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Question and Answer for Quality Control

What Is SOP?
  • Standard Operating Procedure (SOP) is a certain type of document that describes step by step.

What Is 21 CFR Part 11?
  • Title 21 CFR Part 11 of the Code of Federal Regulations deals with the Food and Drug Administration (FDA) guidelines on electronic records and electronic signatures in the United States. Part 11, as it is commonly called, defines the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and equivalent to paper records.

What Are User Requirements?
  • User Requirements Specification describes what users require from the System. User requirement specifications are written early in the validation process, typically before the system is created. It is written by the System Owner and End Users, with input from Quality Assurance. 
  • Requirements outlined in the URS are usually tested in the Performance Qualification. User Requirements Specifications are not intended to be a technical document; readers with only a general knowledge of the system should be able to understand the requirements outlined in the URS.


What Is A Validation Plan?
  • Validation Plans define the scope and goals of a validation project. Validation plans are written before a validation project and are specific to a single validation project.
  • Validation Plans can include:
  1. Documents to be generated during the validation process
  2. Resources/Departments/Personnel to participate in the validation project
  3. Time-Line for completing the validation project

What is an IQ Document?
Installation Qualifications are a collection of test cases used to verify the proper
  • installation of a System. The requirement to properly install the system was defined in the Design Specification. Installation Qualifications must be performed before completing Operational Qualification and Performance Qualification.

What is an OQ Document?
  • Operational Qualifications are a collection of test cases used to verify the proper functioning of a System. The operational qualification tests requirements defined in the Functional Requirements. Operational Qualifications are usually performed before the system is released for use.

What is PQ Document?
  • Performance Qualifications are a collection of test cases used to verify that a System performs as expected under simulated real-world conditions. The performance qualification tests requirements that were defined in the User Requirement Specification (or possibly the Functional Requirements). Due to the nature of performance qualifications, these tests are sometimes conducted with power users as the system is being released.

What is Validation Summary Report?
  • Validation Summary Reports provide an overview of the entire validation project. When regulatory auditors review validation projects, they typically begin by reviewing the summary report.
  • The validation summary report should include:
  1. A description of the validation project
  2. All test cases performed, including if those test cases passed without issue
  3. All deviations reported, including how those deviations were resolved

What is Change Control?
  • Change Control is a general term describing the process of managing how changes are introduced into a controlled System. In validation, this means how changes are made to the validated system. Change control is required to demonstrate to regulatory authorities that validated systems remain under control after system changes. Change Control systems are a favorite target of regulatory auditors because they vividly demonstrate an organization capacity to control its systems

Why Water for Pharmaceutical use is Always Kept in Close Loop in Continuous Circulation?
  • Water is the best medium for many microorganisms, microorganisms can be a highly pathogenic which causes serious diseases (many diseases are water born), these pathogens infect after consumption of contaminated water, microorganisms tend to settle on a surface if water is allowed to stand in a stagnant position for a few hours, these settled Microorganisms form a film over the surface of vessel and piping, such film is formed by microorganisms are also called biofilm, biofilms are very difficult to remove, once a biofilm is formed at a particular point then that point may form a biofilm again even after cleaning very easily as seed from this point it may not completely get removed effectively.


Water for Pharmaceutical use Shall be Free Cations, Anions and Other Impurities Why?
  • Water for pharmaceuticals must be free from inorganic as well as organic impurities, minerals, and heavy metals. Some impurities like calcium, magnesium, and ferrous are responsible for degradation of the drug molecule, many cations like ferrous and calcium magnesium act as catalysts in the degradation reaction of the drug molecule, anions like chloride are highly active they participate in nucleophilic substitution reactions, wherein they break a double bond between -C=C- into a single bond as CL –CH-CH2-, which a reason why do we observe that color dies to tend to be fed in presence of chlorine as most of the dies used are diazo compounds which have plenty of places for nucleophilic substitution reactions, which is also a reason why the stability of drugs is drastically affected in presence of cations and anions from mineral origin present in water.

Water For Pharmaceutical use Shall be Free Heavy Metals Why?
  • Heavy metals like lead and arsenic are highly cumulative neurotoxic metals, heavy metals are not eliminated from our body easily like other drugs and molecules but heavy metals bind with proteins and tend to get accumulated in fatty tissues, nerve tissue is most likely to get damaged heavy metals, heavy metal causes nervous tissue damage there for water must be free from heavy metals.

Brazil Falls Under Which Climatic Zone?
Zone IVB (30 degree celsius and 75% relative humidity)

Change in the Size or Shape of the Original Container Requires any Stability Study?
  • A change in the size or shape of the original container may not necessitate the initiation of new stability study.


Forced Degradation (stress Testing) and Accelerated Stability Testing are Same?
  • Forced degradation and stress testing are not the same. Stress testing is likely to be carried out on a single batch of the drug substance. The testing should include the effect of temperatures (in 10°C increments (e.g., 50°C, 60°C) above that for accelerated testing), humidity (e.g., 75 percent relative humidity or greater) where appropriate, oxidation, and photolysis on the drug substance. The testing should also evaluate the susceptibility of the drug substance to hydrolysis across a wide range of pH values when in solution or suspension. Photostability testing should be an integral part of stress testing.

According To Who Guidelines What is the Storage Condition of Climatic Zone IVA and Zone IVB?
  • Zone IV a: 30°C and 65% RH (hot and humid countries)
  • Zone IV b: 30°C and 75% RH (hot and very humid countries


Countries Come Under Climatic Zone IVb?
  • Brazil, Cuba, China, Brunei, Cambodia, Indonesia, Malaysia, Myanmar, Philippines, Singapore, Thailand

What is the Purpose of Stress Testing in Stability Studies?
  • Stress testing of the drug substance can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic stability of the molecule and validate the stability indicating the power of the analytical procedures used. The nature of the stress testing will depend on the individual drug substance and the type of drug product involved.

What is a Dead Leg?
  • A dead leg is defined as an area in a piping system where liquid can become stagnant and not be exchanged during flushing.

What is the Recommended Bio Burden Limits of Purified Water & WFI?
  • Purified water has a recommended bioburden limit of 100 CFU/mL, and water for injection (WFI) has a recommend.

Brief About ICH Stability Guidelines?
  • Q1A- Stability testing of new drug substances & products

What are Significant Changes In Stability Testing?
  • A 5% change in an assay for the initial value.

If Leak Test Fail During In Process Checks What Needs To Be Done?
  • Immediately stop the packing process and check for:
  1. Sealing temperature
  2. Verify for any possible changes like foil width, knurling etc.
  3. Check & quarantine the isolated quantity of packed goods from the last passed inprocess.
  4. Collect random samples & do a retest.
  5. Blisters from the leak test passed containers shall allow to go further and rest must be deblistered/defoiled according.

Explain About Revalidation Criteria Of AHU System?
  • AHU system shall be revalidated periodically as mentioned in the regulatory standards.
  • AHU shall be revalidated in the following cases also:
  1. When the basic design of AHU is changed,
  2. When clean room volume is changed,
  3. When new equipment is installed
  4. When construction is carried out, that calls for a reconstruction of AHU system.


What Needs To Be Checked During AHU Validation?
  1. During AHU validation, the following tests shall be carried out:
  2. Filter efficiency test,
  3. Air velocity & number of air changes,
  4. Air flow pattern (visualization)
  5. Differential pressure, temperature, and RH
  6. Static condition area qualification
  7. Dynamic condition qualification
  8. Non-viable count
  9. Microbial monitoring
  10. Area recovery and power failure study.

Explain In Detail About the Qualification For Pharmaceutical Water System?
  • Qualification of pharmaceutical water system involves three phases:
  1. Phase -1
  2. Phase -2
  3. Phase -3

Phase -1
  • A test period of 2-4 weeks should be spent on monitoring the system intensively. During this period the system should operate continuously without failure or performance deviation. Water cannot be used for pharmaceutical manufacturing in this phase. The following should be included in the testing approach.
  • Under take chemical & microbiological testing in accordance with a defined plan.
  • Sample incoming feed water daily to verify its quality.
  • Sample each step of the purification process daily.
  • Sample each point of use daily.
  • Develop appropriate operating ranges.
  • Demonstrate production and delivery of product water of the required quantity and quality.
  • Use and refine the SOP’s for operation, maintenance, sanitization, and troubleshooting.
  • Verify provisional alert and action levels.
  • Develop and refine test failure procedure.

Phase -2
  • A further test period of 2-4 weeks. The sampling scheme will be the same as Phase – 1. Water can be used for the manufacturing process in this phase. Approach should also
  1. Demonstrate consistent operation within established ranges.
  2. Demonstrate consistent production & delivery of water of required quality and quantity.

Phase - 3
  • Phase 3 runs for one year after satisfactory completion of phase-2. Water can be used for manufacturing process during this process.
  • Objectives & Features of Phase -3:
  1. Demonstrate extensive reliable performance.
  2. Ensure that seasonal variations are evaluated.
  3. The sample locations, sampling frequencies and test should be reduced to the normal routine pattern based on established procedures proven during Phase -1 & phase - 2.

Briefly Explain About ICH Climatic Zones For Stability Testing & Long Term Storage Conditions?
  • ICH STABILITY ZONES:
Zone: Type of Climate
Zone I: Temperate zone
Zone II: Mediterranean/subtropical zone
Zone III: Hot dry zone
Zone IVa: Hot humid/tropical zone
Zone IVb:

  1. ASEAN testing conditions hot/higher humidity
  2. Long term Storage condition
  3. Climatic Zone
  4. Temperature
  5. Humidity

Minimum Duration:


What Are The Common Variables In The Manufacturing Of Tablets?
  • The particle size of the drug substance:
  1. Bulk density of drug substance/excipients
  2. Powder load in granulator
  3. Amount & concentration of binder
  4. Mixer speed & mixing timings
  5. Granulation moisture content
  6. Milling conditions
  7. Lubricant blending times
  8. Tablet hardness
  9. Coating solution spray rate

Whether Bracketing & Validation Concept Can Be Applied In Process Validation?
  • Both Matrixing and Bracketing can be applied in validation studies.
  • Matrixing
  • Different strengths of the same product
  • Different sizes of the same equipment
  • Bracketing - Evaluating extremes
  • Largest and smallest fill volumes
  • Fastest and slowest operating speeds

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