Leveraging Track-And-Trace Technology To Improve Packaging-Line Quality

By Frank Bieganousky, founding member, Montesino Associates, LLC.

Don’t think of ePedigree as just another regulation, but as an opportunity for continual improvement.

Whether it comes from the global market or a national regulatory body, implementing a track-and-trace system is a complex, expensive, and resource-intensive endeavor. It is complex since there are numerous technical and design challenges; expensive since it can involve many and varied pieces of equipment; and resource intensive since it needs cross-functional teams and top management involvement. As noted in HCP’s Playbook on Serialization, “Success in both strategizing and implementing a serialization program can only be guaranteed with a structured approach where all stakeholders are onboard from the beginning — not just at the execution stage.”

At the same time, expiring patents, low price generics, high R&D costs, and narrowing margins are pressuring pharmaceutical companies to improve costs. Understandably, the pharmaceutical industry is looking to minimize its cost while implementing ePedigree solutions, but installing systems that only minimally reach compliance may be shortsighted. Pharmaceutical companies should consider Quality by Design (QbD) principles in their overall serialization strategy. Beyond just complying with pedigree legislation, pharmaceutical companies have an opportunity to leverage track-and-trace technologies as a tool for continual quality improvement in order to reduce cost and minimize risk. For example, serialization allows companies to critically analyze product movement data and look for additional revenue, differentiation, and product value, in short, ROI. This can be done, practically speaking, in real time.

QbD And Serialization Can Work Hand In Hand
Global regulatory authorities have made it clear that applying QbD principles in the development and manufacture of pharmaceuticals is desired to assure product quality. Process Analytical Technology (PAT) techniques are used to move from the current “testing to document quality” to a continuous quality-assurance state. The FDA’s Guidance on PAT notes:

“Conventional pharmaceutical manufacturing is generally accomplished using batch processing with laboratory testing conducted on collected samples to evaluate quality. This conventional approach has been successful in providing quality pharmaceuticals to the public. However, today significant opportunities exist for improving pharmaceutical development, manufacturing, and quality assurance through innovation in product and process development, process analysis, and process control.”

The QbD principle of continual process improvement is well understood as a key element to improve product quality and reduce the cost of poor quality. The foundation of this concept is the understanding of the process and process controls at initial design and through continual process monitoring. Properly implemented tracking technologies offer the opportunity to make a quantum improvement in the information acquired in the packaging process. The past several years have seen an emphasis on reducing the cost of packaging, but not necessarily through continual quality improvement. Material and packaging component global tenders, Internet auctions, and current Overall Equipment Effectiveness (OEE) initiatives are the “low hanging fruit.” While these initiatives are all well and good, a primary focus on OEE, without the continual quality improvement component, will not fully realize the potential cost and risk benefits. A new approach is necessary by applying total quality principles in the packaging operations to strive for continual incremental quality improvements.

Detecting patterns and trends is fundamental in understanding and reducing the causes of variation, and thus the key to continual improvement. It’s about acquiring better information, and here is where serialization presents an opportunity. The FDA’s thought on this is expressed in its Guidance on Process Validation:

“A successful validation program depends upon information and knowledge from product and process development. This knowledge and understanding are the basis for establishing an approach to control of the manufacturing process that results in products with the desired quality attributes. Manufacturers should:

• Understand the sources of variation
• Detect the presence and degree of variation
• Understand the impact of variation on the process and ultimately on product attributes
• Control the variation in a manner commensurate with the risk it represents to the process and product.”

Pre-serialization packaging is primarily focused on the lot, while serialization is focused on the individual piece. Serialization will make it possible to track containers in real time and space on the packaging line. This tracking provides a method for detecting patterns and trends in a way that is not practical or feasible now. It now becomes possible to maximize the information from the significant quality-control points in the process, through the ability to map patterns and trends in a very robust way. Better understanding of the process will result in higher quality, reduced cost, expedited trouble shooting, and, ultimately, reduced risk by helping to identify and mitigate potential problems before they occur. In addition, applying Process Analytical Technology (PAT) techniques and tracking each container through the process create the potential for real-time release without, or greatly reduced, quality-control sampling.

Compare the above state with where the industry is now. Pharmaceutical manufacturers are using a variety of PAT techniques on their packaging operations such as check weighers, insert/instruction leaflet detection, verification of caps and safety seals, inspection for particulates or flawed tablets/capsules, label position, and text and code verification. They are using these PAT techniques, but are focused on efficiency and providing packaging that meets a certain quality standard, not as a matter of course on continual quality improvement.

Track And Trace Can Change The Course Of Quality Control
Current quality-control methods employed in the pharmaceutical industry typically rely on sampling and on-line detection of defects that “sound alarms” or reject the package. Once a defect level reaches a certain threshold, the line operator investigates and takes corrective action. For example, if a certain percentage of bottles with short tablet counts are rejected at the check weigher, the operator would investigate possible causes at the filler. This method works well when the root cause is obvious (such as a blocked filler slat), but becomes much more challenging when the root cause is random (or worse yet seems random), or is an interaction between more than one variable. Having data that can be used to map patterns would be much more useful in troubleshooting, and would help distinguish commodity issues from line issues. Think of how much more effective the response would be if the operator had access to data showing that the short count is always from a particular filling slot, or that it is in fact a random occurrence. In the first case it is clearly a line issue; in the second case perhaps the tablet dimensions are out of specification.

Another common quality-control practice is to reject three containers when a defect is detected on the line (one on each side of the suspect defective container). If you are tracking where each container is in real time and space, you would know exactly which container has the defect and reject only one, reducing rework by two-thirds! However helpful in troubleshooting or reducing waste, both of the above examples illustrate managing quality by attempting to “inspect the quality in” rather than designing a more robust process and reducing variation of the inputs. Only through a culture of commitment to collect, analyze, and consistently act upon the information will continual quality improvement be realized, along with the resultant benefits.

A fundamental understanding of the process is key to developing a design space and subsequent control space for the packaging operation. This understanding, along with continual quality improvement, will continue to minimize the risk and the cost of poor quality. Coupled with the proper application of PAT techniques, this environment creates the potential for real-time release or substantial reduction in quality-control sampling. If you utilize PAT techniques at the critical-to-quality operations, and track every container in time and space through those operations, you are assured with a very high degree of confidence that every container meets the quality standard.

The basic requirement in any ePedigree solution is to serialize containers on the packaging line, then track the container through the distribution system. The simplest way to accomplish this is to serialize the label placed on the container. However, the labeler is normally placed towards the end of the packaging line after filling and capping; therefore, several critical-to-quality processes are bypassed. One of the important points to consider is where you choose to serialize your container on the packaging line. Serializing the container at the beginning of the packaging line provides the opportunity to track the container throughout the entire packaging process. Serializing packages at the end of the line may minimally meet pedigree requirements, but it will be an opportunity lost in terms of quality assurance.

Consider The Cost Of Poor Quality Above Additional Costs Of Serialization
As previously indicated, the ability to map patterns and trends is now limited, and so the available information is a constraint on continual process improvement and better-process knowledge. Pharmaceutical companies need to incorporate QbD concepts in their track-and-trace implementation strategy to take advantage of the serialization opportunity. There are technologies that serialize and track individual containers from the beginning of the packaging line. Pharmaceutical companies are considering and evaluating these systems primarily as a robust way to assure security and to eliminate inference for bundled containers prior to packing into a shipper, but not necessarily for its significant quality-assurance benefit. Companies would be wise to factor in the ability to capture data in a much more robust and useful way as a tool for continual quality improvement.

Frank Bieganousky is the founding member of the consulting group, Montesino Associates, LLC. Prior to this, his pharmaceutical packaging career has spanned more than 30 years, having held positions at Bristol-Myers Squibb, Becton-Dickinson, Tekni-Plex, Inc, AlliedSignal (now Honeywell), and Rexam Medical Packaging (now Amcor). Frank has an MBA in finance from Fairleigh Dickinson University and a BS in packaging engineering from Michigan State University.