Validation Approach

The water facility and HVAC system of the manufacturing plant is designed to minimize the chemical, microbial
and other contaminants that may affect the process of manufacture and quality of the Paracetamol Pyrenil© tablets.
Prospective approach is carried out since the risks that may affect the product quality are evaluated and investigated.
Acceptance Criteria

Design Qualification (DQ) and Installation Qualification (IQ)

Acceptance Criteria
Criteria Rationale
Ensure that the system meets all the requirements, as
specified in the user requirement specification (URS), and
capacities as specified by the designer or developer.
A well-designed air handling system must not only be
properly designed, but also properly installed,
qualified and maintained (sealed ducts, tight filters).
There should be no failure of a supply air fan, return air
fan, exhaust air fan or dust extract system fan.
Failure can cause a system imbalance, resulting in a
pressure cascade malfunction with a resultant air flow
reversal
Air should be dried with a chemical drier (e.g. a rotating
desiccant wheel which is continuously regenerated by
means of passing hot air through one segment of the
wheel). The desiccant should be ensured to be efficient to
remove humidity from air.
It is necessary for humidity sensitive products to have
a very dry air on the manufacturing rooms.
Possible additional components that may be required
should be considered depending on the climatic conditions
and locations.
These may include items such as dust eliminators on
air inlets in arid and dusty locations. These will
prevent the entry of unwanted particles in the supply
air from the environment.
Dampers are present to control pressure differentials. As
filters get dirty the system pressure losses increase, and if
airflow is not regulated, the flow decreases and pressure
differentials change. This could cause flow reversal and
cross-contamination.
The components associated with the flow rate control
are essential, as they allow adjustment of the air
volumes supplied to the rooms, which in turn forms
the base for a pressure differential concept.
As filters get dirty the system pressure losses increase,
and if airflow is not regulated, the flow decreases and
pressure differentials change. This could cause flow
reversal and cross-contamination.
Filters are certified by the suppliers through
challenge/efficiency test and proper installation should
follow.
These can avoid the presence of leaks that can lead to
poor quality of the air produced and the disrupted air
system of the facility.
Filters should be properly maintained and replaced. Testing
should be done to ensure that filters are working properly,
not clogged and still able to filter the desired particle sizes.
Filters are one of the main components, as they
determine the size of airborne particles that pass
through them, and thus the hygiene class.
As filters get dirty the system pressure losses increase,
and if airflow is not regulated, the flow decreases and
pressure differentials change. This could cause flow
reversal and cross-contamination.
If filters are not properly maintained, micro-organisms
may grow through the filters and be carried towards
the production rooms
Prefilters should always be checked and tested for their
capability to filter the indicated particulate sizes
These are used to protect the finer filters, thus
extending their life cycles, and making them less
prone to clogging.
If filters are not properly maintained, microorganisms
may grow through the filters and be carried towards
the production rooms
Inspectors must verify that ducts do not have internal
insulation as this is a great source of contamination.
Ducts transport the air from the air handling units to
and from the rooms. Any leakages may cause
contamination.
Cooling units of the AHU should be free of stagnating
water and routine sanitization is done.
Stagnating water or condensed water can bring
bacterial growth which can contaminate the filters,
pass through them (depending on their retention
properties) and end up contaminating production
areas.
There should be no risk of contamination or cross-
contamination (including by fumes and volatiles) due to
recirculation of air through the ducts and AHU
If particles and unwanted materials are present in the
recirculated air, contamination is of high risk for the
products. With this, filters and other components of
the AHU should always be cleaned and monitored if
they are functioning properly.
HEPA filters (EN1822 H13) are required for the air supply
stream for recirculation systems. It is not required in a
single product facility with no risk of cross-contamination
and in a facility where dust is not generated.
HEPA filters can remove contaminants and thus
prevent cross-contamination upon recirculation of the
air supply.
Training should be provided to personnel after installation
of the system, and should include operation and
maintenance
People are the ones that will be responsible for the
maintenance and monitoring of the operations of the
HVAC system. Knowledge and training on the
handling of the equipment and machine are important.
An automated monitoring system should be capable of
indicating any out-of-specification condition without delay
by means of an alarm or similar system.
The presence of a warning/alarm system is important
to alert the personnel immediately about a failure so
that necessary corrective measures may be taken
ensuring the qualification of the system.
The supply air outlets must be placed at the ceiling level
while the return air must be at the floor level.
Air turbulence in the space can cause particulates
which have settled onto the floor and work surfaces to
become re-entrained in the air.




Operational Qualification (OQ) and Performance Qualification (PQ)
Parameter Acceptance criteria Criteria Rationale
Room Temperature The areas are designed to provide
room temperatures from 19°C and
25°C with a control point of 22°C.
The temperature may be adjusted to
suit the protective clothing worn by
the operators.
Temperature control is important for ensuring
product quality, maintaining environmental
control and conserving energy.
Relative Humidity RH of 50 ± 5% Automatic control of the RH is essential for
maintaining continued product quality. Control
of humidity is necessary for personal comfort, to
prevent corrosion, to control microbial growth,
and to reduce the possibility of static electricity.
Control Airborne
Particles: Cleanroom
type
Class 100,000 The cleanroom classification dictates the quality
of air cleanliness to avoid or prevent
contamination.
Control Airborne
Particles: Maximum
viable organisms and
maximum particle size
2.5 per ft
3

0.5 micron or above
Clean rooms have a controlled level of
contamination specified by the number of
particles at a specified particle size.
Room Pressure
Differentials: Space
Pressurization
0.05 inch-w.g / 12.5 Pa The positive pressurization of cleanrooms is
desired in order to ensure containment and to
prevent flow reversal as well as infiltration of air
from adjacent areas.
Air flow rate Minimum 20 air changes/hr Qualification for air flow rate is significant to
achieve desired particulate cleanliness levels.
% HEPA Coverage 10-20% The qualification for HEPA filters may help in
preventing contamination while ensuring that the
desired room cleanliness is achieved at the same
time.
Air Velocity 5-10 feet per minute (FPM) Air flow velocity should be kept within limits to
avoid noise and unacceptable friction loss and
energy consumption.
Air flow pattern Non-unidirectional with the supply air
outlets at the ceiling level and the
return air at the floor level
Air turbulence in the space can cause particulates
which have settled onto the floor and work
surfaces to become re-entrained in the air.





Acceptance Criteria DQ IQ OQ PQ
HVAC system meets all requirements and capacities as specified by USR and
developer/designer.
 

There shall be no failure in any system fan.  
Air shall be dried by a chemical desiccant which efficiently removes air humidity.  
Additional components such as dust eliminators on air inlets in arid and dusty
locations shall be in place to prevent the entry of unwanted particles in the supply
air.
 

Dampers shall be present to prevent flow reversal and cross-contamination.  
Filters used are certified and installed properly.  
Filters should be properly maintained and replaced.  
Prefilters should be regularly checked and tested for efficiency.  
Ducts should not have internal insulation to avoid contamination.  
Cooling units of AHU should be free of stagnant water and should be routinely
sanitized.
 

There should be no risk of contamination or cross-contamination due to
recirculation of air through the ducts and AHU.
 

HEPA filters (EN1822 H13) are required for the air supply stream for
recirculation systems.
 

Personnel should be properly trained on the operation and maintenance of the
system.
 

An alarm or a similar system should be in place to automatically monitor out-of-
specification conditions.
 

Air outlets should be properly situated in the facility.  
The areas are designed to provide room temperatures from 19°C and 25°C with a
control point of 22°C.

 
Relative humidity should be maintained within 50 ± 5% RH.  
Rooms are classified as Class 100,000.  
The population of viable organisms with greater than or equal to 0.5 micron in
size should be no more than 2.5 per cubic feet.

 
Room pressure differentials are kept within 0.05 inch water gauge or 12.5 pascal.  
Air flow should have a minimum of 20 air changes/hr  
The HEPA filter should cover 10-20% of the air.  
Air velocity should be maintained within 5-10 feet/min  
Air flow pattern should be non-unidirectional with the supply and return air
outlets are located at the ceiling level and at the floor level, respectively.
 
 