Quality Assurance Question Bank.pdf

MOST FREQUENTLY ASKED QUESTIONS Page 1 of 1 1 What is the definition of SOP? SOPs are detailed written instructions for the operations routinely performed in the course of any activities associated wi[.]

SOPs are detailed written instructions for the operations routinely performed in the course ofany activities associated with pharmaceutical manufacturing.

Or

A written authorized procedure which gives instructions for performing operations notnecessarily specific to a given product / material, but of a more general nature the equipmentspreventive maintenance and cleaning; recall of products; purchasing; cleaning of premises andenvironmental control; sampling and inspection etc

Or

These are guidelines which describe how the activity is to be performed To achieve uniformity

of results by each individual, it is mandatory to follow these guidelines SOP is like a “TELL andSHOW”concept

Tell – means to establish and teach how the activity is to be carried out

Show – means to provide the documented proof for the activity carried out

2 What are the contents of the SOP?

Objective/Purpose, Scope, Responsibility, Accountability, Procedure, List of formats/Annexure,Abbreviations, Reference, Revision History

3 Which information should master document carry on every page not just one of the pages to

meet GMP?

Page number, document reference number and authorizing signatures

4 How many SOPs required for equipment and what are those?

Operation, Cleaning, Preventive maintenance/ Calibration, Sampling procedure

5 What is the Batch production and control record (BPCR)?

BPCR are prepared for each intermediate and API and include the complete informationrelating to the completion of each significant step in the Batch production

6 What is the Master production & control record (MPCR)?

To ensure the uniformity from batch to batch, master production instructions for eachintermediate and API are prepared, dated and signed by one person, immediately checked,dated and signed by a person in the quality unit

7 What are the content of the MPCR?

 The name of the intermediate or API being manufactured and an identifying document

 A complete list of raw materials and intermediates designated by names or codessufficiently specific to identify any special quality characteristics.

 An accurate statement of the quantity or ratio of each raw material or intermediate to

be used, including the unit of measure Where the quantity is not fixed, the calculationfor each batch size or rate of production should be included Variations to quantitiesshould be included where they are justified

 The production location and major production equipment to be used

 Detailed production instructions, including the:

- Sequences to be followed

- ranges of process parameters to be used

- sampling instructions and in-process controls with their acceptance criteria, whereappropriate

- time limits for completion of individual processing steps and/or the total process,where appropriate

- expected yield ranges at appropriate phases of processing or time-Where appropriate, special notations and precautions to be followed, or cross-references to these

The instructions for storage of the intermediate or API to ensure its suitability for use,including the labeling and packaging materials and special storage conditions with timelimits, where appropriate

8 What is the list SOPs required in QA department?

SOP for SOP, SOP for format preparation, change control, deviation, Non-conformanceproducts, market complaints, product recall, returned goods, vendor qualification, preparation

of BPCR & MPCR, Assigning of Mfg date & Expiry date, annual product review, correctiveaction & preventive action, process validation, cleaning validation, equipment qualification,glossary of terms, document control, Review of BPCR & analytical test report, batch numberingsystem, labeling practice, personnel training, BPCR issue and retrieval, batch release, selfinspection (internal audit), file numbering system, preparation of organo-gram, preparation ofCOA, specimen signatures, Reprocess & rework of intermediates / API, Job responsibilities,Technology transfer, measurable quality objectives etc

Intermediate: A material produced during steps of the processing of an API that undergoesfurther molecular change or purifications before it become an API (Reference: ICH Q7A).

API: Any substance or mixture of substances intended to be used in the manufacturing of adrug (medicinal) product and that when used in the production of a drug, becomes an API ofthe drug product Such substances are intended to furnish pharmacological activity or otherdirect effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affectthe structure & function of the body (Reference: ICH Q7A)

10 What is the difference between drug substance and drug product?

Drug substance (API): Any substance or mixture of substances intended to be used in themanufacture of a drug (medicinal) product and that, when used in the production of a drug,becomes an active ingredient of the drug product Such substances are intended to furnishpharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, orprevention of disease or to affect the structure and function of the body (Reference: ICH Q7A).Drug product: The dosage form in the final immediate packaging intended for marketing(Reference: ICH Q7A)

11 What is the clean room?

Clean rooms are defined as especially constructed, environmentally controlled enclosedspaces with respect to airborne particulates, temperature, humidity, air pressure, air flowpatterns, air motion, vibration, noise, viable (living organisms) and lighting

Particulate control includes:

 Particulate & microbial contamination

 Particulate concentration & dispersion

12 What are the classifications of clean rooms?

Generally clean rooms are classified in to the following types as per different guidelines:

Schedule M: Grade A, Grade B, Grade C, Grade D

USFDA (US 209E): Class 1, Class 10, Class 100, Class 1000, Class 10000, Class 100,000

WHO 2002: Grade A, Grade B, Grade C, Grade D

EU GMP: Grade A, Grade B, Grade C, Grade D

ISO 14644-1: ISO-3, ISO-4, ISO-5, ISO-6, ISO-7, ISO-8, ISO-9

Britian (BS 5295): Class C, Class D, Class E or F, Class G or H, Class J, Class K

Germany (VDI 2083): 1, 2, 3, 4, 5, 6

13 What is the difference between GMP & cGMP?

GMP: GMP is the part of Quality assurance which ensures that products are consistentlyproduced and controlled to the quality standards appropriate to their intended use and asrequired by the marketing authorization

GMP are aimed primarily at diminishing the risks inherent in any pharmaceutical production.Such risks are essentially of two types:

1 Cross-contamination (in particular of unexpected contamination)

2 Mix-ups (confusion)

cGMP: Current Good Manufacturing Practices This means any procedure / system adopted bythe manufacturer which proves to be necessary and important for identity, strength and purity

of a product

14 What is the difference between Qualification and Validation?

Qualification is equipment / instrument oriented but validation is process oriented

15 What is the definition of Validation?

Validation is the documented program that provides a high degree of assurance that a specificprocess, method or system will consistently produce a result meeting predeterminedacceptance criteria

16 What is the definition of Qualification?

Qualification is the action of proving and documenting that any equipment or ancillary systemsare properly installed, work correctly, actually leads the expected results Qualification is part

of validation, but the individual qualification steps alone do not constitute process validation

17 What are the types of validation?

Process validation, Analytical method validation, cleaning validation, facility validation, Utilityvalidation & software validation

18 Definition of process validation and types of process validation?

Process validation is the documented evidence that the process, operated within establishedparameters, can perform effectively and reproducibly to produce an intermediate / API meeting

Process validation is three types:

1 Prospective process validation

2 Concurrent process validation

3 Retrospective process validation

19 What is the prospective, concurrent and retrospective validation?

Prospective process validation: Prospective Process validation shall be carried out for all theintermediate stages and Active Pharmaceutical Ingredients prior to the distribution of a newproduct [ICH: GMP, EU: GMP, PIC/S: GMP]

Concurrent process validation: Any validated process undergoes a change either for theequipment or addition, deletion of a critical manufacturing process step, scale up or scaledown, the same needs to be validated concurrently

The validation is carried out only after a change of an existing validated process to support thechange made or involve with the requirements

Or

A subset of prospective validation in which API batches are released for distribution, based onextensive testing, before completion of process validation Once data from additionalbatches produced under replicated conditions show uniformity, the process may beconsidered validated

Or

Concurrent validation can be conducted when data from replicate production runs areunavailable because only a limited number of API batches have been produced, API batchesare produced infrequently, or API batches are produced by a validated process that has beenmodified [ICH: GMP, EU: GMP, PIC/S: GMP]

Retrospective process validation: Validation of a process for a product already in distributionbased upon accumulated production, testing and control data [ICH: GMP, EU: GMP, PIC/S:GMP]

20 What do you mean by validation protocol and its contents of process validation?

A written plan stating, how validation will be conducted and defining acceptance criteria

parameters, and / or operating range, product characteristics, sampling, test data to becollected, number of validations runs and acceptance test results.

 List of equipments used in the manufacturing process

 List of raw materials used in the manufacturing process

 Critical operations with justification

 In-process controls with acceptance criteria

 Sampling & testing plan with frequency

21 What is the definition of the procedure?

A documented description of the operation to be performed, the precautions to be taken, andmeasures to be applied directly or indirectly related to the manufacture of an intermediate /API (Reference: ICH Q7A)

Master document is a formally authorized source document relating to specifications, and / ormanufacturing / analytical methods, which is protected from un-authorized access oramendment.

 Documents required describing the quality system requirements in the organization

 Documents required describing the process or product characteristics

 Documents required by various regulatory agencies as part of compliance to GMPrequirements

 Documents required for legal/ regulatory supports of the organization to meet the localregulations

 Any other documents required by government / regulatory agency

23 What is documentation?

All the written production procedures, instructions and records, quality control procedures andrecorded test results involved in the manufacturing of a medicinal product

24 What is the Technology Transfer?

In the pharmaceutical industry, “technology transfer” refers to the processes that are neededfor successful progress from drug discovery to product development to clinical trials to full-scale commercialization or it is the process by which a developer of technology makes itstechnology available to commercial partner that will exploit the technology

To assure the drug quality, it is desire to make sure 5 W’s and 1 H, that is what1, when2, andwhy3 information should be transferred to where4 and by whom5 and how to transfer, thenshare knowledge and information of the technology transfer each other between stake holdersrelated to drug manufacturing

25 What are the names of different countries of GMP guidelines for manufacturing of API?

PIC/S GMP- Germany

Schedule M – Indian

26 What is preventive maintenance?

It is periodic inspection and minor repairs of equipment as per schedule given in the SOP Thisenables smooth operation and long life of the equipment It also avoids major breakdown ofthe equipment during manufacturing of the product

There are two types of maintenance

Preventive maintenance: Schedule maintenance before any break down of machinery whichprevents the machine break down

Breakdown maintenance: Maintenance was done after stopping machine breakdown

Weekly, Monthly, Quarterly, Half yearly and Yearly preventive maintenance

27 What do you mean by “Quality Assurance”?

The sum total of the organized arrangements made with the objects of ensuring that all APIsare of the quality required for their intended use and the quality systems are maintained

28 What are the types of different training programs?

30 What are the requirements for the equipment used in the manufacturing of process of API?

Material of construction used for equipment should not

 React with component

 Get corroded, cause rusting

 Impart any impurities, absord

31 How are cGMP implemented?

Training, compliance to SOPs, control on operations, following procedures / systems,monitoring through compliance audits

32 What is solvent?

An organic or inorganic liquid used as a vehicle for the preparation of solutions or suspensions

in the manufacturing of an intermediate / API

33 What are the classifications of residual solvents?

Residual solvents are classified into three class based on the possible risk to human health:Class-I (Solvents to be avoided)

Class-II (Solvents to be limited)

Class-III (Solvents with low toxic potential)

34 What is the difference between Responsibility and Accountability?

Responsibility: Personnel directly associated with the implementation of the procedure

Accountability: Person directly associated with the implementation of the system under whichthe procedure falls

35 Write the names of the different countries regulatory body (Like for India, USA, UK, Australia,

South Africa, Brazil, Hungary, Germany, Philippines etc.)

India – Schedule M

United Status of America – USFDA (United state Food and Drug Administration)

Australia – TGA (Therapeutic Goods Administration)

United Kingdom – MHRA (Medicines & Health care products Regulatory Agency)

South Africa – MCC (Medicine Control Council)

Brazil – ANVISA (Brazilian Health Surveillance Agency or National Sanitary Surveillance Agency)Hungary - PIC/S (Pharmaceutical Inspection Convention or Pharmaceutical Inspection Co-operation Scheme)

Germany – NIP (National Institute of Pharmacy)

Philippines – BFAD (Beaureu of Food & Drug)

36 What is the abbreviation of MSDS and how many contents are mentioned & what are those?

MSDS means Material Safety Data Sheet and it contains 16 contents Those are given below:

1 Product Identification

3 Hazards identification

4 First Aid measures

5 Fire fighting measures

6 Accidental release measures

7 Handling & storage

8 Exposure controls / Personal protection

9 Physical & Chemical properties

10.Stability & Reactivity

37 What is the static electricity?

Denoting / pertaining to electricity which is at rest The electricity which is present on surface

of a non-conductive body, where it is trapped from escaping, is called static electricity

38 What is the different types of Qualifications and write its flow?

Qualifications are as follows: Design Qualification, Installation Qualification, OperationalQualification, and Performance Qualification

URS/DS -FAT -SAT -DQ -IQ -OQ -PQ

39 What is audit/inspection and Why quality audit? Write different types of audits/inspection?

A planned and systematic examination and check of a system, procedure or operation in order

to monitor compliance with and the effectiveness of established standards and to allow forimprovement and corrective measures where required

Quality audit because of:

 To assess the effectiveness of the quality management system

 Assessing conformance

 Continual improvement of performance

 Assessing for Registration

 Reducing cost of operation

 Legal requirement

Types: 1 Study/test based inspection

2 Facility based inspection

3 Process based inspection

40 Why nitrogen gas used in the manufacturing area at room temperature and why not other gas?

Because of nitrogen is chemically less reactive and does not react with other elements atordinary temperature It is due to strong bonding in its molecule

41 What are the different types of cleanings?

There are three types of cleanings:

 Batch to Batch cleaning

43 What is expiry date & re-test date?

Expiry date: The date place on the container / labels of an API designated the time duringwhich the API is expected to remain within established shelf life specifications if stored underdefined conditions and after which it should not be used

Re-test date: The date when a material should be re-examined to ensure that it is still suitablefor use The period of time during which the drug substance is expected to remain within itsspecifications and therefore, can be used in the manufacturing of the drug product, providedthat drug substance has been stored under the defined conditions

44 What is difference between reprocess & rework?

Reprocess: Introducing an intermediate or API, including one that does not conform to

appropriate chemical or physical manipulation steps (e.g., distillation, filtration,chromatography, and milling) that are part of the established manufacturing process.Continuation of a process step after an in-process control test has shown that the step isincomplete, is considered to be part of the normal process, and is not reprocessing.

Reworking: Subjecting an intermediate or API that does not conform to standards orspecifications to one or more processing steps that are different from the establishedmanufacturing process to obtain acceptable quality intermediate or API (e.g., recrystallizingwith a different solvent)

45 What is deviation & its types?

Deviation is departure from the approved instructions /established standards

There are two types of deviation and given below:

Controlled / planned deviation: Any deviation from documented procedure opted deliberatelyfor temporary period to manage unavoidable situation or improving the performance of theoperations, without affecting the quality & yield of drug substance and safety of the operationsshall be termed as controlled / planned deviation

Uncontrolled / unplanned deviation: Any deviation occurred in unplanned or uncontrolledmanner such as system failure or equipment breakdown or manual error shall be termed asuncontrolled / unplanned deviation

46 What is change control and its types?

Change control is a system that control change by

i Identifying ownership of the change

ii Allowing for review and approval of the change

iii Preventing changes that could adversely affect product quality or conflict withregistration or regulatory requirement

iv Providing an assessment of change and monitors the impact of change

Level 1 (Minor): Are those that are unlikely to have any detectable impact on the quality

attributes of the product

quality attributes of the product.

The type of reasons for change control:

47 What is contamination and cross-contamination?

Contamination: The undesired introduction of impurities of a chemical or Microbiologicalnature, or of foreign matter, in to or onto a raw material, intermediate, or API during production,sampling, packaging or repackaging, storage or transport

Cross-contamination: Contamination of a material or of a product with another material orproduct

48 What is Batch number and batch?

Batch Number: A unique combination of numbers, letters, and/or symbols which identifies abatch (or lot) and from which the production and distribution history can be determined

Batch: A specific quantity of material produced in a process or series of processes so that it isexpected to be homogeneous within specified limits In the case of continuous production, abatch may correspond to a defined fraction of the production Batch size may be defined either

by a fixed quantity or the amount produced in a fixed time interval

49 What is quarantine?

The status of materials isolated physically or by other effective means pending a decision ontheir subsequent approval or rejection

50 What is definition of critical process parameters?

A process parameter whose variability has an impact on a critical quality attribute and

51 What is mother liquor?

The residual liquid which remains after the crystallization or isolation processes Mother liquormay contain un-reacted materials, intermediates, levels of the API and/or impurities It may beused for further processing

52 What is the difference between theoretical and expected yield?

Theoretical yield: The quantity that would be produced at any appropriate phase of production,based upon the quantity of material to be used, in the absence of any loss or error in actualproduction

Expected yield: The quantity of material or the percentage of theoretical yield anticipated atany appropriate phase of production based on previous laboratory, pilot scale, ormanufacturing data

53 What is OOS?

Out of Specification (OOS) results are those results, generated during testing that do notcomply with the relevant specification or standards or with the defined acceptance criteria

54 What is CAPA?

CAPA is the Corrective Action & Preventive Action

Corrective Action: Action taken to eliminate the causes of an existing non-conformity, defect orother undesirable situation to prevent recurrence [Actions taken after the occurrence of adefect or problem to stop the same from recurrence]

Preventive Action: Action taken to eliminate the causes of potential non-conformity, defect orother undesirable situation to prevent occurrence [Actions initiated before the occurrence of adefect or problem to prevent the same occurrence]

55 What is the ICH? Write its aim/purpose and names of the different parties & different regions?

ICH means “International conference on harmonization”

Aim/Purpose: “Ensure good quality, safety and effective medicines are developed andregistered in the most effective manner, through harmonization of technical requirements”Different Parties:

1 European commission – European Union (EMEA)

3 Minister of health, Labour & Welfare, Japan (MHLW)

4 Japan Pharmaceutical Manufactures Association (JPMA)

5 US Food & drugs Administration (FDA)

6 Pharmaceutical Research & Manufactures of America (PhRMA)

Different regions:

1 European Union (EMEA)

2 United states of America (USFDA)

57 Difference between validation & testing?

Both are not same Testing is defined as the identification of errors (difference betweenexpected & actual results) in a system Validation is defined as documented evidence that asystem performance as expected Validation includes testing but it is more – for instance,checking the documents for completeness & correctness

58 Why water is used extensively as a coolant in heat exchange equipments?

Because of the abundance and high heat capacity, water is used as coolant in heat exchangeequipment

59 What are the different characteristics of the fluid are to be considered while deciding its

The following characteristic of the fluid are to be considered while deciding its route in a heatexchanger: a) Viscosity b) Fouling c) Corrosiveness d) Pressure

60 When steam distillation recommended?

a) To separate appreciable quantities of higher boiling materials

b) To separate relatively small amounts of volatile impurity from a large amount of

material

c) Where use of direct-fired heaters is detrimental to the materials

d) Where the material is to be subjected to distillation is thermally unstable or will react

with other component associated with it at the boiling temperature

e) Where the material cannot be distilled by in-direct heating even under low pressure

because of the high boiling temperature

61 What is the difference between instrument & equipment?

Instrument: A device that takes a physical measurement and displays a value or has no control

or analytical functions e.g.: Stop watch, timers & thermometer

[A device <chemical, electrical, hydraulic, magnetic, mechanical, optical, pneumatic> used totest, observe, measure, monitor, alter, generate, record, calibrate, manage or control physicalproperties, movements, or other characteristics]

Equipment: A device or collection of components that perform a process to produce a result.[The collective analytical measurement instruments in conjunction with firmware, assembled

to perform a mechanical process]

62 What is HVAC?

The HVAC is designed to circulate the air in the area after passing it over cooling & heatingcoils to maintain the required environmental conditions & passing it through the series offilters to maintain desired cleanliness level in the area The air in-take and out-take of thesystem is designed to maintain certain degree of pressure gradient in the area as perrequirements

Or

HVAC system function is to condition (heating & cooling), replace (makeup, fresh air, oxygenreplacement), and pressurize (contaminant) and clean (filter) the air in the environment tomeet the required operational conditions

several configurations such that they produce the expected results.

63 What is the meaning of Q, S, E, M in the ICH?

“Q” stands for Quality; “S” stands for Safety, “E” stands for Efficacy and “M” stands for Multidispensary

64 How many guidelines are present in Q & what are those, describe in detail?

In Quality (Q), total 10 guidelines are present Those are as follows:

9 Q9 - Quality Risk Management

10 Q10 - Pharmaceutical Quality System

65 How many types of raw material and packing material?

Raw materials are classified into two types Those are as follows:

1 Key raw material

2 Other raw material

Packing materials are classified into two types Those are as follows:

1 Primary Packing material

2 Secondary Packing material

66 Define the Key raw material/ starting material & primary packing material?

Key raw material/starting material:

Starting material shall be defined as that which is

 Incorporated as a significant structural fragment of the API / Drug Intermediate and

 Having significant effect on the Quality and Yield of the product

 Starting material shall be identified in TDP

Primary Packing material: Packing material, which come in direct contact with theAPI/Intermediate are considered as Primary packing material

Cleaning validation is documented evidence that an approved cleaning procedure will provideequipment which is suitable for processing of pharmaceutical products or APIs.

Cleaning validation is the confirmation of reliable cleaning products so that the analyticalmonitoring may be omitted or reduced to a minimum in the routine phase

It describes the validation of cleaning procedures for the removal of contaminants associatedwith the previous products, residues of cleaning agents as well as the control of potentialmicrobial contaminants

68 What are the sampling techniques used in the cleaning validation?

Swab sampling: Areas which are reasonably accessible & hardest to clean can be evaluated,leading to level of contamination or residue per gives surface area

Rinse sampling: Large areas or parts of equipments which could not be swabbed should berinse sampled or directly extracted by solvent Tubes, nozzles, pipes or containers with surfacethose are not reasonably accessible for direct surface sampling have to be rinsed with solvent

In addition, inaccessible areas of equipment that cannot be routinely disassembled can beevaluated

69 What parameters considered during performance qualification of HVAC?

The following parameters are to be considered during the performance qualification of HVAC:

1 Calibration test certificates of instruments

2 Training records of validation team

3 Pressure drop across the HEPA & fine filters

4 Air velocity measurement & calculation of Air changes

5 Integrity test of HEPA filter

6 Differential pressure test

7 Temperature & Relative Humidity test

8 Air flow direction test

9 Cleanliness class verification (Non-viable particle count)

10.Sound level test

11.Light level test

12.Air borne viable particle monitoring

13.Recovery Study

BPCR contains the following contents, but not limited:

1 Product Name 2 Stage

3 BPCR Document Number 4 MPCR Reference Number

5 Batch Number 6 Date of Manufacturing

7 Date of Expiry/Re-test 8 Batch release details

9 List of equipments used 10 List of raw materials & Quantity with UOM

11 General instructions, Control & Safety instructions

12 Detailed step wise written manufacturing procedures

13 Actual results record for critical process parameters

14 Identity of In-process & Laboratory test results

15 Signatures of person performing details along with supervising details

16 Description of Packaging details

17 Yield calculation

18 Representative of labels for intermediates / raw materials

19 Deviation details

20 Batch starting & completion date

71 What is OOT and define?

“OOT” stands for Out Of Trend It means any test results obtained for a particular batch that ismarkedly different the results of the batches in a series obtained using a same validatedmethod

72 How will you prevent cross-contamination between two different products manufactured in

the one production block?

By maintaining the proper pressure differential between the rooms with two Air handling units(if re-circulation) / one Air handling unit (if 100% fresh air)

73 What is limit of Temperature and relative humidity in the pharma area?

Temperature: 25±2˚C & Relative Humidity: 50±5%

74 What is the difference between dedicated and non-dedicated equipments?

Dedicated equipment: It is used solely for the production of a single product or product line.Concerns over cross-contamination with other products are markedly reduced Dedicatedequipments must be clearly identified with the restrictions of use in order to prevent potential

Non-dedicated equipment: Where the same piece of equipment is utilized for a range ofproducts formulations The prevent of cross-contamination between products becomes themain objective in the cleaning validation effort Clearly, cleaning non-dedicated equipmentsrepresents a more significant obstacle to overcome.

75 Which instrument is used for the measuring of RPM?

Techo meter is used for the measurement of RPM

76 Why three batches consider for the validation?

Because of First one is for information, Second one is for confirmation and Third one is forevidence

77 If one batch is failed during the validation, then what will you do for completion of validation?

 When a quality parameter fails with respect to the specification, a deviation report shall

be raised and the investigation shall be conducted immediately for the identification offailure

 If the reason for failure is identified, one more consecutive batch shall be considered for

the validation run by taking preventive actions to avoid those failures (If necessaryrevise the MPCR and BPCR)

 If the reason is unidentified, another three consecutive batches shall be taken for

validation

78 What are specifications of Purified water as per any pharmacopoeia?

Tests Ph Eur

Description Clear, colorless liquid

Acidity /Alkalinity The solution is not colored red/The solution is not colored

blue

Oxidisable substances The solution remains faintly pink

Chlorides The solution shows no change in appearance for at least 15

minSulphates The solution shows no change in appearance for at least 1

hourAmmonium Maximum 0.2 ppm

Calcium and magnesium A pure blue colour is produced

Residue on evaporation Maximum 0.001 per cent

Aluminum Maximum 10 ppb,

Nitrates NMT 0.2 ppm

79 Write the different storage conditions as per any guidelines (specify the name of guideline)?

The different storage conditions are given below as per USP:

Freezer : -25°C to -10°C

Cold : Any temperature not exceeding 8°C

Refrigerator : Between 2°C and 8°C

81 Write the names of some fumigation agents?

82 Write the different types of fires, which are generally used in the pharmaceutical industry?

a) Chemical fireb) Electrical firec) Metal fired) General firee) Gaseous fire

83 What is ISO 9001, ISO 14001, ISO 18001, ISO 22001?

ISO 9001 : Quality Standard Management

ISO 14001 : Environmental Standard Management

ISO 22001 : Hazop Standard Management

84 What is HACCP?

HACCP : Hazard Analysis Critical Control Point

85 What is OHSAS?

OHSAS : Occupational Health & Safety Assessment Series

86 Why one liter of water is equivalent to one kilogram of water at room temperature?

Because of at normal room temperature is between 25°C and 35°C at plant operating conditionand the variation in weight Vs Liter of water is negligible compared to volume

87 What is room temperature?

The temperature at prevailing working area

88 What is calibration?

The demonstration that a particular instrument or device produces results within specifiedlimits by comparison with results produced by a reference or traceable standard over anappropriate range of measurements

89 What is the maximum time allowed after cleaning with water as last rinse?

Equipment should not be left with water it after cleaning The last step of the cleaningprocedures involve drying with solvent or flushing with nitrogen, thus ensuring that there is noopportunity for microbial growth

90 What is the efficiency of the High Efficiency Particulate Air (HEPA) filter?

This type of air filter can remove at least 99.97% particles in air up to 0.3μm in diameter

91 What is the micron size of HEPA filter?

The micron size of HEPA filter is 0.3μm

92 Do you have any idea about schematic diagram of HVAC system?

Fresh Air

Filtering of Air with Pre filter

Cooling & Heating coil

Filtering of Air with Fine filter

Filtering of air with HEPA filter, If required

Suction of air through return ducts from the process area using some pre filters as per

Air is exhausted to atmosphere after filtration wherever required

Portion of air then passes through a dehumidifier wherever dehumidifier is required

In the mixing chamber, return Air & Fresh air get mixed

Process repeats from

93 If two different products are manufacturing in two modules of one production block, then will

you accept the common air handling unit for both pharma area? Write “Yes” or “No” withreason?

No, because of cross-contamination (if re-circulation of return air)

Yes, if 100% of fresh air is circulated through the respective area

94 Why blending validation is required? What quality parameters of product are considered for

validation and what parameters of equipment are to be considered during validation?

Because of to provide sufficient documented evidence to assure that the blending operation ofproduct is capable of repeatedly and reliably producing a homogeneous material to meetestablished specifications when operated under defined standard conditions

The following Quality parameters are to be considered, but not limited:

a) Loss on Drying / Water contentb) Bulk density / tapped densityc) Residual solvent

d) Particle sizeThe following parameters are to be considered for the equipment during validation, but notlimited:

a) Blender capacityb) RPM of the blenderc) Occupancy of the blenderd) Number of individual batches to be taken for each blende) Mixing time

95 What is the formula for calculation of “Air changes per hour” during HVAC validation?

Total CFM of the blower/Filter x 60Air changes per hour= -

96 During the performance qualification in the vacuum tray dryer, how many temperature probsused?

Total 16 to 24 temperature probes are to be kept during the performance qualification of thevacuum tray dryer (or number of probes specified in the protocol)

97 What is the formula for the calculation of “MACO” while cleaning between one API to anotherAPI?

Minimum therapeutic dosage of previous product X Minimum batch size of nextproduct

MACO =

-Safety factor X Maximum therapeutic dosage of the next product

98 What is the limit for “Individual unknown Impurity” in API as per ICH Q2A?

The limit of the “Any individual unknown Impurity” is not more than 0.1%

99 What are the class-I solvents as per ICH Q3C?

Benzene - 2 ppm Carbon tetrachloride - 4 ppm

1,2-Dichloroethane - 5 ppm 1,1-Dichloroethene - 8 ppm

1,1,1-Trichloroethane - 1500 ppm

100 What is the abbreviation of CAS Number?

CAS Number : Chemical Abstract Service Number

101 What is the specific gravity of Methylene chloride?

Specific gravity of Methylene chloride is 1.308 g/ml

102 If equipment is cleaned with water, then finally it should be rinse with suitable solvent as per

guidelines, why?

Because of the last step of the cleaning procedures involve drying with solvent or flushing withnitrogen, thus ensuring that there is no opportunity for microbial growth

103 What is mean by “4M”?

“4M” means Man, Machine, Method and Material

104 If supposed your pharma area is class 100000, then what is the maximum light and sound

level as per guidelines?

The light & sound level limits are given below for class 100,000 / ISO 8:

Light Level : Not less than 300 Lux

Sound Level : Not more than 80 decibels

Physical : Dust, Dirt, Grit, Fiber, Lint & Fly ash

Chemical : Organic compound, Inorganic salts, vapor, mist, fume & smoke

Biologic : Bacteria, Fungus, Spore, Pollen, Virus, Human skin & cells

Energy:

Energy : Thermal, Light, Electromagnetic (EMI), Electrostatic (ESD), Radiation &Electrical

106 What is mean by “Clean-in-Place” and “Clean-out-Place”?

Clean-in-Place: The cleaning of large pieces of equipment may be performed in theequipments permanent location Generally, in a configuration very similar to that in which it isutilized for production This procedure widely known as Clean-in-Place (CIP)

Clean-out-Place: The smaller items are frequently transported to a designated cleaning orwashing area where the cleaning procedures is performed This practice is known as clean-out-place (COP)

107 What is the name of the instrument, which is used for measuring of vacuum (in Tars) during

high vacuum distillation?

Macleod gauge

108 Is cGMP requirement only for personnel in the manufacturing?

No, this requirement is for each and every employee of the organization who must know therelevant cGMP requirements in his/her area

109 Why cGMP should be followed?

This is a regulation that each one of us is trained in cGMP and practices cGMP

- It minimizes the possibilities of any errors caused by subjectivity

- It makes you do your job right the first time and every time

110 For which areas do we have SOPs?

We have SOPs for the following areas:

- Quality Assurance

- Quality Control

- Production

111 Why do we conduct trainings?

It brings awareness and helps us in becoming competent

112 What is personal hygiene?

Each personal should:

- Wear clean uniform

- Take bath daily

- Report illness or injury

- Be medically fit

- Develop good hygiene habits

113 What are cGMP requirements for building and facilities?

Following are the cGMP requirements:

- Suitable size, construction and location

- Facilitate cleaning, maintenance and proper operation

- Adequate space

- Defined areas of adequate size

- Water supply: continuous and of good quality

- Power supply: continuous

- Adequate lighting, ventilations, air filtration, plumbing sewage, toilet facilities

114 What is mean by designated area?

By designated area we mean:

- Specific area for a specific operation: e.g packing operation shall be carried out only inpacking room and not elsewhere

115 How do we know that the gauges are ok?

Gauges are periodically calibrated and they bear the calibration status tag

116 What is in-process control?

In-process control of the process provides an acceptable and achievable level of built in qualityassurance for the product This is possible through appropriate GMP during all manufacturingsteps.

Or

Checks performed during production in order to monitor and, if necessary to adjust theprocess and / or to ensure that the intermediate or API conforms to its specifications

117 What is critical process parameter?

A process parameter whose variability has an impact on a critical quality attribute andtherefore should be monitored or controlled to ensure the process produces the desired quality.Or

A process condition or material or a test when it is essential to maintain a predetermined rage

in order to reproducibly meet the specification is called critical parameter Critical parametershave direct impact on the quality of a product

118 What precautions are to be observed while working in the powder processing room?

Following precautions should be observed while working in the powder processing rooms:

- Absolute discipline w.r.t complete uniform

- Bunny suit, clean shoe covers, hand loves, snoot mask etc and SOPs compliance

- Positive pressure

- House keeping

- Avoid foreign objects (pens, pencils, tools etc.)

- Identification / status card on materials

- Stage slips on equipments

- Temperature (less than 25°C)

- Avoid extraneous contamination from dust, insects, micro-organism, foreign particles etc

- Check the condition of sieves used in multi mill and sifter

- Cleaning and calibration of weighing balances

- Usage of fresh, clean drums and poly bags for final packing

119 What precautions do we take during storage of API?

All APIs are stored under controlled conditions of temperature and humidity in their designatedarea

House keeping is done on daily basis and records are kept for the same.

Insects, pests and rodent control procedures are follows

120 What is mean by the word “Quality”?

Quality is basically customer’s satisfaction through sensitivity

Or

A measure of a product’s or service’s ability to satisfy the customer’s stated or implied needs

121 Inspection can be of three types, what are those?

Inspections are three types:

- Study /test based inspection

- Facility based inspection

- Process based inspection

122 Define stability study and its necessity?

Stability study is defined as “stability testing is to provide evidence how quality varies with timeunder influence as: temperature, humidity & light”

- Establish re-test period for drug substance

- Establish shelf life for drug product

- Recommended storage conditions

123 Write the different types of stability study conditions as per ICH guidelines?

General storage conditions:

Name Temperature (°C) Relative humidity (%)

124 What do you mean by “Reference standard” and “Working standard”?

Reference Standard: A substance that has been shown by an extensive set of analytical tests

officially recognized source or may be prepared by independent synthesis or by furtherpurification of existing production material.

Working Standard: A substance of established quality and purity, as shown by comparison to aprimary reference standard, used as a reference standard for routine laboratory analysis

125 What is abbreviation of CTD?

“CTD” means Common Technical Document This is addressed in the ICH guidelines in thesection of “M” and in the part of “M4”

126 What do you mean by market complaint?

Any communication, written or verbal, received regarding the quality, packing directly from anytraders or product manufacturer and marketing staff or any other such complaints shall beconsidered as a Market Complaint

127 What is maximum time period for the sending of the final response to concerned customer

regarding the market complaint?

Within 30 days or as specified in the Market compliant SOP

128 Describe the categories of the market complaints?

Market complaints are categorized into three types and are as follows:

Critical: Complaints related to suspected contamination, adulteration and mislabeling

Major: Complaints related to the product not meeting its pre-determined critical specifications

and damage to primary packaging

Minor: Complaints related to the product not meeting non-critical quality attributes, or damage

to secondary packaging or shortages etc

129 What are the types of non-compliances in the internal audit?

Non-compliances shall be categorized as follows:

Critical: Those findings that warrant stoppage of any further operations in the facility until the

corrective actions have been completed

Major: Those findings that require immediate corrective action plan and compliance although

operations can be continued

department Head and Quality Assurance.

130 How many phases are divided the performance qualification of purified water system and

write the duration of each phase?

Performance qualification of purified water system is divided into the three phases anddescribed below:

Phase-I: (a) Develop & finalize operating, preventive maintenance, sanitization procedures

(b) Demonstrate production & delivery of water of required quality

(c) To finalize SOP on sanitization, Alert & Action limits

(d) Phase – I shall be conducted for 30 days

Phase-II: (a) Demonstrate consistent operation within established ranges

(b) Demonstrate consistent production & delivery of water of required quality

(c) Phase – II shall be conducted for 30 days

Phase-III: (a) Demonstrate extended performance

(b) Ensure that potential seasonal variations are evaluated & treated

(c) Phase-III shall be conducted for 10 - 12 months

131 What is the abbreviation of “TDP” and its contents?

“TDP” means Technical Data Package and shall contain the following contents, but not limited:

 Brief manufacturing process

 Solvents used in the manufacture

 Impurity profile

 Working standard profile (If any)

 Characterization data (if any)

 Specifications and test procedures of the supplier

 TSE / BSE free Certificate

 Stability studies/ Hold time data

 Storage conditions

 Packing details

 MSDS

 Certificate Of Analysis (COA)

 DMF Number (if any)

Material

Evaluate minimum 3 consignments as per specifications

Quality Complies/

Approved

Quality complies?

Lab/Plant trial/stability Ok?

Request purchase of samples of three distinct lots

Raw material Vendor Qualification – QA Activities

Data shall be available for 3 consignments

Organic

Polymeri

c

Food Grade certificati

Compliance Certificate for

21 CFR?

Approved Vendor Reject vendor

Vendor samples quality OK?

135 What do you mean by “worst case”?

A condition or set of conditions encompassing upper and lower processing limit andcircumstances, within standard operating procedures, which poses the greatest chance ofproduct or process failure when compared to ideal conditions Such conditions do notnecessarily induce product or process failure

136 What do you mean by “performance qualification”?

The performance qualification documents describes the procedures for demonstrating that asystem / piece of equipment can consistently perform & meet required specifications underroutine operation and where appropriate, under worst case situations

137 How will you close a market complaint?

(a) If satisfactory response obtained from complainant against our written reply

(b) If the material is recalled

(c) If no response obtained from the complainant after 90 days (or specified in SOP) fromdate of our written reply

138 Describe about swab and rinse sampling?

Swab: Areas which are reasonably accessible & hardest to clean can be evaluated, leading tolevel of contamination or residue per given surface area

 Take the clean swab having surface area of 10mmX10mm

 Put the swab in the test tube containing 10 ml suitable solvent and squeeze the swabalong the sides of the test tube to remove the excess of water from it

 Identify the locations for swab sampling

 Take out the wet swab from the test tube without touching the tip of swab

 Place the one side of swab over the identified location and apply it on the 10 X 10 sq

cm area first in vertical fashion without changing face of the swab

 Turn the swab to other side and apply it on the area in horizontal fashion covering allthe areas

 Place the swab stick in to the test tube having 10 ml suitable solvent without touchingthe tip

 Lave the test tube with the location

Rinse: Large area or parts of equipments which could not be swabbed should be rinse

direct surface sampling have to be rinsed with suitable solvent.

 Use specified volume of suitable solvent for rinsing

 Rinse the identified locations using the following procedure

 Take specified quantity of suitable solvent in a graduated bucket

 Use a clean mug to splash the solvent in the reactor

 Close the bottom valve of the reactor

 Take solvent in the mug splash at all side of the reactor

 Attention to be applied particularly on the blind sides in the inside top of the reactor

 Splash the solvent at the agitator shaft and blades

 Open the bottom valve and collect the washed solvent in a clean bucket Collect about

100 ml (specified quantity in the protocol) in a sample bottle from the bucket Close thelid and label it properly

 When more than one equipment is involved (equipment chain) for rinsing, suitablequantity of solvent shall be used and the rinse volume shall be measured

139 What is the difference between specification and Limit?

Specification: A document giving a description of a starting material, packaging material,intermediate, bulk or finished product in terms of its chemical, physical & possibly biologicalcharacteristics A specification normally includes description clauses & numerical clauses, thelatter stating standards & permitted tolerances

140 What are the possible causes for “Out of Specification”?

The following are the possible causes for out of specification:

 Lab equipment malfunctioning or off-calibrated

 Production equipment malfunctioning or off-calibrated

 Operator/human errors

141 What is the clean room specifications for different classes (for >= 0.5 μm and >=5.0 μm

particles) as per EU GMP/US 209E/ISO 14644-1/ Schedule M/ WHO GMP?

D 3520000 29300 Not defined Not defined

As per USFDA (US 209E):

Clean Area Maximum permitted number ofparticles/ft3 Maximum permitted number of

Maximum permitted number of

particles/ft3 Maximum permitted number of