Re-validation: partial or full

[pshighe]

Hi everyone,

I cannot make up my mind about validation, verification, revalidation, partial validation, full validation. I would be very grateful if anyone can explain the situation through a few cases:
1. What should I do if the HPLC method developed for the determination of paracetamol from a tablet containing only Paracetamol is applied for the determination of paracetamol from a tablet containing paracetamol + chlorpheniramine maleate (combined)?
2. The analysis of paracetamol in a tablet is performed by a validated HPLC method. What should I do if the HPLC is moved to the other laboratory ? Apart from the OQ/PQ of the instrument
3. Robustness studies have shown that a flow rate between 1 - 1.2 mL/min does not affect the quality of analysis. What should I do if the flow rate is changed to 0.5 mL/min to save solvent?

Thanks in advance.

[Consumer Products Guy]

I cannot make up my mind about validation, verification, revalidation, partial validation, full validation. I would be very grateful if anyone can explain the situation through a few cases:
1. What should I do if the HPLC method developed for the determination of paracetamol from a tablet containing only Paracetamol is applied for the determination of paracetamol from a tablet containing paracetamol + chlorpheniramine maleate (combined)?
2. The analysis of paracetamol in a tablet is performed by a validated HPLC method. What should I do if the HPLC is moved to the other laboratory ? Apart from the OQ/PQ of the instrument
3. Robustness studies have shown that a flow rate between 1 - 1.2 mL/min does not affect the quality of analysis. What should I do if the flow rate is changed to 0.5 mL/min to save solvent?

Thanks in advance.

I'm retired, did use cGMP for our pharmaceuticals. That said: I am NOT a cGMP or validation expert, so take that into consideration with my comments.

Case 1. I'd document that chlorpheniramine maleate did NOT interfere in the retention region of paracetamol using placebo tablets, and run a mini-study to show that placebo tablets spiked with paracetamol + chlorpheniramine maleate combined delivered correct results for paracetamol.

Case 2. A cGMP validation documents that the test method is valid, not that a certain HPLC unit it appropriate. I'd say do the OQ/PQ of the instrument and then do what your company does to document test method transfer, to demonstrate and document equivalent results.

Case 3. USP <621> and FDA ORA have guidelines about what parameters can be changed without requiring re-validation. I'm retired, and haven't looked up current regulations, but I'd guess that you'd need to go to a smaller-diameter column to use 0.5ml/min flow rate without re-validation.

[DR]

agree w/ CPG 100%, just adding that if you cut flow rate and use a smaller bore column, you're going to have to reduce injection volume as well.
This will impact your validation as your ranges for accuracy, linearity and precision no longer match your new testing parameters.

Frankly, you're going to spend more $ on redoing a bunch of validation work than you're likely to save on solvents unless your forward plan is to run this method for about 100 years.

Someone needs to be told to quit wasting their time trying to save a nickel instead of figuring out how to make a dollar.

[Consumer Products Guy]

Someone needs to be told to quit wasting their time trying to save a nickel instead of figuring out how to make a dollar.

[vmu]

3. Robustness studies have shown that a flow rate between 1 - 1.2 mL/min does not affect the quality of analysis. What should I do if the flow rate is changed to 0.5 mL/min to save solvent?

Other parameters being equal, reducing the flow rate does not decrease the solvent consumption since retention volume is independent of the flow rate.

See also the latest version of USP chapter 621 Chromatography (section Adjustment of Chromatographic Conditions).
https://www.usp.org/sites/default/files ... m99380.pdf

[DR]

lol @ CPG