items to be evaluated. The more thought
and preparation the client puts into preparing the checklist, the greater certainty
the client will have that the CMO is prepared for the manufacturing campaign.
Each of the readiness areas of interest
are reviewed in more detail in the following text, and examples of checklist questions and line items are provided.
• Are the batch records approved, effective, and issued?
• Is the product specification approved, effective, and issued?
• Have all planned changes been incorporated into the batch records and have all
change control actions been closed?
• Is the stability protocol approved?
Raw materials and consumables
• Are all materials and components available in sufficient supply, have they been
QC released, and will they be within
expiry by the time they are used? It is
helpful to have a complete list of all raw
materials and consumables along with
the quantity needed. If the CMO utilizes
an enterprise resource planning (ERP)
software, they should be able to provide
a complete list and may even be able to
run an“Exception Report”to show which
items are not in stock or which ones are
in stock but are not yet released.
•Have there been any requirements/
specification changes with any of the
raw materials or consumables and have
these been incorporated into the specifications?
• Have there been any vendor notices for
any of the raw materials or consumables
or have there been any vendor complaints filed within the past 6 months?
•Are all critical manufacturing equip-
ment current in calibration, preventa-
tive maintenance, and qualification? A
complete list of critical equipment along
with the due dates for calibration, PM,
and re-qualification is essential for this
readiness step. This should include sup-
porting equipment such as washers,
autoclaves, depyrogenation ovens, cold
rooms, and freezers. All equipment that
the raw materials, process intermediates,
and final product is exposed to during
manufacturing and storage should be
• Are there sufficient spare parts on hand
for critical process equipment? Spare
parts are very important for equipment
with moving parts prone to failure for
which there is no backup. For example,
this could include components of a filling machine, bioreactor, or chromatography skid. A risk assessment may help
determine where equipment failure has
the highest impact. In many cases the
CMO probably has already conducted
• This part of the checklist is usually reserved for process-specific questions or
follow-up items. For example, “Review
the column performance data for the
Protein A column with the manufacturing team.” This requires some pre-plan-ning but can really be valuable and can
lead to insightful discussions.
• Is the HVAC system current in calibration, preventative maintenance, and
•Are room differential pressure sensors current in calibration, preventative
maintenance, and qualification?
• Have the environmental monitoring re-
sults for the facility been trended for the
previous 3, 6, and 12 months and been
reviewed by management? This should
include the monitoring results from
clean steam and water systems, if ap-
plicable. It is helpful to review these en-
vironmental monitoring reports and pay
attention to any trends that may indicate
the facility is not in control.
• Are all personnel performance trained
on the process(es) and are they up to
date on all of the training in their curriculum?
• Are all internal and external QC labs and
personnel aware of the in-process and
release testing schedule for the product?
How is this information communicated
to the QC teams?
• Are all test reagents in stock and within
their expiration date?
• Have there been any changes in the test
methods or reagents and have these
changes been incorporated and approved by quality?
• Are all QC instruments current in calibration, preventative maintenance, and
qualification? Like the manufacturing
equipment, it is helpful to have a list of
instrumentation used in the testing of
• Is there adequate reference standard in
stock at all test labs, including subcontractors, to support the testing of the
product in-process and release?
Packaging and labeling
• Is the final container in stock in sufficient quantity; is it released and within
• Have the final labels been approved by
• Is there a procedure in place for final
product pack-out for shipment?
• Have all shipping personnel been trained
on the pack-out of the final product?
“As it relates to biopharmaceutical
manufacturing, the definition [of readiness] can be
refined as: The active review of all processes and
procedures of a manufacturing campaign at a
CMO so as to ensure successful manufacture of
the product on time and within budget.”