Interview Preparation Question and Answers for CQV Engineers

Topic: Equipment Qualification

Question: What is the V model in Qualification?

Ans. V- Model means Verification and Validation model. It is a widely accepted reference model for computer system validation and was introduced by International Society of Pharmaceutical Engineers (ISPE) in 1994 in the first edition of their Good Automated Manufacturing Practices guideline (GAMP)

Question: Which guideline you refer for the commissioning and qualification of process Equipments

Ans. ISPE Baseline Guide: Commissioning and Qualification-Vol 5, WHO TRS, EU Annexure-15, USFDA Part 210 and 211

Question: What is C&Q Planning Approach for new project?

Ans. The amount of planning, documentation, reporting and level of details of C&Q plan should be based on the expectations of the organization/site , size and complexity of the project and the potential impact on the quality and safety of the product

Question: What is Installation Qualification?

Ans. The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manufacturer's recommendations.

Question: what are the tests parameters required for Installation qualification of Equipments?

Ans. The following are test parameters for IQ of the equipment but not limited to

• Verification of physical conditions like undamaged product free of physical defects (i.e. Scoring/Roughness, Dent/Pitting, Scratch, Crack, Discoloration and Rusting).
• Verification of Documents for completeness.
• Verify system P&ID as required
• Verify any system components defined in the protocol
• Verify utility connections and ensure required utilities as appropriate
• Verify instrument connections from field to PLC
• Check connection to peripheral devices (printers, data loggers, etc.)
• Check manual functionality (all switches, buttons and settings in manual mode).
• Verify that complete Parts List has been filed in maintenance Records/engineering store.
• Installation of equipment checked to current engineering drawing and Specification
• Identification of critical instruments for Calibration requirement
• Verification of material of construction
• To ensure that the machine is installed at its designated place.
• To measure the dimension wherever possible.

Question: What is material of construction for product contact surface area?

Ans. Non Reactive Like SS 316/SS316L/ Teflon, Silicon, Toughen Glass, PVC etc.

 

Question: How you verify the material of construction of the equipment?

Ans. By using 9 V battery and Molybdenum test kit, if drop of Solution turns pink after passing the 9 V current through the Molybdenum solution drop on the surface of test metal remain pink more than 30 sec, that means it is SS316 and if diminish immediately then it is SS304.

Question: How you will do System impact assessment for the equipment?

Ans. Direct impact system having the direct impact on the product quality, safety, efficacy, potency. Indirect impacts system may have impact on product quality, safety, efficacy, potency or linked with direct impact system. No impact system having no impacts on the product quality, safety, efficacy, potency

Question: How you will draft SOP for new equipments?

Ans. Referring the Equipment user/Operational manual, Maintenance manual

Question: What is User Requirement Specification?

The first document prepared for any proposed new equipment or system.  This document is written by the user to describe the user requirements for the new equipment or system. The set of owner, user and engineering requirements necessary and sufficient to create a feasible design meeting the intended purpose of the system.

Question: What is Design Qualification

Ans. The documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose and comply with the requirements of URS. The design documents (drawings, specifications, etc.) are to be compared to the URS requirements and confirmed that they are in compliance. DQ will be conducted for all new equipment, facilities and critical utilities.

Question: What is Direct Impact System –

Ans. The systems which have direct impact on product quality are termed as direct impact system. These are Critical equipment is that equipment needed for processing, packaging, holding, or supporting of products and those unit operations that have the potential to impact critical process parameters and quality of the product.

Question: What is Equipment Qualification Master Plan?

Ans. A document prepared as part of project planning that describes overall philosophies, approaches, and objectives to all aspects of qualification. The document defines responsibilities and expectations for the various components of the qualification exercise.

Question: What is Factory Acceptance Test?

Ans. Documented verification that the Equipment or System meets design specification and conforms to agreed performance intent at manufacturer site before dispatch of the machine.

Question: What is Indirect Impact System?

Ans. The systems which do not have direct impact on product quality however they support or linked to a direct impact systems are termed as indirect impact systems.

 

Question: What is Operational Qualification

Ans. The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges.

Question: What is Performance Qualification

Ans.The documented verification that systems and equipment can perform effectively and reproducibly based on the approved process method and product specification and parameters, for prolonged periods.

Question: What is Re Qualification

Ans. Equipment, facilities, utilities and systems should be evaluated at an appropriate pre-defined frequency to confirm that they remain in a state of control.

Question: What is Site Acceptance Test

Ans. Documented Verification that the receipt of the item at site confirms with the standards laid down in the purchase order, DQ and URS.

Question: What are the tests parameters required for Operational qualification of Equipments?

Ans. The test parameters are

• Verification of Calibration status and review of calibration certificates of instruments identified during Installation Qualification
• Verification of Draft SOPs
• Verification of Equipment Operation
• Verification of Ranges of Parameters
• Verification of Input & Output of PLC, HMI verification, communication verification, security and access verification, backup and recovery and verification of configurable parameter and range testing and Password Verification
• Power Failure Challenge
• Verification of Safety features
• Verification of Safety Features, Alarms and Interlocks:
• Instructions for Verification of HMI Screen

Question: What are the tests parameters required for Performance qualification of Compression machine?

Ans. The Test Parameters are

• Verification of Effective Sops
• Verification of RPM of Turret, Feeder Minimum/Maximum Range
• Verification of Physical Parameters of Tablets at various speeds like Min. , Max. Hopper Level, Feeder Speed, Short punch challenges tests, Rejection Mechanism Test, Minimum and Maximum Thickness pressure

Question: What are the test parameters for Facility Qualification

Ans. The Test Parameters are

• Verification of Dimensions, Finish and Structure
• Verification of Facility against User Requirements Specification
• Verification of Facility against as Built Drawings
• Verification of Man, Material and Equipment Movement
• Measurement of Light Intensity and Noise Level.
• Location and number of Supply diffusers, Return Air Raisers, Door, Windows
• Verification of Utilities available and Drain Points

Topic: Utility Qualification (HVAC Validation)

Question:  What is the test for HVAC PQ as per ISO 14644-1, 2,3

Ans. The Test Parameters are

• Air Balancing
• Air velocity/ACPH (NLT 20 ACPH for Grade D Area)
• HEPA filter integrity (NMT 0.01 % leakage of Upstream Concentration)
• Non Viable particle count (Refer  ISO 14644-1- For Grade A, B,C,D)
• Viable Particle count (NMT 100CFU/4 Hrs Settle plate Exposure)
• Recovery Study (NMT 15 Minutes)
• Air flow Pattern (For LAF-Laminar Air Flow. For Other Grade Supply to return, High Pressure to Lower Pressure)
• Temperature/RH Monitoring
• Differential Pressure Monitoring
• Contamination Leakage Test
• Segregation Test

Topic: Utility Qualification (Compressed Air)

Question:  What are the tests required for the PQ of Compressed air as per ISO 8573

Ans. The tests are

• Dew Point
• Water Vapors
• Oil Mist
• Non Viable Particle count
• Viable Particle Count
• Carbon dioxide (CO2)
• Carbon monoxide (CO)
• Sulphur Dioxide (SO2)
• Nitrous Oxide/ Nitrogen Dioxide (NO/No2)

 

Topic: Utility Qualification (PW/WFI Qualification)

Question:  What are the Phases of PQ for Purified/WFI Water Systems?

•  Phase 1: Duration 2 to 4 Weeks: Primary objective to develop appropriate operating ranges and daily sampling and testing of chemical and microbiological parameters from all user points
• Phase 2: Duration 2 to 4 Weeks: Primary objective to demonstrate consistent operation within established ranges and established Alert and Action limits of testing parameters based on Phase – I data. Establish cleaning, regeneration and   sanitization frequency based on Phase 1 and Phase 2 data for loop, tanks, filters, and components as applicable. Daily sampling and testing of chemical and microbiological parameters from all user points
• Phase 3: Duration One Year: Primary objective is water system should continue to be monitored and evaluated on an on-going basis following a life cycle approach using online instruments or samples for laboratory based testing. To ensure that seasonal variations are evaluated. Sampling based on SOP schedule (All user point shall be covered once in week and Supply/Return Daily basis)

Question:  What is Reynolds number in Purified water distribution system?

Ans. The Reynolds number should be more than 4000 and it indicates the relative significance of the viscous effect compared to the inertia effect and the number is proportional to the inertial force divided by the viscous force

Reynolds number can be expressed as can be expressed as

Re = (ρ u2) / (μ u / L)  = ρ u L / μ  = u L / ν (1)

Where

Re = Reynolds Number (non-dimensional)

ρ = density (kg/m3, lbm/ft3 )

u = velocity based on the actual cross section area of the duct or pipe (m/s, ft/s)

μ = dynamic viscosity (Ns/m2, lbm/s ft)

L = characteristic length (m, ft)

ν = μ / ρ = kinematic viscosity (m2/s, ft2/s)

Question:  What is minimum value of flow velocities in Purified water distribution system?

Ans. Distribution systems should operate with nominal flow velocities of 3 feet per second or higher. (Ref. ISPE baseline pharmaceutical engineering guide, water and steam system, first edition Jan 2001, Vol. 4 pg.no.122.

Question:  What is Maximum Limit for Online Conductivity of Purified water?

Ans. It should not more than 1.3 µs/cm (Micro Siemens (µs)

Question:  What is Maximum Limit for TOC (Total organic Carbon) of Purified water?

Ans. It should not more than 500 ppb (part per billion)

Question:  What is Pore size of filter installed on the top of Purified/WFI water tank?

Ans. 0.2 micron and it is hydrophobic in nature and remain heated above 80 ⁰C

Question:  What is dead leg and what is the allowable limit?

Ans. Dead legs are sections of water piping systems that have been altered, abandoned or capped such that water cannot flow through them. This includes isolated branch lines, pipe sections with closed valves and pipes with one end capped. Dead legs experience periods of no flow which leads to stagnation and microbial proliferation. Dead leg should not significantly exceed 3 times of the branch diameter as measured from the Inner diameter pipe wall to center line of point of use valve. (Ref. WHO TRS 970, pg.no. -87)

Question:  What is the acceptance criterion for Slope in water system pipeline?

Ans. Slope measurement shall be made with a digital level or a digital protractor. The instrument used should be capable of displaying slope in degrees, percent, and In./ft (mm/m).

Unit of measurement	Ratio of  slope to length	Minimum Slope (gradient)	Minimum Slope
	NMT	mm/meter	%
GSD2*	1:100	10	1.0

 

*As per ASME BPE standard slope designation is defined as GSD2 for gravity drained lines

Question:  What are the tests required in IQ of Water system?

Ans: The Test are:-

Material of Construction: Materials should be used that are “not reactive, additive, or adsorptive” to the water. The component and piping material certificates should be traceable to drawings for the system (including heat marks & certificates).

Surface finish: Mechanically polish surfaces in contact with feed water to 25 micro inch Ra Max (0.64 micrometer) and to electro polish surfaces in contact with Pure steam and WFI to 20 micro inch Ra Max (0.51 micrometer).  (Ref. ISPE baseline guideline, Volume 4).

Dead Leg verification: Dead leg should not significantly exceed 3 times of the branch diameter as measured from the Inner diameter pipe wall to center line of point of use valve

Orbital Welding and Boroscopy: Internal welds are inspected by indirect visual methods (i.e. boroscopy) by facility owner or third party designee at minimum of 25 % boroscopy and minimum of 25 % radiography of total daily completed welds for automatic machine welds and 100 % of daily completed manual welds. Weld locations should be documented on the Weld map drawing should identify weld location. The heat numbers of metals jointed on either side of weld should be included. The heat numbers should be traceable to material certificates of analyses. (Heat number corresponds to the chemical composition of the material). (Ref. ISPE Commissioning and Qualification)

Line Slope:  Ratio of slope to length NMT 1:100

Hydrostatic Pressure Test: This test is performed to verify that the water or steam system is free of leaks, which can lead to contamination of the water or steam. (Ref. ISPE baseline pharmaceutical engineering guide, water and steam system, second edition 2014, pg.no.32. After Installation and before passivation, the piping systems should be pressure tested. Hydrostatic test or flushing pressure shall not be greater than the manufacturer's recommended test pressure or NMT 1.5 times of recommended pressure and then monitoring of pressure decay for four hours

Cleaning and Passivation: Cleaning and passivation procedures should include, cleaning agent used, cleaning temperature and times, passivation chemical solutions used, temperature and contact times, identification of line sections, components passivated etc

Sanitization: During validation of thermal sanitization methods, a heat distribution study should be performed to demonstrate that sanitization temperatures are achieved throughout the system; return loop shall be monitored as a worst case.

Question: Spray Valve Should be _______Rotation

Ans: Should be 360⁰. Spray Pattern shall be verified by using riboflavin dye and UV Torch light.

Question: How you define the Alert and Action Levels of Parameters

Ans: Average +2 *SD= Alert Limit

        Average +3 *SD= Action Limit

 

Topic:- Utility Qualification (Pure/Clean Steam Validation)

Question: What is the Performance Qualification Test for the pure/Clean Steam as per HTM 2010?

Ans: Non Condensable Gases: - NMT 3.5 %

         Dryness Value: ≥0.95

         Super Heat: NMT 25⁰C

         Endotoxin: NMT 0.25 EU/ml

 

Topic: Utility Qualification (Nitrogen Gas Validation)

Question: What is the Performance Qualification Test for the Nitrogen gas as per USP?

Ans: Identification: Complies to USP

        Assay of Nitrogen Gas: NLT 99.5 %

        Oxygen Contents: NMT 0.5 %

        CO2

        CO

        Water Contents

 

Topic: Sterilization (Autoclave/Tunnel/DHS)

Question: What is D Value?

Ans: D-value, or decimal reduction time, is the time it takes to reduce a microbial population by 1 logarithm, or 90% of its initial value, under specified conditions (e.g., sterilant concentration, exposure temperature, relative humidity, package configuration).

Question: What is Z Value?

Ans: The Z value is the number of degrees (temperature) or dosage units required for a one-log reduction in the D value. In other words, the Z value is the change in the sterilization condition that affects a 10-fold (one-log) reduction in the D value.

Question: What is F0 Value and how you calculate?

Ans: F0 value is used to determine the exposure time of material for sterilization at a particular temperature. F0 value is the time in minute for the specified temperature that gives the same thermal lethality as at 121 °C in one minute..

F0 =   (T-121/Z)

T= Temperature for sterilization

= Time Interval

Z Value= 10⁰C

Question: How you calculate FH Value for Depyrogenation Tunnel or DHS?

Ans:

FH =   (T-250/Z)

T= Temperature for sterilization

= Time Interval (in second)

Z Value= 46.4⁰C

Question: What is SAL (Sterility Assurance Level)?

Ans: Sterility assurance level is the probability that a single unit that has been subjected to sterilization nevertheless remains nonsterile. It is never possible to prove that all organisms have been destroyed, as the likelihood of survival of an individual microorganism is never zero. Typical SALs are 10−6

F0 = D121 (Log A-Log B)

D121 = 1.9 (From Certificate of Biological Indicator)

Log A = Initial Population (106)

Log B = Final Population After sterilization (10-6)

12 Log Reductions= Sterility Assurance Level

Question: How many log reduction occur in Depyrogenation tunnel?

Ans. 3 log reduction

Question: What are the tests required to check the performance of Depyrogenation tunnel?

Ans. Heat Distribution

        Heat Penetration (Endotoxin Challenged Vial)

        Conveyor Belt Speed (mm/Minutes)

HEPA Filter Test for Tunnel:

Air Velocity, HEPA filter integrity, Non Viable Particle Count, Air Flow Pattern at the inlet and outlet

Topic: Cleaning Validation

Question: What is Cleaning Validation?

Ans. Documented evidence with high degree of assurance that a cleaning process will result in product meeting their predetermined quality attributes throughout its lifecycle

Question: What is NOEL – No Observed Effect Level?

Ans. The highest tested dose of a substance that has been reported to have no harmful health effects on targeted people or animals.

Question: What is PDE - Permitted Daily Exposure

Ans. Permitted Daily Exposure represents a substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed at or below this dose every day for a lifetime.

Question: What is LD50 – Lethal Dose

Ans. An LD50 is a standard measurement of acute toxicity that is stated in milligrams (mg) of substance per kilogram (kg) of body weight. An LD50 represents the individual lethal dose required to kill 50 percent of a population of test animals (e.g., rats, pigs, monkeys).

Question: How you will develop Cleaning validation program

Ans. Cleaning validation program shall be organized by

• Identification of Equipment Train
• Identification of Worst Case Product
• Calculation of Limit
• Defining Sampling and Cleaning Procedure
• Analytical Method Development and Validation
• Acceptance criteria
• Documentation (Preparation, Execution of Cleaning Validation Protocol and Compilation of Report)
• Establishment of Hold Times period for Clean / Dirty equipment
• Cleaning Verification
• Cleaning Re- Validation
• On Going Monitoring

Question: How you identify the worst case product (Product A) for cleaning validation program

Ans. The Factor that consider for identification of worst case molecule are

• Type./Category of API
• API Solubility in cleaning Agent (i.e. Purified Water)
• PDE value (mg/ kg)
• LD50 (mg/ kg)
• Smallest Recommended Daily Dose (SRDD) (mg).
• Total Quantity of Insoluble, very slightly soluble & slightly soluble Excipient
• Colors/Flavours
• Equipment Train

Question: What are the criteria to calculate the MACO/ARL

Ans. There are four methods to calculate the criteria

• Dose Based Criteria
• Toxicity Based Criteria (LD50)
• HBEL (ADE/PDE)
• 10 ppm Criteria

Minimum Value out of four criteria shall be selected as acceptance criteria

Question: What is the minimum recovery factory recommended for swab and rinse Sample

Ans. NLT 70 % for Swab and NLT 50 % for rinse Sample acceptable

Question: What is the Swab Sampling Area

Ans. It can be 5 X5 cm (25 cm2) to 10 X 10 cm (100 cm2). It based on internal company policy

Question: What are the guideline for the Cleaning Validation

Ans. PDA TR29, EMA-EU, PIC/s- PI-006, APIC, USFDA-2011, WHO TRS 1033 Anx-2, ISPE Guide for cleaning validation

 

 

 

 

 

 

 

 

Question: How you calculate the Maximum Allowable Carry Over (MACO)

Ans.

1.0 Dose Criteria

SF

X

SRDD X

M.B.S

X

SA

=

MACO/ARLSWAB

LRDD

SSA

Where

ARLSWAB

=

Acceptable Residual Limit (mg/swab)

SF

=

0.001 of a dose of product A (Contaminating product) expressed as milligrams of active per single unit dose.

LRDD

=

Largest recommended daily dose (In mg) of product B (Subsequently manufactured product) taken per day.

SRDD

=

Smallest recommended daily dose (in mg) of Product A.

M.B.S

=

Minimum Batch Size (In mg) of product B (Subsequently manufactured product)

SSA

=

Shared surface area (cm2).

SA

=

Surface area swabbed (25 cm2).

2.0 HBEL Criteria (ADE/PDE)

 

MACO =	ADE (mg/day)	X	Min. Batch Size (mg)	X	SA	=	mg/swab
			LRDD (mg/Day)		SSA

3.0 Toxicity Based Criteria (LD50)

MACO=	NOEL	X	M.B.S	X	SA	=	ARLSWAB
	SF	X	LRDD	X	SSA

 

Where:	ARLSWAB	=	Acceptable Residual Limit (mg/swab)
	NOEL	=	No Observed Effect Level	NOEL = LD50 x (BW/E)
	LD50	=	Lethal Dose 50 in g/kg animal for active ingredient in product A.
	E	=	Empirical Constant (2000)
	BW	=	Weight of an average adult (70 Kg)
	SF	=	Safety Factor (1000)
	M.B.S	=	Minimum Batch Size (In mg) of product B (Subsequently manufactured product)
	LRDD	=	Largest recommended daily dose (In mg) of product B (Subsequently manufactured product) taken per day.
	SSA	=	Shared surface area (cm2).
	SA	=	Surface area swabbed (25 cm2).

 

 

4.0 10 Parts per Million Criteria (10ppm)

	R	X		M.B.S	X		SA		=	ARLSWAB
				SSA
Where:			ARLSWAB			=		Acceptable Residual Limit (mg/swab)
			R			=		10 mg of product A per kilogram of product B (10 PPM).
			M.B.S			=		Minimum Batch Size (In Kg) of product B (Subsequently manufactured product)
			SSA			=		Shared surface area ( cm2)
			SA			=		Surface area swabbed (25 cm2).

 

Topic: Process Validation

Question: What is Process Validation

Ans. Process Validation is defined as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product

Question: What is Quality by Design (QbD)

Ans. A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.

Question: What is Design Space

Ans. The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality

Question: What is Quality Target Product Profile (QTPP)

Ans. A prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the drug product.

Question: What is Capability of a Process

Ans. Ability of a process to produce a product that will fulfil the requirements of that product. The concept of process capability can also be defined in statistical terms

Question: What is Target Value/ Set Point

Ans. A value of the process parameter during operation, around which the control system regulates the value.

Question: What is Scale up Batch

Ans. The batch having higher batch size.

Question: What is Exhibit Batch / Submission Batch

Ans. A batch that is manufactured with the final recipe intended for commercial batches, under CGMP conditions, to generate physical and chemical data for registration support, evaluate stability etc.

Question: What is Engineering Batch

Ans. Batch(s) of the size that will be manufactured during routine marketing of the product and data of such batch size is not available prior to approval. Such batch (s) may be manufactured to evaluate characterization and optimization of the critical process parameter and conditions

Question: What is Commercial Batch

Ans. The validated batch size to be manufactured for commercial supply

Question: What is Proven Acceptable Range (PAR)

Ans. A characterized range of a process parameter for which operation within this range, while keeping other parameters constant, will result in producing a material meeting relevant quality criteria

Question: What is Normal Operating Range (NOR)

Ans. A defined range, within the Proven Acceptable Range, specified in the manufacturing instructions as the target and range at which a process parameter is controlled, while producing unit operation material or final product meeting release criteria and Critical Quality Attributes.

Question: What is Commercial Manufacturing Process

Ans. The manufacturing process resulting in commercial product (i.e., drug that is marketed, distributed, and sold or intended to be sold). For the purposes of this policy, the term commercial manufacturing process does not include clinical trial or treatment IND material.

Question: What is Concurrent Release

Ans. Releasing for distribution a lot of finished product, manufactured following a qualification protocol, that meets the lot release criteria established in the protocol, but before the entire study protocol has been executed.

Question: What is Continued Process Verification

Ans. Assuring that during routine production the process remains in a state of control.

Question: What is Process Design

Ans. Defining the commercial manufacturing process based on knowledge gained through development and scale-up activities.

Question: What is Process Qualification

Ans. Confirming that the manufacturing process as designed is capable of reproducible commercial manufacturing.

Question: What is Process Validation

Ans. The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products.

Question: What is Quality

Ans. The degree to which a set of inherent properties of a product, system, or process fulfils requirements.

 

 

Question: What is State of Control

Ans. A condition in which the set of controls consistently provides assurance of continued process performance and product quality.

Question: What is Control Strategy

Ans. A planned set of controls, derived from current product and process understanding that ensures process performance and product quality. The controls can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control.

Question: What is Critical Material Attributes (CMA)

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

Question: What is Critical Process Parameter (CPP)

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.

Question: What is Critical Quality Attribute (CQA)

Ans.  A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality.

Question: What is Process Performance Qualification (Validation) Protocol

Ans.  A written protocol shall be prepared, reviewed and approved prior to initiation of Process performance qualification, which specifies the manufacturing operations, critical process controls, sampling, testing, acceptance criteria and sampling location of equipment used at various stages of the process.

Question: What is Process Performance Qualification (Validation) Report

Ans. A Process Performance Qualification report shall be prepared after completion of performance qualification which includes the results, summary and conclusion of the Process Performance Qualification (validation) exercise.

Question: What is Scale Dependent Parameter

Ans. These are the parameters which are impacted due to increase in batch size, scale and equipment. For example: blending time, lubrication time, compression force etc.

Question: What is Scale Independent Parameter

Ans. These are the parameters which do not have any impact due to increase / decrease in batch size, scale and equipment. For example: PSD

Question: What is Stratified Sampling

Ans. It is the process of collecting a representative sample by selecting units deliberately from various identified locations within a lot or batch, or from various phases or periods of a process to obtain a sample dosage units that specifically targets locations throughout the compression / filling operation that have a higher risk of producing failing results in the finished product uniformity of content

Question: What is Blend Uniformity

Ans. It is defined as the degree of uniformity in the amount of drug substance in the powder blend.

Question: What is Weight Correct

Ans. It is a mathematical correction to eliminate the effect of potentially variable tablet weight on measurement of mix adequacy. For example, a tablet with strength of 19.4 mg and weight of 98 mg then we have to calculate content of active in that particular table i.e. 19.4 ÷ 98 = 0.198 mg/mg. if theoretical weight of tablet is 100 mg and it contains 20 mg as active ingredient per tablet then weight corrected result would be 0.198 ÷ 0.20 × 100 = 99 % of target blend assay.

Question: What is Uniformity of Dosage Units

Ans.  It is defined as the degree of uniformity in the amount of drug substance among dosage units.

Question: What is Variant Component Analysis (VCA)

Ans.  A way to assess the amount of variation in a dependent variable that is associated with one or more random-effects variables.

Question: Role of Project Manager in Validator

Ans. A Project Manager is a person that is assigned the overall responsibility for initiating (creating), planning, designing, executing, monitoring, controlling (Task Assessment) and closing of a project in process validation

Question: Describe the three stages of Process Validation.

Ans. The Process Validation involves a series of activities taking place over the lifecycle of the product and process. These activities are described in three stages

• Process Design Stage (Stage 1): Involves designing the manufacturing process suitable for routine commercial manufacture, based on knowledge gained through development & scale up activities, so as to deliver product that meets the Pre-defined critical quality attributes.
• Process Qualification Stage (Stage 2): Involves completion of prerequisite qualification checks for facility, equipment, utilities and personnel, followed by performance qualification of the process to confirm whether it is capable of reproducibly yielding quality product at commercial scale.
• Continued Process Verification Stage (Stage 3): This is documented evidence for assurance which shows that the product is within specified limit of predetermined quality aspects and the process is within control during commercial manufacturing to continuously produce quality product.

It involves generating on-going assurance that the process remains in a state of control during routine commercial manufacture.

 

 

 

 

 

Topic: Computer System Validation (CSV)

Question:  What are the Software Categories as per GAMPS 5 Guide

Ans. The categories are

Cat 1 : Standard Layered Software like operating system

Cat 3 : Firmware software-non customizable (QC Instruments)

Cat 4: Software: customizable (SCADA/BMS SAP/ Trackwise)

Cat 5: In-house developed customizable:- For specific Company/ Excel sheets used for Calculation using VBA

Question:  What are the Hardware Categories as per GAMPS 5 Guide

Ans. The categories are

Cat 1 : Standard Hardware components Preassembled

Cat 2 : Customized Hardware components assembled at site

Question:  What is audit trail?

Ans. An audit trail is a process that captures Meta data details such as additions, deletions, or alterations of information in electronic record without obscuring or over-writing the original record. An audit trail facilitates the reconstruction of the history of such events relating to the record regardless of its media, including the “who, what, when and why” of the action.

• System Audit Trails:  System audit trails provide a trail of user access management related to creation, modification and deactivation/deletion along with changes in user privileges. System audit trails may also provide the details of system configuration. It also provides login- logout details of available users, logs related to back up activities, deletion of data and data import/export activities.
• Data Audit Trails: Data audit trails provide a trail of data generation, modification, deletion and record of system electronic data (including meta data) accessed and modified either by individuals or system (in built logic) during system operation. Data audit trail also include evidences of electronic signature if applicable in system.

Question:  What is your role in Manufacturing?

Ans. Providing the support to the validation team for the qualification of SCADA software, Handling and resolve all the query break downing of SCADA s system. Perform the Audit Trails Review

Question:  How you handle the Critical alarms arrived during the process.

Ans. The alarm shall be acknowledged and immediate action shall be taken based on criticality of the alarm. In case the noticed alarm is critical, Concerned Operator shall inform. Production shall acknowledge the critical alarm (whether quality impacting or quality non-impacting) and identify the reason of alarm in consultation with Quality Assurance personnel shall evaluate the requirement of impact assessment. In case alarm found to be quality impacting, an investigation shall be performed to identify the root cause of alarm and then decision to raise the event log (deviation) shall be taken based on the impact assessment. This impact assessment section shall mention the impact on product quality. The event shall be logged and investigation shall be performed as per guideline for event reporting and investigation.

Question:  What is the Procedure for User management (Activation/Deactivation/New user etc.)

Ans. On Receiving the Approved request with justification for the Activation or deactivation of user account, login through the administration role and Activation or deactivation of user account.

Question:  What are the minimum parameters verify in Batch audit Trails of manufacturing equipments

Ans. The parameters are

• Product Name or  Recipe Name
• Batch Number
• Batch start Date and Time
• User ID, User login and log out time.
• Process interruption (If any)
• CPP Parameter with in specified limit
• Any Alarm Critical/Non Critical
• Data audit trail (Satisfactory/not Satisfactory)
• Batch end date and time

Question:  What are the minimum parameters verify in System audit Trails of manufacturing equipments

Ans. The parameters are

• Audit Trail of User Access Management
• Privileges Right Matrix of All Users:
• Data Deletion from the Software:
• Date / Time Security:
• Drive Security (Access of C and D Drive is restricted to operators/User)
• Backups
• Verification of data base or flat file randomly review to discover of omitted/orphan data like data generated with file name like ABC, XYZ etc, aborted data  or duplicate data generated for same batch number etc. If it is available or not justified than handle through QMS document.
• Verification of superseded or obsolete recipe is not access to operator/supervisor or No obsolete /generic recipe available in the software.
• Audit trail function is enabled (Yes / No)