Categorized | Expert Insights

When Is a CPP Not a CPP?

    By Alistair Gillanders, CTO & VP North America, DynoChem

    I had a interesting discussion recently with a colleague in one of our major pharma customers about what should be used as a CPP. His concern was that often the CPP’s are basic parameters that are not scale sensitive and so if a process is moved between equipment and/or scales the parameters do not fully capture the challenges to retain quality and performance.

    For example: His example was for reacting systems where RPM is used as a CPP or is sometimes extended to a dimensionless group for mixing such as PPV (power per unit volume) or Pumping rate. However this does not get at the essential process metrics as effectively as something that compares reaction rates and mixing/mass transfer rates like the Damköhler or second Damköhler numbers (here is a reasonable summary). Similarly Péclet numbers for comparing advection and diffusion forces in heat and/or mass transfer.

    And of course he is right but are these really CPP’s? I suggest he is actually addressing a different topic that has not had enough discussion as part of QbD but that probably should be just as significant as CPP’s during development and scale-up … namely process equivalence. Some of us “oldies” will remember that process equivalence as a concept has been around in the regulatory space for many years and was even discussed as a possible topic for inclusion in a Design Qualification (DQ) that was very nearly included alongside the IQ/OQ/PQ triumvirate that has been our validation mantra for so long.

    Where CQA’s are controlled via CPP’s during a batch or on a batch to batch basis, process equivalence is focused on establishing the suitability of equipment as operations are moved within or between facilities. Surely the impact of scale and/or equipment constraints is important enough to warrant distinct attention from controlling variability after equipment selection is fixed? Maybe DQ’s time has come as a way to demonstrate specific understanding of scale and equipment constraints on quality?

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    One Response to “When Is a CPP Not a CPP?”

    1. Bikash Chatterjee, Pharmatech Associates says:

      As a fellow “oldie” I think you have hit upon an interesting observation which has been a source of confusion in the pharma world in terms of applying ICH Q8. Biotech has grappled with this conundrum since its incarnation. The first processes which were developed were face with the dilemma of how to balance the risk of capital commitment with product efficacy and process stability. The solution was to develop qualified models at the intermediate process development phases which could then demonstrate equivalency at the commercial levels once efficacy could be established. In order to do this we needed to know the CPP’s that drive variation of the process and affect product performance.

      Now the grey areas between process equivalence and process comparability come into play. Unfortunately on the pharma side there is no equivalent driver. Many generic companies go right to their equivalency batch , test against their specification and file. Translating that world to the Q8 world is going to take redefining the benefits and drivers. I think those that have had the opportunity to apply QbD components as part of either a troubleshooting or scale-up exercise recognize the value it has in terms of process understanding and the value it has in terms of downstream cost avoidance. DQ’s have been very valuable in ensuring baseline understanding exists prior to launching into a C&Q or validation program. Facilities have been one of the best examples of DQ application. Automation projects are another good area. So given this, even if a CPP may not be a primary CPP, the fact the organization is looking for CPP’s is a good thing and could be an important step in moving towards a QbD mindset.

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