Therapeutic Dose: The Importance of Design Qualification

But (don’t all my columns seem to have a "but"?), what about measuring the parameters that we are becoming aware of being truly important, not the “same-old, same-old?” How do the converted “one size fits all” lab analyzers measure the physical parameters we are finding to be the real controlling factors? At what cost in time and money?

One beauty of current hardware is that they may be used for a myriad of tests. They are, as my co-instructor (Jack Carroll) named them, “genius” machines. Unfortunately, when you are measuring one simple (or complex, but one) parameter, it is desirable to have a monitor (or per Jack, “idiot savant”) that does that one thing very well, repeatedly and inexpensively.

This is where the materials scientists and engineers and physical chemists come in. The instrument companies are good at one thing — building well-behaved and reliable instruments. They cannot be expected to do our R&D for us. They need to be told what we are looking for in the new paradigm of PAT (i.e. QbD). In fact, most “normal” instrument manufacturers may not have the personnel to make specialty hardware and software for, say, monitoring the degree of crystallinity of the API and excipients during a blending operation. This sort of design may take physicists, optics engineers, software writers, mechanical engineers and spectroscopists. Most instrument companies are too small to carry this large staff for specialty orders. (Later, when the “specialty” instrument is sold in the thousands, they may be the best candidates to produce them, however.)

Hence, like software, “third party” vendors will make an impact here. I am aware of a number of engineering companies capable of (and good at) this type of work. I was pleased to visit one recently in Finland named VTT (Finnish Research Institute). VTT is quite an impressive operation. The people there showed me an array of machinery that can construct anything I could imagine. Tie that in with the engineers and scientists and, well, you see what I mean.

It may well be that PAT instrumentation for these new parameters will not be “off-the-shelf” instruments, but will have to be designed as a cooperative effort between the pharmaceutical scientists and specialty engineering firms. The “D” in DQ stands for design…not “what do you have in the showroom?” but design!

Remember those head-count additions I mentioned last month: engineers, materials science-types, physical chemists/pharmacists? Put the ads in the Sunday papers — we’re gonna need them sooner than later. We will need to ascertain what parameters we need to measure, then control. We will then have to sit down with either current instrument companies or engineering firms and actually work together on hardware and software that will give us the control of our processes that will enable us to “design quality in” to our products. Then we set parameters for raw materials, when we know what to measure and have designed instruments to make the measurements correctly and accurately. Piece of cake, no?