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Good Manufacturing Practice

GMP
(PT912)
Processes validation and
contamination control

Dr / Maha Mostafa
Ghalwash
Department of Pharmaceutics
and drug manufacturing
 The FDA defines process validation as:
“The collection and evaluation of data, from the process
design stage through commercial production, which
establishes scientific evidence that a process is capable of
consistently delivering quality product.”

Process Validation is Key important factor for the Pharmaceutical Industry to

maintain consistent quality in product which claimed by the manufacturer

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• The United States Food and Drug Administration (USFDA) guidance
discusses general principles and practices that manufacturers can
use to validate manufacturing processes. It covers different categories of
drugs such as human, veterinary, and biological or biotechnology
products.
• A voluntary organization of regulatory agency officials called the
Global Harmonization Task Force (GHTF) provided process
validation guidelines for medical devices
• The international medical device regulators forum (IMDRF) replaced
the GHTF, taking over its mission to standardize medical device
regulations around the world.
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 Stages of Stages of Process Validation
Process Validation

Stage3
Stage 1 Stage 2
Continued Process
Process Design Process Qualification
Verification

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Stage 1: Process Design
During this stage, based on knowledge gained through development and scale-
up activities.
• The manufacturing process is defined
• The validation team should have a clear grasp of how the process works.
• Consider the following sources and methods to capture process information:

➢ Product development activities

➢ -Functionality and limitations of production equipment
➢ -Predicted contributions to variability
➢ -Design of experiment (DOE) studies
➢ -Risk analysis tools
➢ -Experiments or demonstrations at laboratory or pilot scale
➢ -Computer-based or virtual simulations

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Stage 2: Process Qualification
During this stage
• Determine if the process is effective for quality commercial production
• Everything is according to the requirements of current good
manufacturing practice (CGMP).

Stage 3: Continued Process Verification

• Ongoing assurance that the validated process remains in such control
state during routine production. Continued process verification often
incorporates the use of Statistical Process Control (SPC),
• Process validation is categorized according to the time it is performed in
relation to the production schedule

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 Types of Process Validation
Process Validation
Type 1
Prospective Validation
Type 2
Retrospective Validation
Type 3
Concurrent Validation
Type 4
Revalidation 8
Type 1: Prospective Validation (Premarket validation)

• Starts before commencing routine production (experimental plan, protocol)

• For any product will be manufactured with a new formula or within a new
facility.

Type 2: Retrospective Validation

➢ It is conducted only when the manufacturing process has not formally
undergone a documented validation.
➢ With the use of historical data and trends analysis to provide evidence that
the process is at a state that it is intended to be in.
➢ It is no longer an acceptable approach to process validation because any
product should have already been validated before its commercial
distribution
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Type 3: Concurrent Validation
• It is done during regular pharmaceutical production to demonstrate that
the process performs at the level.
• Concurrent validation is still an acceptable approach to process validation
under certain circumstances (e.g. manufacturing medically necessary
drugs in coordination with the USFDA to prevent a short supply),
Type 4: Revalidation
• More widely used for medical devices than drug products.
• It is executed when prospective validation reaches a conclusion that the
manufacturing process is unable to produce the product
• a criteria for revalidation may be indicated in the original validation
protocol.

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What is Contamination?
contaminating or polluting, including either intentionally or accidentally,
unwanted, and potentially dangerous substances or factors. Also, simply the
state of being contaminated (with something you don’t want and don’t expect
to be present)

Contamination can be:

• Physical – e.g. dust, fibres, human skin cells, particles
• Chemical – e.g. cleaning agent residues, process gasses, molecules, vapour
• Microbiological – e.g. bacteria, virus, yeast, mould

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 Cross-contamination
Contamination of a material or of a product with another material
or product.

Aseptic Processes includes:-

• Floors, walls, and ceilings of smooth and hard surfaces.
• Temperature and humidity control
• Filtered air supply through high efficiency particulate air filters(HEAP filter)
under positive pressure, regardless of whether flow is laminar or non-
laminar

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• System for cleaning and disinfecting the room and equipment used
to control the aseptic conditions.

• System for maintaining any equipment used to control the aseptic

condition

• Operations relating to the manufacture, processing and packaging

of biological preparations (e.g. from living organisms), certain
antibiotics (e.g. Penicillin), certain hormones or cytotoxic drugs
should be performed in facilities separate from those used for other
drug products.

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• Internal wall surfaces (all surfaces in processing areas) should be:
• Impervious, nonporous, non-shedding, and be free of cracks, dirt
retaining holes, and flaking paint.
• They should be washable and able to resist repeated applications of
cleaning and disinfecting agents.

• Floors should be:-

• Even-surfaced, be free from cracks,
• Allow for easy cleaning and removal of any spillages.
• They should conform to the requirements similar to those indicated
for walls above. They need to be tough.

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Doors and window-frames should be:-
• All have a smooth, hard, impervious finish, and should
close tightly.

• Window and door frames should be fitted flush, at

least on sides facing inward to processing areas, e.g. a
door or window between a transit corridor and a
processing room may need only to be flush fitted i.e.,
no window ledges, etc., on the processing side.
• A door or window fitted between two processing rooms
should be flush fitted on both sides.
• Any windows from production areas to the outside
should be tightly sealed and not normally open.
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