Q10 changed the significance and use of knowledge management?

Ans: Q10 defines knowledge management as: “Systematic approach to acquiring, analyzing, storing, and disseminating information related to products, manufacturing processes and components.” Knowledge management is not a system; it enables the implementation of the concepts described in ICH Q8, Q9 and Q10.

Knowledge management is not a new concept. It is always important regardless of the development approach. Q10 highlights knowledge management because it is expected that more complex information generated by appropriate approaches (e.g., QbD, process analytical technology (PAT), real-time data generation, and control monitoring systems) should be better captured, managed, and shared during product life-cycle.

In conjunction with quality risk management, knowledge management can facilitate the use of concepts such as prior knowledge (including from other similar products), development of design space, control strategy, technology transfer, and continual improvement across the product life cycle.

Q. Does Q10 suggest an ideal way to manage knowledge?

Ans: No. Q10 provides a framework and does not prescribe how to implement knowledge management. Each company decides how to manage knowledge, including the depth and extent of information assessment based on its specific needs.

Q. What are potential sources of information for knowledge management?

Ans: Some examples of knowledge sources are:

Prior knowledge based on experience obtained from similar processes (internal knowledge, industry scientific and technical publications) and published information (external knowledge: literature and peer-reviewed publications)Pharmaceutical development studiesMechanism of actionStructure/function relationshipsTechnology transfer activitiesProcess validation studiesManufacturing experience, e.g., — Internal and vendor audits — Raw material testing dataInnovationContinual improvementChange management activitiesStability reportsProduct quality reviews/annual product reviewsComplaint reportsAdverse event reports (patient safety)Deviation reports, recall InformationTechnical investigations and/or CAPA reportsSuppliers and contractorsProduct history and /or manufacturing historyOngoing manufacturing processes information.

Information from the above can be sourced and shared across a site or company, between companies and suppliers/contractors, products, and across different disciplines (e.g., development, manufacturing, engineering, quality units).

Q. Is a specific dedicated, computerized information management system required for the implementation of knowledge management with respect to ICH Q8, Q9, and Q10?

Ans: No, but such computerized information management systems can be invaluable in capturing, managing, assessing, and sharing complex data and information.

Q. Will regulatory agencies expect to see a formal knowledge management approach during inspections?

Ans: No. There is no added regulatory requirement for a formal knowledge management system. However, it is expected that knowledge from different processes and systems will be appropriately utilized. Note: “formal” means: it is a structured approach using a recognized methodology or information technology (IT) tool, executing and documenting something in a transparent and detailed manner.

Umbrella Guideline on Process Validation

WHO publishes Draft of an Umbrella Guideline on Process Validation

At the end of 2015, the WHO adapted its Appendix 7 to the latest technological standards. Appendix 7 provides support with regard to non-sterile process validation. Now, further changes to WHO guidelines are in sight. One of these changes concerns the guideline on process validation which is currently available as a draft and can be commented on until July, 12th 2016. Please find here an analysis of this draft.

The draft contains 21 pages divided into 13 chapters and one part with references.

The guideline serves as a sort of umbrella guideline and should replace in the future Annex 4 of the WHO Technical Report Series No. 937 from 2006. In so far, the draft refers to other guidelines about the topic validation which will thus have to be updated too as subordinated guidelines (Appendices). The following appendices are named:

Appendix 1 Validation of HVAC systems (currently already available as a revised draft)

Appendix 2 Validation of water systems for pharmaceutical use (will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical use for consideration in qualification of water purification systems)

Appendix 3 Cleaning Validation
Appendix 4 Analytical method validation
Appendix 5 Validation of computerized systems
Appendix 6 Qualification of systems and equipment
The introduction describes validation as an essential part of GMP and GCP. Validation also includes qualification and a lifecycle comprising an "ongoing review" for continuous improvements. The necessity, scope and depth of validation activities should be based on quality risk management principles.

The following resources are listed:

Personnel (multidisciplinary team). So far, a summary of the introduction.
The chapter “Scope“ points out that the draft describes an overall validation concept which could be applicable to the manufacture and control of starting materials and finished pharmaceutical products. The qualification aspects included in the document could also apply to premises, equipment, utilities and systems.

Made up of three pages, the glossary is very extensive. It is interesting to see that this chapter offers a definition for the terms "Commissioning" and “Good Engineering Practice”. The definition for process validation is very close to that of the FDA. Performance qualification is described as applicable to equipment and systems. In the context of systems, the term “process validation” could also be used. There is also a own definition for the term “validation“ (“Action of proving and documenting that any process, procedure or method actually and consistently leads to the expected results”). The term “retrospective validation“ is not listed but the term “revalidation“ - also in the sense of a periodic (re)validation.

Chapter 4 addresses the relationship between validation and qualification. “Qualification and validation are essentially the same” whereby qualification is normally used in relation to equipment and utilities, and validation in relation to systems and processes.

Chapter 5 “Validation” and its subchapter “Approaches to validation” include some interesting requirements. Where appropriate, statistical calculations should be used to deliver the scientific proof that the process, systems and other related aspects are appropriately validated. Moreover, the senior management is explicitly spoken to with respect to the availability of resources. Both the management and the persons responsible for quality assurance should be actively involved in the validation activities as well as in the authorization of protocols and reports. Regarding the topic risk management which should be used, it is referred to a specific WHO guideline. Where necessary, worst-case tests or so-called "challenge tests" should be performed like for example stress load tests and volume verification tests in computer systems.

The documents needed to accompany the validation activities (Chapter 6) include among other things protocols and reports as well as a validation master plan. By means of own (superordinate?) plans, it should be ensured that a validation review is available which guarantees the maintenance of the validated status. The next chapters look at the validation master plan, protocols and reports.

A validation master plan – concise and clear - should be available (Chapter 7). However, 28 minimum requirements are listed. One should notice that this high number is mainly due to the fact that for the qualification activities each sub item is respectively listed for the qualification of premises, equipment, utilities. The same applies to the validation activities (cleaning, process, analytical methods, and computerised systems). The validation master plan should be regularly reviewed and the GMP status should be kept up-to-date.

The minimum requirements concerning the validation and qualification protocols are fairly detailed too (15 items). Chapter 8 also points out that there should be a description of how results should be analysed (including statistical analyses where appropriate).

Also in the following Chapter 9 on qualification and validation reports, the focus of reporting is put on statistical analyses where possible. The final approval of reports should be done by the quality assurance department.

Chapter 10 Qualification

Made up of almost 3.5 pages, Chapter 10 (Qualification) is relatively extensive. It suggests that there are different approaches to qualification. The V-Model for Direct Impact Systems is given as an example. Yet, the model presents abbreviations which are not explained (e.g. UAT). “Normally” – quoting the text – „qualification should be completed before process validation is performed”. "Normally", qualification should begin with user requirement specifications (URS). Depending on the object considered, the following steps are: FAT, SAT, DQ, IQ, OQ, PQ. According to the document though, major equipment and critical systems may require at least URS, DQ, IQ, OQ, PQ. Now, there may be some equipment which only requires IQ and OQ when those two qualification stages already indicate the performance of the equipment. It is explicitly mentioned that a qualification stage should be completed before the next one can start. An own paragraph addresses computerised systems requiring user and functional requirements specifications, design and configuration specifications. Stress tests are also required for those systems. Apart from that, it is referred to the respective WHO on computerised system validation. Not as clearly as in Annex 15, it is pointed out that the URS should be the starting point for the next qualification stages. Each qualification stage FAT, SAT, DQ, IQ, OQ, PQ is then addressed whereby FAT and SAT are listed as “should be” provisions where appropriate. In the course of OQ, worst-case studies are required and when measurements are made with a statistical approach, they should be described. Test results and continuous process verification (continued process verification is likely to be meant) should be collected over an appropriate period of time and /or within periodic reviews and monitoring to demonstrate that the equipment operates consistently.

The subchapter “Requalification” expressly mentions that full requalification is not required for the replacement of parts but a "like for like" replacement. Where items of equipment haven’t been used for a longer period of time, requalification may have to be considered.

Another subchapter on revalidation points out that where periodic revalidation is performed, this should be done within defined cycles. Periodic revalidation should be considered when small process changes occur over a longer period of time. The frequency and extent of revalidation should be determined on a risk-based approach taking into account historical data.

Within one paragraph only, the subchapter “Process validation” addresses the new approach and lapidary refers to other process validation guidelines. Another paragraph is dedicated to the traditional process validation and expressly underlines the necessity of validation when applying the traditional approach (e.g. through product quality reviews).

Chapter 11 and 12

The contents of Chapter 11 (Change Management – only 3 paragraphs) and Chapter 12 (Deviation Management, just one paragraph) are relatively low compared to Chapter 13 on calibration and verification which is considerably more extensive (one page). Here, the text highlights the necessity of regular calibration with traceable calibrated measuring devices. IQ is considered as appropriate qualification stage for calibration and verification of equipment. Whether devices or instruments should be calibrated should be based on an impact or risk assessment.


Although this guideline has been thought as superordinate guideline for other validation and qualification guidelines, it has – in its current draft status – relatively  little relation to the validation lifecycle approach as required in Annex 15 and FDA’s process validation guideline. There are no references to development which represents the basis for a modern validation approach. Still, periodic revalidation is basically required. Interestingly, references to the application of statistical methods – where appropriate – recur again and again. Another interesting aspect is the mention of “GEP” and “Commissioning“ in the glossary whereby no further explanation is given as for the V-Model. In the course of qualification tests, conditional approvals (as mentioned in Annex 15) are not intended. The specification according to which a "like for like" replacement requires requalification is very interesting. This is a contrast to PIC/S’s document “PI 006-3, Recommendations on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation, Cleaning Validation” in which a "like-for-like" replacement normally doesn’t require requalification. All in all, a closer alignment with other process validation guidelines would be preferable.

The draft can be commented on until July, 12th 2016. Delegates and former delegates of ECA events as well as ECA members have access to the Members Area where the draft of WHO Guidelines on Validation can be downloaded.

Media Fill - Interview Question

Q :What are Interventions in Aseptic manufacturing? and its various types…

Aseptic manufacturing has shown some brilliant improvements scientifically and technically over the past several years, however the pharmaceutical industry is still accepting the aseptic manipulations in the form of human interventions. In this post we are going to know the reason for interventions in aseptic manufacturing and followed by various types with examples.
Def: Interventions are the aseptic manipulations or activities that occur in the critical area (USFDA: Guidance for Industry Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice)

Q: Why interventions are required in aseptic manufacturing?

Generally, very few operations are often initiated in a click of a button but the majority of the activities involve human interventions to control some of the manual operations like adjusting the machine speed, adjusting fill weights, wiping up the spills, collecting the product samples, clearing the vial jams on the filling lines etc. Each of these processes involve human interventions with the sterilized components and the equipments and thus these shall be simulated as a part of media fill. This is because all interventions prior to or during aseptic manufacturing process poses a greater risk in terms of contamination and hence they shall be controlled and challenged via media fill.

Types of interventions:

There are 03 types of interventions

Inherent interventions:
Also called as routine interventions. These are the interventions that are regularly involved in a manufacturing process like aseptic connections, sterile ingredients addition (stoppers, vials), doors opening and closing etc.

Here is a list of inherent interventions which are needed to be performed in an aseptic operation.

1. Bouncing of vials
2. Clearing of rubber stoppers
3. QA/ Micro sampling
4. Rubber stoppers charging
5. Inprocess fill volume check
6. Door open , closed studies
7. Filling machine assembling
8. Removal of vials without rubber stoppers
9. Clearing of fallen vials on the line
10. Filling needle adjustments to prevent touching the vials
11. Adjustment of filling machine speed
12. Operator Fatigue
13. Shift Change over

Corrective interventions:
Also called as a no routine interventions where few kinds of interventions are not at all routinely involved in an aseptic operation. Interventions like power failure are falls under this category. We need to verify that the maximum possible time for which the entire aseptic area/system is aseptically controlled during the period of power failures.

Similarly, other interventions like increased man power in the aseptic process, fluctuations in area temperature falls under corrective interventions.

Worst case interventions:
This is an optional intervention which can be planned in an aseptic manufacturing process, however care must be taken to avoid contamination of the sterilized components while performing the study. Here is a list of studies which may be performed

a. Hold time of the stoppers, SS items, all other components for 48 hrs after sterilization
b. Manufacturing bulk and filtration bulk hold time
c. Depyrogenated vials before filling hold time

All these interventions that are described above has to be simulated as a part of every media fill to demonstrate that there is no risk involved in terms of contamination while performing such interventions.

Note: The duration of the media fill run should be determined by the time it takes to incorporate manipulations and interventions, as well as appropriate consideration of the duration of the actual aseptic processing operation. Interventions that commonly occur should be routinely simulated, while those occurring rarely can be simulated periodically

Care shall be taken to avoid simulating insignificant interventions in a media fill. For example

Touching the sterile components using non integral gloves
Entering the filling area without disinfecting the hand
There are quite a few number of warning letters issued by the FDA basis the insignificant interventions demonstrated in a media fill.

Validation in Pharma

Validation is a process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in production or testing maintains the desired level of compliance at all stages. In Pharma Industry it is very important apart from final testing and compliance of product with standard that the process adapted to produce itself must assure that process will consistently produce the expected results. Here the desired results are established in terms of specifications for out come of the process. Qualification of systems and equipment is therefore a part of process of validation. It is a requirement of food and drug, pharmaceutical regulating agencies like FDA's good manufacturing practices guidelines. Since a wide variety of procedures, processes, and activities need to be validated, the field of validation is divided into a number of subsections including the following:

Equipment validation
Facilities validation
HVAC system validation
Cleaning validation
Process Validation
Analytical method validation
Computer system validation
Packaging validation
Cold chain validation
Similarly, the activity of qualifying systems and equipment is divided into a number of subsections including the following:

Design qualification (DQ)
Component qualification (CQ)
Installation qualification (IQ)
Operational qualification (OQ)
Performance qualification (PQ)
The concept of validation was first proposed by two Food and Drug Administration (FDA) officials, Ted Byers and Bud Loftus, in the mid 1970s in order to improve the quality of pharmaceuticals. It was proposed in direct response to several problems in the sterility of large volume parenteral market. The first validation activities were focused on the processes involved in making these products, but quickly spread to associated processes including environmental control, media fill, equipment sanitization and purified water production.

The concept of validation was first developed for equipment and processes and derived from the engineering practices used in delivery of large pieces of equipment that would be manufactured, tested, delivered and accepted according to a contract The use of validation spread to other areas of industry after several large-scale problems highlighted the potential risks in the design of products. The most notable is the Therac-25 incident. Here, the software for a large radiotherapy device was poorly designed and tested. In use, several interconnected problems led to several devices giving doses of radiation several thousands of times higher than intended, which resulted in the death of three patients and several more being permanently injured.

In 2005 an individual wrote a standard by which the transportation process could be validated for cold chain products. This standard was written for a biological manufacturing company and was then written into the PDA's Technical Report # 39, thus establishing the industry standard for cold chain validation. This was critical for the industry due to the sensitivity of drug substances, biologics and vaccines to various temperature conditions. The FDA has also been very focused on this final area of distribution and the potential for a drug substances quality to be impacted by extreme temperature exposure.

Reasons for validation
FDA, or any other food and drugs regulatory agency around the globe not only ask for a product that meets its specification but also require a process, procedures, intermediate stages of inspections, and testing adopted during manufacturing are designed such that when they are adopted they produce consistently similar, reproducible, desired results which meet the quality standard of product being manufactured, such procedures are developed through the process of validation. This is to maintain and assure a higher degree of quality of food and drug products. Validation is "Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.". A properly designed system will provide a high degree of assurance that every step, process, and change has been properly evaluated before its implementation. Testing a sample of a final product is not considered sufficient evidence that every product within a batch meets the required specification.

Validation Master Plan
The Validation Master Plan is a document that describes how and when the validation program will be executed in a facility. Even though it is not mandatory, it is the document that outlines the principles involved in the qualification of a facility, defines the areas and systems to be validated and provides a written program for achieving and maintaining a qualified facility with validated processes. It is the foundation for the validation program and should include process validation, facility and utility qualification and validation, equipment qualification, cleaning and computer validation. The regulations also set out an expectation that the different parts of the production process are well defined and controlled, such that the results of that production will not substantially change over time.

The validation process

Figure 1: Traditional Qualification Process (adapted from the typical V-Model)
The validation scope, boundaries and responsibilities for each process or groups of similar processes or similar equipment's must be documented and approved in a validation plan. These documents, terms and references for the protocol authors are for use in setting the scope of their protocols. It must be based on a Validation Risk Assessment (VRA) to ensure that the scope of validation being authorised is appropriate for the complexity and importance of the equipment or process under validation. Within the references given in the VP the protocol authors must ensure that all aspects of the process or equipment under qualification; that may affect the efficacy, quality and or records of the product are properly qualified. Qualification includes the following steps:

Design qualification (DQ)- Demonstrates that the proposed design (or the existing design for an off-the-shelf item) will satisfy all the requirements that are defined and detailed in the User Requirements Specification (URS). Satisfactory execution of the DQ is a mandatory requirement before construction (or procurement) of the new design can be authorised.
Installation qualification (IQ) – Demonstrates that the process or equipment meets all specifications, is installed correctly, and all required components and documentation needed for continued operation are installed and in place.
Operational qualification (OQ) – Demonstrates that all facets of the process or equipment are operating correctly.
Performance qualification (PQ) – Demonstrates that the process or equipment performs as intended in a consistent manner over time.
Component qualification (CQ) – is a relatively new term developed in 2005. This term refers to the manufacturing of auxiliary components to ensure that they are manufactured to the correct design criteria. This could include packaging components such as folding cartons, shipping cases, labels or even phase change material. All of these components must have some type of random inspection to ensure that the third party manufacturer's process is consistently producing components that are used in the world of GMP at drug or biologic manufacturer.
There are instances when it is more expedient and efficient to transfer some tests or inspections from the IQ to the OQ, or from the OQ to the PQ. This is allowed for in the regulations, provided that a clear and approved justification is documented in the Validation Plan (VP).

Figure 2: OPQ Validation Process (adapted from the typical V-Model)
This combined testing of OQ and PQ phases is sanctioned by the European Commission Enterprise Directorate-General within ‘Annex 15 to the EU Guide to Good Manufacturing Practice guide’ (2001, p. 6) which states that:

"Although PQ is described as a separate activity, it may in some cases be appropriate to perform it in conjunction with OQ."

Computer System Validation
This requirement has naturally expanded to encompass computer systems used both in the development and production of, and as a part of pharmaceutical products, medical devices, food, blood establishments, tissue establishments, and clinical trials. In 1983 the FDA published a guide to the inspection of Computerized Systems in Pharmaceutical Processing, also known as the 'bluebook'. Recently both the American FDA and the UK Medicines and Healthcare products Regulatory Agency have added sections to the regulations specifically for the use of computer systems. In the UK, computer validation is covered in Annex 11 of the EU GMP regulations (EMEA 2011). The FDA introduced 21 CFR Part 11 for rules on the use of electronic records, electronic signatures (FDA 1997). The FDA regulation is harmonized with ISO 8402:1994, which treats "verification" and "validation" as separate and distinct terms. On the other hand, many software engineering journal articles and textbooks use the terms "verification" and "validation" interchangeably, or in some cases refer to software "verification, validation, and testing (VV&T)" as if it is a single concept, with no distinction among the three terms. The General Principles of Software Validation (FDA 2002) defines verification as "Software verification provides objective evidence that the design outputs of a particular phase of the software development life cycle meet all of the specified requirements for that phase." It also defines Validation as "Confirmation by examination and provision of objective evidence that software specifications conform to user needs and intended uses, and that the particular requirements implemented through software can be consistently fulfilled". The software validation guideline states: “The software development process should be sufficiently well planned, controlled, and documented to detect and correct unexpected results from software changes." Annex 11 states "The validation documentation and reports should cover the relevant steps of the life cycle."

Weichel (2004) recently found that over twenty warning letters issued by the FDA to pharmaceutical companies specifically cited problems in Computer System Validation between 1997 and 2001.

Probably the best known industry guidance available is the GAMP Guide, now in its fifth edition and known as GAMP5 published by ISPE (2008). This guidance gives practical advice on how to satisfy regulatory requirements.

Scope of Computer Validation
The definition of validation above discusses production of evidence that a system will meet its specification. This definition does not refer to a computer application or a computer system but to a process. The main implications in this are that validation should cover all aspects of the process including the application, any hardware that the application uses, any interfaces to other systems, the users, training and documentation as well as the management of the system and the validation itself after the system is put into use. The PIC/S guideline (PIC/S 2004) defines this as a 'computer related system'. Much effort is expended within the industry upon validation activities, and several journals are dedicated to both the process and methodology around validation, and the science behind it.

Risk Based Approach To Computer Validation
In the recent years, a risk-based approach has been adopted within the industry, where the testing of computer systems (emphasis on finding problems) is wide-ranging and documented but not heavily evidenced (i.e. hundreds of screen prints are not gathered during testing). Annex 11 states "Risk management should be applied throughout the lifecycle of the computerised system taking into account patient safety, data integrity and product quality. As part of a risk management system, decisions on the extent of validation and data integrity controls should be based on a justified and documented risk assessment of the computerised system."

The subsequent validation or verification of computer systems targets only the "GxP critical" requirements of computer systems. Evidence (e.g. screen prints) is gathered to document the validation exercise. In this way it is assured that systems are thoroughly tested, and that validation and documentation of the "GxP critical" aspects is performed in a risk-based manner, optimizing effort and ensuring that computer system's fitness for purpose is demonstrated.

The overall risk posed by a computer system is now generally considered to be a function of system complexity, patient/product impact, and pedigree (Configurable-Off-The-Shelf or Custom-written for a certain purpose). A lower risk system should merit a less in-depth specification/testing/validation approach. (e.g. The documentation surrounding a spreadsheet containing a simple but "GxP" critical calculation should not match that of a Chromatography Data System with 20 Instruments)

Determination of a "GxP critical" requirement for a computer system is subjective, and the definition needs to be tailored to the organisation involved. However, in general a "GxP" requirement may be considered to be a requirement which leads to the development/configuration of a computer function which has a direct impact on patient safety, the pharmaceutical product being processed, or has been developed/configured to meet a regulatory requirement. In addition if a function has a direct impact on GxP data (security or integrity) it may be considered "GxP critical".

Product life cycle approach in validation
Validation process efforts must account for the complete product life cycle, including developmental procedures adapted for qualification of a drug product commencing with its research and development phase, rationale for adapting a best fit formula which represents the relationship between required outputs and specified inputs, and procedure for manufacturing. Each step is required to be justified and monitored in order to provide a good quality food and drug product. The FDA emphasizes the product life cycle approach in its evaluation of manufacturer regulatory compliance as well.