My definition of “specification” is rather simple: it’s a
Just like any other promise—you’d better be sincere when you
make it and able to keep it. Failure to keep a promise brings disappointment.
Frequent failure leads to distrust. And consciously breaking a promise is
nothing less than deceitful.
Just as in our personal lives, the pharma industry makes a
promise to its healthcare professionals and patients every time it establishes
a product specification.
Whether it is a raw material or component from a supplier,
in-process material, or final product, a specification is your promise to
provide a product that possesses the attributes known to make it work.
Anything outside of the specification range is either
unknown because it has not been studied, or known to have some probability of a
negative effect. Neither is acceptable.
The same could be said for process control ranges. Although
they are applied to the manufacturing process and facilities, they nonetheless
are “promises” based on a scientific field of study with respect to product
Thus it seems to be particularly egregious when
specifications and process controls are capriciously established or changed.
Take for example
River’s Edge. The Warning
Letter1 stated that Lidocaine HCL 3%/ Hydrocortisone 0.5% lots were
released and distributed even though they failed the initial release and
stability viscosity testing at 3, 6 and 9-month time points. The firm responded
by revising the specification range.
Additionally, after failing to investigate over 30
complaints of discoloration of Hydroquinone 4% Cream, River’s Edge responded
that it would address the issue by revising the labeling to describe the cream
as “tan to slight brown on storage.”
Another example is Gilead.
The Warning Letter2 stated that their aseptic processing room was
not adequately constructed to meet design specifications. The room, in which
partially-opened sterile drug is transported, failed to meet ISO design
criteria. The firm responded by reclassifying the room to a lower
FDA was not amused in either case.
Quality Assurance is responsible for being the guardian of
specifications and making sure that systems are in place and followed for
developing and changing specifications.
It is a system based on statistical analysis of experimental
studies, which is part of the process and product knowledge base. You know—the
institutional knowledge of the scientific and technical aspects of what you
make, how to make it and why your specifications are what they are.
I am aware of some shoddy specification-setting practices,
like—taking the highest and lowest values on record, plus or minus your shoe
size—just to file the NDA quickly to beat the competition.
But this always causes problems. Manufacturing processes are
not efficient and varied product attribute results are obtained. It all adds to
a high nonconformance rate and adds cost to the operation.
So a specification is not only a promise, but established
properly you get something in return. It’s the “sweet spot” for economical
1 River’s Edge Pharmaceuticals, LLC, Warning
Letter 10-ATL-05, May 20, 2010.
2 Gilead Sciences?,
Warning Letter 44-10, September 21, 2010.
About The QA Pharm:
“I am an observer of the pharmaceutical industry from inside and out
with over 30 years experience from the lab bench to the management board. If
you have a passion for the value and the direct relationship that quality
assurance and current Good Manufacturing Practices have to your patients and
your business, you will find a kindred spirit here.” For more insight from
The QA Pharm visit his blog here.
Pharmaceutical Processing has been given permission to
reprint The QA Pharm’s blogs as long as his identity remains a secret.