PHARMACEUTICAL QUALITY ASSURANCE INTERVIEW QUESTIONS

PHARMACEUTICAL QUALITY ASSURANCE INTERVIEW QUESTIONS

1. Q. Why water for pharmaceutical use is always kept in close loop in continuous circulation?

A. Water is a best medium for many microorganisms, microorganism 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 few hours, these settled microorganism form a film over the surface of vessel and piping, such film formed by microorganisms is also called as biofilm, biofilms are very difficult of 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 is may not completely get removed effectively. Biofilms then can become a source of microbial contaminations; therefore purified water after collection in a distribution system is always kept in a closed loop in a continuous circulation. A continuous circulation is also not enough at some points, therefore it is aided with high temperature range from 65 °C to 80°C, a minimum temperature of 65 °C is considered a selfsanitizing, but better assurance is obtained with a temperature of 80°C . Purified water collected should be stored in a stainless still vessel which must facilitate distribution to the point of use in a closed loop of continuous circulation, tank should be made of corrosion free material of construction, and must facilitate sanitization and easy cleaning.

2 Q. Water for pharmaceutical use shall be free cations,anions and other impurities why ?

A.Water for pharmaceutical must be free from inorganic as well as organic impurities, minerals, and heavy metals. Some impurities like calcium, magnesium, ferrous are responsible for degradation of drug molecule, many cations like ferrous and calcium magnesium act as catalysts in degradation reaction of drug molecule, anions like chloride are highly active they participate in nucliophylic substitution reactions, where in they break a double bond between -C=C- in to a single bond as CL –CH-CH2- , which a reason why we observe that color dies tend to fed in presence of chlorine as most of the dies used are diazo compounds which has plenty of places for nucliophylic substitution reactions, which is also a reason why stability of drug is drastically affected in presence of cations and anions from mineral origin present in water.

3. Q. Water for pharmaceutical use shall be free heavy metals why ?

A. Heavy metals like lead and arsenic are highly cumulative neurotoxic metals, heavy metals are not eliminated out of 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 by heavy metals, heavy metal causes nervous tissue damage there for water must be free from heavy metals.

4. Q. Brazil falls under which climatic zone ?

A. Zone IVB (30 degree celsius and 75% relative humidity)

5. Q. 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.

6. Q. Forced degradation(stress testing) and accelerated stability testing are same?

A. Forced degradation and stress testing are not 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. Photo stability testing should be an integral part of stress testing.

7. Q. According to WHO guidelines what is the storage condition of climatic zone IVa and zone IVb?

A. 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

8. Q. Countries comes under climatic zone IVb?

A.Brazil,Cuba,China,Brunei,Cambodia,Indonesia,Malaysia,Myanmar,Philippines,Singapore,Thailand

9. Q. What is the purpose of stress testing in stability studies?

A. 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 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.

10. Q. What is the formula for calculating number of air changes in an area?

A. Number of air changes/hour in an area is = Total Room Airflow In CFM x 60/Total Volume of room in cubic feet

For calculating Total Room Airflow in CFM, first calculate air flow of individual filter. Formula is given below.

Air flow (in cfm) = Avg.air velocity in feet/Minute x Effective area of filter

Then find Total air flow. Formula is Total Air flow = Sum of air flow of individual filter.

Air flow Velocity can be measured with the help of Anemometer.

11. Q. What is dead leg?

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

12. Q. What is the recommended bio burden limits of purified water & WFI?

A. Purified water has a recommended bioburden limit of 100 CFU/mL, and water for injection (WFI) has a recommended bio burden limit of 10 CFU/100 mL.

13. Q. Brief about ICH stabilty guidelines?

A. Q1A- Stability testing of new drug substance & products

Q1B- Photo stability testing of new drug substances & products

Q1C-Stability testing of new dosage forms

Q1D-Bracketing & Matrixing designs for testing of new drug substances and products

Q1E-Evaluation of stability data

Q1F-Stability data package for registration applications in climatic zone III & IV (Withdrawed)

14. Q. What is significant changes in stability testing?

A. 1. A 5% change in assay for initial value.

2. Any degradation products exceeds its acceptance criterion.

3. Failure to meet acceptance criterion for appearance,physical artributes and functionality test.

4. Failure to meet acceptance criteria for dissolution for 12 units.

15. Q. If leak test fail during in process checks what needs to be done ?

A. Immediately stop 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 last passed inprocess.

4.Collect random samples & do retest.

5.Blisters from the leak test passed containers shall allow to go further and rest must be

16. Q. How many Tablets shall be taken for checking friability?

A. For tablets with unit mass equal or less than 650 mg, take sample of whole tablets

corresponding to 6.5g.For tablets with unit mass more than 650mg,take a sample of 10 whole tablets.

17. Q. What is the formula for calculating weight loss during friability test?

A. %Weight loss = Initial Weight - Final Weight X 100 Initial Weight

18. Q. What is the pass or fail criteria for friability test?

A. Generally the test is run for once.If any cracked,cleaved or broken tablets present in the tablet sample after tumbling,the tablets fails the test.If the results are doubtful,or weight loss is greater than the targeted value,the test should be repeated twice and the mean of the three tests determined.A mean weight loss from the three samples of not more than 1.0% is considered acceptable for most of the products.

19. Q. What is the standard number of rotations used for friability test?

A. 100 rotations

20. Q. What is the fall height of the tablets in the friabilator during friability testing?

A. 6 inches.Tablets falls from 6 inches eight in each turn within the apparatus.

21. Q. Why do we check hardness during inprocess checks?

A. To determine need for the pressure adjustments on the tableting machine. Hardness can affect the disintegration time.If tablet is too hard, it may not disintegrate in the required period of time. And if tablet is too soft it will not withstand handling and subsequent processing such as coating,packing etc.

22. Q. What are the factors which influence tablet hardness?

A. 1.compression force

2.Binder quantity(More binder more hardness)

3.Moisture content

23. Q. Which type of tablets are exempted from Disintegration testing?

A. Chewable Tablets

24. Q. Which capsule is bigger in size - size '0' or size '1'?

A. '0' size

25. Q. What is the recommended temperature for checking DT of a dispersible tablet?

A. 25 ±10C (IP) & 15 – 250C (BP)

26. Q. What is mesh aperture of DT apparatus ?

A. 1.8 -2.2mm (#10)

27. Q. What is the pass/fail criteria for disintegration test?

A. If one or two tablets/capsules fails to disintegrate completely, repeat the test on another 12 additional dosage units. The requirement is meet if not fewer than 16 out of 18 tablets/capsules tested are disintegrated completely.

28. Q. What is the recommended storage conditions for empty hard gelatin capsules?

A. 15 - 250C & 35 -55% RH

29. Q. Which method is employed for checking “Uniformity of dosage unit”?

A. A.)Content uniformity

B.) Weight Variation

Weight variation is applicable for following dosage forms;Hard gelatin capsules,uncoated or film coated tablets,containing 25mg or more of a drug substance comprising 25% or more by weight of dosage unit.

30. Q. What is the recommended upward and downward movement frequency of a basket-rack assembly in a DT apparatus?

A. 28 – 32 cycles per minute.

31. Q. When performing the ‘uniformity of weight’ of the dosage unit, how many tablet/capsule can deviate the established limit?

A. Not more than two of the individual weights can deviates from the average weight by more than the percentage given in the pharmacopeia,and none can deviates more than twice that percentage.

Weight Variation limits for Tablets

IP/BP Limit USP 80 mg or less 10% 130mg or less More than 80mg

or Less than

250mg

7.5% 130mg to 324mg

250mg or more 5% More than 324mg

Weight Variation limits for Capsules

32. Q. What needs to be checked during inprocess QA checks?

A. a.) Environmental Monitoring

b.) Measured values obtained from the process equipment (ex:temperature,RPM etc.)

c.) Measured values obtained from persons (ex:timmings,entries etc.)

d.) Process attributes (Ex:weight,hardness,friability etc.)

33. Q. What precautions shall be taken while collecting inprocess samples ?

A. While collecting inprocess samples, avoid contamination of the product being sampled (Don’t collect samples with bare hands) & avoid contamination of sample taken.

34. Q. In a tablet manufacturing facility ‘positive’ pressure is maintained in processing area or service corridors?

A. In tablet manufacturing facilities, pressure gradients are maintained to avoid cross contamination of products through air. Usually processing areas are maintained under positive pressure with respect to service corridors.

35. Q. If sticking observed during tablet compression what may the probable reason for the same?

A. 1.If the granules are not dried properly sticking can occur.

2.Too little or improper lubrication can also leads to sticking.

3.Sticking can occur because of too much binder or hygroscopic granular.