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For some manufacturers, the goal was to be fully compliant with the DSCSA, including both serialization and aggregation, from day one.
Enacted by Congress on Nov. 27, 2013, the US Drug Supply Chain Security Act (DSCSA) is intended to build a more secure supply chain in the United States with the ability to identify and trace drug products and limit exposure to counterfeit, contaminated, and otherwise harmful drugs. Everyone in the pharmaceutical supply chain has had to pivot to meet the DSCSA requirements, including manufacturers, repackagers, wholesale distributors, dispensers, and third-party logistics providers (trading partners). Manufacturers, specifically, have had to incorporate serialization into their manufacturing and packaging lines and will need to consider aggregation implementation as well if they haven’t already.
“At Catalent, we started planning and implementing serialization over five years ago,” says Rebecca Mullis, Engineering Project Manager, Catalent Biologics. “But Catalent, being a contract development and manufacturing organization [CDMO], wanted to be ahead of the curve and ahead of our competitors to have serialization available for our customers. In doing so, we evaluated multiple vendors and evaluated different types of equipment.”
According to Mullis, Catalent selected vendors, purchased equipment, and integrated software and data management platforms. In the process, they moved from a manual process to a more automated one. For line-level equipment, Catalent chose to work with Mettler Toledo, which included an automated print and inspection station. For a cloud provider, they chose to work with TraceLink.
For some manufacturers, from day one, the goal was to be fully compliant with the DSCSA, including both serialization and aggregation. Catalent, for example, didn’t wait for the 2023 aggregation deadline. Instead, the company worked toward full compliance from the beginning, integrating both serialization and aggregation into their manufacturing process immediately.
“When the operators go to pack the cases, there's another piece of equipment with the overhead camera, and it takes a snapshot of every layer in the case and captures every serial number of every carton. Once that's done, it goes to the database and prints a label. We manually apply the label to the case, put the case on the pallet,” says Mullis. “At this point, the operator will take a hand scanner and scan the serial number of every case going onto that pallet. Once the pallet is full, we’ll print a separate label. That label is applied to the pallet, and it's all tied to the batch … Again, all the serial numbers are going into this database that resides on the server side. When we go to ship the product, we already have the process. This is from day one that we implemented this.”
After this, the product is shipped and all serialized data are stored in cloud-based storage, which is provided by TraceLink. It's also how Catalent sends the data back to the client.
Like Catalent, Thermo Fisher Scientific also included aggregation in their initial serialization design even though it wasn't required in the initial phase of serialization. For Thermo Fisher, once they selected their equipment and software vendors, they moved straight to validation.
“Learning the systems now and the processes and how they all tie together, that was key to developing the qualification protocols, SOPs [standard operating procedures], and then training of all those individuals from packaging to IT and QA [quality assurance] as well,” says David Bond, senior manager and serialization program lead, Thermo Fisher. “Overall, coaching of employees from all levels in the organization on a new process just so everyone was aware of what was going on and what needed to be done for serialization.”
Since Thermo Fisher’s initial implementation, Bond states there have been ongoing process improvements to keep up with the evolving landscape for serialization. From a training perspective, specifically, there was much to learn and standardize. Bond recalls how the company developed training plans for different levels and different users of the serialization system—from QA to operations.
“On the operations floor, taking samples became a different process for them, managing the serial numbers, managing the overall process for serialization. It was something new initially,” says Bond. “To be honest with you, a lot of packaging operators were really afraid of serialization. Just working with them and giving them that comfort level. Before you know, they were making suggestions.”
Meanwhile, for manufacturers with a global footprint, such as Recipharm, serialization and aggregation involved creating a global program. Across 15 sites, Recipharm acquired equipment, hardware, and software and established a global program that took approximately three years to implement at all the sites, according to Staffan Widengren, Director Corporate Projects, Recipharm.
Similar to Catalent and Thermo Fisher, Recipharm selected vendors for serialization. For equipment, the company chose Marchesini; for software and hardware, they chose SEA Vision; and for data reporting, they chose TraceLink. Widengren estimates the process of ordering the equipment to having the equipment installed and qualified on the site took around 10 months from when it was started to when everything was connected. However, it’s important to note that aggregation is not a requirement in Europe as it will be in the US as of 2023.
“First, it was the machine, which we took from Marchesini, and then we prepared all the documents required for that. Then we ordered the machine together with the software. The software came from SEA Vision, and it was the responsibility of Marchesini to see that the machine and the software were integrated,” says Widengren. “The next step after the order—it took around six months from when the order was placed and when the machine was ready for what we call the factor acceptance test (FAT). So, we went down to the supplier for the FAT and when that was successful, we got approved to ship the machine to the site. And that was another two to three months, depending on when the site needed or could install it. Then we do what we call the ‘site acceptance test.’ Then the machine was ready for you to use for serialization packs. The last thing was to connect it with TraceLink and the customers in TraceLink.”
Widengren adds that, as a CDMO, Recipharm isn’t allowed to connect to the European Hub. Only the market authorization holder can do that. Therefore, Recipharm reports the serialization data to their customers, and then their customers report it to the EU-hub.
For Catalent, Thermo Fisher, and Recipharm, it seems that serialization—and aggregation—efforts are well underway. But that doesn’t mean there haven’t been a few unexpected hiccups along the way.
The biggest challenge Catalent, specifically, has had relates to data storage. According to Mullis, because the company has been expanding, the database that houses serialized data is filling up more quickly than expected. Therefore, their current challenge is finding a way to archive the data while still maintaining data integrity and meeting requirements.
“With data management, this became a big target for our data integrity team,” says Bond. “There was an enormous volume of new data that had to be retained for specific regulations—storage backup, security all had to be considered. And of course, keeping Part 11 [21 Code of Federal Regulations Part 11] compliance in mind along with the data. Reviewing audit trails as a part of that. Data review became a key factor in managing overall data for serialization.”
Manufacturers are the first step in the serialization process. As such, they must be the first ones to have serialization—and aggregation—in place for the essential data to be accessed by downstream partners. Hopefully, there will be no further delays due to the COVID-19 pandemic and smooth sailing ahead for global serialization efforts.
Meg Rivers is a senior editor for Pharmaceutical Technology, Pharmaceutical Technology Europe, and BioPharm International.
Volume 46, Number 2
When referring to this article, please cite it as M. Rivers, “Serialization and Aggregation from a Manufacturing Perspective," Pharmaceutical Technology 46 (2) 2022.