Radio frequency identification (RFID) technology is finding applications beyond serialization and anticounterfeiting protection to improve supply chain management and benefit caregivers and patients, particularly patients with disabilities. Broader deployment in the healthcare industry will help propel the global RFID tag market to a compound annual growth rate of about 10% to reach $29.4 billion in 2030, according to a study by Transparency Market Research (1).

For the caregiver side, Fresenius Kabi has added RFID-tag-equipped labels on medications commonly used in operating rooms. The company’s +RFID portfolio launches with products in prefilled syringes and vials. John Ducker, president and CEO of Fresenius Kabi USA, explained, “Inventory management is a high priority for hospitals, especially in the current environment. This combination of smart technology with the comprehensive range of our anesthesia and analgesia portfolio is designed to answer our customers’ call to make it easier to assure that the right products are in the right places at the right time (2).”

Based on GS1 global standards for RFID, the tag contains all the data that hospitals use to identify, locate, and manage inventory. The technology also enables item-level serialization and enhances patient safety. Adherence to GS1 standards ensures full interoperability and compatibility. “Our customers will now be able to get RFID smart-labeled medications directly from a manufacturer,” noted Gordon Krass, CEO of IntelliGuard, one of the first pharmacy automation vendors to read and manage +RFID medications (2).

United Kingdom-based Elucid Digital Health has developed a smart cap dispenser based on its Pill Connect bottle. “We believe that reducing the pill dispensing mechanism from a bottle to a cap means that any pharma [manufacturer] can now use the Pill Connect system without having to make changes to … existing production lines,” said James Burnstone, CEO of Elucid Digital Health (3).

Under consideration for clinical trials and high-value medicines, the screw-on dispenser cap encourages compliance, messages patients, records ambient temperature and humidity, provides real-time reports for doctors or monitors, and maintains a comprehensive adherence record. The cap also can be made to fit any bottle and adjusts to any tablet/capsule size. A mobile phone app prompts the patient to take a dose. If dose dispensing doesn’t occur, an automated text or call can generate an immediate intervention. Patients can also respond through the app about why they are skipping a dose. If the patient’s phone is unavailable or not charged, the cap can be unscrewed manually to dispense a dose. When the phone becomes available, a message is sent to update the dosing record. A clock-based lock prevents double dosing (3). 

For visually impaired consumers, CVS Pharmacy has introduced Spoken Rx, a feature in the CVS Pharmacy app that makes it possible for a smartphone to read aloud an RFID-tagged prescription label including patient name, medication name, dosage, and directions. “The in-app feature gives patients more flexibility, providing the pertinent prescription information out loud wherever and whenever they need it,” said Ryan Rumbarger, senior vice-president, Store Operations at CVS Health. Hearing this information in English or Spanish enhances safety, adherence, and independence for visually impaired patients. The number of CVS Pharmacy locations capable of offering the RFID labels will ramp up from 1500 at the end of 2020 and is expected to reach all locations by the end of 2021. Developed in collaboration with the American Council of the Blind, the Spoken Rx capability is said to be the first in-app prescription reader available from a national retail pharmacy. Enrollment can be completed via smartphone or in-store and is free (4). 

Transparency Market Research, “RFID Tags Market,” 

www.transparencymarketresearch.com/rfid-tags-market.html

Fresenius Kabi, “Fresenius Kabi Introduces RFID Smart Labels for a Range of Essential Medications,” Press Release, August 18, 2020.

Elucid Digital Health, “Smart Pill Bottle Becomes One-Size-Fits-All Dispenser Cap,” Press Release, May 21, 2020.

CVS Health, “CVS Pharmacy Introduces New App Feature for Reading ‘Talking’ Prescription Labels,” Press Release, July 8, 2020.

Articles

Broader application of RFID in pharmaceutical packaging benefits caregivers and patients. 

Pharma Packaging Employs RFID Technology in Labels and Caps

As the industry gears up for the expectation of high demand for COVID-19 vaccine containers, suppliers of traditional glass vials are increasing capacity, and suppliers of alternative primary packaging materials are offering potential solutions as well. Honeywell recently introduced its Aclar Edge polymer bottles and vials for pharmaceutical packaging that are made from polychlorotrifluoroethylene (PCTFE). The compay says the containers can eliminate the risk of breakage found with glass containers; the containers are also 75% lighter than their glass counterparts, which reduces transportation costs (1). The containers meet the requirements of the compendia pharmacopeia for extractables, elemental impurities, and biological reactivity and are classified as Medical Grade Class VI, says Kori Anderson, general manager for Honeywell Healthcare Packaging

 spoke with Anderson about designing containers for vaccines.

 What are the key requirements for vaccine containers?

 Vaccine packaging must ensure suitability, safety, protection, compatibility, and performance. The primary package must be tested and validated to ensure container closure integrity, sterility, drug stability, and manufacturing feasibility. Materials of construction need to demonstrate low to no levels of detectable extractables, leachables, particulates, bacterial endotoxins, impurities, degradation products, volatile and involatile organics, and free ions to avoid adverse interaction that may react with the drug product and render the product unstable or ineffective. Materials of construction must not create changes in pH of the drug product and must meet stringent biocompatibility safety standards through appropriate compendia testing.

Vaccine vials must establish and maintain appropriate moisture and oxygen barrier levels to ensure against drug product degradation or loss of potency or efficacy. Since many vials are stored and transported in cold-chain environments, the vials must be tested in accordance with the recommended storage and transportation environmental conditions to ensure container closure integrity, stability, and functional performance are maintained throughout the distribution lifecycle of the product. Distribution testing should be mapped to include temperature excursions to demonstrate the robustness of the packaging system to maintain drug stability and container closure integrity. Vials must not exhibit any surface characteristics that may cause the proteins or other active ingredients to bind to the walls of the container. They need to exhibit a high level of clarity in order to permit inspection the product for visible particulates and cross-contamination.

 What do you see as the key challenges for distributing vaccines on a global scale?

 There are many variables that need to be addressed, including general shipping and freight issues with temperature control to ensure the stability and efficacy of vaccines. The sheer numbers for the COVID-19 vaccine could stress the supply chain to the max. It’s important for pharmaceutical companies to develop a back-up plan. We see Aclar Edge as a solution to alleviate those constraints.

 What are the requirements for filling equipment and automated inspection equipment using this container type?

 Vials must be evaluated for manufacturing feasibility and demonstrate resilient performance with high-speed packaging lines. Vials must demonstrate robust mechanical and physical strength to avoid jamming and impact damage during unpacking, collating, conveying, filling, capping, labeling, shipping, and distribution. PCTFE vials exhibit excellent physical properties, which prevent breakage during filling and capping as well as during transportation testing.

Automated inspecting equipment differs based on several factors, but any equipment that is compatible with plastic containers should also be compatible with Aclar Edge. Since the exterior is PET [polyethylene terephthalate], any labels used on PET bottles should work well with Aclar Edge bottles and vials. We have not performed testing specifically for automated inspecting equipment for Aclar Edge, but the containers have been run by one of our lead customers working on glass alternatives, with no major issues on their commercial lines.

Polymeric containers offer an alternative to glass.

Considering Materials for Vaccine Containers

Rapid changeover of biologic production processes carries numerous challenges. Challenges to rapid changeover come from many sources, including the equipment, room configuration, documentation, people, and environmental monitoring, according to Sebastien Ribault, head of end-to-end solutions at MilliporeSigma.

The traditional method of completely stripping down all equipment and installing dedicated materials and components for each product has proven to be a cumbersome and costly process for multiproduct facilities, adds Piergiuseppe Nestola, senior platform technology consultant at Sartorius. “It is not unusual for changeover to require weeks to complete when traditional methods are followed. With the changing industry tide favoring multiproduct manufacturing facilities, methods to enhance efficiency without sacrificing quality or safety are needed,” he says.

Several activities must be performed in a facility to avoid any risk of cross-contamination between Product A and Product B, in particular via a thorough cleaning-in-place of all equipment surfaces in contact with intermediates and the end product, Thibaud Stoll, global head of commercial biologics operations at Lonza, specifies.

For certain biologics, most notably viral vectors, vaccines based on live viruses, and spore-formers, precautions must be taken to prevent spread through the air and more extensive cleaning protocols are generally required, typically with airborne peroxide methodology, says Katarina Stenklo, enterprise solutions commercial activation leader with Cytiva. Any live biological agents, whether they be the host organisms or adventitious agents, must be effectively removed/inactivated from HVAC, facility, and equipment surfaces (both exterior and product paths) prior to introduction of a subsequent product, adds Syed T. Husain, senior vice president and CDMO business unit head at Emergent BioSolutions.

Stainless-steel equipment specifically presents a common challenge, as it requires cleaning and validation of product contact surfaces before the equipment can be used for a subsequent project, according to Evan Shave, director of biomanufacturing—global network operations for Thermo Fisher Scientific. Cleaning and sterilization of stainless-steel equipment is well understood, but often “overdone” in terms of cleaning and rinse times, mostly due to conservatism or a lack of time to properly optimize the process, adds John Machulski, vice president of engineering for Catalent Biologics.

Changeover of processes performed in a ballroom setting can be even more difficult than for processes run in individual suites due to the added risk of cross-contamination with other processes on top of concerns regarding product carryover, notes Steve Gravallese, enterprise solutions program director at Cytiva.

Stoll adds that some product-dedicated equipment must also be installed, in particular chromatography columns with packed resin for drug substance purification. “All these activities may potentially be quite long and on the critical path if not optimized and sequenced properly, and if the facility layout has not been designed accordingly,” Stoll states.

For drug product manufacturing, it is critical to have a lean process design due to its highly kinetic nature, according to Machulski. “Although barrier isolation technology provides the highest level of aseptic processing, long bio-decontamination cycle times remain one of the biggest challenges for achieving a rapid changeover,” he says. Stoll also notes that given the completely different types of equipment, changeover times are difficult to compare. “A change in vial format may require some significant setup activities for a filling line; the number of such changes can be optimized via the proper yearly planning and sequencing of campaigns,” he observes.

Strategies for optimization of process changeovers differ because the equipment and room configurations for each process are different, but all are driven by the same constraints and rational, according to Ribault. “A combination of primary (process design), secondary (facility design and operation), and procedural controls and studies should be used,” states Husain.

Stoll identifies three key approaches to optimizing changeover activities: making them as short as possible, performing them during “hidden time” or in parallel, and reducing the number of changeovers by running longer campaigns. “Operational excellence/lean methodologies can be quite powerful for optimizing changeover processes, as can the use of redundant equipment or dedicating packing rooms for chromatography columns. In the latter case, there is additional capital expense, but it is usually a good investment,” he says. Running longer campaigns, though, carries a trade-off with the optimization of product inventory.

The ultimate goal, according to Gravallese, is optimizing the facility around unit operations so they can be segregated where open processing cannot be avoided and staggered changeovers are possible. “It really comes down to identifying the best methodologies and designs to stagger processes in facilities without impacting operations in the balance of the site,” he states.

Properly optimizing cleaning and sterilization cycles where stainless-steel equipment is used, validating procedures, having a well-trained staff, and having a robust yet simplified supply chain are keys to facilitating rapid changeovers, according to Machulski. “Additionally, ready-to-use primary and secondary components can be helpful, along with automation and robotic technology for drug product fill/finish manufacturing,” he says.

Ribault also asserts that it is important to look across the entire value chain and consider how to ensure the interface between process development and manufacturing works well; another consideration is to put together a team that will make the project a success in record time. “You do these things by having templates in place for process development and manufacturing that reduce the transition time. So, while rapid changeover is certainly an integral aspect of operations, it is important to keep in mind that it is one piece within the entire value chain,” he says.

In addition, a quality risk management approach may be applied to assess and continuously improve established changeover processes, according to Nestola. “All processes, including changeovers, can be improved with investment of money and resources, parallel activities, equipment design improvements, and standardization,” he asserts.

Cynthia Challener is a contributing editor to 

Equipment and facility cleaning is crucial, with more extensive protocols needed for some biologics.

PharmTech Equipment and Processing Report eNewsletter 09-16-20

Pharma Packaging Employs RFID Technology in Labels and Caps

Considering Materials for Vaccine Containers

Considering Changeovers in Multiproduct Biologics Manufacturing Facilities