Should You Be Using Unique Container Identification?

A conversation with R. Tod Urquhart and Alessandro Pelizzi

In a fully traceable supply chain, non-serialized primary packaging can be a fatal flaw in the links.

There’s a growing movement among leading biopharmaceutical companies and organizations to roll out higher levels of traceability, and possibly mitigate writing off full batches when problems in process steps arise.

Unique container identification (CUID) could prevent mix-ups, help manage quality at the unit level, and inform investigations when deviations come to light downstream. These are all advantages that, at the moment, are mostly out of reach. Unit-level identification presents enormous logistical challenges, but one industry group recently published a standard to help inform implementation for trading partners up and down the supply chain.

In May, the International Society for Pharmaceutical Engineering (ISPE) published the ISPE Good Practice Guide: Unique Identification of Glass Primary Containers in Pharmaceutical Fill and Finish Operations.

Industry consultant Tod Urquhart, founder and CEO of Eagas, and Alessandro Pelizzi, an associate manager of LifeBee, a ProductLifeGroup company, helped lead the team that developed the 86-page guide.

We reviewed the guide and had questions for them about technical considerations, interoperability, and how the authors expect biopharma companies to implement it. Urquhart and Pelizzi offered to help answer them. Here’s what they told us.

Considering that regulators don't require CUID, what outcomes do you expect and hope for from this Good Practice Guide?

The industry has an average manufacturing efficiency (OEE) of less than 40%. By contrast, other industries perform at much higher efficiency levels — some as high as 90%.

At the same time, we need to look at some of the bottlenecks in injectable medicines. The first is the challenges of sourcing, qualifying, and validating new manufacturing capacity, which has a timeline of two to three years depending on the complexity of the machine. This situation is made more challenging as there are a limited vendor base and a lack of skilled personnel in a market that is forecast to grow by around 30% over the next five years.

Improving operational efficiency and increasing the output of existing machines will help to bridge this gap. Unique containers deliver a range of benefits that can be taken on their own, including:

• preventing drug mix-ups,
• simplifying segregation when a problem occurs,
• more robust root cause identification and corrective actions,
• process optimization, and
• providing unit-level batch data.

However, they become much more powerful when they are combined and ultimately assist companies to deliver a much higher and controlled output from filling to automated visual inspection.

The objectives in creating the guide were three-fold:

• ensuring a uniform approach globally by using contributors from the whole stakeholder ecosystem,
• ensuring process interoperability among the different actors supporting parenteral manufacturing processes, and
• enabling the industry to speak with governments and regulatory agencies from a position of strength and to be able to influence emerging standards for primary container serialization.

The team that created the guide was drawn from all the stakeholders in the industry and, in many cases, they are fierce competitors. They all worked together as a team to deliver a comprehensive document that:

• provides users a guide to the best practice for implementation,
• dispels/removes the myths/perceptions that exist on the use of unique containers,
• creates a common platform among competing suppliers for the collection and management of data in machines,
• outlines how the machine data should be managed for later use, and
• provides a validation approach.

When serialization started , there were very few standards and no interoperability. Thanks to the efforts of thousands of people globally, serialization of secondary packs is now relatively straightforward. That process was the inspiration for the guide as well as ensuring interoperability among the stakeholders.

Finally, the regulators are looking for increased levels of traceability in injectable medicines and the existing methods are reaching the end of their technical capabilities. Furthermore, the move toward automated batch release and the autonomous line cannot be achieved without much higher levels of data on the product and the process. This is where the unit level batch report becomes a necessity, as the key quality attributes are tracked and saved for each container.

Can you share some examples of why secondary packaging identifiers fall short? In other words, why do we need container-unique identification?

The primary container serialization was not created because secondary packaging serialization was thought to fall short. The two solutions are just focused on different needs.

Secondary package serialization was created first by the U.S. and European regulatory authorities to tackle the increased prevalence of counterfeit medicines. In the U.S., the DSCSA is designed to track a saleable unit (item, box, or carton) from the manufacturing line to the final point of dispensing. In the EU, the FMD is designed to deliver product verification at the point of dispensing by referencing both country centric and a centralized EU database of serialized products.

On the other hand, creating unique containers or serialized containers is designed to improve the visibility and traceability of single items within the internal manufacturing processes to prevent issues and improve production efficiency, as explained in the answer to question 1.

Can you talk about some of the physical challenges with primary packaging shapes, sizes, materials, and handling that make CUID difficult?

Primary containers for injectable medicines are designed to deliver a sterile barrier between the drug substance and the outside world. They are manufactured from borosilicate glass, which is chemically inert and highly resistant. It is the ideal solution for containing all types of injectables and the most delicate treatments.

Marking these containers with a machine-readable unique identity (UID) needs an understanding of the container and processes.

• The surface is curved, with diameters as small as ø= 6.85 mm.
• The container has a glossy, non-absorbent, inert glass surface.
• Specific machines and inks had to be developed to deliver a high-definition machine-readable 2D bar code.
• The size of the bar code and, hence, the length and type of the serial number need to be adjusted to allow high-speed readability at a variety of process speeds and operational checkpoints (up to 800 per minute), which is higher than any speeds on secondary packaging lines.
• It requires positional flexibility for the marking of the bar code.
• The bar code is bonded to the glass for the life of the product.

In addition, glass packaging components used in pharmaceutical drugs and medical devices undergo scrupulous cleaning and sterilization processes to ensure patient safety. All glass components are washed and then undergo different sterilization techniques depending on the type of glass container and shipping format.

More than 90% of vials and cartridges are processed in bulk and the most common technique used to sterilize these containers is depyrogenation, in which containers are exposed to dry heat with a peak temperature approaching 350 degrees C. As such, the glass must be marked with a unique identity that can withstand the different process steps used during manufacturing. Labels, tags, RFID labels, etc., are simply not an option until the container has been filled and stoppered.

If we consider syringes, more than 90% of the supply is processed in ready to use (RTU) or ready to fill (RTF) formats in which the sterilization is carried out using ethylene oxide (EtO) gas. In the process, the sealed tubs hold a nest that contains either 100 or 160 syringes. During the gas sterilization the syringes are processed at pressure of 6 bar and at a temperature of 60 degrees C.

In this environment the new technology solution of using an RFID label embedded in the rigid needle shield (RNS) can be used and is most likely to become the “go to” choice for syringes.

How does the guide address them?

The guide has separate sections detailing the processing of these types of containers as well as the type and size of the serial numbers that can be used for each type. This is detailed in chapters 3, 4, and 5.

Interoperability seems like it will be a challenge if multiple suppliers are developing solutions. Do we need more regulator input to enforce standards?

Interoperability is at the heart of the approach for the guidance document. Glass manufacturers are aligned on the type of UID to be used for vials and cartridges and the format for machine readability. For syringes, as the RFID chip has sufficient memory, the serialized global trade item number (SGTIN ) is the preferred use for the RFID RNS as this ensures that it is aligned with other GS1 supply chain standards.

All the machine suppliers — filling and automated inspection — have aligned on what data should be collected in their machines. All the competitors sat down and agreed on a plan for the data: what is “mandatory” — required for the batch and batch release — and what is “optional”. This is data that will add much greater transparency to the manufacturing processes.

The data management solution has again been derived from an alignment of different stakeholders in how best to manage the data in these machines for later use and investigation.

So, in summary, multiple stakeholders from across the industry have, as a collective, agreed on an approach that we know can be used effectively within the current manufacturing processes. Simply put, the vendors and the stakeholders are ready to start.

Involvement by the regulators could be productive if they want to understand more and be part of the solution.

Pharma has not adopted RFID as widely as other industries, but the technology has a big part in the Good Practice Guide. Can you talk about the role RFID plays in CUID?

RFID has traditionally been seen as expensive and that is, generally, a historical perspective. In the interim, technologies have advanced as have the providers. Like most computer chips, the price has fallen with new technologies and the capabilities and performance have increased. It is this reduction in size and improved performance that have allowed an RFID label to be incorporated into the RNS.

Just to put this in perspective, RFID labels are now used in the garment industry, which consumes 30 billion of these chips and labels annually.

Every RFID chip has a globally unique serial number irrespective of who manufactures it. It also has a small amount of memory that facilitates the writing of a serialized GTIN (SGTIN), which, again, is unique. As I detailed above, given the syringe’s size, curvature, and sterilization approach, RFID fits closely with the use cases for syringes.

Does the Good Practice Guide recommend a dual approach with RFID and bar codes, one or the other, or is it simply a tool to aid the user's decision?

If a pharma company wants to use a bar code across all three product types — cartridges, syringes, and vials — this is possible, and they can have uniformity of readability. They will then need to adopt the aggregated nest and tub method for the syringes that are, as I mentioned above, processed in a nest and tub format. Reading a data matrix code (DMC) on a syringe in a nest and tub in a sterile filling line is a big issue, so the team developed the aggregated tub. The same approach can be used for the RFID RNS as it allows for bulk reading of the containers in the nest.

The dual approaches — RFID and bar codes — suggest that all downstream trading partners should be equipped with RFID readers and optical scanners. All that equipment just to process serial numbers seems like a potential obstacle. Wouldn't it be easier to endorse a single system?

The two approaches have both pros and cons that are strictly related to the type of product, the production process, and the type and dimension of the container. Companies have the right and duty to be able to choose the best solution for their production processes and to pursue their goal of traceability and visibility in their internal supply chain.

Bar code readability is a standard technique widely used across the world. RFID readers are used every day in the retail trade. In pharma, RFID is gaining traction in hospitals, clinics, etc.

About The Experts:

Tod Urquhart has more than 14 years’ experience of working in the field of product traceability including software systems, regulatory compliance, process efficiency and supply chain visibility. He has an extensive knowledge of planning, managing, and delivering cross-functional projects with companies such as Pfizer, GSK, Merck, Danone, and the Stevanato Group. Tod is currently a pharma industry advisor working with digitalization systems to deliver process optimisation, traceability, and continuous manufacturing. He is also the vice chair of an ISPE Community of Practice [CoP] and the chair of the Filling & Inspection working group who are creating an industry standard for the traceability of parenteral containers. Tod has a degree in chemical engineering from University of Cape Town, and an MBA from Stirling University.

Alessandro Pelizzi is a telecommunication engineer with more than 16 years of experience in consultancy field, nine of them in the pharmaceutical sector. Currently, Alessandro is the serialization and supply chain business unit associate manager in LifeBee, a ProductLifeGroup company. He specializes in consulting and digital services for life sciences, focusing on operational excellence, digitalization, and compliance in production, logistics, QA, labs, regulatory, and pharmacovigilance. Alessandro has extensive experience in serialization projects working with national and multinational pharmaceutical companies, starting with European FMD and expanding to compliance in various countries all over the world. He has been an ISPE member since 2017 and from 2020, he has been part of ISPE working groups, contributing as a chair of the Data Management working group to publish the ISPE Good Practice Guide: Unique Identification of Glass Primary Containers in Pharmaceutical Fill and Finish Operations.