Speed Process Validation with Limited OQ

When FDA published its guidance document on process validation in 2011 it re-affirmed the importance of process development.  This sounds like a lot of extra work for people who are barely managing IQOQPQ.

FDA had forced the issue a decade earlier with medical devices and design control.  Now they are telling manufacturers of drugs and biologicals that the DESIGN of their process is just as important as the qualification of their equipment.  But simply documenting Stage 1 of Process Validation is not enough.

Manufacturers need to have a complete understanding of the technology underlying their manufacturing process.  FDA is saying in no uncertain terms that you can’t be compliant until you have deep knowledge of your technology.

So, assuming that your development team doesn’t have spare time on their hands, how do you ensure that you’ve documented that thorough understanding of your manufacturing technology.  More than that, how do gain that knowledge when time is critical?  What if you’re competing for contracts, and your ability to get the bid depends on how fast you can deliver the product, on budget, and in total compliance?

If you start each new product with Stage 1, follow it with Equipment Qualification, and then Process Qualification in a linear sequence, your timelines and costs will drive you to drink.  Here’s an idea for a better way:

Realize that although FDA now places more emphasis on understanding your manufacturing process, it also gives you flexibility.  There is no requirement that you establish your critical process parameters in any particular phase of new product development.  Let’s see how we can use that flexibility to save time and money.  This is an example of how streamlining your processes enables speed.

The following scenario might apply to contract manufacturers, whether they sell finished products or components that must be validated; or it might apply to generics manufacturers.  Whatever category you fit into, this concept depends on your having a sound understanding of your basic technology.  Since you’re required to have that information anyway, this shouldn’t be too much of a stretch.

Group your products into families.  Your technical personnel will have to put some serious resources into this effort, possibly DOE studies, or whatever kind of testing their inventive minds can imagine.  At the end of the process, they will create a technical justification for the groupings.  They may pick certain worst case products to subject to more intensive testing.

Create a design space for each family.  Now, I’m not suggesting that you try for parametric release.  I am suggesting, though, that you have a documented multidimensional space for each family that is defined by the Critical Process Parameters and Proven Acceptable Ranges for each family. 

The design space should be conservative.  By that I mean that any product within a family must be able to be produced reliably (within specifications), if the CPPs are held within the design space for that family.

With all this Stage 1 type work done, you are now ready to attack a new product and conquer it quickly

1. When you decide to make a new product, you first decide which product family it fits into.  You must document your decision with a good scientific justification.
2. Now that you know what family your new product is in, you know what the design space looks like.  You should have the confidence based on your previous testing, that if produced within that design space, the product will be within specification reliably.
3. But you are not going to stop there.  You are going to validate that your new product is, in fact contained within the established design space for that family.  You are going to confirm the limits of the design space by testing a very limited number of extremes of the design space; possibly only two, all the high levels of all the CPPs and all the low values, as an example. We call this the Limited OQ method.
4. Now you can use the information that you gathered in Stage 1, plus the design space that you confirmed in the Limited OQ to decide on setpoints for your CPPs during normal production.  Conduct your Process Qualification batches at those setpoints and you have product you can ship!

If you follow this model you will beat the competition to the market place, your costs will be lower, and you will know for sure that you are making a quality product.  Remember one caveat, though.  This is all contingent on having a thorough understanding of your own technology.