Pharma Interview Questions
1.
What is GMP?
GMP is a
system for ensuring the products are produced consistently and controlled
according to pre-determined acceptance criteria.
2.
Why GMP
is required?
GMP is
designed to minimize the risks involved in any pharmaceutical production that
cannot be eliminated through testing the final product.
3.
What is c
GMP?
CGMP: Current
good manufacturing .cGMP means any procedure /system adopted by the
Manufacturers
which prove the necessary and important for identity, strength and purity of
a product.
4.
What is
validation?
Validation is
the documented program that provides the high degree of assurance that a
specified system, process or method will consistently produce a results
meeting predetermined acceptance criteria.
5.
How many
types of validations?
6 types
validations they are Process validation, method validation, cleaning
validation, facility validation, utility validation and software validation.
6.
What is
process validation?
To collection
and evaluate the data from process design stage throughout production which established scientific evidence that process is a
capable for consistently delivering quality product.
7.
How many types
of process validations? Explain individually?
1.
Prospective
process validation
2.
Concurrent
process validation
3.
Retrospective
process validation
Prospective
process validation: To check the new process capability by executing, before
going to commercial manufacturing and same data will be evaluate for
reference of process capability. It is useful to identify the risks are
involved if any in the process and rectify the same for smooth commercial
production.
Concurrent
process validation: Concurrent validation can be conducted when the data from
replicated runs are not available .Because a limited number of batches have been
produced. Retrospective process validation: To collect and evaluate the data
from already completed production batches, it is useful to check the existing
process trend.
8.
When did
done the process validation?
Validation
shall be carried out in the following cases :
1.
New
product introduction.
2.
Change in
manufacturing formula.
3.
Change in
approved vendor source of active pharmaceutical ingredient.
4.
Change in
Process Batch size.
5.
Change in
Equipment.
6.
Change in
manufacturing site.
7.
Any other
change as deemed necessary for validation through change management system.
The Process
validation shall be performed on at least three successful commercial batches
or as per respective country’s regulatory requirement.
9.
What type
of the check points is need before going to process validation?
Before
going process validation studies,
ensure the following availabilities:
Ø All instruments are calibrated.
Ø All the equipment’s have necessary preventive
maintenance done or not.
Ø Availability of all the required materials.
Ø All equipment’s, utilities and area are qualified.
Ø All personnel are trained and qualified.
Ø Process validation protocol is approved.
10. When validation is required?
Ø Change in Batch Size.
Ø Change in location of product manufacturing site.
Ø Change in Major Equipment or major part of the
equipment impacting the product quality.
Ø Change in manufacturing formula.
Ø If there is any change in the Regulatory
requirements.
Ø Change in API source.
Ø As per review recommendation in APR.
11. How many batches are used as a guide in prospective
and concurrent process validation?
Three batches
used as a guide in prospective and concurrent process validation .Sometimes
based on the requirement additional runs wanted to prove the consistency of
process.
Batch 1:if we
are get the desired(wanted) quality in
the first batch .it is feel an accident (test batch)
Batch2:if same
quality is obtained as first validation batch ,second validation batch to be
considered as quality regulator (proof)
Batch 3: if
the quality parameters meted with 1st and 2nd validation batches, 3rd
validation batch to be considered as validation conformation batch (conformation).
When two
batches are taken as validation the data is not be sufficient for evaluation and
prove the reproducebilty.Because static evolution cannot be done on two
points .it needs minimum three points. Three points because, two points
always draw a straight line.
12. How many batches are used as a guide in
retrospective process validation?
10 to 30
batches should be examined to assess process consistency.
13. What is process qualification?
Qualification
of production or manufacturing process to conform they are able to operate at
certain standard during sustained commercial manufacturing.
14. What is reprocessing?
After
completion of manufacturing process, if any abnormality observed, Take a
material and re-introducing it to an existing process for recovering of that
material is called Reprocess.
15. What is Re work?
After
completion of manufacturing process, if any abnormality observed, Take a
material and introducing it to different process from established process for
recovering of that material is called Rework.
16. What is revalidation? Explain?
Revalidation
of any process is very important part in validation. It improves the quality
of the product and increases the smoothness of the process.
Revalidation
is done in two conditions:
1.
Periodic
re validation: Periodic validation is done to identify the change in process
that may happen during a period of time. There may be any change in SOPS, master
formula, calibration, Analytical method etc. During the period.
2.
Revalidation
after any change: Re validation should be done after any change in the
process or system that can be effect in the quality of the product.
Ex: Raw
material change, Materials source change, Equipment modifications done,
Equipment utility’s change, packing materials change etc.
17. What is validation master plan?
Validation master plan is a written document,
which is describes company’s intention and validation need through the
description about the process, equipment, system, facility. Validation master
plan describes the approach validation, responsibilities, step wise
activities and step frequency of revalidation.
Validation
master plan shall be revised at the end of the calendar year or as and when
required through change control management system. Validation master plan is
prepared at initial stage of commissioning of a facility after the civil design,
type, drawing are established.
18. What is master formula?
A document or
set of documents specifying the raw materials with their quantities and the
packaging materials, together with a detailed description of the procedures
and precautions required to produce a specified quantity of a finished
product as well as the processing instructions including the in-process controls.
19. What is cleaning validation?
Cleaning
validation is a methodology used to assure that a cleaning process is
suitable for removes product residues from the piece of equipment which is
involved in the manufacturing of that product.
20. What is qualification?
An action of
providing that equipment or ancillary systems are properly installed, works correctly
and actually lead to the expected results.
Types of
Qualifications:
1.
User
requirement specifications: it is documented evidence in which user
department provide sufficient information to the manufacturer regarding the
equipment
2.
Design
qualification: Document evidence that the
premises, supporting utilities, equipment and process have been
designed in accordance with the GMP requirements
3.
Installation
Qualification: Documentary evidence to verify that the equipment has been
built and installed in compliance with the design specifications.
4.
Operational
Qualification: : Documentary evidence to verify that the equipment operates
accordance with design specifications in its normal operating range and
performs as intended throughout all
operating anticipated ranges.
5.
Performance
Qualification: Documentary evidence that equipment or system operates
consistently and gives reproducibility with in defined specifications and
parameters for prolong period.
21. How many types of the pass boxes used in the
manufacturing plants? What are they?
2types of pass
boxes are used in the manufacturing plants. They are Static and dynamic pass
boxes.
Static pass
boxes: static pass boxes are used for transfer of material between two clean
rooms that is equally clean. Static pass boxes should not be used in between
clean room non clean room.
Dynamic pass
boxes: Dynamic pass boxes are installed in between uncontrolled area and
controlled area. Ex: intermediate manufacturing area and Clean room.
22. What is flash point?
The lowest
temperature which liquid can generate the ignition mixture in air near the
surface of the liquid. The lower flash point, easier it is to ignite the
material.
23. What is distillation? Types of distillations?
Distillation
is the Process of separating components or substances from a liquid mixture
based on different boiling points.
Types of
distillations: simple distillation, Fraction distillation,
vacuum distillation, Azeo tropic distillation.
24. What are the differences between atmosphere and
vacuum distillation?
25. What is batch?
A specified
Quantity of material produced in single process or series of processes, so
that expected to be homogeneous with in specified limits.
26. What is batch number?
A unique
combination of numbers, letters and/or symbols, which uniquely identifies a
batch on the labels, its batch record and corresponding certificates of
analysis, etc.
27. What is API?
Any substance
or mixture substances intended to be used in the manufacturing of a
pharmaceutical dosage form, when so used it became an active ingredients of
that pharmaceutical dosage form. Such substances are intended to furnish
pharmacological activity or other direct effect in the diagnosis, cure,
mitigation, treatment, or prevention of disease or to affect the structure
and function of the body.
28. What is an intermediate product?
Partially
processed product that must undergo further molecular change or purification
before it becomes an API.
29. What is bulk product?
Any product
that has completed all processing stages up to, but not including, final
packing.
30. What is Finished/medicinal/drug product?
Finished
Product is defined as the medicinal product that has undergone all stages of
production, including packaging in its final container. The specifications
for release of the finished product must comply with the FDA regulations.
31. What is consignment?
The Quantity
of pharmaceuticals made by one manufacturer and supplied at one time in
response to a particular request or order. A consignment may be comprise one
or more packages or containers and may include material belongings to more
than one batch.
32. What is in process control?
Check the
process performance before completion of manufacturing process, if necessary
to adjust the process parameters to get the product with in the
specifications.
33. What is critical parameter?
An operation
in the manufacturing process that may cause variation in the quality of the
pharmaceutical product.
34. What is critical operation?
The operation
which is involving in impact of the product quality is termed as critical
operation.
35. What is packing material?
Any material,
including printed material employed in the packaging of pharmaceutical product.
But excluding any outer packaging used for transportation or shipment.
Packing materials are referred to use as primary or secondary according to
whether or not they are intended to be in direct contact with the product.
Or
Any material
intended to protect an intermediate or API during storage and transport
36. What is reconciliation?
A comparison
between the theoretical quantity and the actual quantity.
37. What is starting material?
Any substance
of a defined quality used in the production of a pharmaceutical product, but
excluding packing material (or) A raw material, intermediate, or an API that
is used in the production of an API and that is incorporated as a significant
structural fragment into the structure of the API.
38. What is solvent?
An inorganic or
organic liquid used as a vehicle for the preparation of solutions or
suspensions in the manufacture of an intermediate or API.
39. What is drying?
Drying is a
mass transfer process consisting of the removes of water or solvent by evaporation
from solid, semi-solid or liquid.
40. What is drug?
A medicine or
other substance which has a physiological effect when ingested or otherwise
introduced in the body.
41. What is reaction?
Reaction is a
process that leads to the transformation of one set of substances to another.
42. What is Expiry Date?
It is the date,
till which a finished product expected to remain within established shelf
life specifications, if stored under defined conditions.
43. What is manufacturing date?
The date when
the material is finally unloaded from the drier in to container shall be
considered as the manufacturing date of the intermediate /drug substances
/Ingredient’s.
Manufacturing
date of the blend batch shall be considered from the oldest tailing batch in
the blend.
**After
completion of the analysis material to be transfer to material staging area
to designated storage area within 7
days.
44. What is retest date?
The date when
a material should be re-examined to ensure that is still suitable for use.
45. What is solution? Write About solution types?
A solution is
defined a homogenous mixture which mainly contains of two components namely
solute and solvent.
Types of
Solutions:
Depending upon
the dissolution of the solute in the solvent, solutions can be categorized
into supersaturated, unsaturated and saturated solutions.
A supersaturated solution contains a large amount of
solute (more than saturated solution) at a temperature wherein it will be
reduced as a result the extra solute will crystallize slowly.
Ex: 110 gm of sugar in 100 ml water at given temperature.
An unsaturated
solution can be defines as a solution with solute that dissolves completely,
no more substance remaining the bottom.
Ex:10 gm sugar
in 100 ml water
A saturated
solution can be defined as a solution with solute that dissolves until it is
unable to dissolve any more, leaving the un dissolved substances at the
bottom.
Ex: 110gm
sugar in 100 ml water.
Homogeneous
solutions are solutions with uniform composition and properties throughout
the solution. For example a cup of coffee, perfume, coughs syrup, a solution
of salt or sugar in water etc.
Heterogeneous
solutions are solutions with non-uniform composition and properties
throughout the solution. A solution of oil and water, water and chalk powder and solution of water and sand etc.Heterogenious
solutions is known as also suspensions
46. What is crystallization?
Explain?
Crystallization is the process of forming a solid crystalline
material precipitating from solution, gas or amorphous solid.
Types of Crystallization:
Crystallization
occurs when the solubility of a solute in solution is reduced by some means.
Common methods to reduce solubility include:
a.
Cooling. Anti-Solvent
Addition. Evaporation. Reaction (Precipitation).
The choice of
crystallization method depends on the equipment available for
crystallization, the objectives of the crystallization process and the
solubility and stability of the solute in the chosen solvent.
47. What is acid?
Acids: An acid
is a substance that gives hydrogen ion H+ or a hydronium ion H3O+when
dissolved in water. A substance, which has an acidic nature, contains one or
more hydrogen and an anionic group in its formula.
Example: H2SO4 (sulphuric
acid) contains two hydrogen’s or hydrogen ion 2H+and sulfate anion
Base:A Base is a substance which gives hydroxide ion OH-when
dissolved in water.
Example: NaOH It is a base since it contains OH- ion or
hydroxide ion.
Acids donate hydrogen ions and bases accepted
hydrogen ions this is the major identification of Acids and bases.
48. What is contamination?
The undesired
introduction of impurities of a chemical or microbiological nature, or of
foreign matter, into or onto a raw material, intermediate, or API during
production, sampling, packaging or repackaging, storage or transport.
49. What is cross contamination?
Contamination
of a material or product with another material or product.
50. What is deviation? Explain about types of
deviations?
Departure from
an approved instruction or established standard.
Deviations are
2 types they are :
Planned deviation:
Any deviation from documented procedure chose purposely for temporary period
to manage unavoidable situations or improving the performance of the
operations without affecting the quality And yield of the drug substance and
safety of the operation shall called as planned deviation.
Un planned deviation:
Any deviation occurred in unplanned manner such a system failure or equipment
break down or manual error shall be termed as Un planned deviation.
Planned
deviations are described under change control system.
Planned and
unplanned deviations are divided in to two types they are:
1.
Critical
Deviation
2.
Non
critical deviation.
Critical
deviation: Deviation is impact on the Quality of the product, system, safety
,efficacy is termed as critical deviation.
Examples for
critical deviation:
·
Using
different equipment other than that specified in BPCR.
·
Operation
instructions not followed as per the BPCR.
·
Proposed
to use other solvents in manufacturing process.
·
Calibrations
not performed on due date.
·
Incorrect
order of materials charging.
·
Breakdown
of process equipment.
·
Procedures
not followed as per the STPs.
·
Equipment
modifications with in the same product.
Non critical
deviation: Deviation is no impact on the Quality of the product, system, safety,
efficacy is termed as non-critical deviation.
Examples for
non-critical deviations:
52. What is OOS?
The result does not comply with the pre-determined specified acceptance criteria.
If OOS found valid for stability samples, The stability study shall be continued for testing sa
·
Procedures
not followed as per the SOPs.
·
Editorial
and transcriptional errors.
·
Preventive
maintenance not performed as per the schedule.
·
First in
first out deviation.
51. What is OOT?
The data is
within the specified limit, but it is abnormal pattern from remaining data
pattern imples of further stations. If the results of the next station
sample does fails with respect to the test for which OOS was reported, the
stability study shall be discontinued.OOS investigation shall be completed
within 30 days,.
53. What is corrective action?
An action
required to correct and prevent a re-occurrence of something that happened
yesterday.
Or
Action taken
to eliminate the cause of nonconformities in order to prevent recurrence.
54. What is preventive action?
An action
required to prevent an occurrence of something happening tomorrow.
Or
Action taken
to eliminate the cause of potential nonconformities in order to prevent their
occurrence.
55. What is dirty hold time?
The time from
the end of manufacturing till the beginnings of the cleaning process of
equipment.
56. Clean equipment holds time?
The time from
the end of the equipment cleaning till next usage of equipment.
57. What is the difference between Equipment and
instrument?
1 Equipment is
the machine, That is processing the work .Instrument is the measure the data
that comes out of the machine to get feedback of the machine and the
process.\
2 Equipment
used for a specific work. Instrument is a measuring parameter like
temperature and pressure.
3 Equipment is
a processing device. Instrument is a measuring device.
4 instrument s
are parts of equipment, number of instruments comprises in a equipment.
58. What is clean room?
A clean room
is a controlled environment that has a low level of pollutants such as dust,
airborne microbes, aerosol particles, and chemical vapors. To be exact, a clean
room has a controlled level of contamination that is specified by the number
of particles per cubic meter at a specified particle size. The ambient air
outside in a typical city environment contains 35,000,000 particles per cubic
meter, 0.5 mm and larger in diameter,
or
An area with
defined environmental control of particulate and microbial contamination
constructed and used in such a way as to reduce the introduction, generation,
and retention of contaminants with in the area.
59. What is change control? What is the intention of
change control?
Change
control is a systematic approach to managing all changes made to a product or system.
The purpose is
to ensure that no unnecessary changes are
made, that all changes are documented, that services are not unnecessarily
disrupted and that resources are used efficiently.
Change control
types:
1. Tmporary
change: Temporary changes are the changes which are there only for a short
period.
2. Permanent change: Permanent changes are the changes which
remain for a longer time.
Temporary and permanent changes are divided in to 2
types they are:
1.
Major
change: if change is impact on the Quality, yield, purity, identity,
Efficacy, safety is known as major change.
Examples for
Major changes:
·
Introduction
of new drug substances or new drug products in the manufacturing plant.
·
Equipment
like to unlike changes in the validated processes.
Changing in
MOC/Agitator type/Capacity/RPM of the reactor used in the reaction
/crystallization processes.
Different
types of driers. Difference types of powder processing Equipment’s.
·
Change in
manufacturing site of validates APIs and change in the manufacturing block
within the site.
·
Changes
within the same Equipment Agitator/, RPM, condenser capacity, vapor column
height
·
Changes
in the manufacturing process of validating products.
·
Introducing
the New Raw materials
·
Changes
in critical process parameters/input Quantities.
·
Removal/relaxation
of in process test parameters.
·
Change in
the cleaning solvent./using the recovered solvent in place of the cleaning
solvent.
·
Changes
in the Packing materials.
·
Changes
in the Expiry and retest dates.
·
Introducing
new vendors of Key starting materials.
2.
Minor
change: if change is no impact on the quality, yield, identity, purity,
safety and system is called as minor change.
Examples for
Minor changes:
·
Repetition
of washing/purification operations within the same step.
·
Deletion
of the use of recovered materials in the process.
·
Deletion
of an optional reprocessing step.
60. What is safety?
Safety is one
of the intentional part of every life and every ware. The word Safety
indicates and decides the behavior of every movement in life for living
without any problems.
61. What is risk?
A situation
involving exposure to danger.
62. What is sublimation?
Sublimation is
the transition of a substance directly from the solid phase to gas phase
without passing through the intermediate liquid phase.
63. What is condensation?
The conversion
of a vapor or gas to liquid.
64. What is humidity?
The Quantity
amount of water present in the atmosphere or in gas.
65. What is air change per hour?
A volume of
Air equivalent to the room volume that enters and exist a room in 1 hr. is
called an air change per hour. As per the FDA guidelines only specify a
minimum of 20 air changes per hour.
Calculation
part:
1.
Calculate grill total FPM (feet per minute):
Take air flow
readings from 5 various grills and calculate the average air flow.
Average
=640/5=128 FPM
2.
CFM (cubic feet per minute) calculate:
Grill surface area X FPM
Ex: if grill surface area=1.6 cubic feet
Then CFM=128 X 1.6=204.8
CFM.
Here 204.8
indicates one grill CFM, now calculate all the grills CFM.
If total area
have 10 grils,then total CFM
=10X204.8=2048
CFM.
Here 2048 CFM
indicates all the room CFM.
3.
ACPH(air change per hour calculation):
=Total CFM X60
min/Room volume.
Total CFM=2048
60=1 hour time
in minutes.
Room
volume=width X height X Length
Ex Room
width=8CFM,Room height=12CFM,length=11CFM
Room volume
=8X12X11=1056 CFM
ACPH=2048
X60/1056=116.36 ACPH
**Anemometer
is used for calculating the velocity of AIR.
66. What is exothermic reaction? Explain with examples?
Exothermic reaction is reaction that
release energy into the environment in the form of heat. Exothermic reactions feel warm or hot or may even be explosive
a) When adding calcium chloride to water,
hydrochloric acid and calcium hydroxide oxide will form.
CaCl2 +2H2O ‡ Ca(OH)2 +2HCl
b) HCl + NaOH -->NaCl + HOH
67. What is Endo thermic reaction? Explain with
Examples?
An endothermic reaction is any chemical reaction that absorbs heat from its environment
Ex 1) In a test tube, when a small quantity
of ammonium chloride (NH4Cl) is
dissolved in water, the tube becomes colder. Heat is absorbed from the
surroundings during the chemical reaction.
NH4Cl(s) + H2O(l) →→ NH4Cl(aq) – heat
Ex 2) When crystals of sodium thiosulphate
(Na2S2O3.5H2O), also known as hypo get dissolved in water, a cooling effect
takes place.
Na2S2O3.5H2O + H2O →→ Ns2SO3(aq) – heat
68. What are the usages of Epoxy coating in clean rooms?
·
Floor
areas with epoxy coating can easily be wiped free of dust and dirt.
·
Epoxy is
thermo setting resin with form tightly linked cross polymer structers.This
makes it uphold it toughness and strong adhesion. When used as a floor coating,
any floor surface can stand the test of time.
69. For stability studies how many batches are required?
For new drug product,
samples of at least three consecutive validation batches shall be kept for
accelerated and long-term stability.
For routine
stability study, one commercial batch shall be kept for long term stability
on every year.
70. What type of the factors effecting on the stability
product? Of the
Below
mentioned factors are effecting on the stability of the product:
·
Temperature:
The rate of chemical reaction increases exponentially for each 10°C increase
in temperature. This relationship has been observed for nearly all drug
hydrolysis and some drug oxidation reaction.
·
Light:
Exposure to primarily, UV illumination may cause oxidation (photo oxidation)
and scission (Photolysis) of covalent bonds.
·
Air:
Presence of oxygen, nitrogen.
·
Humidity
(Moisture): Esters & beta-lactoms are the chemical bonds that are most
likely to hydrolyze in the presence of water. E.g. the acetyl ester in
aspirin is hydrolyzed to acetic acid and salicylic acid in the presence of
moisture, but in a dry environment the hydrolysis of aspirin is negligible.
71. What is MACO?
MACO:
Acceptable transferred amount from the investigated product (previous).
72. What is the static electricity?
Denoting
/pertaining to electricity which at rest. The electricity which is present on
surface of a nonconductive body, where it is trapped from escaping, is called
static electricity.
73. Why nitrogen gas is used in the manufacturing area
at room temperature and why not other gas?
Nitrogen gas
is chemically less reactive and does not react with other elements at
ordinary temperature. it is due to strong bonding in the molecule.
74. What is blending?
Blending is
the process of combining materials within the same specification to produce a
homogeneous intermediate or API.
75. Why water is used extensively as a coolant in heat
exchange equipment’s?
Because of the
abundance and high heat capacity, water is used as coolant in heat exchange
equipment.
76. What is the difference between Qualification and
validation?
Qualification
is equipment /instrument oriented but validation is process oriented.
OR
Validation is
the documented programmed that provide the high degree of assurance that a
specific process, Method or system will consistently produce a result meeting
the pre-determined acceptance criteria.
But qualification refers to the validation part of equipment&
System.
77. What is preventive maintenance?
Schedule
maintenance before any break down of machinery which prevents the machine
break down.
78. What is breakdown maintenance?
Maintenance
was done after stopping the machine occurrence of Breakdown.
79. What is the classification of residual solvents?
Give examples?
Residual solvents are separated In to 3 classes
based on their potential toxicity. they are :
1.
Class-I (solvent
to be avoided): Class-I solvent s should be avoided in all pharmaceutical
manufacturing .Because they have known human carcinogens/Environmental hazards.
Examples :
2.
Class –II
solvents (solvents to be limited)|: Class-II residual solvents should be
limited in drug substances, Excipients, and Drug products.
Examples :
3.
Class
–III solvents (solvent low toxic potential):Class 3 residual solvents are
limited by GMP or other quality based requirements in drug substances
,excipients. Class 3 type solvents used LOD
should be 0.5%s
Examples :
80. What is LEL(Lower Explosive Limit) and UEL? Explain?
LEL: Lowest
concentration (percentage) of a gas or vapor in air capable of producing a
flash of fire in presence of an ignition source (arc, flame, heat).
Concentrations lower than LEL are 'too lean' to burn. Also called lower flammable limit (LFL).
UEL: Highest
concentration (percentage) of a gas or vapor in air capable of producing a
flash of fire in presence of an ignition source (arc, flame, heat). Concentration
higher than UEL are 'too RICH ' to burn. Also called Upper flammable limit (LFL).
Lower and
Upper exposure limits units are % by volume in air.
To fire an
explosion, three conditions should occur at the same time:
1.
The
presence of combustible gas, the fuelling element, in a specific
concentration
2.
Presence
of oxygen.
3.
The
existence of a sparking element (that ignites the two elements)
The proportion
of fuel and the oxygen needed to generate an explosion depends on the type of
combustible gas. Gases will ignite only when mixed with air within a specific
concentration range. If the gas is mixed with oxygen with too low or too high
concentrations, the gas will not ignite and explode.
81. What are the percentages of gases present in atmosphere?
Air contains
78.09% nitrogen, 20.95%oxygen, 0.93% argon, 0.04% carbon dioxide, and
small amounts of other gases 0.92%.
82. What are the differences between SS 316, SS 316L and SS 304?
83. What is an agitator? Explain about types of
agitators and their usages?
Agitator: An agitator is something which is used to stir liquid or
mixture of liquids.
Types of agitators:
PADDLE TYPE
AGITATOR
ANCHOR TYPE AGITATOR
PROPELLERTYPE AGITATOR
PITCHED BLADE TURBINE
84. Common Solvents names and their properties:
85. What is OEL?
OEL: An
occupational exposure limit
An
occupational exposure limit is the maximum allowable concentration of hazard
substances in a work place. It is defined as the upper limit of concentration
in the air.
Based
on the Occupational exposure limit, toxicity and pharmacology action only fixed
the Occupational exposure band limit as below mentioned table.
OEB limits (Occupational exposure band )
86. What are the advances of ANFD?
Ø Vacuum or pressure filtration possible.
Ø Inert gas atmosphere can be maintained.
Ø Minimal contamination of the cake.
Ø Very high solvent recovery.
Ø Considerable saving in manpower.
Ø Solvents are in closed systems, so no toxic vapors are let off in the
atmosphere.
Ø Personal safety is maintained and heat transfer surfaces can be
provided to maintain filtration
temperature.
Ø Easy slurry washing.
Ø High cake resistance.
Ø Effective drying of the compound.
87. What is containment?
Example for containment equipments?
The action of
keeping something harmful under control or within limits.
Ex: changing isolators,
glove boxes, sampling and milling isolators etc..
88. What is
high potent and Low potent drug?
High potent
drug: Which drug is gives good response in low concentration is called as
high potent drugs.
Ex: respridone
(1 to 2 mg per a day)
Low potent drug:
which drug is gives good response in high concentration is called as low
potent drugs.
Ex: diazepam
(5 to 10mg per a day).
89. What are the usages of air lock system? How many
types of air locks? Explain?
Air lock
system in pharmaceutical manufacturing to avoid the chance of cross
contamination and to separate different process area.
Air locks are
three types they are:
a.
Cascade
air lock: High pressure on one side of the air lock and low pressure on
another side.
b.
Sink airlock:
Low pressure in side of the air lock and high pressure on both side.
c.
Bubble
airlock: High pressure inside the air lock and low pressure on both sides.
90. What is
the purified water Specifications?
Purified water
specifications and limits of test according to USP ,BP.EP.IP given below in
table
91.
Weighing balance calibration calculation procedure
For 60 kg capacity weighing balance Quarterly calculation:
Calculate the standard deviation by using this
formula:
Here
X= Observed weight
(‾‾x)= average
observed weight
N= number of readings
First calculate the difference between individual weight and
average weight:
For 5% weight standard deviation calculation
:
SD=√ 0.00/4=0
For 25% weight standard deviation calculation
:
=0.00044/9=0.000049
√0.000049=0.007
For 50% weight standard
deviation calculation :
=0.0009/9=0.0001
√0.0001=0.01
For 100% weight standard
deviation calculation :
=0.0018/4=0.00045
√0.00045=0.021
Reputability test:
Take 5 readings 5% ,25%, 50% ,100% of the weights and calculate relative
standard deviation (%RSD)
%RSD=SD/observed average weight X100
Acceptance criteria 0.2%
Accuracy test :
Take 5 readings 5%, 50%
,100% of the weights and calculate relative standard deviation (%RSD)
%RSD=SD/observed average weight X100
Acceptance criteria 0.1%
Uncertinity test:
Take 10 readings 25%,50% of the weights and calculate relative
standard deviation
Uncertainty =3 xSD/standard weight.
Acceptance criteria 0.001%
Linearity :
[N∑XY- (∑X) (∑Y)
R=
----------------------------------
SQ.{[N∑X2-(∑X)2]
[N∑Y2-(∑Y)2]}
Acceptance criteria: correlation co efficient should be ≥0.99
=∑X X ∑Y=21681.088
=∑XY=6276.88
=N∑XY=6 X 6276.88=37661.28
= N∑X2 =6 X 6273.04=37638.24
=(∑X)2 =147.2 X 147.2=21667.84
= N∑Y2 =6 X 6280.723=37684.34
= (∑Y)2 = 147.29 X 147.29=21694.34
=15980.192
SQ 15970.4 X 15990
=15980.192
SQ 255366696
=15980.192
15980.196
=0.9999
Eccentricity test:
50% of the weighing
balance capacity to be take for Eccentricity test.
Difference from centre
weight (Kg)
% OF DIFFERENCE
=_____________________________ X100
Observed centre weight
(Kg)
EX:0.02/30.01X100=0.067
Acceptance criteria: The obtained reading should be ±least count
/with in ±0.1% of the standard weight.
92. What is MACO? Explain calculation procedure?
MACO: Acceptable
transferred amount from the investigated product (previous).
Methods of Calculating
Acceptance Criteria:
Based on Therapeutic Daily Dose:
This method only applies
when the therapeutic daily dose is known. It is generally used for final
product changeover API Process ìAî to API Process “B”.
Establish the limit for Maximum Allowable Carryover (MACO) according
to the following equation.
TDDprevios X MBS(next)
MACO= -----------------------------
SF x TDDnext
MACO: Maximum Allowable Carryover: acceptable transferred amount from
the investigated product ("previous") TDDprevious: Standard
therapeutic dose of the investigated product (in the same dosage form as
TDDnext)
TDDnext: Standard therapeutic dose of the daily dose for the next
product
MBS: Minimum batch size for the next product(s) (where MACO can end
up)
SF: Safety factor (normally 1000 is used in calculations based on
TDD).
Example :1
Product A will be cleaned out. The product has a standard daily
dose of 10 mg and the batch size is 200 kg. The next product B has standard a
daily dose of 250 mg and the batch size is 50 kg. Both A and B are
administrated orally and SF is set to 1000. Calculate the MACO for A in B!
10 (mg) X50(kg)
MACO= -----------------------
1000 x250(mg)
Above formula therapeutic dose is in milli gram, But next
product in kilogram. So to be converting the next product from kilogram to
milli gram.
10 (mg) X50 000 000(mg)
MACO= ------------------------------ =2000mg
1000 x250(mg)
Results :MACO=2000mg(2gm)
Example :2
Now product B in example 1 will be cleaned out. The following
product is product A in example 1. Calculate the MACO for B in A!
250 (mg) X200 000 000(mg)
MACO=
------------------------------ =5000 000mg
1000 x10(mg)
Results: MACO=5 000 000mg
(5kg).
As per the example 2 very
high MACO value is observed. the figure obtained is clearly unacceptable. If
5 kg of material is present in equipment the equipment would be obviously
dirty. So general limit should be chosen for maco calculation.
Based on Toxicological Data:
If investigated product therapeutic dose is not known (e.g. for intermediates and
detergents), toxicity data may be used for calculating MACO. LD50(g/kg) X 70 (kg a person)
NOEL =
-----------------------------------------------
2000
Here LD50 indicates how much substance is required for killing
of 50% animals within 15 days is called LD50.
70
kg is the weight of an average adult.
2000
is an empirical constant
Example 1:
IF LD50 =331mg/kg
331 X 70
NOEL = ------------------=11.58
mg
2000
Now calculate the MACO by using above NOEL value.
NOEL X MBS(next)
MACO =
-----------------------------------------------
SF X TDD(next)
Example :
NOEL:11.58 mg, TDD(next)=10 mg ,MBS(next)=50kg, SF:1000
11.58(mg) x50 000 000(mg)
MACO =
-----------------------------------------------
1000X 10(mg)
579 000 000
MACO =
-----------------------------------------------=5790mg
10000
Results =5790 mg (5.79 gm)
Note:if therapeutic dose is not known for next product then chose the general limit for MACO calculation.
Based on the general limit:
This Method to be used ,when the result in unacceptably high or
irrelevant carryover figures, or
Toxicological data for intermediates are not known, the approach
of a general limit may be suitable.
The concentration (CONC) of the investigated substance which can
be accepted in
the next batch, according to dose related calculations, is:
MACO(ppm)
CONC = ----------------------
MBS(next
product )
MAXCONC: General limit for maximum allowed concentration (kg/kg
or ppm) of "previous" substance in the next batch.
MBS: Minimum batch size for the next product(s)
In generally to be considered the MACO limit for API is 10 PPM
(0.001%) and for intermediates is 100 ppm(0.01%). Of the minimum batch size.
Establish MACO ppm, based on a general limit, using the
following equations.
MACOppm = MAXCONC x MBS
Example: Minimum batch size of the previous product is 54 kg.
standard daily dose of next product is
10 mg and the batch size is 500 kg.
So 10 ppm =10(mg)/1000000(Mg)=0.00001(Mg/Mg).So maximum
concentration=0.00001(mg/mg).
To be convert the Next product batch size in to mg =500 X
1000000=500000000 (mg).
To be incorporate the above values in to formula :
MACOppm = 0.00001 x 500000000=5000mg (5 gm).
Results MACO ppm=5gm (5000mg).
Acceptance criteria using health-based data:
The Maximum Allowable Carryover (MACO) should be based upon the
Acceptable Daily Exposure (ADE) or Permitted Daily Exposure (PDE) when this
data is available. The principle of MACO calculation is that you calculate
your acceptable carry-over of your previous product, based upon the ADE /
PDE, into your next product.
Procedure
Calculate the ADE (Acceptable Daily Exposure) or PDE (Permitted
Daily Exposure) according to the following equations and use either result
for the calculation of the MACO.
NOAEL x BW (70)
ADE =
------------------------------
UFc x MF x PK
NOAEL x BW (70)
PDE =
------------------------------
F1 x F2 x F3 x F4 x F5
From the ADE / PDE number, a
MACO can be calculated according to:
ADE / PDE previous
x MBS next
MACO =
---------------------------------------------
TDD next
F1: A factor (values between 2 and 12) to account for
extrapolation between species
F2: A factor of 10 to account for
variability between individuals
F3: A factor 10 to account for
repeat-dose toxicity studies of short duration, i.e., less than 4-weeks
F4: A factor (1-10) that may be applied
in cases of severe toxicity, e.g. non-geotaxis
carcinogenicity, neurotoxicity or teratogenicity
F5: A variable factor that may be
applied if the no-effect level was not established. When only an LOEL is
available, a factor of up to 10 could be used depending on the severity of
the toxicity.
If ADE / PDE values are not available, if occupational exposure limit
(OEL) data is available the ADE ,PDE
can be derived from the OEL by using the following formula.
PDE(µg/Day)=OEL(µg/m3) X
103 (the volume of AIR
breathed by a worker in 8hrs)
If 2000 µg of substance exposure in 10m3 Area in 8 hrs calculate
the MACO as below Mentioned.
PDE (µg/Day)=2000 µg m3 X 10 m3 =20000 µg=20 mg.
After completion MACO value calculation, calculate the allowable carryover
limit in particular equipment.
Rinsed sample acceptable limit calculation :
Target value
(mg/L) = MACO (mg) / Volume of rinse or boil (L)
Ex: If
MACO(mg)=2000
Rinsed solvent
volume is 30 Lt.
Hence
acceptable ppm Limit for that particular Equipment=2000(mg)/30=67 ppm.
Swab sample acceptable limit calculation :
Total surface of swab area (m2 )
X MACO (mg) X safety factor
Target value(mg/M2)=___________________________________________________
Total surface of the
Equipment (m2 ) X diluted volume
Swabbed surface area =10 x10 cm2
So 10cm =0.1 m=0.1 X 0.1=0.01(m2 )
Ex:MACO =2000(mg)
Safety factor=1000
Total surface of the Equipment =14 m2
Diluted volume 10 ml
=0.01 X2000 X 1000 / 14 X10
= 20000/140=142 ppm.
Note :
If calculated Rinse and
swab liomit is more than General limit ,then to be considered the General
limit criteria.Ex:100 ppm for
intermediates and 10 ppm for API .If caliculated rinse and swab limits
is below the general limit. Then
considered the actual calculated limit .
if number of equipments is used in process,
then rinse and swab sample results to
be calculate with the total; surface
of the chain equipments
Safety factor to be considered as below mentioned.
Topical s (ointment ) 10 -100
Oral products(tablets) 100- 1000
Parenterals ( injection) 1000 – 10 000
93.
What is theoretical yield? How to calculate theoretical yield?
Theoretical yield is the
maximum amount of product that could be formed from the given amounts of
reactants.
Out molecular weight
% of theoretical yield per
kg =______________________ X input weight
Input molecular weight
94. What is passivation?
Passivation is the process of
treating or coating a metal in order to reduce the chemical reactivity of its
surface. In stainless steel, passivation means removing the free
iron from the surface of the metal using an acid solution to prevent rust.
During this passivation processes nitric acid reacts the chromium that’s the
reason some chromium oxide layer forms on the inner surface of the equipment.
It is reduce the chemical reactivity on its surface.
95. How many LUX of illumination is required for
pharmaceutical industry?
History: UK government had
published a document on lighting at work in 1987 describing the minimum light
recommendations and health and safety risks from light at a work place.
LUX is the standard unit for light
intensity measurement. 1 LUX equal to the light intensity of the surface 1
meter away from a single candle. Light intensity is measured by using an
instrument called a LUX meter at working height about 1 meter from the
ground. Light intensity is measured at a minimum 5 locations and average of
all readings is calculated to determine the final light intensity of the room.
An Ideal light intensity for office is 300 –
500 LUX.It should be about 400LUX in all production areas and above 300 LUX
in sampling and dispensing booth.for intermediate area 150 LUX is enough.
Monitoring the light intensity in all areas
including manufacturing ,Stores ,and laboratory should be doe yearly.
Importance of lighting in
working areas:
1. Sufficient light is necessary at the work place to
get better work out put .Less lighting in working area can results in errors
in difference ways.
2. Poor lighting can affect the health of the people
working at work place causing headache, eyestrain and migraine.
1 LUX=0.0929 foot candle.
96. FDA audit check points for manufacturing area
1. Block layout at Entrance area with up dated version
and authorization.
2. Entry exit procedures for
visitors/Employees/Helpers.
3. Check for floor and wall gaps.
4. Availability of water flow and disinfectant solution
in wash room.
5. Check the unwanted documents present in personnel
cupboards.
6. Checklist for area cleaning.
7. Check list for waste transfer.
8. Check for proper illumination and ventilation.
9. Check for web cobs.
10. Check for empty of dustbins.
11. Check for availability of proper PPE.
12. Check for proper labeling of process lines and
equipments.
13. All the Equipment s which is used in the process was
Qualified or not.
14. Check for calibration status of instruments like
temperature sensors and DTI.
15. Check for calibration status of pressure and vacuum
gauges.
16. Check the status of weighing balance stones and
weighing balance certificate.
17. Daily weighing balance calibration check list.
18. Check for working condition and calibration of pH
electrodes.
19. Check for proper working of scrubber system.
20. Check for reconciliation records.
21. Check for unwanted documents.
22. Check for SOP display copies as per present version.
23. Visual inspection of equipment inside cleaning.
24. Preventive maintenance status for all the
equipments.
25. Equipment usage logs and relegated documents.
26. Running batch to inline with the BPCR.
27. All the materials are sag grated.
28. All the containers have a proper labeling.
29. All the material stored as per the storage condition
along with proper labeling.
30. All the solvent
or material Quantities matched as per the reconciliation records.
31. Availability of MSDS for all intermediates, API and
RM.
32. Check the
calibration status of utensils (like buckets, Measuring cylinders, bins
Etc..).
33. Availability of movable equipment list.
34. Availability of Department oregano gram.
35. Availability of Quality policy.
36. Availability of EHS policy.
37. Updating of all the equipments status cards as per
the present position.
38. Availability of waste disposable procedure.
39. All work order to be in line.
40. All the safety equipment placed as mentioned in
safety lay out.
41. Availability of all the products flow charts.
42. Proper labeling of utensils and equipments with
proper identification numbers.
43. In process sampling procedures and physical
observations.
44. Hose/Pipes stored at designated area with proper
labeling
45. Comparison of equipment status Vs Equipment status
board.
46. Temperature and humidity maintenance record.
47. Color coding of solvents and utility lines.
48. Record for prevent of cross contamination during the
charging, loading and unloading.
49. Rust freeness of utensils and Equipments.
50. Filter meshes and bags reconciliation record.
51. Training on product for all the employs who is
involved in the manufacturing.
52. Training on the all related sops for employs.
53. Awareness should be creating all the employs all the
employs about issues of data integrity.
97. Guide words
No or not, More
,less, after ,before, late ,early, instead of /other than, part of ,reverse,
As well as.
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