Where Will FDA Target Next? What IVD Manufacturers Should Know Before Their Next FDA Audit

The regulation says that for receiving, in-process, and finished
device acceptance "Each manufacturer shall establish and
maintain procedures for ... inspections, tests, or other
verification activities."

The regulation further states in "Sec. 820.72 Inspection,
measuring, and test equipment.

(a)...Each manufacturer shall ensure that all inspection,
measuring, and test equipment, including mechanical, automated,
or electronic inspection and test equipment, is suitable for its
intended purposes and is capable of producing valid results."

This section of the regulation has a lot of implications. One of
which is that all of your instrumentation has to be properly
calibrated. Any standards that are used to calibrate the
instruments need to be traceable to a nationally or
internationally recognized organization like the National
Institute of Standards and Technology, NIST.

For instance, any scale that is used in your manufacturing
process must be calibrated relative to a NIST traceable weight.
You must keep a record in your files that proves that your
standard weight is traceable to NIST.

Simple calibration is usually adequate for instruments that
directly measure physical or chemical characteristics. An example
of a direct physical measurement would be a temperature
measurement with a simple device, like a thermometer or a
thermocouple. A pH meter would be an example of a direct chemical
measurement.

However, if a more complicated measurement is done, then you must
validate the method. What do I mean by this statement? Some
measurements cannot be made directly. They may involve a
separation process wherein the analyte needs to be isolated
before that physical or chemical measurement can be made.

This happens if you are using a more complex method, like an HPLC
or an enzyme assay. These methods must be validated through a
process called Analytical Method Validation (AMV).

In a moment we will briefly review the components of AMV. But
first let's discuss the purpose of AMV. The answer, of course,
is to make sure that the analytical method itself is a high
quality operation. In other words, we want to prove that the
method is accurate, precise, and otherwise capable of telling us
what we need to know about the analyte.

And how do we find out whether our measurement system is
accurate, precise, and otherwise capable? We measure it. Unless
we have measured the measurement system we have no knowledge
whatever that the numbers it generates are any good at all.

Any money spent running manufacturing processes with unvalidated
analytical methods is wasted. In fact, it's worse than wasted
because it makes us think we have a reliable number when the
reality is that we know nothing. If we didn't run any test at
all, at least we'd know that we know nothing.

There are eleven main components that need to be considered for
an analytical method validation protocol. These factors are to be
applied to each and every laboratory test that is critical to the
IVD manufacturing process, as well as the stability program, and
any process validation.

Not all of the eleven factors may apply to each type of testing
that is performed. However, a thorough review must be done in
order to ensure a complete protocol has been written.

The factors are Specificity, Linearity, Accuracy, Precision,
Robustness, Range, Detection Limit (LOD), Quantitation Limit
(LOQ), Ruggedness, Selectivity,and System Suitability.

When you validate your analytical methods, you assure that the
numbers that you generate are believable – believable by you, so
that you can make good business decisions, but also by the FDA
when they inspect your facility.

In conclusion, if you are an IVD manufacturer you should review
the measurement systems that are critical to your manufacturing
process. If any of those measurements are not simple, direct
physical/chemical methods, they need to be validated.