Enhanced supply chain security is one of the primary drivers for the serialization mandates that are impacting the pharmaceutical industry. Imprinting a unique identifier on each saleable unit is being required to verify package authenticity and to track product movement through the supply chain to thwart diversion and counterfeiting. Specific regulatory requirements vary by country; some (e.g. South Korea) require near real-time data reporting prior to product being released to the market.

Beginning in February 2019, the European Union’s Falsified Medicines Directive requires E.U. Marketing Authorization Holders to upload lot-based data to the European Medicines Verification System (EMVS) prior to the lot being transferred to saleable stock. At the point of dispense, the unique identifier must be scanned and the data verified in a national verification system.

In order to achieve the goal of product traceability, serialized product data must be compliant from the time it is generated and printed on a package until the moment that package is dispensed. To ensure the quality of master data and the accuracy of production data prior to the product being transferred to saleable stock, data reconciliation must be integrated into the quality release process. In order to execute this reconciliation accurately and quickly, an automated process is key.

At Bristol-Myers Squibb we are implementing the same data reconciliation processes in all our packaging sites regardless of market. Our team has concluded that the benefits of standardizing operational processes, and implementing automated “checks” in the reconciliation process to ensure data integrity far outweigh the temporary impact of making the changes.

Standardizing data and processes for regulatory compliance
The nearly universal adoption of GS1 coding attributes supports standardization as critical for enabling data exchange throughout a global industry. Common practice has been to post the commissioned data notification following the transfer to saleable stock. As long as serialized data remained internal, i.e. within the four walls of the Marketing Authorization Holder (MAH), errors and investigations can be managed with little to no impact to the supply chain.

However, this process leaves the MAH vulnerable to the possibility of data and/or process errors that could impact product flow in the supply chain. For example, there can be changes in the physical count of a batch in the warehouse without the corresponding data records being corrected. Operational errors might be missed if the counts reported in the ERP and the serialization repository are not reconciled before shipment. Or, product could ship without the shipment event being triggered resulting in product in the market without its requisite data set.

Under product traceability mandates, errors in serialized data can have potentially serious consequences, including government fines, suspension of sales, confiscation of product as “suspect,” and more.

To prevent errors, additional controls are needed following closure of the packaging line and prior to the quality release. Regardless of where the data resides—within the packaging site’s ERP and serialization repository, or internally at the MAH—the physical count of a batch and the serialized data must be reconciled immediately prior to transfer to saleable stock.

This final data reconciliation should be executed prior to shipment. The multiple “checks” inherent in these process changes ensure that the serialized data and the physical product are accurate and will be able to move together through the supply chain as required.

Regulatory requirements mandate packaging line changes
The E.U. Falsified Medicines Directive is the primary diver for these process changes. Article 33 of the Delegated Regulation (DR) 2016/161 of the Falsified Medicines Directive explicitly states that the required data must be uploaded into the authority repository “before the medicinal product is released for sale or distribution.” This requirement, coupled with E.U. GMP Annex 16 (“Certification by a Qualified Person and Batch Release”), makes it incumbent on the MAH to ensure the integrity of the product and its corresponding serialized data prior to product transferring to saleable stock.

Implementation of these process changes may not be a welcomed activity. These particular changes also involve financial impact: cost of time and money to modify systems and train employees, as well as the implications of altering the timing of when ownership of the product is transferred from site to MAH. Adopting a standard quality release process for all serialized product regardless of market helps to ensure fewer operational errors. In addition, an automated data reconciliation process, as described above, is critical to reducing issues downstream. 

Conclusion – supply chain of data
Product and serialized data can only move within the supply chain when the data truly reflects the physical product. If a supply chain partner or Health Authority receive inaccurate data, there is a potential risk of the product being stopped. This could be detrimental to patient care.

Implementing the proper controls allows for data errors to be discovered prior to release of product to the market. All stakeholders, including patients, benefit when the right controls, processes and quality systems are in place to efficiently and effectively manage serialized data. 

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Miguel Pitarch, Ph.D., is executive director of global serialization at Bristol-Myers Squibb (BMS). The rest of the BMS serialization team that contributed to this article are: Alison Casserly, Barry DeDominicis, Adem Dika, Ismael Herrera, Mahesh Joshi, Kathryn Kempf, Brian Lee, Diane Redler, Daljeet Sahni, Sanjay Sabhlok, Sanjay Sengar, and Arvind Sharma. For more information: Miguel.Pitarch@bms.com.