The World Health Organization (WHO) estimates that counterfeit medicines cause 1 million deaths annually and 10% of all drugs sold globally are fake. Global events such as the COVID-19 pandemic intensify these risks by disrupting supply chains and increasing internet purchases. The track and trace (T&T) of medicines is a key tool to stop their counterfeiting.
According to WHO definitions, in the T&T model, “track” is the ability to know (after a pharmaceutical has left the manufacturer) where the product currently is, and “trace” is the ability to know where a product has been within a supply chain before its current location.
To provide necessary functionality, each pack must be marked with a unique product identifier (UPI) during packaging operations. Serialization is the process of defining, assigning, and affixing UPIs or unique serial numbers to product packaging at any level to enable products to be traced through a supply chain. In addition, serialized packs are often aggregated to shipping containers and pallets to further enhance T&T.
Aggregation is the documented parent/child relationship between uniquely identified items and their uniquely identified outer containers. Serial numbers are entered into a digital repository at the time of packaging and follow products through the supply chain.
More than 10 years after introducing T&T, the pharmaceutical industry still faces a number of technical challenges and limitations related to regulatory expectations, with many pharmaceutical companies still transforming their packaging operations to meet them. In response to these challenges, the BioPhorum Secondary Packaging Team completed an industry benchmark survey on the serialization of sellable units.1
The purpose of this benchmark was to identify common industry challenges with serialization, broaden the knowledge of good practice and industry capabilities, and identify the quickest route to implementation and compliance with global serialization requirements. The benchmark was completed in 2020 by 11 pharmaceutical companies and covered the following topics: governance, training, grading of print, overall equipment effectiveness (OEE), decommissioning of serial numbers, technology limitations, primary unit serialization, and non-standard requirements.
The top four industry challenges and processes related to serialization are discussed below. The BioPhorum team is working collaboratively to address these challenges.
1. Track And Trace And OEE System Performance
The OEE measurement is key to ensure equipment (in this case, secondary packaging equipment) is performing well. It supports continuous improvement initiatives within a company’s manufacturing network and, used correctly, allows a company to optimize capacity usage before any investment is made to bridge capacity gaps.
However, there is a concern about the potential negative impact on the packaging line’s OEE of installing serialization equipment, and a recent survey quoted in the BioPhorum publication reported as much as a 30% drop in OEE levels. Installing serialization and/or aggregation equipment into a brand-new packaging line is considered better than installing it into an already operational packaging line because requirements can be factored into the machine design from the outset.
It is important to consider process equipment flow when implementing T&T; failure to do so can introduce problems impacting the OEE. Yet, replacing any manual aggregation process (e.g., manual scanning) with aggregation per automated case packer should be considered.
In terms of automation and OEE, automated bundling equipment is the best option for aggregation and labeling processes for applications requiring a bundling aggregation and a bundle label. Automated palletizing of shipper cases and pallet aggregation are considered the best OEE option as it minimizes the operator’s intervention.
The mandatory Good Automation Manufacturing Process 5 standard (GAMP 5) from the International Society for Pharmaceutical Engineering provides pragmatic guidance toward achieving compliant computerized execution systems. However, it is essential to describe all roles and responsibilities and ensure they align across functional departments before applying GAMP 5. By collecting and analyzing serialization data (e.g., output and downtime) and contextualizing it with manufacturing execution system and enterprise resource planning system data sources, industry packaging operations can learn much about improving their overall OEE.
2. Serialization Technology Limitations
Fundamental changes to the technical configuration of manufacturing lines and packaging processes require a potential investment of around $100,000 or more. However, the lack of global standardization of T&T requirements means that systems cannot be designed in a future-proof way. As a result, future requirements can very quickly outgrow the capabilities of installed hardware and drive further investments to keep systems current. Therefore, continuing dialogue between regulatory agencies, the pharmaceutical industry, and system suppliers is essential to ensure readiness for the future, patient safety, and keep costs to healthcare systems low.
Regarding regulatory requirements, commonly accepted approaches decrease the risk of failures, reduce the cost of implementation, and improve patient safety. As a result, industry is striving for standardization of regulatory requirements and the GS1 standards (from the non-profit organization that develops standards-based solutions to address the challenges of data exchange) are widely endorsed by the healthcare industry.
Global endorsement of the standard codification of packaging enables quick approvals, limits the need for country-specific redressing activities, improves the sustainability of packaging, and, ultimately, makes drugs available to patients more quickly and cheaply. While industry strives for standardization of regulatory requirements, reducing the complexity of its systems should also be a priority, and different systems must be able to exchange data in a safe and error-free way. A full implementation of standards defined by GS1 and Open-SCS (Open-Serialization Communication Standard) to facilitate optimal system design and integration is needed.
3. Decommissioning Serial Numbers
According to a requirement of the EU regulation of the Falsified Medicine Directive (FMD) Q&A document (version 18 question 8.6): “Serial numbers that are not actually used as data elements in unique identifiers should not be uploaded and stored in the repositories system as they represent a security risk for the system.” However, this leaves room for interpretation, and discussions are ongoing about whether the translation of a goal of non-accounted-for serial numbers close to 0% is accurate. Many companies interpret this as 100% reconciliation.
Aggregation of serialized products can eliminate the need for decommissioning serial numbers by the manufacturer, but 100% aggregation requires costly line upgrades. Yet, this is often weighed against the fact that only some countries require aggregation.
Regardless of whether a company performs 100% manual reconciliation or uses aggregation, and in terms of the OEE, the percentage of loss should be continuously reduced. Good line design is the best option and is key to avoiding damage or loss and the need for decommissioning in the first place.
4. Training For Serialization
A training plan must be available for each company role/position that interacts with the L1–L5 serialization system levels, and existing curricula should be updated with the additional training required for serialization/aggregation. Also, developing internal company experts in serialization/aggregation processes should be part of an overall training goal and will adjust for the lack of experience of training for serialization in the industry.
Due to market variability and frequent system updates, periodic or corrective retraining is highly recommended, and systems must be established to successfully identify when retraining is needed.
Since serialization processes on the line include various activities, the training team should be multidisciplinary to cover the range of topics related to IT, quality, engineering, automation, and production. Also, certifiable exams can help showcase transferable industry knowledge and motivate trainees, and a dedicated training facility or line for L1–L3 level training will avoid unwanted production downtime.
The introduction of T&T regulations has driven specific changes to industry packaging practices. Digital information related to drugs has become a major quality-relevant part of the drug packaging process. This paradigm shift has triggered considerable modifications to drug packaging processes and technologies. Addressing the four main priority challenges will enable serialization, which is demanded by regulators and will bring many benefits to industry.
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- Serialization – Challenges and Good Practices in Packaging Operations Based on Experience of Track and Trace Systems, BioPhorum, 2021, www.biophorum.com/download/serialization-challenges-and-good-practices-in-packaging-operations-based-on-experience-of-track-and-trace-systems