QC Flashcards
How would you approach cleaning validation?
Product knowledge- Solubility/Toxicity
Effectiveness of cleaning solutions
Validation of analytical method
-LOD, LOQ, Accuracy, Specificity
Non specific methods- Conductivity
Surface material of construction
Surface area
Surface proximity
Visibly clean
Rinse samples
Swab samples
Efficiency studies of rinse/swab
Clear criteria for specification
When can you release material if an OOS has unassignable cause?
No manufacturing cause
Robust product history
Retest results within known variability
95% Ci in spec
All other results consistent with re-test
What rules are there for averaging QC data in OOS investigation?
Can’t average certain data (mass)
Outlier test
If not outlier then include in average- average must be within 95% CI
Define Method validation, method verification and method transfer
Method validation- demonstrate new method suitable for use (ICHQ2)
Method verification- Demonstrate pharmacopoeial method is suitable for use (Chapter 6 QC)
Method transfer- Documented protocol for transferring method between labs (Tech transfer WHO annex 7)
Method validation characteristics
Accuracy
Precision (intermediate, repeatability)
Specificity
LOD
LOQ
Linearity
Range
Robustness
What process/maths would you expect to see in method validation?
Accuracy- 9 results in triplicate (80, 100, 120%), Mean, SD
Precision- Repeatability, one analyst prep triplicate 80, 100, 120%. Compare data sets- TOST, Confidence interval
Precision- Intermediate. Two analysts, different days, different kit. Triplicate for each (18 data points), dixons outlier, TOST, CI, P value 0.05.
Specificity- Spike impurity into analyte and demonstrate separation.
Linearity- minimum of 5 concentrations, Linear regression, r value >0.999
Y intercept
Define specificity
Ability of method to unequivocally identify analyte of interest in presence of other material expected in sample (imps, matrix)
Define precision
Closeness in agreement (scatter) between samples taken from the same homogenous stock expressed as SD
Define accuracy
Closeness in agreement between value known as true value and the value found
What is source data for specifications?
Pharm Dev, Toxicology, Stability, process variability, Pharmacopoeia
What do you know about UV analysis?
Absorption based
Structurally dependent
Compound must be chromophore
Beer lambert law- concentration proportional to absorbance
Usual detector in HPLC
What do you know about Gas Chromatography?
Used for volatile compounds and some packaging components
Sample injected and mobile phase is helium gas.
Oven is in main chamber at 250 degrees
Stationary phase is column inside oven coiled.
Detector is flame ionisation
What do you know about IR?
Infrared analysis
Vibration of bonds within compound- structural groups
Presented in oil and KBR discs
What do you know about atomic absorption?
Elemental impurities
Energy emission post flame
ICP + Mass spec
High temp
All metals in PT
What do you know about HPLC?
Chromatographic method- separation (size/charge)
Mobile phase of liquid (solvent)
Stationary phase of column
Injection site for prepped sample +diluent
Pump to move sample and mobile phase through stationary phase
Sample results based on retention time in column
UV detector