1. What is an SOP ?

A Standard Operating Procedure (SOP) is a certain type of document that describes in

a step-by-step outline form how to perform a particular task or operation. Everyone
in a company must follow the same procedures to assure that tasks are performed
consistently and correctly. Most companies have a wide variety of SOPs that describe
how to do different tasks. In many companies technicians and operators are trained
in how to follow individual SOPs and their training record specifies which SOPs they
are trained on and are authorized to use.
2. What is 21 CFR part 11 ?
Title 21 CFR Part 11 of the Code of Federal Regulations deals with the Food and Drug
Administration (FDA) guidelines on electronic records and electronic signatures in the
United States. Part 11, as it is commonly called, defines the criteria under which
electronic records and electronic signatures are considered to be trustworthy, reliable
and equivalent to paper records
3. What are user requirements ?
User Requirements Specification describes what users require from the System. User
requirement specifications are written early in the validation process, typically before
the system is created. It is written by the System Owner and End Users, with input
from Quality Assurance. Requirements outlined in the URS are usually tested in the
Performance Qualification. User Requirements Specifications are not intended to be a
technical document; readers with only a general knowledge of the system should be
able to understand the requirements outlined in the URS.
4. What is a validation plan ?
Validation Plans define the scope and goals of a validation project. Validation plans
are written before a validation project and are specific to a single validation project.
Validation Plans can include:
Deliverables (Documents) to be generated during the validation process
Resources/Departments/Personnel to participate in the validation project
Time-Line for completing the validation project
5. What is an IQ document ?
Installation Qualifications are a collection of test cases used to verify the proper
installation of a System. The requirement to properly install the system was defined
in the Design Specification. Installation Qualifications must be performed before
completing Operational Qualification or Performance Qualification.
6. What is an OQ Document ?
Operational Qualifications are a collection of test cases used to verify the proper
functioning of a System. The operational qualification tests requirements defined in
the Functional Requirements. Operational Qualifications are usually performed before
the system is released for use.
7. What is a PQ Document ?
Performance Qualifications are a collection of test cases used to verify that a System
performs as expected under simulated real-world conditions. The performance
qualification tests requirements that were defined in the User Requirement
Specification (or possibly the Functional Requirements). Due to the nature of
performance qualifications, these tests are sometime conducted with power users as
the system is being released.
8. What is a Validation Summary Report ?
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Validation Summary Reports provide an overview of the entire validation project.

When regulatory auditors review validation projects, they typically begin by
reviewing the summary report. The validation summary report should include:
A description of the validation project
All test cases performed, including if those test cases passed without issue
All deviations reported, including how those deviations were resolved
9. What is a Change Request ?
Change Control is a general term describing the process of managing how changes
are introduced into a controlled System. In validation, this means how changes are
made to the validated system. Change control is required to demonstrate to
regulatory authorities that validated systems remain under control after system
changes. Change Control systems are a favorite target of regulatory auditors
because they vividly demonstrate an organization capacity to control its systems.
Q. Why water for pharmaceutical use is always kept in close loop in
continuous circulation ?
A. Water is a best medium for many microorganisms, microorganism can be a highly
pathogenic which causes serious diseases(many diseases are water born), these
pathogens infect after consumption of contaminated water, microorganisms tend to
settle on a surface if water is allowed to stand in a stagnant position for few hours,
these settled microorganism form a film over the surface of vessel and piping, such
film formed by microorganisms is also called as biofilm, biofilms are very difficult of
remove, once a biofilm is formed at a particular point then that point may form a
biofilm again even after cleaning very easily as seed from this point is may not
completely get removed effectively.
Biofilms then can become a source of microbial contaminations;
therefore purified water after collection in a distribution system is always kept in a
closed loop in a continuous circulation.
A continuous circulation is also not enough at some points, therefore it is aided with
high temperature range from 65 C to 80C, a minimum temperature of 65 C is
considered a self sanitizing, but better assurance is obtained with a temperature of
80C .
Purified water collected should be stored in a stainless still vessel which must
facilitate distribution to the point of use in a closed loop of continuous circulation,
tank should be made of corrosion free material of construction, and must facilitate
sanitization and easy cleaning.
Q. Water for pharmaceutical use shall be free cations,anions and other
impurities why ?
A.Water for pharmaceutical must be free from inorganic as well as organic impurities,
minerals, and heavy metals. Some impurities like calcium, magnesium, ferrous are
responsible for degradation of drug molecule, many cations like ferrous and calcium
magnesium act as catalysts in degradation reaction of drug molecule, anions like
chloride are highly active they participate in nucliophylic substitution reactions,
where in they break a double bond between -C=C- in to a single bond as CL CH-CH2, which a reason why we observe that color dies tend to fed in presence of chlorine
as most of the dies used are diazo compounds which has plenty of places for
nucliophylic substitution reactions, which is also a reason why stability of drug is
drastically affected in presence of cations and anions from mineral origin present in
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water.
Q. Water for pharmaceutical use shall be free heavy metals why ?
A. Heavy metals like lead and arsenic are highly cumulative neurotoxic metals, heavy
metals are not eliminated out of our body easily like other drugs and molecules but
heavy metals bind with proteins and tend to get accumulated in fatty tissues, nerve
tissue is most likely to get damaged by heavy metals, heavy metal causes nervous
tissue damage there for water must be free from heavy metals.
Q. Brazil falls under which climatic zone ?
A. Zone IVB (30 degree celsius and 75% relative humidity)
Q. Change in the size or shape of the original container requires any
stability study?
A. Change in the size or shape of the original container may not necessitate the
initiation of new stability study.
Q. Forced degradation (stress testing) and accelerated stability testing are
same?
A. Forced degradation and stress testing are not same. Stress testing is likely to be
carried out on a single batch of the drug substance. The testing should include the
effect of temperatures (in 10C increments (e.g., 50C, 60C) above that for
accelerated testing), humidity (e.g., 75 percent relative humidity or greater) where
appropriate, oxidation, and photolysis on the drug substance. The testing should also
evaluate the susceptibility of the drug substance to hydrolysis across a wide range of
pH values when in solution or suspension. Photo stability testing should be an
integral part of stress testing.
Q. According to WHO guidelines what is the storage condition of climatic
zone IVa and zone IVb?
A. Zone IV a: 30C and 65% RH (hot and humid countries)
Zone IV b: 30C and 75% RH (hot and very humid countries
Q. Countries comes under climatic zone IVb?
A.Brazil,Cuba,China,Brunei,Cambodia,Indonesia,Malaysia,Myanmar,Philippines,Singa
pore,Thailand
Q. What is the purpose of stress testing in stability studies?
A. Stress testing of the drug substance can help identify the likely degradation
products, which can in turn help establish the degradation pathways and the intrinsic
stability of the molecule and validate the stability indicating power of the analytical
procedures used. The nature of the stress testing will depend on the individual drug
substance and the type of drug product involved.
Q. What is the formula for calculating number of air changes in an area?
A. Number of air changes/hour in an area is
= Total Room Airflow In CFM x 60
Total Volume of room in cubic feet
For calculating Total Room Airflow in CFM, first calculate air flow of individual filter.
Formula is given below.
Air flow (in cfm) = Avg.air velocity in feet/Minute x Effective area of filter

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Then find Total air flow. Formula is

Total Air flow = Sum of air flow of individual filter.
Air flow Velocity can be measured with the help of Anemometer.
Q. What is dead leg?
A. A dead leg is defined as an area in a piping system where liquid can become
stagnant and not be exchanged during flushing.
Q. What is the recommended bio burden limits of purified water & WFI?
A. Purified water has a recommended bioburden limit of 100 CFU/mL, and water for
injection (WFI) has a recommended bio burden limit of 10 CFU/100 mL.
Q. Brief about ICH stabilty guidelines?
A. Q1A- Stability testing of new drug substance & products
Q1B- Photo stability testing of new drug substances & products
Q1C-Stability testing of new dosage forms
Q1D-Bracketing & Matrixing designs for testing of new drug substances and products
Q1E-Evaluation of stability data
Q1F-Stability data package for registration applications in climatic zone III & IV
(Withdrawed)
Q. What is significant changes in stability testing?
A.
1. A 5% change in assay for initial value.
2. Any degradation products exceeds its acceptance
criterion.
3. Failure to meet acceptance criterion for
appearance,physical artributes and functionality
test.
4. Failure to meet acceptance criteria for dissolution
for 12 units.
Q. If leak test fail during in process checks what needs to be done ?
A.
Immediately stop packing process and check for
1.Sealing temperature
2.Verify for any possible changes like foil width,knurling etc.
3.Check & quarantine the isolated quantity of packed goods from last passed
inprocess.
4.Collect random samples & do retest.
5.Blisters from the leak test passed containers shall allow to go further and rest must
be deblistered/defoiled accordingly.

Q. How many Tablets shall be taken for checking friability?

A. For tablets with unit mass equal or less than 650 mg, take sample of whole tablets
corresponding to 6.5g.For tablets with unit mass more than 650mg,take a sample of
10 whole tablets.
Q. What is the formula for calculating weight loss during friability test?
A. %Weight loss = Initial Weight - Final Weight X 100
Initial Weight
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Q. What is the pass or fail criteria for friability test?

A. Generally the test is run for once.If any cracked,cleaved or broken tablets present
in the tablet sample after tumbling,the tablets fails the test.If the results are
doubtful,or weight loss is grater than the targeted value,the test should be repeated
twice and the mean of the three tests determined.A mean weight loss from the three
samples of not more than 1.0% is considered acceptable for most of the products.
Q. What is the standard number of rotations used for friability test?
A. 100 rotations
Q. What is the fall height of the tablets in the friabilator during friability
testing?
A. 6 inches.Tablets falls from 6 inches eight in each turn within the apparatus.
Q. Why do we check hardness during inprocess checks?
A. To determine need for the pressure adjustments on the tableting machine.
Hardness can affect the disintegration time.If tablet is too hard, it may not
disintegrate in the required period of time. And if tablet is too soft it will not
withstand handling and subsequent processing such as coating,packing etc.
Q. What are the factors which influence tablet hardness?
A.
1.compression force
2.Binder quantity(More binder more hardness)
3.Moisture content
Q. Which type of tablets are exempted from Disintegration testing?
A. Chewable Tablets
Q. Which capsule is bigger in size - size '0' or size '1'?
A. '0' size
Q. What is the recommended temperature for checking DT of a dispersible
tablet?
A. 25 10C (IP) & 15 250C (BP)
Q. What is mesh aperture of DT apparatus ?
A. 1.8 -2.2mm (#10)
Q. What is the pass/fail criteria for disintegration test?
A. If one or two tablets/capsules fails to disintegrate completely, repeat the test on
another 12 additional dosage units. The requirement is meet if not fewer than 16 out
of 18 tablets/capsules tested are disintegrated completely.
Q. What is the recommended storage conditions for empty hard gelatin
capsules?
A. 15 - 250C & 35 -55% RH
Q. Which method is employed for checking Uniformity of dosage unit?
A.
A.)Content uniformity
B.) Weight Variation
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Weight variation is applicable for following dosage forms;Hard gelatin

capsules,uncoated or film coated tablets,containing 25mg or more of a drug
substance comprising 25% or more by weight of dosage unit.
Q. What is the recommended upward and downward movement frequency
of a basket-rack assembly in a DT apparatus?
A. 28 32 cycles per minute.
Q. When performing the uniformity of weight of the dosage unit, how
many tablet/capsule can deviate the established limit?
A. Not more than two of the individual weights can deviates from the average weight
by more than the percentage given in the pharmacopeia,and none can deviates more
than twice that percentage.
Weight Variation limits for Tablets
IP/BP
80 mg or less
More than 80mg or Less than 250mg
250mg or more
IP
Less than 300mg
300mg or More
Weight Variation limits for Capsules

Limit
10%
7.5%
5%

USP
130mg or less
130mg to 324mg
More than 324mg
Limit
10%
7.5%

Q. What needs to be checked during inprocess QA checks?

A.
a.) Environmental Monitoring
b.) Measured values obtained from the process equipment (ex:temperature,RPM
etc.)
c.) Measured values obtained from persons (ex:timmings,entries etc.)
d.) Process attributes (Ex:weight,hardness,friability etc.)
Q. What precautions shall be taken while collecting inprocess samples ?
A. While collecting inprocess samples, avoid contamination of the product being
sampled (Dont collect samples with bare hands) & avoid contamination of sample
taken.
Q. In a tablet manufacturing facility positive pressure is maintained in
processing area or service corridors?
A. In tablet manufacturing facilities, pressure gradients are maintained to avoid cross
contamination of products through air. Usually processing areas are maintained
under positive pressure with respect to service corridors.
Q. If sticking observed during tablet compression what may the probable
reason for the same?
A.
1.If the granules are not dried properly sticking can
occur.
2.Too little or improper lubrication can also leads to
sticking.
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3.Sticking can occur because of too much binder or

hygroscopic granular.
Q. What checks shall be carried out, while calibrating DT apparatus?
A. While calibrating DT apparatus, following checks shall be performed.
1.)
Number of strokes per minute (Limit:29-32 cycles/min)
2.)
Temperature by probe & standard thermometer
(Limit: 37 1 OC).
3). Distance travelled by basket (Limit:53 -57mm)
Q. What is In process checks?
A. In process checks are checks performed during an activity,In order to monitor
and,if necessary,to adjust the process to ensure that product confirms to its
specification.
Q. What is the difference between disintegration and dissolution?
A. Disintegration is a disaggregation process, in which an oral dosage form falls apart
in to smaller aggregates.(Disintegration time is the break up time of a solid dosage
form).
Where as dissolution is a process by which solid substance enters in the solvent to
yield a solution.It is controlled by the affinity between the solid substance and the
solvent.
In other word disintegration is a subset of dissolution.
Q. Why do we calibrate a qualified equipment/instrument on definite
intervals?
A. An equipment or instrument can drift out of accuracy between the time of
qualification and actual use.So it is recommended to calibrate and recalibrate the
measuring devices and instruments on predetermined time intervals, to gain
confidence on the accuracy of the data.
Q. Why do we consider three consecutive runs/batches for process
validation? Why not two or four?
A. The number of batches produced in the validation exercise should be sufficient to
allow the normal extent of variation and trends to be established and to provide
sufficient data for evaluation and reproducibility.

First batch quality is accidental (co-incidental),

Second batch quality is regular (accidental),

Third batch quality is validation(conformation).

In 2 batch we cannot assure the reproducibility of data,4 batches can be taken but
the time and cost are involved.
Q. Explain about revalidation criteria of AHU system?
A. AHU system shall be revalidated periodically as mentioned in the regulatory
standards. AHU shall be revalidated in following cases also.

When basic design of AHU is changed,

When clean room volume is changed,

When new equipment is installed

When a construction is carried out, that calls for reconstruction of AHU system.
Q. What needs to be checked during AHU validation?
A. During AHU validation, following tests shall be carried out
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Filter efficiency test,

Air velocity & number of air changes,
Air flow pattern (visualization)
Differential pressure, temperature and RH
Static condition area qualification
Dynamic condition qualification
Non-viable count
Microbial monitoring
Area recovery and power failure study.

Q. Position of oblong tablets to be placed in hardness tester to determine

the hardness? Lengthwise / widthwise?
A. Position of oblong tablets should be length wise because the probability of
breakage is more in this position.
Q. Explain in detail about qualification of pharmaceutical water system?
A. Qualification of pharmaceutical water system involves three phases

Phase -1

Phase -2

Phase -3
Phase -1
A test period of 2-4 weeks should be spent for monitoring the system
intensively. During this period the system should operate continuously without failure
or performance deviation.Water cannot be used for pharmaceutical manufacturing in
this phase.The following should be included in testing approach.

Under take chemical & microbiological testing in accordance with a defined

plan.

Sample incoming feed water daily to verify its quality.

Sample each step of purification process daily.

Sample each point of use daily.

Develop appropriate operating ranges.

Demonstrate production and delivery of product water of required quantity and

quality.

Use and refine the SOPs for operation,maintenance,sanitization and trouble

shooting.

Verify provisional alert and action levels.

Develop and refine test failure procedure.

Phase -2
A further test period of 2-4 weeks. Sampling scheme will be same as Phase
1.Water can be used for manufacturing process in this phase.
Approach should also

Demonstrate consistent operation within established ranges.

Demonstrate consistent production & delivery of water of required quality and

quantity.
Phase - 3
Phase 3 runs for one year after satisfactory completion of phase-2.Water can be used
for manufacturing process during this process.
Objectives & Features of Phase -3

Demonstrate extensive reliable performance.

Ensure that seasonal variations are evaluated.

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The sample locations, sampling frequencies and test should be reduced to the
normal routine pattern based on established procedures proven during Phase -1 &
phase - 2.
Q. What are the recommended environmental monitoring limits for
microbial contamination?
Q. What is the difference between calibration and Validation?
Calibration is a demonstration that, a particular
Instrument or device produces results with in specified limits by comparisons
with those produced by a reference or traceable standard over an appropriate
range of measurements.
Whereas Validation is a documented program that provides high degree of
assurance that a specific process, method or system consistently produces a
result meeting pre-determined acceptance criteria.
In calibration performance of an instrument or device is comparing against a
reference standard. But in validation such reference standard is not using.
Calibration ensures that instrument or measuring devices producing accurate
results. Whereas validation demonstrates that a process, equipment, method
or system produces consistent results (in other words, it ensures that uniforms
batches are produced).
Q. Briefly explain about ICH climatic zones for stability testing & long term
storage conditions?
A.ICH STABILITY ZONES
Zone
Type of Climate
Zone I
Temperate zone
Zone II
Mediterranean/subtropical zone
Zone III
Hot dry zone
Zone IVa
Hot humid/tropical zone
Zone IVb
ASEAN testing conditions hot/higher humidity
Long term Storage condition
Climatic Zone
Temperature
Humidity
Minimum Duration
Zone I
21C 2C
45% rH 5% rH
12 Months
Zone II
25C 2C
60% rH 5% rH
12 Months
Zone III
30C 2C
35% rH 5% rH
12 Months
Zone IV
30C 2C
65% rH 5% rH
12 Months
Zone IVb
30C 2C
75% rH 5% rH
12 Months
Refrigerated
5C 3C
No Humidity
12 Months
Frozen
-15C 5C
No Humidity
12 Months
Q. What is bracketing & matrixing in stability testing?
A.Both Matrixing & Bracketings are reduced stability testing designs
Bracketing
The design of a stability schedule, such that only samples of extremes of certain
design factors (ex:strength,package size) are tested at all time points as in full
design.The designs assumes that the stability of any intermediate level is
represented by the stability of extremes tested.
Matrixing
The design of a stability schedule, such that a selected subset of possible samples for
all factor combinations is tested at a specified time point.At a subsequent time point
another subset of samples for all factor combination is tested.The design assumes
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that the stability of each subset samples tested represents the stability of all samples
at a given time point.
There for a given time point other than initial & final ones not every batch on stability
needs to be tested.
Q.What are the common variables in the manufacturing of tablets?
A.

Particle size of the drug substance

Bulk density of drug substance/excipients

Powder load in granulator

Amount & concentration of binder

Mixer speed & mixing timings

Granulation moisture content

Milling conditions

Lubricant blending times

Tablet hardness

Coating solution spray rate

Q. Whether bracketing & validation concept can be applied in process
validation?
A.Both Matrixing & Bracketings can be applied in validation studies.
Matrixing
Different strength of same product
Different size of same equipment
Bracketting - Evaluating extremes
Largest and smallest fill volumes
Fastest and slowest operating speeds

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