APR Nov/Dec 2022 - 23

« DRUG DEVELOPMENT
Figure 3. The analytical risk survey workflow.
* Holistic analytical controls
evaluation: Each project team's
analytical lead (AL) initially evaluates
the holistic analytical controls
within the context of the API release
requirements and CQAs with respect
to ICH guideline Q6 and phase
of development. All the tests in
the analytical controls, including
intermediate release and IPCs, are
chosen to impart the quality, safety,
and efficacy of the drug substance.
Relevant data should have been already
collected as part of the development
and campaign knowledge.
* Triage tests into common risk
categories: All testing methods are
evaluated and placed into the relevant
project risk categories shown in Table
2. The performance history of each
method is assessed, and key analytical
concerns captured for a project using
a templated format. Table 2 provides a
list of key analytical categories that are
common areas of concern; however, as
every project is different, the category
population can differ.
* Assessment of tests with
performance and gaps: For each
individual method, the performance
is compared to that expected (see
examples in Table 3). Any unusual
method conditions, such as
uncommon instrumentation, hard to
source materials, atypical operating
parameters, or parameters near
the edge of typical calibrations are
specifically evaluated. Where possible,
data from the method innovator lab
and from other vendor labs is compared
to check the method reproducibility.
With the above information and the
risk band catalog, the risk factor level of
each method is standardized to drive
consistent evaluation and expectations.
* Collate controls and risks into
common document templates:
Knowledge gathered from the activities
above is used to generate a slide deck
from a pre-generated template that
includes project background information
and risk factors. Banding for each risk
characteristic is additionally collated into
a spreadsheet template where detailed
reasoning of the risk band is explained.
On average, ALs will only need a few hours to
collate the requisite information and make or
update their template-based documentation
(for return visits). Once the AL and their
project team have gathered all their required
information, the risk survey committee
meeting is held. During the meeting, ALs
present the assembled risk evaluation
using the common document templates
to a team of experienced SMEs who have
a strong background in analytical method
development, validation, and transfer
activities. SMEs evaluate the control strategies
and the risk banding of each method during
the meeting so they may provide their
opinions on the project team's evaluation.
SMEs also provide feedback and suggestions
to ALs on the control strategies, gaps, method
risk banding, and risk mitigation. For all cases
where high risks exist, a mitigation plan is
required.
The ultimate goal is to ensure alignment
between the project team and expert
committee on the recommendations and
action items, with a commitment for the AL
to return with improvements and a revised
risk survey in 6 to 12 months if the project
is still active. The risk survey meetings are
typically 1 to 1.5 hours with approximately
30 minutes presentation time and 30 minutes
discussion. The ALs will record all the action
items in the spreadsheet comments section.
The spreadsheets and presentation decks are
stored on a commonly accesible platform,
such as a Microsoft SharePoint site.
Risk survey program metrics
So far this program has provided help to more
than 40 projects within BMS over 5 years. The
collated results of medium to high-risk areas
across the portfolio of projects has enabled
periodic evaluation by the department leadership.
This has helped justify improvements
in trainings, SME resourcing, technology and
method development workflows across the
department and projects.
In Figures 4 and 5, the method performance
risk bands identified throughout the year and
across many methods are plotted against the
risk categories for 2020 and 2021, respectively.
In 2020 the area with the most prevalent
high risk was due to analyte degradation
either in solution or on the LC column. This
degradation may be caused by: intrinsic
compound instability; incompatible
mobile phases, diluents, or other sample
preparation operations; or due to a specific
reactive property of the column, such as
residual metals. When dealing with such
risks, root cause analysis experiments are
www.americanpharmaceuticalreview.com |
| 23
»
http://www.americanpharmaceuticalreview.com
APR Nov/Dec 2022

Table of Contents for the Digital Edition of APR Nov/Dec 2022
