Introductory Validation and the Cleanroom

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Introductory Validation and the Cleanroom
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What we see

• FDA regulations require Documentation
• These regulations do not provide Guidelines on
  how specifically to product the documentation
• It is left up to the specific companies to
  design their own documentation system.
• This includes the process of validation

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Validation and Qualification

• Validation contains premises from which a
  conclusion can be logically derived
• Qualification is a condition or circumstance that
  must be met or complied with

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Can anyone give examples of validation?
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Validation organization

• As a department validation should cover
• Process
• Equipment
• Facilities
• Computer
• Cleaning

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Steps in developing Validation are
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• Setup a validation dep.
• Write a validation plan
• Write policies, sops and admin procedures
• Establish change control board
• Establish document reviewers and approvers

• Establish document distribution
• Identify equipment to validate and make a list
• Assign protocols to all functions
• Validate most critical equipment first

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• Assign equipment numbers
• Assign protocol numbers
• Assign change control numbers
• Change protocols
• Perform commissioning at the original equipment
  manufacturer

• Write and execute qualification protocols
• Deficiencies
• Deviations
• Addendums
• Archiving
• Requalifiction
• Internal audits
• FDA audits

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Qualification Testing

• Written qualification protocols are prepared that
  specify the tests to be conducted and the data to
  be collected.
• Observations are documented.

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What needs to be tested?

• Almost everything needs to be tested
• How does one know?
• Observe the equipment in operation
• Major components are typical.

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What level of testing is required

• A standard for equipment testing has not been
  made in the pharmaceutical industry
• Object is to gain confidence that the equipment
  is operating under a state of control. Some
  include
• Minimum/maximum operating ranges
• Worst case

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How much testing is Enough?

• The number of repetitions of a process step
  during qualification should be based on
  statistical significance.
• Conventional wisdom
• Once is chance
• Twice is nice
• Three times is validation
• Sorry but we need to use Statistics.

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The Cleanroom

• A room that is clean

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ISO standard 14644-1

• A room in which the concentration of airborne
  particles is controlled, and which is constructed
  and used in a manner to minimize the
  introduction, generation, and retention of
  particles inside the room and in which other
  relevant parameters, e.g. temperature, humidity,
  and pressure, are controlled as necessary.

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Who uses clean rooms

• Electronics
• Semiconductor
• Optics
• Biotechnology
• Pharmacy
• Medical Devices
• Food and Drink

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2 major types of cleanrooms

• Turbulently ventilated room
• (diffuses)
• 20 changes per hr min
• Unidirectional flow
• Air sweeps across the room (80ft/min)
• Both have clean air on top, moving to the bottom.

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Particles

• Human Hair (100um)
• Visible particle (50um)
• E. coli (A bacteria) 1um
• Particles we typically measure 0.5um

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Some Numbers of ISO classes limits (particles/m3
of air)

• Class 1 10
• Class 2 100
• Class 3 1000
• Class 4 10,000
• Class 5 100,000

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Also limits on microbe contam
Grade Air sample Settle plates
A lt1 lt1
B 10 5
C 100 50
D 200 50
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Some Cleanroom Disciplines

• A walking person generates 1,000,000 particles
  permin (0.5um)
• Some conditions will preclude work in a cleanroom
• Skin conditions (dermatitis)
• Respiratory conditions
• Microfloura
• Allergies

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Other Conditions

• Good personal hygiene
• Cosmetics
• Jewelery
• Smokers particles and out gassing

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Control of air transfer

• Enter and exit through change areas
• Do not leave doors open
• Open and close doors quickly
• Doors usually open inward in production
  facilities
• Respect the airlocks

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Behavior

• Sitting 100k, moving 1milK, walking 5milk
• Positioning so do not drip on product
• Use no touch techniques
• Do not support materials on body
• Do not talk over product

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Entry and Exit of Personnel

• Hygiene
• Cloths, makeup and jewlery
• Wash before and after
• Check yourself and check others
• Are you protecting product or yourself.