Chemistry Reference
In-Depth Information
6.3.2 P
erIodIc
or
S
kIP
t
eStIng
Periodic or Skip Testing is the performance of specific tests on preselected batches
at predetermined intervals as opposed to testing every batch. Of course, it is under-
stood that all the untested batches must still conform to the acceptance criteria for
that product. Batch selection and intervals must be justified and approved by the
regulatory authorities prior to test implementation. Because often only a limited
amount of data is available when an application is filed, this concept is generally
implemented post-approval.
6.3.3 r
eleASe
verSuS
S
helf
-l
Ife
A
ccePtAnce
c
rIterIA
Sometimes, for drug products, more restrictive acceptance criteria are set for release
of the drug product than are applied to the shelf-life. This concept is sometimes
applied to assay and impurity (degradation product) testing levels. Sometimes an
applicant may choose to have tighter in-house limits at the time of product release
to provide additional assurance that the product will remain within the regulatory
acceptance criteria throughout its shelf-life.
6.3.4 I
n
-P
roceSS
t
eStS
In-process tests are performed during the manufacture of the drug substance or
product, as opposed to the traditional prerelease testing. When the acceptance cri-
teria are identical to or tighter than the release specification, the in-process test can
be included in the release specification. However, this approach must be validated
to show that the characteristics of the product do not change from the in-process
stage to final release. In-process tests that are used only to adjust process parameters
within an operating range are not normally included in the specifications.
6.3.5 P
ArAmetrIc
r
eleASe
Parametric release testing involves monitoring of specific batch parameters (e.g.,
temperature, pressure, time) as an alternative to routine release testing. Appropriate
physical or chemical laboratory tests may also be included in parametric release test-
ing. Sometimes, these parameters can be more easily controlled and measured than,
for example, sterility. The parametric release process should be maintained in a vali-
dated state, as demonstrated by revalidation at established intervals, and the attribute
that is indirectly controlled together with the associated parametric test procedures
should be included in the specifications.
6.3.6 P
hArmAcoPeIAl
t
eStS
Wherever they are appropriate, pharmacopeial procedures should be followed. One
of the main goals of the ICH process is harmonization of procedures on a global
basis, and the United States, Japan, and European pharmacopeias have all expressed
a commitment. Eventually, all three pharmacopeias will be considered equivalent
and interchangeable.
