Integrated serialization systems topped the agenda of many exhibitors and attendees at this year’s INTERPHEX show (Apr. 23&ndash25, 2012, at the Javits Center in New York City). With California’s 2015 e-pedigree deadline rapidly approaching, serialization technology providers presented integrated solutions and emphasized retrofit capabilities. Serialization and collection of code data at each stop in the supply chain serve as the foundation of pedigree records. 

Serialization depends on a complex interaction between packaging line hardware and software to apply a unique code at the item level; confirm code quality and correctness; aggregate code data and label bundles, cases, and pallets; communicate with line-, plant- and enterprise-level software; handle manual operations and rework; and decommission codes on rejected packs. 

Seidenader Maschinenbau GmbH displayed its T&TSolutions hardware and software integrated into a serialization-capable line from primary-container marking to pallet-label generation. 

Mettler-Toledo ran demonstrations on a line capable of handling up to 400 packs per minute. The integrated line consists of the DataMatrix Station (DMS) XMV marking and verification system, the Advanced Bundle Station, and the Shipping Case Station, plus a manual pallet-labeling station (see Figure 1). For less automated lines, there is provision for a manual case station. Pilot Line Manager software manages the serialization function from the operator interface on one machine (including code printing, verification, and aggregation). The software also typically communicates with the Pilot Site Manager software, which oversees multiple packaging lines and transmits serialization data to the enterprise system. Another function is grading the quality of the serialized human-readable information and DataMatrix codes. If print quality does not meet specifications or the code itself is incorrect, the pack is rejected.

Serialization can generate valuable data beyond the information needed to track and trace product through the supply chain. For example, the Integrated Bottle Center from Uhlmann Packaging Systems LP embeds production and quality details, such as cap torque and number of desiccants, in the serialized code on each container.  

Other serialization news at INTERPHEX included the US introduction of the Traceable Quality System from OCS Checkweighers. This modular system provides single-point control, sends code data to the printer and camera at the same time, and includes Line Manager software, as well as unit- and bundle-level systems. A TQS-HC-A module combines serialization with checkweighing to ensure packaging is not only coded properly, but also complete. 

With thousands of lines in operation, implementing serialization frequently depends on retrofits. To meet this need, MG America has engineered coding and verification modules, which can be added to cartoners, bundlers, and case packers already in the field. The hardware- and software-agnostic technology makes it possible to configure systems with the coding, vision system, or serialization software options preferred by the end user. 

Retrofits also are supported by a turnkey serialization solution from Acsis. Serialization in a Box consists of Acsis Site Management and Line Management Software, printers from Domino North America, and vision components from Cognex. 

Moving beyond the packaging line to the warehouse, Optel Vision relies on track-and- trace technology from ROC IT Solutions to handle rework and shipping of serialized products. Working in conjunction with Optel’s TrackSafe platform, the ROC IT Track & Trace hardware and software prints, applies, captures, verifies, aggregates, decommissions, and submits serial numbers on products being shipped. 

A case-packing cell that supports serialization for track-and-trace requirements integrates the TaskMate Robotic Case Erector/Loader from ESS Technologies with the Xyntek-Antares Turn-key Serialization solution from Xyntek. Although shown with a FANUC LR Mate 200iC/5L multi-axis robot with ESS-designed end-of-arm tooling, the case packer can be built with other robot models to meet payload needs. During the show floor demonstration, bottles were conveyed through the Xyntek-Antares Omnivision 360° Bottle Tracking System, which captured and aggregated codes on the label and base of the container. The robot picked up a four-by-three collated group of 12 bottles. Before placing the bottles in the case, a high-resolution smart camera from Cognex read the codes on the bottom of the bottles and the Xyntek-Antares Tracking System software confirmed the serial numbers and printed a case label. The robot then pushed the loaded case onto an exit conveyor for manual or automatic sealing. Capable of handling up to five cases per minute, the system provides an alternative to manual case packing. 

Another serialization-ready machine and a first-time exhibitor, the entry-level Compact 4 Vertical End Load Cartoner from ADCO prints and inspects DataMatrix codes on tablock or glued cartons and verifies the code on any leaflet. Light-curtain guarding and automatic indexing help operators manually load products and/or leaflets at speeds of up to 40 cartons per minute. However, loading can be automated if higher throughput is needed. A patented eight-pocket, quick-size-adjust starwheel and quick-adjust levers and scales expedite changeover. Other features include stainless-steel construction and standard or washdown configurations. Carton sizes range from a 25 x 18-mm (1 x 0.71-inch) opening with a 60-mm (2.36-inches) depth to a 120 x 90-mm (4.72 x 4.54-inch) opening with a 180-mm (7.09-inch) depth. 

INTERPHEX is always a great place to see packaging innovations. Next year the show returns to Javits Center in Manhattan, but is scheduled a bit earlier than in recent years, March 18-20, 2014. In the interim, the Pharmaceutical Pavilion at PACK EXPO Las Vegas (Sept. 23–25, 2013 at the Las Vegas, Nevada Convention Center) provides an opportunity to address packaging needs.

Hallie Forcinio is Pharmaceutical Technology's packaging editor, 

Articles

Packaging

Integrated serialization systems keep pace with industry demand.

INTERPHEX Highlights Serialization

Solid tablets are perhaps the most commonly used dosage form for pharmaceuticals. Tablet hardness serves both as a criterion to guide product development and as a quality-control specification. Tablets should not be too hard or too soft. An extremely hard tablet could indicate excessive bonding potential between active ingredients and excipients, which can prevent proper dissolution of the tablet needed for an accurate dosage. By the same token, a softer tablet could be due to weak bonding and may lead to premature disintegration when ingested by the patient. A soft tablet could also chip or break during processing stages in manufacturing, such as coating and packaging.

Knowing the mechanical properties of a solid-dose tablet can provide valuable information for optimizing material constituents and the manufacturing process. The types of binders used, the nature of the active ingredient(s), and the composition of the ingredient(s) in the tablet will affect the hardness of the tablet; the tablet-press speed, granulation flow, and air in the powder can also potentially affect tablet hardness (1). These factors must be controlled during production and verified after manufacture. As the production-to-market timeline of pharmaceutical products becomes tighter, it is essential to efficiently and effectively quantify the critical properties that will affect product development and performance. Methods for measuring the mechanical strength of a tablet include crushing, fracturing, and bending tests (2).

The crush test is usually performed on a round tablet standing on its rim, or, for a capsule-like tablet, parallel to the longest axis. This test is sometimes known as a diametrical compression test. The test sample is placed on a base table and compressed against a flat surface cylindrical probe, as shown in Figure 1 (CT3 Analyzer, Brookfield Engineering). The cylindrical probe surface, which is larger than the test sample, is moved down to crush the tablet at a constant speed, and the force applied to crush the tablet is measured. The load-force values obtained will depend on the construction and size of the tablet. A plot of force load (g) vs. time (s) as the test progresses is obtained (TexturePro CT software program, Brookfield Engineering). The highest point on the graph, peak load, is the load required by the analyzer to break the tablet. This point also indicates the tablet’s maximum strength before breaking. 

The fracture test is accomplished by driving a smaller hemispherical ball probe into the flat surface of a solid tablet (see Figure 2). A suitable probe deformation distance must be chosen to avoid base effect, which is the external influence of the substrate surface on which the tablet is placed. Base effect is caused by compression of a thin sample against the test bed of the analyzer instrument, which inadvertently renders incorrect results. A deformation distance of not more than 60% of the sample height is usually enough for the ball probe to fracture the tablet without causing base effect. The maximum strength of a tablet before breaking is the peak load on the graph plot. The recorded force applied to fracture the tablet is useful for determining mechanical properties, such as Young’s modulus and tensile strength. Young’s modulus, which is the ratio of stress over strain deformation (E = σ/ε), describes the stiffness and toughness of a material.

Another common fracture test on tablets is the snap or bending test. This test is common for an oval tablet shaped like a capsule (i.e., caplet) as well as on a fairly large round tablet. The test is performed with a three-point bend fixture; the tablet is supported at either end and deformed in its center with a knife-like probe, causing it to fracture and break at its weakest point. To ensure comparability of results, the tablet’s orientation in the fixture must be standardized, preferably in a manner that is most readily and easily reproduced by operators (e.g., align the score line of the tablet with the probe blade). The peak load indicates the tablet hardness; harder tablets will give a higher peak load. The distance to peak load is an indication of the elasticity of the test sample. Brittle samples (such as solid-dose tablets) will have a shorter distance or time at failure hardness compared to elastic samples.

These tablet hardness tests provide a meaningful picture as to the amount of force required to fracture the solid-dose tablet. This knowledge will be useful in gauging the tablet’s resistance to damage that might occur during production handling, packaging, and storage. Based on this testing, guidelines for acceptable hardness values can be established. The test is also useful for quantifying the internal bonding strength of powder, which will help to achieve compatibility of formulation with performance specifications. Tests can also be used to enhance the production evaluation of tablet consistency between different batches, shifts, and facilities.

P. N. Davis and J.M. Newton, “Mechanical strength” in 

Pharmaceutical Powder Compaction Technology

, G. Alderborn and C. Nystrom, Eds. (Marcel Dekker, New York, 1996), pp. 165–191.

J.M. Newton, G. Alderborn, and C. Nystrom, 

Eric Chiang is product manager for texture analyzers at Brookfield Engineering Laboratories, Middleboro, MA; tel: 1.800.628.8139; email: 

Troubleshooting

Crushing, fracturing, and bending tests quantify hardness.

Measuring Tablet Hardness: A Primer

At the INTERPHEX show last month in New York City, several conference sessions focused on quality by design (QbD). One of these was a panel discussion sponsored by 

, “Lessons Learned: Successes and Challenges in Implementing Quality by Design.” Panelists agreed that QbD approaches have proven to offer benefits to industry, although it was clear that there is more work to be done in implementing QbD.

Panelist Dr. John Lepore, senior director of Chemical Process Development and Commercialization for Global Pharmaceutical Commercialization at Merck, noted that a benefit of QbD is increased process understanding, which results in higher quality at a lower cost. He emphasized that QbD encompasses both customer needs and business requirements, because a science- and risk-based approach results in a high level of assurance that patient needs will be met. 

A second panel member, Dr. Chris Moreton, partner at FinnBrit Consulting, discussed how QbD methods can be used to incorporate excipient variability into a design of experiments. He explained that samples at the extremes of specification are most often not available and that there are other ways to attain the necessary understanding.  

Panelist Jonathon Thompson, senior manager of Compliance Services Consulting at Invensys Operations Management, discussed using process analytical technology (PAT) and inferential sensing (i.e., simple measures, such as pressure and temperature, correlated to parameters) to obtain real-time data. He also discussed using advanced process control (APC) of manufacturing processes. APC is a dynamic optimization of the process either via an open loop (i.e., engineers make a decision to adjust the process) or closed loop (i.e., the control system automatically makes changes directly to the process).  Dynamic optimization is a cultural change, noted Thompson, but has the potential to improve reliability and consistency and to reduce release time. 

Real-time release (RTR) is ready to be implemented and is, in fact, already being used, agreed the panelists.  Challenges for RTR include controlling risk (a factor to which regulators are particularly attuned) and managing analysis failures. Parallel testing early in manufacture can be used to verify RTR. 

Going forward, Lepore noted a need for improved global harmonization of regulatory expectations. Actions toward more consistent interpretation and application of International Conference for Harmonization (ICH) guidelines and greater collaboration involving industry and regulators would form important first steps. He also suggested that industry members need to share more real examples to continue to drive alignment and understanding. 

Other conference sessions at INTERPHEX did present examples of using QbD. Dr. Carl Anderson from Duquesne University, for example, presented an example of how cycle time was significantly improved using PAT. Richard Creekmore from AstraZeneca discussed improving process robustness and gave examples of risk assessments. 

Examples of applying QbD were also the focus of a recent webcast, "

A Pragmatic Application of QbD: Turning Theory into Tangible Success

 earlier this month with experts from Patheon.  The complimentary, on-demand webcast can be accessed 

Production Trends

Making the effort to apply new methods to pharmaceutical processing will bring benefits.

Experts at INTERPHEX Discuss Quality by Design

Romaco
     Filling machines are designed for bottling pharmaceutical liquids

L.B. Bohle
 High-efficiency dry granulator enables high-production capacity

Equipment and Processing Report-05-15-2013

INTERPHEX Highlights Serialization

Measuring Tablet Hardness: A Primer

Experts at INTERPHEX Discuss Quality by Design

May 2013 Editor's Picks: Products from Romaco and L.B. Bohle