APR May/June 2023 - 19

« FORMULATION AND DEVELOPMENT
Given the novelty of MDPF-CCS, a specific
set of methods acting as best practices for
container-closure ingress testing has not
been established. CDER is open to assessing
any validation study that represents worstcase
conditions and challenges the CCS while
it is in use. While no single best practice has
been established, there is one general type of
method that is unacceptable, since it does not
represent a worst-case challenge of the CCS.
An example scenario for this unacceptable
testing protocol is, as follows: An MPPFCCS
is actuated in a laboratory setting by a
laboratory technician once per day over the
span of the product's labeled in-use period.
At the conclusion of this period, the product
remaining in the CCS is tested for sterility.
The manipulation of the MDPF-CCS in a
laboratory setting with a trained technician
does little to represent actual administration
conditions or challenge the system. In this
scenario, it is unclear if the product is ever
truly exposed to contamination. Further,
reliance on the sterility test exposes the
method to the possibility of false negative
results. A true test of the ingress-preventing
properties of an MDPF-CCS directly
challenges the system with microorganisms
and includes appropriate controls. One
example of a successful method that has
been presented in marketing applications is
the repeated actuation of a growth mediafilled
MDPF-CCS in a microbial suspension,
followed by
an
incubation period and
examination of the contents of the CCS. This
relatively simple method has the benefits
of directly challenging the system, and the
use of properly growth-promoted media
helps to eliminate the possibility of false
negative test results. It is also recommended
to consider any unique mechanisms that
are specific to a particular CCS and ensure
that these mechanisms are discussed and
validated as applicable.
Developing Standards
and Components
As MDPF-CCS products attain wider use
in the pharmaceutical community, the
regulatory standards for them will continue
to develop. However, at this time, the authors
recommend
examining two additional
www.americanpharmaceuticalreview.com |
| 19
aspects of MDPF-CCS to ensure that the
systems perform as expected both in their
interaction with the drug product and over
the shelf-life of the product. Given that
MDPF-CCS may encompass a variety of
bacterial ingress preventing mechanisms,
there may be mechanism components
that have significant
interaction with the
drug product. It is important to know if and
when these interactions affect the CCS's
ingress-preventing capabilities. Therefore,
applicants should plan to devise testing
methods to ensure that such interactions are
not detrimental. Finally, how does age affect
the ingress-preventing mechanisms of the
MDPF-CCS? Regardless of the in-use periods
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»

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APR May/June 2023

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