1. VALIDATION OF UTILITIES
Prepared by : Masarrat M. Khan.
Designation: Assistant Professor
College: YB. Chavan College of Pharmacy,
Aurangabad
2. Points mentioned in syllabus
• Validation of water system-for production of DM
water, distilled water.
• Validation of Air handling units: classification of
environment (class 100, 10,000, 1,00,000)
• Performance qualification and parameters of
cleanliness such as no. of airborne particles,
microbes filter integrity test of HEPA filter, air
velocity, air flow pattern, no of air changes,
pressure differentials, etc.
VALIDATION OF UTILITIES
3. CONTENTS
• INTRODUCTION
• PURPOSE OF VALIDATION
• STRATEGY OF VALIDATION
a) Validation concept
b) Validation life cycle
c) Steps of Validation
d) Control during routine operation
5. PURPOSE OF VALIDATION
• High quality water and air are essential for
manufacture of pharmaceuticals.
• Water is most commonly used as raw material in
pharmaceutical manufacturing of all dosage forms
for cleaning manufacturing equipment, and is also
used as a major component which constitutes
injectable products.
• It is one raw material that is usually processed by
the pharmaceutical manufacturer prior to use
because it cannot be used as supplied by the
vendor.
6. • Water should be regarded as one of major raw
materials for the manufacture of pharmaceuticals
weather or not it remains as a component of
finished dosage form or is eliminated during the
manufacturing process.
• Water is thus an important raw material in GMP
and in validating the manufacturing process.
• The air supplied in the manufacturing area or the
air present in the environment of manufacturing
area always contacts with the pharmaceuticals and
the quality of air influences the quality of
pharmaceuticals manufactured particularly in
their cleanliness, particulates and microbial
quality.
7. • Temperature and humidity in the
manufacturing environment also influence the
quality of pharmaceuticals manufactured.
• The importance of air quality and air handling
system are described in CFR 211-46 as a part
of GMP.
• The USP identifies several grades of water that
are acceptable for use in pharmaceutical and
also defines the quality of the environment or
the quality of air for the manufacturing of
pharmaceuticals according to its criticality.
8. • Water treatment and air handling systems are
highly dynamic, and careful attention has to be
paid to their operation, even though this may
sometimes be somewhat unreliable.
• The purpose of validation is to demonstrate the
capability of the water treatment and air handling
system to continuously supply the required
quantity of water and air with specified quantity
attributes.
• Validation provides the system owner with the
means of assessing when a water treatment and
air handling system is operating outside establish
control parameter limits and provides a means for
bringing the system back into state of control.
10. VALIDATION CONCEPT
• The basic strategy behind the validation is to prove the
performance of processes or systems under all conditions
expected to be encountered during future operations.
• To prove the performance one must demonstrate the
(document) that the processes or systems consistently
produce the specified quantity and quality of water and air
when operated and maintained according to specified
written operating and maintenance procedures.
• Validation means proving
1. Engineering design.
2. Operating procedures and acceptable ranges for control
parameters.
3. Maintenance procedures.
11. • To accomplish this the system must be
carefully designed, installed and tested during
and after constructions and therefore for a
prolonged period of time under all operating
conditions.
• Variations in daily, weekly and annual systems
usage patterns must be validated.
• Systems with ion exchange resins (deionizers)
must be at least partially shut down to generate
the resin when the chemical quality of the
treated water drops below a specified level.
12. • For air handling system same kinds of issues
exsit.
• Clean room should be maintained at their required
cleanliness level, even during the time of no
manufacturing operation.
• If the cleanliness is broken or the air handling
system stops, the whole clean area has to be made
clean according to the initial validation procedure
and assessment.
• Water treatment and air handling system must be
validated under all of these normal operating
conditions in order to prove the adequacy of the
engineering design and the effectiveness of the
operating, control and maintenance procedures.
14. DETERMINATION OF QUALITY
ATTRIBUTES
• Performing the validation means defining the
quality attributes i.e. gaining a clear
understanding of the required quality and
intended use.
• It is the most important issue and should be
determined before starting the validation.
• Without defining the required quality attributes
we cannot establish validation protocols,
which are the basis of all validation studies.
15. THE VALIDTION PROTOCOL
• The validation protocol is defined as “A
written plan stating how validation will be
conducted and defining acceptance criteria.
For example: the protocol for
manufacturing process identifies process
equipment, critical process
parameters/operations ranges, product
characteristics, sampling and test data to be
collected, number of validation runs, and
acceptable test results”.
16. • All the protocols whether for IQ, OQ of a new
equipment or for validating a new process,
have the same basic format.
• The objective session describes the reasons for
conducting the validation study as well as the
results to be achieved.
• The scope session includes, what is to be
included and excluded from the study is
specified establishing the boundaries for the
study.
19. • Establishing standards for quality attributes of
water and air to manufacture pharmaceuticals
• Defining system and subsystem suitable to
produce the desired water and air by
considering the quality grades of water and air.
• Designing equipments, controls and
monitoring technologies.
• Establishing standards for operating
parameters of the selected equipment of the
system.
STEPS IN VALIDATION
20. • Continued…..
• Developing an IQ stage consisting of instrument
calibration, inspection to verify that the drawings
accurately depict the as-built configuration of the
system and special tests to verify that the
installation meets the design requirements.
• These items include pipe and instrument
drawings, air pressure differentials, air velocities,
and airflow patterns.
• Developing an OQ stage consisting of test and
inspections to verify that the equipment, system
alerts, and control are operating.
21. • Continued…..
• Establishing alert and action levels for operational
standards and routine controls.
• Developing a prospective PQ stage to confirm
appropriateness of critical process parameters
operating ranges.
• Supplementing a validation maintenance program
(also called continuous validation life cycle) that
includes a mechanism to control changes to the
system and establishes and carries out scheduled
preventive maintenance, including recalibration
of instruments.
Instituting a schedule for periodic review of the
system performance and requalification.
• Completing protocols and documneting step 1 to
10.
22. STEPS DURING ROUTIEN OPERATIONS
• VALIDATION AND CHANGE CONTROL:
• Once the validation is completed, the standard
operating procedures (SOPs) are formalized.
• Routine operations should be performed
according to the established SOP.
• Any proposed changes should be evaluated for
their impact on the whole system.
• Revalidation and evaluation should be performed
depending upon the impact that might be caused
by the changes.
23. • Alert and action levels:
• Validated and established systems should be
periodically monitored to confirm that they
continue to operate within their design
specifications and consistently produce water
and air of acceptable quality.
STEPS DURING ROUTIEN OPERATIONS
