testing that has already been completed at each step in the data
exchange and serialization process. How should manufacturers
properly assess what needs to be tested with their CMOs? In
order to define an appropriate validation strategy with the right
balance of risk, three key factors should be evaluated:
CMO SERIALIZATION EXPERIENCE
Does the CMO have experience with commercial production
for other markets and customers? Some CMOs have extensive
experience packaging products for markets with long-existing
serialization requirements, while other CMOs might be less experienced. Manufactures should confirm that their suppliers’seri-alization equipment has already been used to package serialized
products for other markets and assess their level of experience in
validating with other customers.
If the CMO has already implemented serialization capabilities for other markets and customers, the manufacturer should be
able to leverage the existing qualifications previously performed.
For example, if the CMO has successfully demonstrated supply
of serialized product, and is actively serializing products for the
same market, the line equipment is already validated and ready
for serialized production. In this case, the validation efforts can be
focused on testing the data connection between the two entities.
If the CMO has limited experience with packaging serialized product or if this if the first time the CMO is exchanging
GMP data with a customer, the manufacturer should be leaning
towards a more comprehensive approach and validate with full
end-to-end testing to ensure nothing breaks in the process. In
this situation, the CMO and manufacturer should test all required
steps needed to package serialized product, including the following: (1) verifying data exchange of serial numbers, (2) printing
serial numbers on the packaging line, ( 3) creating and uploading
a commissioning (and possibly de-commissioning/destruction)
file(s) to the manufacturer serial number management system via
a test connection, and ( 4) processing of the commissioning file by
the manufacturer without errors.
CMO IT INTEGRATION MODEL
Is the manufacturer’s connection to the CMO system at the enterprise, site or line level? The integration architecture between the
manufacturer’s enterprise serialization solution and the CMO’s
system needs to be taken into account when creating the validation plan. In order to avoid unnecessary effort, but at the same time
ensure thorough testing, the validation plan needs to be structured
based the IT integration and data exchange models used across the
manufacturer’s CMO network. For example, if the integration is an
enterprise-to-enterprise model, the manufacturer should consider
an approach with one time extensive testing of the data connection for the first SKU conversion, and subsequently utilize a lighter
approach for each additional site, line or product that is converted
through the same enterprise connection. The CMO might also be
using an enterprise level serialization software that has already
been qualified and setup in their production environment. In this
case, qualification can be executed by leveraging a simulator as
long as it is an accurate reflection of the production environment.
The business benefit of using this approach is avoiding consuming
valuable production resources.
On the other hand, if the connection is established to a site
or line level software, a heavier validation approach should be
taken. The manufacturer should validate each new connection
to the CMO site or line level software that needs to be converted. If the CMO uses a site level solution, the testing approach
for the 1st line will be more extensive than the subsequent lines
that will be converted. This is analogous to the approach for
additional SKUs to be converted on a packaging line that has
already been qualified.
PACKAGING LINE CAPABILITIES
What is the mix of products that is produced on the line? The
right validation strategy also depends on the CMO’s packaging
line capabilities and the mix of products they package. Manufacturers should evaluate how extensive the line qualification is with
respect to different packaging types and configurations.
For example, if the CMO’s packaging line qualification covers configurations consistent with the manufacturer’s product, a
lighter approach to validation can be taken. This is based on the
manufacturer’s ability to leverage the CMO’s validation protocols
that were previously executed. The boundaries that the CMO has
defined in their validation protocol will impact the degree of additional testing needed for the situation and the manufacturer
can utilize supporting documents from the CMO as part of their
If the packaging line is dedicated to the manufacturer’s
product or used for specialty products with unique packaging
specifications, the manufacturer should lean towards a heavier
validation approach of the packaging line equipment and the associated data exchange process. In this case, the manufacturer
and CMO should complete full end-to-end qualification with
tests that positively and negatively challenge both the IT connection and the packaging line equipment.
Consideration of the CMO’s serialization experience, the IT
integration model, and the product configurations qualified on
the packaging line should be used to guide the content of a
comprehensive validation plan that not only meets the business needs for implementation, but also supports on-going sustained operations. CP
*Note: FDA has recently issued draft guidance that suggests a 1-year
delay of enforcement to November 27, 2018.
LINDA KRISTOFFERSEN is a Senior Associate in KPMG’s Life
Sciences Advisory practice where she provides functional and
technical support to clients in the pharmaceutical industry. Linda
is currently focused on compliance programs for global pharmaceutical serialization implementations.
DAVID COLOMBO is a Director in KPMG’s Advisory Services
practice with more than 25 years of operational, engineering
and IT experience in supply chain execution in the pharmaceutical industry, including both clinical and commercial chains. His
responsibilities range from defining solution strategy through
implementation with focus on order-to-cash and purchase-to-pay processes,
warehousing and distribution operations, and supply chain security.