Therapeutic Dose: Life is Just a Bowl of Entropy

Recently, a pharmaceutical company asked me to consult on the feasibility of using NIR for incoming raw materials. Turns out I had already set up exactly such a program for them, at the same site, back in 1993.

These things happen. They even happened at Sandoz, where in 1985, we had a working NIR for the identity (container-wise as per EMEA) of all incoming raw materials at the site. Years later, they “discovered” near-infrared again — in the same building, even!

Now, I can understand losing an ancient city to the sands of the Sahara, but forgetting that you had a worldwide equation for raw materials two decades ago? There must be a way to concisely describe the underlying reason, no? [I wouldn’t be writing this if I didn’t already have an answer, would I?]

OK, let’s bring out the thermodynamic hammer. [Stay with me on this one.] Let’s take the basic equation for work (a four-letter word):

ΔG = ΔH –TΔS.

In classic terms, the amount of possible work (product, profit or defined-as-you-wish) obtainable is equal to the amount of heat released (or tablets in a batch, cash from sales, end-of-quarter gain) minus the temperature (number of plants in operation, available equipment, floor space, analysts — a constant for this example) times the entropy or disarray (non-maintenance of equipment, non-training of analysts, analysts not sent to courses and meetings, and time not allowed for personnel to learn specific techniques).

It rapidly becomes apparent that you can’t squeeze too many more tablets out of a constant-sized batch of granulation. It is just as obvious that the floor space doesn’t increase unless major renovations occur ($$). In other words, there is one sure way to increase (short-term) profit: minimize the last term (a negative). Understaffing (use one analyst for all kinds of techniques) is a money-saver (this is for short-term profit, remember?). Not sending people for specialized training is another. If only one person can run, as in the above examples, the one NIR on campus, it just sits when he/she leaves or is promoted or changes departments.

We cannot forget the ever-popular management trick of canceling employee trips to symposia, conferences and short courses. “If we keep all the people at home, working on analyses (albeit with last decade’s methodology),” the reasoning goes, “we get more work from a lean, mean workforce. And think of the monies saved from no plane fares, no registration fees, no hotel rooms, no meal allowances and no overtime to cover the days absent from work.” (The next thing will be applying hypnosis to help them forget about vacation time.)

So, by this equation —

P(rofit) = S(ales) – O(verhead, a constant) X (cost of maintaining/upgrading)

— the fastest way to a short-term profit is to eat your seed grain, er, uh, keep the status quo. Now, this would be wonderful if only people did not retire or leave the company.

When we take an esoteric technique such as NIR (not taught in school, not ubiquitous in most companies, only made by small instrument companies with limited applications and staffs) and allow only one person on staff any time to learn it well, we are asking for the city to be buried in sand.
 
This translates directly into QbD and PAT scenarios. The energy of activation (another chemistry analogy) for QbD/PAT (in keeping with Hollywood tradition, let us call this couple “Q-Pat”) is a combination of time, money and bodies.

Managers are all for the concept of no more rejects, smaller ranges of actives in products, less waste after the process and better utilization of the existing equipment. What they cannot “Grok¹” is that all this will not happen with the existing framework of bodies and equipment and knowledge.

I have already beaten the concept of new disciplines into the ground, but being in two places at once is also worth mentioning. Some of the new technologies can be learned by any bright scientist — but not while still managing his or her existing workload. NIR, Terahertz, acoustics or Raman need time for one to master them. And, considering that time is money, it is foolish to only have one person in a company even touch these new techniques. None of them is a garden variety subject in college.

Unless our management allows non-traditional education (yes, consultants too) attendance at meetings and symposia, and more than one “specialist” per company, any or all of these “saviors of PAT” will, like an ancient desert city, be swallowed by the sands of entropy and cost savings. PAT will fail and the same people who suffocated it will, of course, blame the understaffed analytical departments for the crime.

Let’s try to think long-term for a change, can we?

References

1. Grok: (ger- ock); verb, trans, a) to fully comprehend or be in concert with, b) to “get it”; ref. Robert Heinlein’s “Stranger in a Strange Land”; title reference to Moses