On 4/27/2022 2:50 AM, Don Y wrote:
> On 4/27/2022 1:15 AM, Phil Hobbs wrote:
>> Don Y wrote:
>
>>> [It's not uncommon to have manufacturing tolerances of -60%, +300%. Easy to
>>> accommodate if you are smart about it.]
>>
>> A pity you didn't just replace NIST. ;)
>
> Lots of things don't need to be qualified in "engineering units".
>
> How do you test that the *hammer* you are building, today, is as good
> as the hammers you've built in the past? Or, a screwdriver? Just
> how "durable" should the finish on a tape rule be?

"Quest" (TV Network) just aired a show, "Modern Marvels", in which
such a device was shown in use. Apparently it's a rerun of a show from
~6 mos ago. I can't seem to find it online (in a free venue).

<https://www.stanleyblackanddecker.com/article/stanley-black-decker-featured-upcoming-modern-marvels-machines-episode-airing-history>

It would have been more interesting if they'd shown how tape rules are
"exercised", hammer handles broken, screwdriver tips sheared off,
tool finishes abraded, etc.

For folks used to seeing things done with "conventional" units of measure,
it would be eye-opening!

They *do* use some "laboratory" tools to augment their collected data.
E.g., rockwell hardness tester to determine the hardness of the steel
used in the tool, etc. And, the fixtures are calibrated to produce
reproducible tests -- so 1135 hammer strikes today represents the
same amount of wear that it did 30 years ago, and a tape rule dropped
from 50 inches experiences the same sort of impact shock that it did
30 years ago, and...

What's particularly interesting is how many tools are easily broken by
careless users. A "nominal" male can easily tear the tip off a #0
Philips screwdriver. And, most can do that on a #1 tip as well!
But, at #2 and larger, you really need to be a bit of a gorilla...
(and capable of holding the screwdriver's tip *in* the screwhead
lest it "cam out")

And, I suspect everyone has a cabinet tip screwdriver whose blade is
no longer flat (overtorqued, bending the ends out of the plane of the
flats). Or, a handle that "spins" on the shaft (cuz you tried to
apply excessive torque with a pair of vice grips)? Or, a wood
chisel that seemed like it would be a great tool for cutting
aluminum gutters? Or, a screwdriver handle that has been cracked because
someone thought it would make a good *chisel*?

> [who, besides the manufacturer, would know how to interpret those data?
> What units? How to evaluate relative to other vendors' products?]
>
> How do you verify that the (pharmaceutical) tablet that you produced NOW
> is as good as the one you produced 5 milliseconds earlier?

Ans: you monitor something that correlates well with the parameters
of the tablet that are important to the regulators AND your own QC.

In addition to being concerned with the amount of actives in the tablet,
regulators are concerned primarily with *consistency* (!) of actives in
a tablet, overall weight, dissolution time and disintegration time.
They're not going to let you sell a bottle with 300mg tablets and
100mg tablets on the argument that the 300mg tablet just has 200 extra
mg of binders and lubricants in its excipients!

[Your QC will step in before the regulator ever sees such an abomination]

Actives can only be determined by assay -- which is destructive in nature.
As are dissolution and disintegration tests.

All of these tests are far too slow to keep up with the production rate
of a high speed tablet press (1M+ tablets/hour). But, you can get an
insight into some of them -- weight, disintegration time (and other
attributes that may be of interest in certain products -- like
hardness for effervescents) -- by monitoring the *forces* encountered
by the tablet at various stages of its formation and production.

[There's no need to express forces in engineering units -- as long as the
calibration is consistent from press to press, lab to production, etc.
Early controllers had an analog meter that showed the current state
of the process -- with "percent deviation" labels (percent of WHAT?)]

As you are dealing with a constant geometry (the cavity in which the
tablet is formed), higher forces indicate more material (granulation)
must be present in that cavity. Lower forces correspond with lower
amounts of material. I.e., you have a good predictor of *weight*
(part of the scale up process is characterizing the relationship
of force to tablet weight in the lab, before releasing to manufacturing).
And, as such, you can put limits on measured forces to determine which
tablets are likely over/underweight. And, can do this at production speeds,
dispatching "bad" tablets on the fly while keeping good tablets ("swatting"
the bad ones off to the side).

You can also learn a lot about the condition of the tooling that you are
using (each product has a different set of tools) to determine wear
and other "maintenance" issues (e.g., a broken punch tip is bad news
as it means there's likely a tablet with a shard of metal in it!).

[There's a second school of thought that applies a constant force to
the tablet during formation and monitors the resulting thickness, in
real time -- by monitoring the motion of the compression rollers
as the tablet's tooling passes between them (not using engineering
units but, rather, fixed thresholds determined in the lab, at scale up).

But, these require significant mechanisms to move at reasonably high
rates... I seriously wonder if they can be as sensitive as simply monitoring
forces.

They also suffer from not being able to address all issues that
force monitoring can detect -- like the force required to eject
a formed tablet from its die (to detect barreling of dies and
a crude indication of capping).]

> [Does the consumer care if a particular batch of tablets have a friability
> of 1.2%? Or, variations of hardness on the order of 2KP? Or, a dissolution
> time that varies by 4% in a particular sample of tablets?]

If the tablets are going to be *coated*, then friability is hugely important
(as a coating pan subjects the tablets to high abrasive forces). So, while
not directly controlled for regulators, it eventually factors into the
quality of the tablet (if regulator notices your coated tablets are "all
coating" and "little tablet"!)

> In many cases, you rely on some other (external) determinant of "acceptable
> quality" and the goal is just to ensure repeatability of process. E.g.,
> those "good" tablets were produced with 4.5 bogounits of force exerted during
> the compression phase; make sure all of them experience a similar force. Or,
> a sample of those hammers struck the test anvil 1825 times, on average, before
> the handle snapped; the competitor's hammers broke at 1615 strikes, on average.
> Etc.
>
> Statistical Process Control becomes more important than traditional control
> theory (use a conventional control loop and wrap SPC around that)

Because you are dealing with repetitive processes, you're concerned with
how repeatable/consistent that process is. Is swaging station #7 producing
a wider distribution of tip shear strengths than station #2? Why??

This is particularly important for a tablet press which can actually be ~100+
presses rolled into one! A 75 station press has 75 sets of tools -- upper,
lower punches and a die per station. Each has manufacturing tolerances and
experiences wear at different rates (based on its "tableting history").

So, a manufacturer makes sure he keeps each upper, lower, die together -- along
with noting which station they occupied -- so their results are more repeatable
on the next run (imagine the number of mix-and-match combinations possible!).

But, each station is measurably different in terms of physical characteristics.
So, any information you observe about the production of a tablet on station #1
doesn't directly translate to the production of a tablet on station #2 -- just
a few ms later! A longer punch can make the force higher (or lower -- depends
on which punch) for the same amount of "fill"

So, ANY CONTROL ACTIONS that you take to keep the tablet weight (as expressed
by compression force) based on observations of the formation event for station
#1 can be "wrong" for the tablet being formed by station #2! Repeat...

[We've actually had customers disable the control system to determine if
it might be INCREASING variability in tablets! In practical terms, you end
up severely overdamping the loops to ensure the process doesn't oscillate
purely as a consequence of the variations in *tooling*! Hence the value of
looking at the distributions of forces (weights) per-tooling-station and
using THAT information to decide when the process is stable.]

A tablet press is often double-sided -- meaning a tablet is formed on the
front side of the machine while another is being formed on the back side.
So, stations #1 and 38 are each in the same state of tablet formation;
ditto #2 & 39...

But, the front and back sides of the machine have different cam profiles,
wear patterns, etc. -- due to mechanical tolerances. And, different
feeders, control loops, etc. So, a tablet formed by the punches in station
#1 on the FRONT side of the press can have different characteristics than a
tablet formed in that station when it's on the BACK side of the press.

And, if you're using a two (or three!) sided press to make a bi-layer
(tri-layer) tablet, the observations of one "side" of the tablet's
production directly factor into the observations of the second (third)
side!

It is a **delightful** control system problem! Someday, they'll be able
to weigh individual tablets at the 2M/hr rate and much of this will be
unnecessary (though likely retained as an inner control loop).