HPLC to UPLC method conversion, cGMP quality concerns

<p>I work at a CMO manufacturing injectable drugs.  Currently I am in charge of methods.  We have recently upgraded to H-Class systems and I am in the planning stages of converting existing methods over to UPLC. </p><p></p><p>Our quality department is being difficult when it comes to the discussion of transferring over methods to UPLC.  Their concern is primarily  related to the regulatory impacts.  Basically they are saying there is no way to do this with established methods, and in particular methods associated with a drug filing.  I know that what I am suggesting is sound from a scientific standpoint.  Basically we need to demonstrate that the new UPLC method is equivalent to the existing HPLC method.</p><p></p><p>I was hoping to start a discussion about what kinds of things need to be done in order to facilitate this transfer, and in particular, satisfy the concerns of my QA group.</p>

Comments

  • I've maintained for a long time that the USP is a guidance and a recommendation; the USP is not the only approach.

    I worked for a cGMP company where I purchased H-Class systems and we had all HPLC methods. I initiated the conversion process from HPLC to UPLC.

    For HPLC methods we checked the system suitability parameters were either met or improved, we checked linearity, specificity, and HPLC vs UPLC equivalcney. A short report was written documenting what was done, why we changed from HPLC to UPLC, and any improvments we noted. If the method was related to a regulatory submission, then they were updated annually.

    Impurity methods were a little bit more difficult. If there was a critical pair, we generally revalidated as if we had no HPLC method because everyone felt more comfortable with this. We would show equivalency between HPLC and UPLC methods. Again, for regulatory concerns we would include the HPLC method in an annual update.

    If there was no critical pair and we had all known degradation compounds we would show system suitability, specificity, linearity on all impurities, and comparison of actual product testing between HPLC and UPLC methods.

    In general we applied typical transfer requriements to UPLC vs HPLC results. 

  • Thanks for the feedback.  I will need to read some and have some more input.  What I a trying to accomplish is hitting the low hanging fruit first.  For us it will be converting our HPLC cleanin verifications to UPLC.  Since these processes are internal it will be very straight forward to revalidate/verify these methods.

    Second we need to look at some of the manufacturing related methods.

    Thanks for taking the time to respond.  Let me see what I can glean from the information your provide

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