4 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 P h a r mTe c h . c o m
Aseptic Manufacturing
W
hen determining what to measure and how, it
is wise to remember what Albert Einstein once
wrote on a blackboard in his off ice at Prince-
ton University's Institute for Advanced Studies:
"Not everything that counts can be counted, and not everything
that can be counted counts"(1). Any measurement comes with
questions, not only of accuracy and precision, but of relevance.
Often, the numbers most critical for managing a given situation
or an organization are "unknown and unknowable," a phrase
that quality advocate W. Edwards Deming of ten repeated (1).
Too often, one may try to force fit measurable limits (e.g., zero
microbes or particles) on situations even though those limits are
impossible to achieve.
Regulators emphasize the importance of measurement and vali-
dation. For instance, FDA's current good manufacturing prac-
tices (cGMPs) regulations stipulate that an organization's quality
control operations should be responsible for "approving or reject-
ing all procedures or specifications [that have an impact] on the
identity, strength, quality, and purity of the drug product"(1). This
requirement embraces design and operational controls in several
areas including utility systems, operating environments, packaging
components, raw materials, and intermediate and finished goods
release, and considers not only physical, but chemical and micro-
bial attributes. Implicit in these determinations is the idea that the
methods of analysis that are used must be valid. As written in the
regulations, "The accuracy, sensitivity, specificity, and reproducibil-
ity of test methods employed by the firm shall be established and
documented"(2).
Unknown and
Unknowable
Quality cannot be verified
through testing, especially
at the limit of detection, and
no test method can confirm
the absence of a microbe or
particle.
SEVENTYFOUR/STOCK.ADOBE.COM
Russell Madsen and James Agalloco
Russell Madsen is principal
of The Williamsburg Group
(madsen@thewilliamsburg-
group.com), and James
Agalloco is principal of
Agalloco & Associates
(jagalloco@aol.com).
