Introductory Validation and the Cleanroom

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

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

Can anyone give examples of validation?

Validation organization

• As a department validation should cover

• Process

• Equipment

• Facilities

• Computer

• Cleaning

Steps in developing Validation are

• 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

• 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

Qualification Testing

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

• Observations are documented.

What needs to be tested?

• Almost everything needs to be tested

• How does one know?– Observe the equipment in operation– Major components are typical.

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

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.

The Cleanroom

A room that is clean

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.

Who uses clean rooms

• Electronics

• Semiconductor

• Optics

• Biotechnology

• Pharmacy

• Medical Devices

• Food and Drink

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.

Particles

• Human Hair (100um)

• Visible particle (50um)

• E. coli (A bacteria) 1um

• Particles we typically measure 0.5um

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

Also limits on microbe contam

Grade Air sample Settle plates

A <1 <1

B 10 5

C 100 50

D 200 50

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

Other Conditions

• Good personal hygiene

• Cosmetics

• Jewelery

• Smokers particles and out gassing

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

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

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.