What do u mean by MACO & NOEL?
- MACO-Maximum Allowable Carry Over
- NOEL – No Observed Effect Level
Both of them are set limits for cleaning validation
Composition of C18 column
Octadecylsilane
How to select columns for specific products?
Column selection based on
- Polarity
- Electrical charge
- Molecular size
- Normal phase is recommended for water sensitive compounds/geo metric isomers/cis-trans isomers/chiral compounds/class separations
- Reverse phase for non polar /polar/ionizable/non ionizable molecules
- Gel permeation for large size compounds like polymers
- Ion exchange for resins
Define validation/validation protocol/validation master plan
- Validation protocol : it is written plan describing the process to be validated, including production equipment & how validation to be conducted.
- Validation master plan : it was also called as VMP which is one of important document in GMP regulated industries. It outlines the principles involved in qualification of facility, defining areas & systems to be validated & provides written programme for achieving & maintaining qualified facility with validity processes
- Validation : it was defined as collection & evaluation of data from the process design stage through commercial production which establishes scientific evidence that the process is capable of producing quality products consistently.
What is process validation?
Establishing documented evidence with high degree of assurance that specific process will consistently produce a product meeting its predetermined specifications & quality characteristics
What do u mean by MKT?
MKT is an expression of cumulative thermal stress experienced by a product at varying temperatures during storage & distribution
Temperature & humidity required for tablet compression?
Temp :- NMT 30°C
Humidity :- 45 ± 5%
What is humidity & relative humidity?
Humidity- it was the amount of water vapour in air
Relative humidity - the amount of water vapour present in air expressed as % of the amount needed for saturation at the same temp
Relative humidity - the amount of water vapour present in air expressed as % of the amount needed for saturation at the same temp
What is vacuum & vapor pressure?
- Vacuum pressure – it was a pressure below normal atmospheric pressure which will be used to remove air from surrounding. Ex: vaccum pumps
- Vapour pressure - it was pressure exerted by a vapour in thermodynamic equilibrium with its condensed phases (solid/liquid) at a given temp. in closed system
What are stability zones & climatic conditions?
- Zone-1: great Britain / north Europe / Canada / Russia ( Temp - 21°C RH – 45%) (Moderate Region)
- Zone-2 : USA / Japan / South Europe (Temp - 25°C RH - 60%) (Subtropical Region)
- Zone-3 : Iran / Iraq / Sudan (Temp - 30°C RH - 55%) (Hot Region)
- Zone-4 : Brazil / Ghana / Indonesia / Nicaragua / Philippines (Temp-30°C RH - 70%) (Tropical Region)
What do u mean by Bracketing & Matrixing in stability studies?
- Bracketing: it was designed with a stability schedule such that at any time point, only the samples on extremes e.g of container size/dosage strength are studied
- Matrixing: it was a statistical design of stability schedule only a fraction of the total number of samples are tested at any sampling point at a subsequent sampling point, different sets of samples of total number would be tested
What is the limit of cleaning validation?
- It should be visually clean & no residue should be visible after cleaning
- No more than 10 ppm of the product will appear in another product
- No more than 0.1% of the normal therapeutic dose of one product will appear in max daily dose of the subsequent product
What is LOD & water content?
- LOD: it is loss of weight expressed as w/w resulting from water & volatile matter of any kind that can be driven off under specified conditions
- Water Content: it is the amount of water to be present in a sample of drug compounds
What is the difference between LOD & Water content?
- LOD: it was determined by heating the sample below its melting point in an oven & it includes all volatile matter including water content & solvents
- Water content: it was determined by KF titration & it consists only of water content
What is the difference between calibration & validation & qualification?
- Calibration - the set of operations that establish under specified conditions the relationship between values indicated by an instrument or system for measuring and corresponding values of the reference standard.
- Validation – the action of proving & documenting that any process actually & consistently leads to expected results
- Qualification - the action of proving & documenting that any premises, systems & equipment are correctly installed & lead to expected results
Define CAPA
Corrective and preventive actions
In Kf Titration Why We Have To Use Di Sodium Tartarate
Both water & di sodium tartrate are generally used for standardization of kf reagent as we going to check capacity of 1ml of kf reagent to neutralize water. Hence water content in standardization is very important one as di sodium tartrate contains 15.66% of hydrate it was recommended for standardization instead of water
What is formula of kf standardization?
Weight of sample x 1000 / titration volume
What type of columns are used in Gas Chromatography?
Capillary & open tubular columns
Any deviation can be changed into change control?
Yes planned deviations
Why we shouldn’t dispatch reprocess material to export?
Because there may be chances out of specification of product like increase in impurity than its limit
What is the difference between sonication & homogenization?
Sonication is the process of making soluble of undissolved particles by degassing while homogenization is the process of making uniform solution
What is capacity factor?
It is how much analyte in the sample is retained with respect to unretained material K= RT1-RT0 /RT0
What is the procedure to prepare placebo?
Take all raw materials other than active ingredient & mix it
What is stationary phase?
It was substance inside of a column through which mobile phase flows during separation process.
What do u mean by end-capping?
A column is said to be end-capped when a small silyating agent is used to bond residual silanol groups on packing surface
How much min recovery should be in swab sampling?
General limit 85 - 115% but in swab sampling it should be 85%
What are closely monitored parameters in stability study?
Temp & humidity
What is Photostability?
It was the study performed to evaluate & demonstrate that light exposure doesn’t result in an unacceptable change in new drug substances
Why 3x sampling plan implemented in process validation?
To get an idea on process capability and whether the intended process gives consistent results or not
What is the wavelength of a polarimeter lamp?
589.3 nm
In stability testing, if significant change occurs what will be the action plan?
During stability testing the term “ significant change “ is used only in case of drug products. when it occurs then do the out of trend analysis
What should be the min level of working standard?
All values may comply to predefined specifications. its no need that its assay close to 100%
How we fix the validity period of the volumetric solution & re-standardization due date?
The protocol shall be prepared for to establish the re-standardization date for the volumetric solution.
Date shall be fixed based on standardization study of volumetric solution on fixed or predefined in protocol interval e.g: 1/2/3/7/15 days etc. the % RSD shall be NMT 0.2% at all intervals
Date shall be fixed based on standardization study of volumetric solution on fixed or predefined in protocol interval e.g: 1/2/3/7/15 days etc. the % RSD shall be NMT 0.2% at all intervals
What is DT for dispersible tablets?
3 mins
What should be the sampling point in dissolution testing?
There is no specific recommendation for sampling in the dissolution test. It is recommended that a specimen should be withdrawn from a zone midway between the surface of the dissolution medium & top of rotating basket/blade NLT 1cm from the vessel wall
Where multiple sampling times are specified, replace the aliquots withdrawn for analysis with equal volumes of dissolution medium at 37°C or where it can be shown that replacement of medium is not necessary, correct for the volume change in calculation
Specimens are to be withdrawn only at stated times within tolerance of ± 2%
Where multiple sampling times are specified, replace the aliquots withdrawn for analysis with equal volumes of dissolution medium at 37°C or where it can be shown that replacement of medium is not necessary, correct for the volume change in calculation
Specimens are to be withdrawn only at stated times within tolerance of ± 2%
What is DT for enteric-coated tablets?
2 hrs in gastrointestinal simulated fluid & 1 hr in phosphate buffer
What is DT for coated tablets?
30 minutes
What is the difference between method validation & verification?
- Method validation: it is a validation of the method we adopt
- Method verification: its high degree of assurance to verify
What is the difference between drug purity & potency?
- Purity: it is the absence of unwanted substances like impurities & contaminants
- Potency : it is a measure of drug activity measured in terms of amount of drug required to produce an effect.
Why pooled sample is required in dissolution test?
It is the primary requirement, the sample should completely expose to dissolution media at all surfaces.
Pooled sample is in completely exposure to dissolution fluid that’s why we use basket apparatus for floating tablets.
Pooled sample is in completely exposure to dissolution fluid that’s why we use basket apparatus for floating tablets.
Which will give more drug release paddle or basket dissolution?
Paddle as we know greater the surface area greater will be volume of water better for dissolution
Which gases are used in GC?
- Helium
- Nitrogen
What is the difference between a polarimeter lamp & IR lamp?
A polarimeter lamp emits polarized light which in range of visibility (400-700nm) while IR lamp emits radiation in IR range (I -1000 micrometers)
What is the difference between temporary change control & deviation?
- Temporary change control : its planned change after assessing the impact on other functions
- Deviation : unplanned change
What is the difference between uniformity of content & content of uniformity?
Both terms are same & they are analyzed by individual assay
What is limit of friability of tablets?
Friability is used to determine physical strength of tablet during packing & transporting with help of a friabilator. For this test accurately weigh 10 tablets & place them in a rotating drum of a friabilator at 25 RPM & it was rotated for 100 times & then remove the tablets & weigh the tablets now.
The sample fails the test if any one of them is cracked / cleaved / broken. If the weight loss is >1 % then the test will be repeated so 1% weight variation will be acceptable in the friability of tabs
The sample fails the test if any one of them is cracked / cleaved / broken. If the weight loss is >1 % then the test will be repeated so 1% weight variation will be acceptable in the friability of tabs
What is the relative response factor in related substances?
It is the resonance of peak concerning main peak response
How do we choose HPLC / GC for sample analysis?
Depending upon compound nature, degradation, polarity, solubility, molecular weight, volatile nature, thermal degradation etc.
What is the recovery factor?
It is used for cleaning validation by following the formula
% recovery = area of individual swab level x std dilution / area of corresponding std solution x sample dilution x 100
Define pka
- It's an equilibrium constant used for the dissociation of a weak acid, & also known as an acid ionization constant
