MOST FREQUENTLY ASKED QUESTIONS IN PHARMA I Pharma Knowledge By SD

MOST FREQUENTLY ASKED QUESTIONS IN PHARMA

1. What is the definition of SOP?

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

Or

A written authorized procedure which gives instructions for performing operations not

Necessarily specific to a given product / material, but a more general nature the equipment's preventive maintenance and cleaning; recall products; purchasing; cleaning premises and environmental 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 and SHOW” 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 the SOP?

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

3. Which information should master document carry on every not just one these to meet GMP?

 Ans. Number, document reference number and authorizing signatures

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

Ans. Operation, Cleaning, Preventive maintenance/ Calibration, Sampling procedure

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

Ans. BPCR are prepared for each intermediate and API and include the complete information relating to the completion each significant step in the Batch production.

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

Ans. To ensure the uniformity from batch to batch, master production instructions for each intermediate 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 the MPCR?

Ans.  The name the intermediate or API being manufactured and an identifying document reference code, if applicable

 A complete list raw materials and intermediates designated by names or codes

Sufficiently specific to identify any special quality characteristics.

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

be used, including the unit measure. Where the quantity is not fixed, the calculation

for each batch size or rate production should be included. Variations to quantities

should 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 process parameters to be used

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

appropriate

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

where appropriate

- expected yield ranges at appropriate phases processing or time

-Where appropriate, special notations and precautions to be followed, or cross references to these

The instructions for storage the intermediate or API to ensure its suitability for use,

Including the labeling and packaging materials and special storage conditions with time

limits, where appropriate.

8. What is the list SOPs required in QA department?

Ans. SOP for SOP, SOP for format preparation, change control, deviation, Non-conformance

products, market complaints, product recall, returned goods, vendor qualification, preparation of BPCR & MPCR, Assigning Mfg. date & Expiry date, annual product review, corrective action & preventive action, process validation, cleaning validation, equipment qualification, glossary terms,  document control, Review BPCR & analytical test report, batch numbering system, labeling practice, personnel training, BPCR issue and retrieval, batch release, self inspection (internal audit), file numbering system, preparation organo- gram, preparation of COA, specimen signatures, Reprocess & rework intermediates / API, Job responsibilities, Technology transfer, measurable quality objectives etc.

9. What is the difference between intermediate and drug substance (API)?

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

API: Any substance or mixture substances intended to be used in the manufacturing a

drug (medicinal) product and that when used in the production a drug, becomes an API of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention disease or to affect the structure & function he body (Reference: ICH Q7A).

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

Ans. Drug substance (API): Any substance or mixture substances intended to be used in the Manufacture a drug (medicinal) product and that, when used in the production a drug, becomes an active ingredient the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention disease or to affect the structure and function 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?

Ans. Clean rooms are defined as especially constructed, environmentally controlled enclosed

spaces with respect to airborne particulates, temperature, humidity, air pressure, air flow patterns, air motion, vibration, noise, viable (living organisms) and lighting.

Particulate control includes:

 Particulate & microbial contamination

 Particulate concentration & dispersion

12. What are the classifications clean rooms?

Ans. 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 146-1: ISO-3, ISO-4, ISO-5, ISO-6, ISO-7, ISO-8, ISO-9

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

 

Australia (AS 1386): 0.035, 0.35, 3.5, 35, 350, 3500

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

13. What is the difference between GMP & cGMP?

Ans. GMP: GMP is the part Quality assurance which ensures that products are consistently produced   and controlled to the quality standards appropriate to their intended use and as required  by the marketing authorization.

GMP are  aimed primarily at diminishing the risks inherent in any pharmaceutical production.

Such risks are essentially two types:

1. Cross-contamination (in particular unexpected contamination)

2. Mix-ups (confusion)

cGMP: Current Good Manufacturing Practices. This means any procedure / system adopted by

the 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?

Ans. Qualification is equipment / instrument oriented but validation is process oriented.

15. What is the definition Validation?

Ans. Validation is the documented program that provides a high degree assurance that a specific process, method or system will consistently produce a result meeting predetermined acceptance criteria.

16. What is the definition Qualification?

Ans. Qualification is the action proving and documenting that any equipment or ancillary systems are 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 is the type’s validation?

Ans. Process validation, Analytical method validation, cleaning validation, facility validation, Utility validation & software validation

18. Definition process validation and type’s process validation?

Ans. Process validation is the documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate / API meeting its pre-determined specifications and quality attributes.

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?

Ans. Prospective process validation: Prospective Process validation shall be carried out for all the intermediate  stages and Active Pharmaceutical Ingredients prior to the distribution a new product. [ICH: GMP, EU: GMP, PIC/S: GMP]

Concurrent process validation: Any validated process undergoes a change either for the

equipment or addition, deletion a  critical manufacturing process step, scale up or scale

down, the same needs to be validated concurrently.

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

Or

A subset prospective validation in which API batches are released for distribution, based on extensive testing, before completion process validation. Once data from additional batches produced under replicated conditions show uniformity, the process may be considered validated

Or

Concurrent validation can be conducted when data from replicate production runs are

unavailable because only a limited number API batches have been produced, API batches are produced infrequently, or API batches are produced by a validated process that has been modified. [ICH: GMP, EU: GMP, PIC/S: GMP]

Retrospective process validation: Validation a process for a product already in distribution based 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 process validation?

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

e.g:  The protocol for manufacturing process identifies process equipments, critical process parameters, and / or operating range, product characteristics, sampling, test data to be collected, number validations runs and acceptance test results.

Contents:

 Protocol Approval

 Table contents

 Objective

 Scope

 Responsibility

 Accountability

 Validation team

 Brief manufacturing process (Description, Flow chart, Reaction scheme)

 Selection batches

 List equipments used in the manufacturing process

 List raw materials used in the manufacturing process

 Critical operations with justification

 In-process controls with acceptance criteria

 Sampling & testing plan with frequency

 Stability program

 Data to be complied

 Acceptance criteria

 Intermediate & final products quality & yield

 Stability specification

 Document review

 Conclusion

 Revalidation criteria

21. What is the definition the procedure?

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

22. What is the master document?

Ans. Master document is a formally authorized source document relating to specifications, and / or

manufacturing / analytical methods, which is protected from un-authorized access or

amendment.

 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 compliance to GMP

    requirements.

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

   regulations.

 Any other documents required by government / regulatory agency.

23. What is documentation?

Ans. All the written production procedures, instructions and records, quality control procedures and

recorded test results involved in the manufacturing a medicinal product.

24. What is the Technology Transfer?

Ans. In the pharmaceutical industry, “technology transfer” refers to the processes that are needed for successful progress from drug discovery to product development to clinical trials to full  scale Commercialization  or it is the process by which a developer technology makes its technology   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, and why  information should be transferred to where4 and by whom5 and how to transfer, then share knowledge and information the technology transfer each other between stake holders related to drug manufacturing.

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

Ans.

WHO GMP - Geneva

ICH Q7A – Europe, Japan & US

EU GMP - Europe

MCC – South Africa

APIC GMP – Active Pharmaceutical Ingredient Committee (A sector group CEFIC)

USFDA GMP – United States America

PIC/S GMP- Germany

Schedule M – Indian

26. What is preventive maintenance?

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

There are two types maintenance.

Preventive maintenance: Schedule maintenance before any break down machinery which prevents 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”?

Ans. The sum total the organized arrangements made with the objects ensuring that all APIs

Are the quality required for their intended use and the quality systems are maintained.

28. What are the types different training programs?

Ans.

1. Induction training

2. Job oriented training

3. cGMP training

4. On-going training

29. What is cGMP?

Ans. Current Good Manufacturing Practices. This means any procedure / system adopted by the manufacturer which proves to be necessary and important for identity, strength and purity product.

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

Ans. Material construction used for equipment should not

 React with component

 Get corroded, cause rusting

 Impart any impurities, absorbed

 Should be appropriate design, adequate size and have smooth surface.

31. How are cGMP implemented?

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

32. What is solvent?

Ans.  An organic or inorganic liquid used as a vehicle for the preparation solutions or suspensions in the manufacturing an intermediate / API.

33. What are the classifications residual solvents?

Ans. 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?

Ans. Responsibility: Personnel directly associated with the implementation the procedure

Accountability: Person directly associated with the implementation the system under which the procedure falls.

35. Write the names the different countries regulatory body (Like for India, USA, UK, Australia, South Africa, Brazil, Hungary, Germany, Philippines etc.)

Ans.

India – Schedule M

United Status 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 Cooperation

Scheme)

Germany – NIP (National Institute Pharmacy)

Philippines – BFAD (Beaureu Food & Drug)

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

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

1. Product Identification

2. Composition / Information on Ingredients

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

11. Toxicological information

12. Ecological information

13. Disposal consideration

14. Transport information

15. Regulatory information

16. Other information

37. What is the static electricity?

Ans. 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 Qualifications and write its flow?

Ans. Qualifications are as follows: Design Qualification, Installation Qualification, Operational

Qualification, and Performance Qualification.

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

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

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

to monitor compliance with and the effectiveness established standards and to allow for

improvement and corrective measures where required.

Quality audit because of:

 To assess the effectiveness he quality management system

 Assessing conformance

 Investigating problems

 Continual improvement performance

 Assessing for Registration

 Reducing cost of preparation

 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?

Ans. Because nitrogen is chemically less reactive and does not react with other elements at ordinary temperature. It is due to strong bonding in its molecule.

41. What are the different types  cleanings?

Ans. There are three types cleanings:

 Batch to Batch cleaning

 Periodically cleaning

 Product change over cleaning

42. What is blending?

Ans. Blending is defined as the process combining materials within the same specification to produce a homogeneous intermediate or API.

43. What is expiry date & re-test date?

Ans. Expiry date: The date place on the container / labels an API designated the time during which the API is expected to remain within established shelf life specifications if stored under defined 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 suitable for use. The period time during which the drug substance is expected to remain within its specifications and therefore, can be used in the manufacturing the drug product, provided that drug substance has been stored under the defined conditions.

44. What is difference between reprocess & rework?

Ans. Reprocess: Introducing an intermediate or API, including one that does not conform to standards or specifications, back into the process and repeating a crystallization step or other appropriate chemical or physical manipulation steps (e.g., distillation, filtration, chromatography, and milling) that are part the established manufacturing process.

Continuation a process step after an in-process control test has shown that the step is

incomplete, is considered to be part the normal process, and is not reprocessing.

Reworking: Subjecting an intermediate or API that does not conform to standards or

specifications to one or more processing steps that are different from the established

manufacturing process to obtain acceptable quality intermediate or API (e.g., re crystallizing with a different solvent).

45. What is deviation & its types?

Ans. Deviation is departure from the approved instructions /established standards.

There are two types deviation and given below:

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

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

46. What is change control and its types?

Ans. Change control is a system that control change by

i. Identifying owner ship the change

ii. Allowing for review and approval the change.

iii. Preventing changes that could adversely affect product quality or conflict with

registration or regulatory requirement.

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

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

Attributes the product.

Level 2 (Major): Are those that are likely to have a significant impact on the

quality attributes the product.

The type reasons for change control:

- Regulatory requirement

- GMP implementation / enhancement

- Quality improvement

- Capacity enhancement

- Introduction new product in existing facility

- Cost reduction

- Automation

- Aging facility

- To manage the unavoidable situation

- Market requirement

47. What is contamination and cross-contamination?

Ans. Contamination: The undesired introduction impurities a chemical or Microbiological

nature, or foreign matter, in to or onto a raw material, intermediate, or API during production, sampling, packaging or repackaging, storage or transport.

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

product.

48. What is Batch number and batch?

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

Batch: A specific quantity material produced in a process or series processes so that it is expected to be homogeneous within specified limits. In the case continuous production, a

batch may correspond to a defined fraction 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?

Ans. The status materials isolated physically or by other effective means pending a decision on their subsequent approval or rejection.

50. What is definition of critical process   parameters?

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

51. What is mother liquor?

Ans. The residual liquid which remains after the crystallization or isolation processes. Mother liquor may contain un-reacted materials, intermediates, levels the API and/or impurities. It may be used for further processing.

52. What is the difference between theoretical and expected yield?

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

Expected yield: The quantity material or the percentage theoretical yield anticipated at

any  appropriate phase production based on previous laboratory, pilot scale, or

manufacturing  data.                                         

53. What is OOS?

Ans. Out of Specification (OOS) results are those results, generated during testing that do not comply with the relevant specification or standards or with the defined acceptance criteria.

54. What is CAPA?

Ans. CAPA is the Corrective Action & Preventive Action.

Corrective Action: Action taken to eliminate the causes an existing non-conformity, defect or

other undesirable situation to prevent recurrence. [Actions taken after the occurrence a

defect or problem to stop the same from recurrence].

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

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

Ans. ICH means “International conference on harmonization”.

Aim/Purpose: “Ensure good quality, safety and effective medicines are developed and

registered in the most effective manner, through harmonization technical requirements”

Different Parties:

1. European commission – European Union (EMEA)

2. European Federation Pharmaceutical Industries & Association (EFPIA)

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

4. Japan Pharmaceutical Manufactures Association (JPMA)

5. US Food & drugs Administration (FDA)

6. Pharmaceutical Research & Manufactures America (PhRMA)

Different regions:

1. European Union (EMEA)

2. United states America (USFDA)

3. Japan (MHLW)

56. What URS, DS, FAT, SAT, DQ, IQ, OQ, PQ?

Ans.

URS:

DS:

FAT:

SAT:

DQ:

Installation Qualification (IQ): Establishing a high degree confidence that the equipment as installed is consistent with manufacture’s requirements and specifications.

Operating Qualification (OQ): Establishing a high degree confidence that the equipment as installed is able to consistently operate within established limits and tolerances.

Performance Qualification (PQ): Establishing a high degree confidence, with appropriate testing that the equipment, under normal operating conditions, will consistently produce a quality product.

57. Difference between validation & testing?

Ans. Both are not same. Testing is defined as the identification errors (difference between expected & actual results) in a system. Validation is defined as documented evidence that a system 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?

Ans. Because the abundance and high heat capacity, water is used as coolant in heat exchange equipment.

59. What are the different characteristics the fluid are to be considered while deciding its route in a heat exchanges?

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

60. When steam distillation recommended?

Ans.

a) To separate appreciable quantities higher boiling materials.

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

material.

c) Where use 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 the high boiling temperature.

61. What is the difference between instrument & equipment?

Ans. 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 to

test, observe, measure, monitor, alter, generate, record, calibrate, manage or control physical

properties, movements, or other characteristics].

Equipment: A device or collection 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?

Ans. The HVAC is designed to circulate the air in the area after passing it over cooling & heating coils to maintain the required environmental conditions & passing it through the series of filters to maintain desired cleanliness level in the area. The air in-take and out-take the system is designed to maintain certain degree pressure gradient in the area as per requirements.      

Or

HVAC system function is to condition (heating & cooling), replace (makeup, fresh air, oxygen

replacement), and pressurize (contaminant) and clean (filter) the air in the environment to meet the required operational conditions.

To achieve this objective, electrical, mechanical & electronic components are arranged in several configurations such that they produce the expected results.

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

Ans. “Q” stands for Quality; “S” stands for Safety, “E” stands for Efficacy and “M” stands for Multi dispensary

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

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

1. Q1 - Stability

2. Q2 - Analytical Method validation

3. Q3 - Impurities

4. Q4 - Pharmacopoeia

5. Q5 - Biotechnological quality

6. Q6 - Specification

7. Q7 - Good Manufacturing Practice (GMP)

8. Q8 - Pharmaceutical Development

9. Q9 - Quality Risk Management

10. Q10 - Pharmaceutical Quality System

65. How many types raw material and packing material?

Ans. 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?

Ans. Key raw material/starting material:

Starting material shall be defined as that which is

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

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

 Starting material shall be identified in TDP.

Primary Packing material: Packing material, which come in direct contact with the

API/Intermediate are considered as Primary packing material.

67. What is cleaning validation?

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

Cleaning validation is the confirmation reliable cleaning products so that the analytical

monitoring may be omitted or reduced to a minimum in the routine phase.

It describes the validation cleaning procedures for the removal contaminants associated

with the previous products, residues cleaning agents as well as the control potential

microbial contaminants.

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

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

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

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

evaluated.

69. What parameters considered during performance qualification HVAC?

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

1. Calibration test certificates instruments

2. Training records validation team

3. Pressure drop across the HEPA & fine filters

4. Air velocity measurement & calculation Air changes

5. Integrity test 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

70. What are the contents in the BPCR?

Ans. 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 Manufacturing

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

9. List equipments used 10. List 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 In-process & Laboratory test results

15. Signatures person performing details along with supervising details

16. Description Packaging details

17. Yield calculation

18. Representative labels for intermediates / raw materials

19. Deviation details

20. Batch starting & completion date

71. What is OOT and define?

Ans. “OOT” stands for Out Trend. It means any test results obtained for a particular batch that is markedly different the results the batches in a series obtained using a same validated method.

72. How will you prevent cross-contamination between two different products manufactured in the one production block?

Ans. 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 Temperature and relative humidity in the Pharma area?

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

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

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

Non-dedicated equipment: Where the same piece equipment is utilized for a range of

products formulations. The prevent cross-contamination between products becomes the

main objective in the cleaning validation effort. Clearly, cleaning non-dedicated equipments represents a more significant obstacle to overcome.

75. Which instrument is used for the measuring RPM?

Ans. Techo meter is used for the measurement RPM.

76. Why three batches consider for the validation?

Ans. Because First one is for information, Second one is for confirmation and Third one is for evidence.

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

 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 necessary

revise the MPCR and BPCR).

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

validation

77. What are specifications Purified water as per any pharmacopoeia?

Ans. 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

min

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

hour

Ammonium 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

Heavy Metals NMT 0.1 ppm

Conductivity (At 25˚C) NMT 5.1ms.cm-1

Total viable aerobic count NMT100 CFU /ml

Pathogens :

E. coli

Salmonella

Pseudomonas

Staphalococcus aureus

Absent

Absent

Absent

Absent

78. Write the different storage conditions as per any guidelines (specify the name guideline)?

Ans. 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

Cool : 8°C to 15°C

Room temp. : The temperature at prevailing working area.

CRT : 20°C to 25°C

Warm : 30°C to 40°C

Excessive heat : Above 40°C

79. Write the different types fires, which are generally used in the pharmaceutical industry?

Ans.

a) Chemical fire

b) Electrical fire

c) Metal fire

d) General fire

e) Gaseous fire

80. What is ISO 9001, ISO 14001, ISO 18001, ISO 22001?

Ans.

ISO 9001 : Quality Standard Management

ISO 14001 : Environmental Standard Management

ISO 18001 : Safety & Health Standard Management

ISO 22001 : Hazop Standard Management

81. What is HACCP?

Ans. HACCP : Hazard Analysis Critical Control Point

82. What is OHSAS?

Ans. OHSAS : Occupational Health & Safety Assessment Series

83. Why one liter water is equivalent to one kilogram water at room temperature?

Ans. Because at normal room temperature is between 25°C and 35°C at plant operating condition

and the variation in weight Vs Liter water is negligible compared to volume.

84. What is room temperature?

Ans. The temperature at prevailing working area

. What is calibration?

The demonstration that a particular instrument or device produces results within specified limits by comparison with results produced by a reference or traceable standard over an appropriate range measurements

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

Ans. Equipment should not be left with water it after cleaning. The last stepthe cleaning

procedures involve drying with solvent or flushing with nitrogen, thus ensuring that there is no opportunity for microbial growth.

86. What is the efficiency the High Efficiency Particulate Air (HEPA) filter?

Ans. This type air filter can remove at least .97% particles in air up to 0.3μm in diameter.

87. What is the micron size HEPA filter?

Ans. The micron size HEPA filter is 0.3μm

88. Do you have any idea about schematic diagram HVAC system?

Ans.

Fresh Air

Filtering Air with Pre filter

Cooling & Heating coil

Filtering Air with Fine filter

Filtering air with HEPA filter, If required

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

Requirements Air is exhausted to atmosphere after filtration wherever required

Portion air then passes through a dehumidifier wherever dehumidifier is required

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

89. If two different products are manufacturing in two modules one production block, then will you accept the common air handling unit for both Pharma area? Write “Yes” or “No” with reason?

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

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

90. Why blending validation is required? What quality parameters product are considered for validation and what parameters equipment are to be considered during validation?

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

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

a) Loss on Drying / Water content

b) Bulk density / tapped density

c) Residual solvent

d) Particle size

The following parameters are to be considered for the equipment during validation, but not limited:

a) Blender capacity

b) RPM the blender

c) Occupancy the blender

d) Number individual batches to be taken for each blend

e) Mixing time

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

Ans. Total CFM the blower/Filter x 60

Air changes per hour= ----------------------------------------------------

Total room volume

92. During the performance qualification in the vacuum tray dryer, how many temperature probes used?

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

93. What is the formula for the calculation“ MACO” while cleaning between one API to another API?

Ans. Minimum therapeutic dosage previous product X Minimum batch size next

product

MACO = -----------------------------------------------------------------------------------------------------------

Safety factor X Maximum therapeutic dosage the next product

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

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

. 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

95 . What is the abbreviation CAS Number?

Ans. CAS Number : Chemical Abstract Service Number

96. What is the specific gravity Methylene chloride?

Ans. Specific gravity Methylene chloride is 1.308 g/ml

97. If equipment is cleaned with water, then finally it should be rinse with suitable solvent as per guidelines, why?

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

98. What is mean by “4M”?

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

99. If supposed your Pharma area is class 100000, then what is the maximum light and sound level as per guidelines ?

Ans. 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