APR May/June 2023 - 63

« MICROBIOLOGY
Why
What
Why do we validate? It is not only for patient safety, but also a
requirement by regulatory agencies. The test methods we use in
our lab for regulated products must meet certain performance
requirements before being released for patient use. If your methods
do not meet these requirements, the results obtained will not be
accepted by regulatory agencies and may lead to product recalls,
impacting availability of supply to the patient.
Who
Who requires me to complete these validations? Regulatory agencies,
such as the Food and Drug Administration (FDA), Medicine and
Healthcare Regulatory Agency (MHRA), and ICH (International
Council for Harmonization), have their own requirements to take
into consideration. Note that all countries have their own regulatory
agencies with specific requirements for method validation. Therefore,
the global market for each product must be taken into account when
developing a method validation strategy.
When
There are many items to keep in mind when validation/verification is
needed in your lab, and it is not just when you have a new product.
Let's discuss what else you need to know and when validation is
deemed necessary.
Method validation/verification is completed through the lifecycle of
your product. These are not just " one and done " validations. If anything
changes during the lifecycle of a particular product it is required to
be revalidated. These changes include formulation or concentration
updates, material source updates, manufacturing process updates,
manufacturing location updates, and so forth. Lifecycle updates
require product re-assessments to verify the parameters of your
validated method are still met.
If a reagent change is needed due to a vendor change or discontinuation.
A revalidation will be needed to affirm the new reagent doesn't inhibit
the results of the current method.
Modern Microbiological methods: if you are implementing these
methods for your product, you will need to revalidate your product
and compare the traditional data currently used for release to the new
data being retrieved from the new method.
This approach of " Vigilant Oversight " of the lifecycles of the products
testing in your laboratory is highly beneficial to ensuring the
implemented methods meet the regulatory agencies' expectations.
Be sure to encourage your analysts to know the manufacturing floor
details and to keep up with process changes being made which could
affect the way your products were originally validated for release.
So, what is required during an actual method validation? There
are certain validation performance parameters required based on
the type of method being evaluated. Is the method quantitative
or qualitative? This aspect of your method will help define the
parameters needed. Not all parameters will be appropriate for each
type of method, or the capabilities of the method being evaluated.
Compendia guidance documents are a reliable guidance when
determining your validation needs.
Establishing these performance parameters is especially important
when it comes to implementing your modern Microbiological
methods. This will help establish the comparability of the traditional
methods to your modern method and be key to showing equivalency.
The correct parameters established in your guidance provide the tools
for a good validation package. Good references for this include United
States Pharmacopeia (USP) 1223, Pharmacopeia Europa (EP) 5.1.6 and
Parental Drug Association (PDA) Technical Report 33.
What parameters need to be included in my validation? Accuracy,
Precision, Specificity, Limit of Detection, Quantitation Limit, Linearity,
Range and Robustness.
Let's look at each parameter individually to better understand what
each one means to your validation. These are going to be your proof
that your method meets the criteria needed to show good results for
your product.
Accuracy: " The accuracy of an analytical procedure expresses the
closeness of agreement between the value which is accepted either
as a conventional true value or an accepted reference value and the
value found. " 1
This parameter is typically associated with range in your
method validation.
Precision: " The precision
of an analytical
procedure expresses
the closeness of agreement (degree of scatter) between a series
of measurements obtained from multiple sampling of the same
homogeneous sample under the prescribed conditions " .1
Sometimes you will see this parameter described or labeled as
repeatability, intermediate precision, or reproducibility.
Examples: Standard Deviation, Coefficient of variation,
Confidence interval
Specificity: " The ability to assess unequivocally the analyte in the
presence of components which may be expected to be present. " 4
Limit of Detection/Limit of Quantitation: The lowest amount of
detectable analyte or microorganisms present in your samples.
This parameter is one of the most important measurements you will
be required to prove in your modern method validation, but also the
one parameter you will need to be careful with when setting up your
acceptance criteria. If you are willing to prove your system can detect
down to a <1 CFU or smaller you will need to show reproducibility for
that result every time you run your test method.
www.americanpharmaceuticalreview.com |
| 63
»
http://www.americanpharmaceuticalreview.com
APR May/June 2023

Table of Contents for the Digital Edition of APR May/June 2023
