1.What is Production :
All operations involved in the preparation of a pharmaceutical product, from receipt of raw materials through the completion of a finished product i.e from Raw material Receipt to Finished product dispatch. It also includes the handling of manpower and recording the manufacturing and the packing activity performed.
2. What is Batch Processing or Batch Manufacturing Record :
Documentation that provides the history of a batch from the raw material dispensing stage to completion of the batch or lot which include Dispensing of raw material, Granulation, Blending Compression, Capsule Filling, Coating, Inspection and yield at different stages. It also includes the details of the activity performed by whom, checked by whom, at what time activity was performed, at what date activity was performed and signature of the personnel involved in the batch or activity.
3. What is Batch Packaging Record :
Documentation that provides the history of a batch from packaging material dispensing, Blister packing, Bottle packing, Jar packing, Dry syrup Filling, labeling, Carton packing and shipper packing up to Dispatch of a Batch or Lot.
It also includes the details of the activity performed by whom, checked by whom, at what time activity was performed, at what date activity was performed and signature of the personnel involved in the batch or activity.
4. Active Pharmaceutical Ingredient :
A substance or a bulk pharmaceutical chemical that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of the disease or to effect the structure or any function of the body of man or other animals.
5. What is Standard Operating Procedure (SOP):
It is an authorized written document which describes the step by step instructions requirements for performing operations or any activity and non-specific to any product, process or material. It provides detailed procedure about systems applicable to various operation e.g. Equipment’s / Instrument’s / System’s Operation / Cleaning / Maintenance etc.
Everybody working in organization has to follow the instruction which are written in SOP and perform their activities accordingly.
6. What is GMP and CGMP :
Good manufacturing practices (GMP) are the practices required in order to conform the guidelines recommended by agencies that control the authorization and licensing of the manufacture and sale of food and beverages, pharmaceutical products, dietary supplements, and medical devices.
These guidelines provide minimum requirements that a manufacturer must meet or follow to assure that their products are consistently high in quality, from batch to batch, for their intended use.
CGMP is Current Good manufacturing practices (GMP) and we have to follow the current practices as there are the changes in regulations so always you have to follow the current practices so it is called current.
7. What are the In processes checks parameters during Tablet compression:
Appearance, Group weight, Individual weight variation, Uniformity of weight, Thickness, Diameter, Hardness, friability, Speed of machine, compaction force, die fill depth and Disintegration time.
8. What are the In processes checks parameters during Capsule Filling:
Appearance, Group weight of filled capsule, Individual weight of filled capsule, Net fill content of the powder, locking length and Disintegration time.
9. What are the In processes checks parameters during Tablet coating:
Appearance, Inlet temperature, out let temperature, pan RPM, Gun distance from tablet bed, spray rate, weight gain, Group weight of Coated tablets, Individual weight of Coated tablets, and Thickness.
10. What are the defects in Compressed tablets :
Picking, sticking, capping, laminating, weight variation, Broken, chipped, Rough Surface, Double compressed, Rough edges, Powdery, Incorrect Description, Black spot, Oil spot, Foreign Product and Debossing/ Embossing.
11. What are the defects in Capsules :
Empty, Cracked, Dented, Telescopic, Unlocked, Partially locked, Improper polishing, Powdery, Long or Short caps, Printing defects, Improper locking length and Weight variation.
12. What is Water For Injection (WFI) :
Water for injection It is the water of extra high quality without significant contamination and Water for injection is generally made by distillation or reverse osmosis.
13. What is Aerosol in Pharmaceuticals :
Aerosol is a pressurized dosage forms containing one or more therapeutic active ingredients which will produce a fine dispersion of liquid and/or solid materials in a gaseous medium during operation.
14. Tell about wet granulation :
It involves Sifting of API & Excipients, Wet mixing, drying, Sifting, Blending and then Blend shall be compressed or Filled in Capsule and then compressed tablets are coated with coating solution.
Sifting of API and Excipients through Sifter, Mixing of API & Excipients then addition of binder solution to form a wet mass in Fluid Bed Processor or Rapid Mixer Granulator, then dried the wet mass in Fluid Bed Processor or Fluid Bed dryer. Dried granules are again screened through a sieve which helps it to break down the granule then it should be lubricated or mixed in Blender. These same size Blend are then compressed or can be filled in capsule.
15. Tell about Dry granulation :
Dry granulation involves mixing, pre-mixing, milling, compression or Capsule Filling. API and Excipients are sifted, milled in roll compactor to product slugs then slug size is reduced in multi mill or Oscillating granulator. Then these granules are Mixed or lubricated in Blended and then blend shall be compressed in compression machine or can be filled in capsule filling machine to form tablets or capsules.
16. What is tablet :
Tablets is defined as the solid unit dosage form of medicines with suitable Excipients and prepared either by molding or by compression. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose.
17. Name any four tablet processing problems :
Mottling, Capping, lamination, picking and sticking
Mottling– unequal colour distribution of a tablet.
Capping– Partial or complete separation of a tablet top or bottom crowns.
Lamination– Separation of tablets into two or more layers.
Picking– Because of adhesion to the punch faces, Localized portion missing on the surface of the tablet.
Sticking– Adhesion of tablet localized portion to the punch faces resulting in rough and dull appearance.
18. What is Disintegration Test :
It is the time required for the Tablet / Capsule to break into particles, the disintegration test is a measure of the time required under a given set of conditions (Temperature) for a group of tablets/capsules to disintegrate into particles.
Cycle of shaft holding the tube basket limit is 29-32 cycles per minutes and distance covered by shaft basket is 50-60 mm and beaker temperature is 35 to 39 º C. Disintegration is to be Performed to determine whether tablets or capsules disintegrate within the prescribed time when placed in a liquid medium at the experimental conditions.
19. What are the Disintegration Time of tablets :
- Uncoated Tablet 15 min as per BP & 30 min as per USP
- Sugar Coated Tablet 60 min as per BP
- Film Coated Tablet 30 min as per BP
- Plain Coated Tablets DT in specific medium for 30 min as per USP
- Enteric Coated Tablets DT in simulated gastric fluid (0.1 M HCl) for 1 hr and then in simulated intestinal fluid (Phosphate buffer 6.8 pH) until disintegrate as per USP.
- Dispersible Tablets 3 min ( 15- 25º C ) as per BP.
- Effervescent Tablets 1 tablet in 200 mL water for 5 min ( 15- 25º C )
as per BP - Buccal Tablets 4 hrs as per USP.
- Soluble Tablets 3 min ( 15- 25º C ) as per BP.
- Chewable Tablets are not require to comply with test
20. What is Disintegration Time of capsules :
- Gastro resistant capsule DT 2 hrs without disk in 0.1 M HCl and phosphate buffer pH 6.8 for further 60 min as per BP.
- Hard and Soft gelatin capsule DT 30 min as per BP & USP.
21. What is Friability Test of Tablet & friability Calculation :
Friability is defined as the percentage of weight loss of powder from the surface of the tablets due to mechanical action and the test is performed to measure the weight loss during transportation.
Friability (%) =W1– W2/W1X100
Where,
W1 = Weight of Tablets (Initial / Before Tumbling) &
W2 = Weight of Tablets (After Tumbling or friability)
Limit : Friability (%) = Not More Than 1.0 %
Tablets with individual weight equal to or less than 650 mg then take the sample of whole corresponding to as near as 6.5 gram equivalent and tablets with individual weight more than 650 mg then take sample of 10 whole tablets to perform friability test. Tablets must be de-dusted prior to and after use.
23. What is Validation :
Documented program or evidence, that provides a high degree of assurance that a specific process method or system consistently produce a result indicating predetermined accepted criteria.
24. What is Calibration :
The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a traceable standard over an appropriate range of measurements.
25. What is Qualification :
The action of proving that any equipment or process work correctly and consistently and produces the expected result. Qualification is part of, but not limited to a validation process, i.e. Installation Qualification (IQ), Operation Qualification(OQ) and Performance Qualification (PQ).
The act of planning, carrying out and recording the results of tests on equipment to confirm its capabilities and to demonstrate that it will perform consistently as intended use and against predefined specification.
26. Design Qualification :
Documented verification that equipment, instrument, facility and system are of suitable design against the URS and all key aspects of design meet user requirements.
27. Installation Qualification (IQ) :
The documented verification that all components of the equipment and associated utilities are properly installed or modified in accordance with the approved design and manufacturer’s recommendations.
28. Operational Qualification :
Operational qualification consists of verification and documentation, of the parameters of the subjected equipment. The documented verification that the equipment, instrument, facility and system as installed or modified, perform as intended throughout the installed operating range.
29. Performance Qualification :
Performance Qualification is designed to prove the process, can consistently produce a product that meets the stated requirements and specifications. It is a documented verification that the equipment, instrument, facility and system as connected together, can perform effectively and reproducibly, based on the approved process method and product specification.
30. Why Three consecutive batches taken for Validation :
Consecutive meaning following closely with no gap or following one after another without interruption.
- The number of batches to be taken under validation depends upon the risk involved in the manufacturing Critical process parameters & critical Quality Attribute so depends upon that manufacturer have to choose the number of batches to be validated.
- If we will consider less than two batches then the data will not be sufficient for evaluation of and to prove reproducibility of data between batch to batch variation & if we consider more than three batches it can increase the time & cost of manufacturer which usually not preferred.
- Generally if we will require quality in the First batch, then it is accidental (co-incidental), Second batch quality is regular & third batch quality is Validation or Confirmation.
Statistical evaluation cannot be done by considering two points, because two points always draw a straight line so minimum three points required for comparison of data.
31. What is Airlock :
An enclosed space with two or more doors, which is interposed
between two or more rooms, e.g. of differing classes of cleanliness, for the
purpose of controlling the airflow between those rooms when they need to be entered.
An airlock is designed for use either by people or for goods and/or equipment.
32. What is Clean Area :
An area with defined environmental control of particulate and microbial
contamination, constructed and used in such a way as to reduce the
introduction, generation, and retention of contaminants within the area
33. What is yield reconciliation :
A comparison between the theoretical quantity of the material and the actual quantity.
Yield Reconciliation can be done in manufacturing and packing stages . i.e Blending, Compression, Capsule filling, Coating, Inspection and packing etc.
34. What is in-process control or checks :
Checks performed during production in order to monitor whether it is meeting the required specification or not and, if necessary, to adjust the process to ensure that the product conforms to its specifications. The control of the environment or equipment may also be regarded as a part of in-process control.
35. What is Finished Products :
A finished dosage form that has undergone all stages of manufacturing
including packaging in its final container with labelling and which is ready for sale or release to market.
36. What is intermediate Product :
Partly or Partially processed product that must undergo further manufacturing steps which includes Blend, Filled capsule, Compressed tablets, coated tablets etc.
37. What are the defects of Coated tablets :
Twins, Cracking, Partially coated, Incomplete drying, Edge broken, Peeling, Print defects, Shade Variation, Weight variation, Debossing/ Embossing fill
38. What is SMF and how it works :
When the product is under drying in FBD, the product loss often occurs due to a puncture or broken filter bag. Solid flow monitor (SFM ) or broken bag detector (BBD) provides good detection of filled filter bag failure or tear in FBD, thus prevent product loss. SFM or BBD located in the exhaust duct of FBD.
39. What is Tolling in compression machine :
In tablet compression machines Punches and dies are used to compressed powder to form table. The dies and punches and their setup on compression machine is called tooling.
40. Tolling are how many Types :
There are four types of tolling in compression machine B Tolling, BB tolling, D tolling and DB tolling. D tolling punch and die diameter is greater than B tolling punch and die diameter. D tolling punch diameter is 25.4 mm and Die diameter is 38.10 mm where as B tolling punch diameter is 19.00 mm and die diameter is 30.15 mm
41. What is Dual time in Compression Machine :
In tablet compression, dwell time is the time that the punch head remains in contact with the compression roller and it is defined as the amount of time that the compression force applied when forming the tablet is above 90% of its peak value.
42. What is the work of Pre compression Rollers in Compression Machine :
These are the very first rollers in rotary tablet press. Basically, these rollers apply a small amount of force on the upper and lower punches.
This gives the initial compression force. The aim of this process is to remove air that could be in the die or powder particles.
43. What is the work of Main compression Rollers in Compression Machine :
Main compression rollers exert a predetermined amount of force (final compression force) for the formation of tablets. The compression force at this stage is higher than the pre-compression force.
It is important that the rollers remain stable with no vibration during the entire process. This is to ensure consistency of the tablets’ thickness and size.
44. What are the units of Hardness in tablets :
Kilogram (kg), Newton (N), Pound (lb), Kilopond (kp) and Strong-Cobb (SC)
45. What is Leak test in Packing :
The test which is used to check the integrity of packed strips, blisters, Bottles and small sachets containing tablets, Capsules and Dry Powders is called leak test.
Leak test Apparatus is used to test the quality of the packaging process and to check that the seals enclosing the product are perfectly intact and no water should go inside the pack. It is designed to find the smallest holes or Puncture and imperfections in packed Products .
46. What is FMD in Packing :
The FMD (Falsified Medicines Directive) is a legal framework introduced by the European Commission to improve the protection of Public health within the European Union. The directive applies since 2 January 2013 & the European Commission Delegated Regulation, (EU) 2016/161, supplements Directive 2001/83/EC with rules regarding safety features for the packaging of medicinal products for human use. The regulation was adopted in October 2015 to counteract to fake medicines include stricter record-keeping of wholesale distributors, pharmaceutical producers, an EU-wide quality mark to identify online pharmacies and mandatory safety features on packages.
47. Which indicator is used in Leak test Apparatus :
In order to identify the leakage in Blister or stripes methylene blue colour is used and the solution in the desiccators required to be changed every day or whenever required.
48. What is NFD & how it works :
Non Fill Detection is an system incorporated into the machine which enables the machine to automatically detect and reject those strips or Blisters that have missing tablets or capsules in cavity. This arrangement involves a sensing system, a control system consisting of a Programmable Logic Controller (PLC) and an HMI (Human Machine Interface), and an electro pneumatically activated auto-rejection system. Both – the Strip & blister Packing Machine as well as the NFD system are designed and built by us at our works and are therefore fully integrated with each other.
49. What is Hold time Study:
Hold Time studies establish the time limits for holding the materials at different stages of production to ensure that the quality of the product does not degrade significantly during the hold time at a required temperature and Relative Humidity.
Hold time can be considered as the established time period for which materials (dispensed raw materials, intermediates and bulk dosage form awaiting final packaging) may be held under specified conditions and will remain within the defined specifications. Hold-time studies establish the time limits for holding the materials at different stages of production to ensure that the quality of the product does not produce results outside the acceptance criteria during the hold time.
50. What is Deviation:
Any unwanted event that represents a departure from approved processes or procedures or instruction or specification or established standard or from what is required. Deviations can occur during manufacturing, packing, sampling and testing of drug products.
Examples of Deviations: Temperature and RH of area goes out of limit during manufacturing, Typographical error observed in approved documents, Standard operating procedure not followed, Breakdown of equipment, Spillage of material during unloading, Instrument calibration results goes out of limit etc. Deviations are of three types Minor, Major and Critical.
51. What is Change Control :
It is a Approved Procedure which is taken to change in any documents, Standard operating procedures, Specification, Process parameters and change in batch size etc. Change control is raised by user department as per requirement and finally the change control is approved by Quality assurance. Change control can be raised through software or through manually.
After Final approval of change control the changes can be made in documents and change control can be closed after completion of required action plan which is mentioned in the Change control form. Change controls are of two types i.e Major and Minor.
52. Corrective action and preventive action :
An action taken to eliminate the cause of the existing deviation , incident or problem in order to prevent its recurrence (occurring again).
An action taken to eliminate the cause of potential deviation, incident or problem in order to prevent its occurrence (an incident or event) is called preventive action.
53. What is the Principle of Coating process:
The basic principle of tablet coating involves the application of coating solution to a moving bed of tablets with the concurrent use of heated air to facilitate evaporation of the solvent. The distribution of coating is achieved by the movement of the tablets either perpendicular (coating pan) or vertical (air suspension).
54. What are the Coating equipments which are being used :
For the coating process use of one of the 3 types of following equipments.
- Conventional coating pan. 2) The perforated coating pan. 3) The fluidized bed coater.
55.What is Conventional Coating Pan:
The Conventional Coating Pan is simple unit, which employs the principle of rolling a batch of tablets in an oval shape pan, spraying the coating solution on it and passing hot air across the tablet bed. An exhaust blower may be used to carry away the excess fumes generated during the coating and drying process.
Improvements in conventional pan are pellegrini system which has a baffled pan and diffuser which improves the drying efficiency and can be suitable for sugar coating process.
The immersion sword system which includes a metal sword that will immerse in the tablet bed and during drying process it will introduce drying air which flows through perforated metal sword then upwards towards bed.
The immersion tube system which includes a tube that will immerse in the tablet bed and this tube has a spray nozzle that delivers both the hot air and coating solution. This is suitable for both sugar coating and film coating.
56. What is perforated coating Pan:
The coating drum is an enclosed housing with various spray nozzles and these spray nozzles atomize the coating solution. This coater have an dry inlet air flows from the upper section of the drum, passing in between the tablets which leaves the drum through the perforations.
There are different type of coating systems which are Accela-cota system, Hi-Coater system, Dria coater and the Glatt coater.
57.What is fluidized bed Coater:
The fluidized bed coaters have enhanced drying efficiency fluidization of tablet mass is achieved by columnar chamber by the upward movement of the drying air. The movement of the tablets is upward through the center of the camber. Then they fall toward the chamber wall and move downward to re-enter into air stream at the bottom of the chamber. It has a basically two spray application systems they are (1) high pressure airless (2) low pressure air atomized.
58. What are the Process parameters which are to be checked during Coating:
Inlet temperature, Outlet temperature, Spray rate, Automizing air pressure, Pan Rpm, Gun distance from tablet bed, weight gain of tablets, Peristaltic pump RPM, tablets thickness, tablet hardness, Group weight of tablets and Appearance.
59. What are the reasons for Twin of tablets in Coating:
The possible causes are If coating solution are sticky, If spray guns are too close to the tablet bed, Inappropriate tablet shape, If pan speed is low & if spray rate is too high.
60. What are the reasons for Picking or Sticking of tablets in Coating: The possible causes are if spray rate is too high, Poor distribution of coating solution, If pan speed is low, Inadequate drying conditions and Inadequate atomizing air pressure.
61. What is the difference between dedicated and non-dedicated equipments
Dedicated equipment: It is used solely for the production of a single product or product line. Concerns over cross-contamination with other products are markedly reduced. Dedicated equipment’s must be clearly identified with the restrictions of use in order to prevent potential errors during cleaning and preparation.
Non-dedicated equipment: Where the same piece of equipment is utilized for a range of products formulations. The prevent of cross-contamination between products becomes the main objective in the cleaning validation effort. Clearly, cleaning non-dedicated equipment’s represents a more significant obstacle to overcome.
62. Which instrument is used for the measuring of RPM
Techo meter is used for the measurement of RPM.
63. What is HACCP
HACCP : Hazard Analysis Critical Control Point
64. What is OHSAS
OHSAS : Occupational Health & Safety Assessment Series
65. Describe the method of testing for checking of MOC of SS material (Molybdenum test)
Procedure:
i) Put one drop of electrolyte solution of molybdenum test kit on clean metal surface,
which is to be tested.
ii) Switch on the detector and touch the metal tip of the detector on metal surface &
carbon point in electrolyte solution.
iii) Do not pass the current for more than 3 to 4 seconds
iv) If the red color appears and is stable for more than 2 seconds then it can be
concluded that MOC of the part being tested is SS-316.
v) If the solution remains colorless or green color appears then it can be concluded
that MOC of the part being tested is SS-304.
vi) If the black color appears & is stable for more than 2 seconds then it can be
concluded that MOC of the part being tested is SS-302.
66. What will happen if cGMP are not followed
Non-compliance to cGMP may lead to:
- Poor quality of product / services
- Batch failure
- Market complaints and product recalls
- Company’s reputation affected
- Business will be affected
- Regulatory action
- Injuries or accidents
- Equipment failures
67. What are the safety systems in the plant
Some of the safety systems used in the plant are:
- Eye washer, safety showers
- Fire extinguishers
- Fire hydrants
- Face shields
- Goggles
- Helmets
- Nose masks
- Safety shoes
- Safety belts
- Hand gloves
- Training on safety rules and use of safety equipments.
68. What are the classifications of clean rooms
Generally clean rooms are classified in to the following types as per different guidelines:
Schedule M: Grade A, Grade B, Grade C, Grade D
USFDA (US 209E): Class 1, Class 10, Class 100, Class 1000, Class 10000, Class 100,000
WHO 2002: Grade A, Grade B, Grade C, Grade D
EU GMP: Grade A, Grade B, Grade C, Grade D
ISO 14644-1: ISO-3, ISO-4, ISO-5, ISO-6, ISO-7, ISO-8, ISO-9
69. What needs to be checked during AHU validation
During AHU validation, following tests shall be carried out ·
Filter efficiency test, ·
Air velocity & number of air changes, ·
Air flow pattern (visualization) ·
Differential pressure, temperature and RH ·
Static condition area qualification ·
Dynamic condition qualification ·
Non-viable count ·
Microbial monitoring
Area recovery and power failure study.
70. What is a DMF
Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. Important facts regarding DMFs It is submitted to FDA to provide confidential information Its submission is not required by law or regulations It is neither approved nor disapproved It is filed with FDA to support NDA, IND, ANDA another DMF or amendments and supplements to any of these It is provided for in the 21 CFR (Code of Federal Regulations) 314. 420It is not required when applicant references its own information.
71. What is the difference between dedicated and non-dedicated equipment’s
Dedicated equipment: It is used solely for the production of a single product or product line. Concerns over cross-contamination with other products are markedly reduced. Dedicated equipment’s must be clearly identified with the restrictions of use in order to prevent potential errors during cleaning and preparation.
Non-dedicated equipment: Where the same piece of equipment is utilized for a range of products formulations. The prevent of cross-contamination between products becomes the main objective in the cleaning validation effort. Clearly, cleaning non-dedicated equipment’s represents a more significant obstacle to overcome.
72. Which instrument is used for the measuring of RPM
Techo meter is used for the measurement of RPM.
