Ade Kujore from Cecil Instruments outlines issues that need to be addressed when writing HPLC methods for transfer.
At last, after a year of hard work, you now have a validated stability indicating HPLC test method for a specific formulation.
Think of all the positive aspects; no more overtime, team party to plan, freshen up for the next challenge, you have made the Regulatory Affairs department happy and your pride and joy method is being used by ten international satellite sites. What could be better, life is looking good.
You may have to reduce the robustness of the method if low pressure mixing is used
A few months later as the euphoria recedes, some ugly messages are coming your way.
The contract laboratory a few miles down the road cannot find any HPLC peaks. The sister site in your country is obtaining spurious peaks. The site in the Far Eastern country cannot manage to get a single batch of the active pharmaceutical ingredient (API) that you have sent them, to dissolve.
What’s more, researchers in another country are unable obtain reproducibility of retention time.
One site can’t see the degradation product standards in the system suitability solutions. Two of the South American sites consistently obtain API concentrations which are out of specification on the high side.
Meanwhile the largest manufacturing site, which is located in Scandinavia, consistently obtains API concentrations which are out of specification on the low side.
These messages increase day by day, and sometimes, it feels like minute by minute. Team members are blaming each other, but that is nothing compared to what the Regulatory Affairs department is threatening to do with you and your team.
You used to be an anonymous cog on your site, and now, everyone, including the cleaning staff and the CEO are giving you strange looks.
Time for action. Book an all-day meeting for the team and shut yourselves away from prying eyes and those strange looks.
Your team has already demonstrated that the method is robust in your laboratory. Despite that, start right at the beginning of the analytical process.
You had best order-in lunch, and the remainder of the day’s meals, as this is going to be a long session.
Here is a checklist of some of the many issues to address with your team in order to develop a robust and stress-free HPLC transfer method:
Are all of the involved laboratories, including your own, operating to Good Laboratory Practice (GLP)?
Have all of the participating individuals been trained to use any required non-instrumental techniques?
Has every individual been trained in the use of laboratory glassware and pipetting techniques to internationally recognised standards? As petty as this sounds, this is often overlooked, as it is taken for granted that everyone knows how to use a pipette and which part of the meniscus is the part to read.
Where were the standards of API, known degradation products, impurity products and excipient standards sourced from?
Have conditions of sample storage, such as temperature, humidity light and formulation batch number been defined? Are the ranges achievable in practice, for all of the involved test sites?
Have you checked that no instrument makes and models have been specified?
Have you specified the type of balance to be used for each type of sample and standard?
Have you defined the material the weighing boat should be comprised of?
Has the linear concentration range of the standard solutions been correctly specified?
Has any heating of a sample or standard solution occurred in any ultrasonication stage?
Is the type and grade of volumetric, general and HPLC autosampler glassware defined?
Is the type of HPLC detection used, appropriate for your analytes?
You may have to reduce the robustness of the method if low pressure mixing is used, as this can cause problems in method transfer. If low pressure mixing has been used in the test method, have the mixing volumes been calculated and defined?
If conversions of units have been used, have the calculations been checked?
As a team, you all worked closely together, were any non-written notes or instructions made or given within the team?
By now, you and your team should have located the areas of discrepancy, and going home, is by now a distinct possibility.