As the November 27, 2017 requirement for serialization as part of the U.S. Drug Supply Chain Security Act (DSCSA) is quickly approaching, pharmaceutical manufacturers are ramping up their efforts to implement capabilities including integration with their contract manufacturing organizations’ (CMO) technology solutions.* For many manufacturers and CMOs, the exchange of serial number allocation and commissioning files will be the first time such a significant amount of GMP data will be transmitted between the two entities.

This presents a unique shift in the validation approach compared to previous qualifications since, to date, manufacturers’ validation experience with CMOs has been mostly limited to reviewing equipment and system qualifications performed by the CMO within their own environment, according to their own policies and procedures. Due to the mixed usage of on-premise and cloud-hosted applications at the enterprise and the packaging site/line level, it is critical that the validation plan accounts for these unique aspects. Manufacturers now need to rethink their CMO validation strategy and determine the right level of involvement in the validation process when implementing and maintaining serialization capabilities with their contract manufacturers. This article will identify considerations and suggestions for manufacturers to evaluate as they define and refine their validation and testing approach.

As a starting point, manufacturers may consider using their internal packaging line validation strategy as a baseline for developing their CMO validation plan. However, there will be some additional factors to consider given the wide range of CMO serialization capabilities within a manufacturer’s supply network. For internal serialization line conversion, IT and equipment validation will typically follow standard testing and processes that have already been established by the manufacturer. As manufacturers convert internal packaging lines to serialized production, the effort required to convert the rest of the products packaged on the same line is reduced since the systems are internal and have already been validated.

In general, the level of validation required with a CMO should leverage both entities testing protocols, resulting in an approach that differs from how a manufacturer would validate their own internal packaging lines and associated systems. This is based on the assumption that both manufacturer and CMOs have their internal systems validated prior to beginning external partner onboarding activities. In order to determine how to right fit a validation strategy, the manufacturer needs to assess the various business scenarios that exist in their CMO network. These scenarios may be driven by criteria such as IT integration model, CMO serialization maturity, and product portfolio. Depending on the scope and complexity of the implementation, there are several pitfalls that can occur along the way that are unique to CMO integration. To prevent costly project delays and issues with the implementation, while at the same time avoiding unnecessary use of resources on validation execution, it’s essential to assess and determine the right level of testing required for each situation.

For CMO integrations, the interactions between the manufacturer and CMO can be viewed as a single system, where the validation plan should be constructed based on the amount of 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’ serialization 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 validation package.

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. 

*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.