Friday, April 3, 2009

protocols for validation

Ø The validation protocol format should be simple and clear & provide information for the incorporation of supportive documentation.
Ø The protocol should include the critical specifications, method of validation, process validation, equipment used etc. The protocol must include:
· Purpose of validation
· Operation being validated
· Major equipment involve
· Components used
· Parameters and ranges
· Sampling and testing plans
· Acceptance and rejection criteria (specifications)
· Recoveries and their addition
· Deviations and corrections
· Review and approvals
· Action to be taken by failure
· Responsible person and functions
2. Validation of Intervals between the Processes
3. Confidence built Intervals

4. The responsibility of approving the protocols for testing of raw materials and finish products and their specifications is already with the manager quality control and production related processes & parameters are with production manager, the testing parameters and specification protocol are already present but they need streamlining.
Validation depends upon validation of critical process is mandatory while non critical process is optional;
Validation of critical processes (Those processes which does effect the quality directly)

Critical Processes
à Manufacturing process
à Cleaning process
à Weighing / Measuring
à Compression / capsule / Encapsulation
à Filling / Packaging / Labeling
Manufacturing Process
à Solid dosage forms
à Semi solid and liquid dosage forms
Solid dosage forms Tablets (Critical Processes)

Validation Protocol
Critical Processes

Written By:



Approved By:



1. Objective:

2. Scope:

3. Responsibility:

Process Step
Control Variables
Measured Responses
Blending time
Load size
Order of addition
Blend uniformity
Load size
Amount of granulating agent
Solvent addition rate
Granulation time
Initial temperature
Load size
Drying temperature program
Air flow program
Drying time
Cooling time
Moisture content

Screen type
Screen size
Feed rate
Granule size distribution
Loose density
Packed density
Load size
Blending time
Blend uniformity
Flow characteristics
Particle size distribution
Compression rate
Granule feed rate
Pre-compression force
Compression force
Weight variation
Disintegration time
Dosage form uniformity

Document No.:

Date Started:

Date Completed:

Page 1 of 1

A) Mixing or Blending
(Mixing blending technique, Mixing blending speed, Mixing or blending time)
a) Drug uniformity
b) Excipients uniformity
(Besides drug uniformity, lubricant uniformity, addition speed or uniformity of distribution, colors addition and uniformity)
c) Addition of lubricant
B) Wet Granulation
(Binder addition, Binder concentration, amount of binder solution/granulation solvent and addition rate)
a) Mixing time, Granulation end point
C) Screen Sizing
a) Screen sizing speed
b) Feed rate
D) Drying
Drying is used for better compression
What type of drying is required for the formulation? justification is required.
(three techniques are applied )
1. Tray drying
2. Fluid bed drying
3. Microwave
After drying moisture content must be determined
Over drying of granules can result in poor hardness and friability
Less drying result in high moisture contents which could result tablet sticking to punch surfaces and poor chemical stability.

1. Inlet / outlet temperature
2. Air flow
3. Timing
4. Moisture uniformity
E) Milling (to reduce the size of granules)
(mill type, screen size, mill speed, feed rate)
F) Tablet Compression
Ø (Tooling, (tablet shape)
Ø Compression speed
Ø Compression / ejection force
G) Tablet coating
Ø Tablet properties (Shape, hardness etc)
Ø Equipment type (conventional or perforated pan, fluid bed coaters)
Ø Coater load
Ø Pan speed
Ø Spray guns
Ø Application of spray rate
Ø Tablet flow
Ø Inlet / outlet temperatures
Ø Air flow
Ø Coating solution
Ø Coating weight
SOP’s for Validation
SOP’s for Coating
Flow Chart (Verification, Approval)
Equipment type
Pan (Automatic, Semi automatic, Manual)
Speed (Adjustable, Constant)
Pan Size (PQ) (Loading Capacity, Actual load)
Spray Gun
Angle of Fixation, Spray Nozzle Size, Even Distribution
Spray Ratio
Spray fast will cause to wet the tablet

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