OR WAIT null SECS
New products for sterile filling, quality control, and anticounterfeiting measures gained notice.
Attendees and exhibitors seemed happy to return to Philadelphia for the annual INTERPHEX trade show Mar. 26–28, 2008, after a three-year run in New York City. Traffic in the aisles was steady, and exhibitors reported high-quality leads.
Attendees looking for packaging innovations found something in every aisle. All facets of packaging were represented, from the beginning to the end of the line. Special emphasis was placed on sterile filling, barrier materials, quality control, and anticounterfeiting measures. Although the California e-pedigree deadline was postponed from Jan. 1, 2009, to Jan. 1, 2011 immediately before the show opened, pedigree solutions were also well represented and will be discussed in detail in August's Packaging Forum.
Integrating closure treatment with an isolator-equipped filling system simplifies delivery of sterile stoppers to the sterile filling line. After stoppers are treated, an elevator lifts the closed vessel in place to dock it with the isolator. A rapid transfer port ensures a sterile connection. Programmable logic control and an identifying chip hard-wired in the vessel track stoppers to ensure they are ready for use and are correct for the product. The lift, which is constructed entirely of stainless steel and specially sealed, is cleanroom compatible and handles 30–300-L vessels (stopper processing, vessels, transfer station, and "Atec Lifting Device," Atec Pharmatechnik, Sörup, Germany).
Tetra Images/Getty Images
Low energy electron-beam (e-beam) technology used in the food industry for surface decontamination also can sterilize the outside of syringe tubs before they enter an isolator. The e-beam system eliminates the use of hydrogen-peroxide vapor, links directly to the isolator, and handles as many as six tubs per minute. Three such systems have been installed, one each in Switzerland, Italy, and the United States ("E-Beam Tunnel," Metall+Plastic, Radolfzell-Stahringen, Germany).
Operators working through glove ports can be the limiting factor on sterile filling lines. Sanofi-Aventis (Paris) has boosted line productivity 100% by installing a six-axis robot on a syringe-filling line at its vaccine plant in Le Trait, France. The robot also reduces operator exposure to toxic products and repetitive-motion injuries. The ISO Cleanroom Class 4 (Class 10 under US Federal Standard 209E) robot features a smooth surface coating, lip seals at joints, internal lines and connections, and a round, smooth base. It also withstands hydrogen-peroxide vapor sterilization ("Stericlean TX60" robot, StÃ¤ubli, Duncan, SC).
The "Stericlean TX60" cleanroom robot from StÃ¤ubli withstands hydrogen-peroxide vapor sterilization.
Because cleaning packaging lines is time-consuming and companies must protect operators from exposure to toxic chemicals, interest is growing in disposable product-contact parts. Commonly used on the processing side in the biotechnology industry, disposable product-contact parts on vial-, ampul-, and syringe-filling lines can eliminate hours of cleaning and validation work while increasing line flexibility and uptime. A single-use product path also cuts changeover time and utility and cleaning-agent consumption while minimizing wastewater generation, cross-contamination, and the capital investment in stainless steel parts.
The first prevalidated, preassembled, and gamma-sterilized system consists of positive-displacement rolling diaphragm pumps, needles, and other product-contact parts. The system meets US Pharmacopeia standards. Accompanying documentation certifies sterility, extractables and leachables levels, and the shelf life of the product-contact parts, which come double-bagged and ready to install with sterile plug-and-use connections. Used parts are generally incinerated ("Prevas Disposable Dosing System," Bosch Packaging Technology, Minneapolis, MN).
The "Prevas Disposable Dosing System" from Bosch Packaging Technology.
Cyclo olefin polymer (COP), a material relatively new to pharmaceutical packaging, is capturing companies' interest because it it is less brittle and more moldable than a related resin, cyclic olefin copolymer, which is used to make syringes. COP can also be used to make vials, bottles, and push-through blister packaging. COP exhibits high transparency, low interaction from protein adsorption, low water-vapor transmission rate, and low residual-metals content. Diluent in COP containers is less likely to experience a pH shift than is diluent in glass and other materials. COP also is compatible with steam, ethylene oxide, and gamma sterilization ("Zeonex" COP, Zeon Chemicals, Louisville, KY).
A four-ply laminate for cold-formed blister packaging combines the light and moisture barrier of foil with enhanced dent resistance and draw depth. The laminate contains 60 μm of polyvinyl chloride (PVC), 25 μm of nylon, 45 μm of foil, and 60 μm of PVC. Polyurethane laminating adhesive ensures that the layers resist delamination. To meet branding, tamper-evidence, and compliance needs, the outer layer of PVC can be reverse printed in as many as 10 colors on a rotogravure press ("Cold Form 4000" foil laminate, Reynolds Packaging Group, Richmond, VA).
"Zeonex" cyclo olefin polymer resin from Zeon Chemicals is suitable for syringes and other types of pharmaceutical packaging.
Another foil laminate makes chevron and four-side-seal pouches that peel cleanly yet provide maximum product protection ("Sure-Peel" pouch laminate, Reynolds).
Expanded capacity for polychlorotrifluoroethylene film helps meet growing demand from pharmaceutical packagers for barrier film. The clear film supports compliance initiatives because it shows whether a dose has been taken ("Aclar" film, Honeywell Specialty Films, Morristown, NJ). To help design optimum blister structures, enhanced analysis software helps compute the total cost of candidate materials. Software also can help fine tune designs and line speeds to minimize material consumption and maximize line output (thermoformed packaging analysis, Honeywell).
Quality control begins with package design, and it can be difficult to manually track all the changes that occur between concept and printing. A web-based artwork-management system, used by Merck & Co. (Whitehouse Station, NJ) in Europe and Mylan Pharmaceuticals (Morgantown, WV), automates this process for generic pharmaceuticals. The system complies with 21 CFR Part 11, provides a complete record of changes, and prevents errors. The software gives drugmakers control over the artwork at all times and provides access to authorized parties such as printers and contract packagers. Because sign-off occurs online, the system is particularly suitable for multisite operations and eliminates the expense and time involved in sending documents by courier ("GL-AMS Global Artwork Management System," Precise Data, Dublin, Ireland).
Another full-range system combines software and vision technology to automate proofreading, prepress doublechecks, color matching and counterfeit detection. Applications include regulatory affairs, clinical-trial labeling, packaging development, document development and prepress, customer and vendor proofing, print-plate inspection, production-document inspection and incoming inspection. Text-verification software identifies deviations between combinations of electronic files and physical output, including proofs, bluelines, plates, inserts, and labels. The personal computer-based system locates, marks, ranks, and tabulates disparities greater than a specified size and contrast. Because the operator only has to check deviations instead of performing a complete visual inspection, efficiency increases nearly 100% ("Avia Proofreading," "Avia Prepress," "Avia Color Matching," and "Avia Private Eye" anticounterfeiting modules, Mnemonics, Mt. Laurel, NJ).
The European Union requires Braille writing on pharmaceutical packaging, and quality-control companies are working on automated contact and noncontact methods to verify the presence and correctness of these codes. Because dot height is critical to legibility, the law requires dots to be 0.02 mm high. One system that uses a contact method to check dot presence, location, and accuracy relies on a pen-like micrometer to measure and verify dot height. The system complies with 21 CFR Part 11 and includes a validation package that features installation-qualification, operational-qualification, and performance-qualification documentation ("Braille Suite," including "Digital-Page" with "Scan-TVS," "Docu-Proof," and "BraillePoint" modules, Global Vision, Montréal).
A nondestructive leak detector for empty or full vials and syringes reportedly exceeds the performance of the standard dye microbial-ingress test because it pinpoints multiple flaws smaller than 1 μm. To identify integrity problems, the vacuum-based system detects vapor or gas release at levels as low as 0.1 μL. The tester currently checks one syringe in a 10-s cycle, but a model that can handle multiple syringes is being built ("VeriPac 325/LV" leak tester, Packaging Technologies and Inspection, Tuckahoe, NY).
Counterfeit drugs are a continuing problem, and they are rampant in some parts of the world. As counterfeiters become more sophisticated, new measures are needed to stymie them.
High-precision laser technology permanently marks foil with fine-line graphics, text, logos, or other microimages during the rolling process. Marked foil is virtually impossible to duplicate and can be made in almost any gauge or alloy. It also converts, lacquers, laminates, coats, prints, and slits like standard foil ("CPI Security Foil," Constantia Hueck Foils, Wall, NJ).
Another high-tech solution creates a digital fingerprint of the packaging for later reference by capturing an image of a specific area at speeds as fast as 15 items/s. The digital image can be stored in a database, converted to a numerical code, and printed as a two-dimensional barcode to serve as the unique item-level identifier required for pedigree records. Authentication is possible at any point in the supply chain using a handheld reader–verifier ("Biometric Authentication," Cortegra Group, Parsippany, NJ).
Cortegra's "Biometric Authentication" transforms information embedded in the structure of a package into a digital signature more distinctive than a fingerprint.
Nanomolecular particles incorporated into paper, adhesive, ink, or other packaging material offer counterfeit protection at a cost of fractions of a cent. The tiny particles function as a synthetic DNA and can be detected and read by a proprietary scanner to authenticate products instantly ("Nano-molecular Forensic Marking System," ATL Security Label Systems, Menomonee Falls, WI).
Med-Health Pharma (Las Vegas, NV), a drug repackager that provides medication in 10- to 30-count packaging for dispensing in physicians' offices, recently began using packaging with invisible markers to prevent counterfeiting and fraud. "Authentication is very important for our industry, and this solution allows us to aggressively confront the issue of counterfeit products that risk innocent lives," says Sam Haddad, vice-president of operations at Med-Health Pharma.
Low levels of tiny mineral markers can be added to virtually any packaging component or material. The markers can be incorporated into ink, toner, varnish, paper pulp, plastic, adhesives, and metals. Detection and authentication are accomplished with a special reader tuned to the mineral and particle level. The marker and reader can provide various levels of security, including basic pass–fail authentication, and can capture and verify a particle image ("Traceless System," Kodak Security Solutions, Eastman Kodak Rochester, NY).
Security labels, tapes, bags, seals, and pallet-protection devices from a cargo-crime specialist protect unattended assets. Multiple technologies such as microprinting, special adhesives, and sequential numbering provide a layered solution. Security-tape options include silicone coating with a reverse-printed sequential number every 9 in. to prevent undetected removal and replacement of the tape. A numbered clip that crimps on at the intersection of two bands of pallet strapping incorporates a similar approach (tamper-evident labels and tapes, "Topp-Clip" pallet protection, CGM Applied Security Technologies, Farmingdale, NJ).
Another company that advocates a layered approach to product security offers overt, covert, forensic, and track-and-trace technologies such as fine-line printing, color-shift coatings, holograms, infrared-and ultraviolet-detectable taggants, and fluorescence ("N'Crypt" overt and covert printed security features, other security features, Alcan Global Pharmaceutical Packaging, Kirkland, Canada).
A permeable, flexible, spunbonded polyolefin allows users to pack more desiccant in less space than is possible with the traditional rigid plastic desiccant canister. The flexible container is printed with the message "Do Not Eat" in several languages. The unit was created from a single web of material in a patent-pending form–fill–seal process. It maintains the same diameter as the rigid canister and handles the same way on high-speed dispensing equipment. Because the flexible canister is shorter, it occupies less space and represents a weight savings of about 50%. The cost of the form–fill–seal design is comparable with that of a rigid canister. The flexible design eliminates the dusting and lost caps that sometimes affect a rigid canister. Desiccant options include silica gel, clay, and a 50/50 silica gel–clay blend in 1–3-g sizes. All components are classified acceptable for food contact under 21 CFR ("CanPack" desiccant canister, Aridien, Belen, NM).
A fifth-panel carton design involves applying the product insert to the inside of the panel during the carton-conversion process, thus eliminating the need to apply it on the packaging line. Once the carton is erected, the scored panel seals the insert in place. A die-cut window displays the barcode on the insert for quick identification ("Insert 2.0," Pharmagraphics, Greensboro, NC).
Hallie Forcinio is Pharmaceutical Technology's Packaging Forum editor, 4708 Morningside Drive, Cleveland, OH 44109, tel. 216.351.5824, fax 216.351.5684, email@example.com