Medical Device Link.

Originally Published PMPN March 2003

Bar Coding Supplement

Even though FDA's bar coding rule is pending, packaging professionals and their suppliers are preparing themselves for stringent requirements

Micron PharmaWorks is developing a  system using multiple readers to scan in-line RSS codes on unit-dose blister webs.

Some may call it the calm before the storm. Pharmaceutical manufacturers and packagers are awaiting FDA’s proposed bar coding rule, announced in December 2001, which may require all pharmaceuticals and biologicals to carry bar codes, down to the unit-of-use or unit-dose level. At the time, the agency wrote that it would require the National Drug Code (NDC), and may require the expiration date and lot number, to be encoded on each drug for automatic identification. 

Some pharmaceutical manufacturers and their packaging and printing vendors aren’t waiting for FDA to make up its mind. Pfizer, Abbott Laboratories, B. Braun, and Baxter Healthcare have all announced new bar codes for their pharmaceuticals used widely in hospitals, and other drug manufacturers are quietly testing their own bar coding solutions. And printing and blister equipment suppliers are readying their units with help from providers of bar code software, print-quality verifiers, and scanners. 

But the feats of these companies are more than interesting success stories. Their efforts have revealed some of the challenges to unit-dose bar coding, such as bar code symbology and data structure selection, high-resolution in-line printing, and symbol-print-quality verification. Their solutions may help establish practices that eventually reduce medical administration errors.

INTENT

FDA has sought much input from both product manufacturers and users on its proposal, holding a public meeting in July 2002 and soliciting written comments. To date, though, the agency has given little hint as to what it has made of those comments. When contacted for this article, the agency explained that it is not answering any questions about the rule until it is issued. 

FDA has, though, reiterated its position that bar coding pharmaceuticals and biologics can reduce errors in healthcare facilities, like hospitals and hospital pharmacies. FDA Commissioner Mark B. McClellan spoke about the agency’s goal of preventing adverse events and reducing medical and medication errors at UBS Warburg’s Global Healthcare Services Conference in New York City in February. He sees the upcoming bar coding regulation as part of this effort. “It will help prevent errors, reduce the cost of storing drugs, and increase their safety and reliability,” he said. He said the agency’s rule would cover drugs and biologics, but he did not say anything about medical devices.

Mary Gross from FDA’s Office of Drug Safety, Center for Drug Evaluation and Research, will be speaking about the status of the rule at an upcoming conference on bar coding in Washington, DC. The event, “Bar Code Implementation Strategies,” will be held March 27–28 and is sponsored by the Institute for International Research (www.iirusa.com/barcode). 

And FDA may soon have the legal authority to enforce unit-dose bar coding. On February 14, The House Energy and Commerce Committee approved legislation that would require pharmaceutical manufacturers to include bar codes on drug packages. HR 663, sponsored by Representative Michael Bilirakis (R–FL), is aimed at reducing administration errors at hospitals and pharmacies and would authorize FDA to implement its rule. 

SYMBOLOGY AND DATA STRUCTURE CONCERNS

Pfizer and Abbott have both publicized their selection of Reduced Space Symbology (RSS) from the Uniform Code Council Inc. (UCC). In January 2003, Pfizer announced that by the end of the year, all 30 of its hospital unit-dose products will bear bar codes encoding NDC, lot number, and expiration date in RSS/Composite Symbology. UCC’s director of healthcare John Roberts reports that Abbott has about 90% of certain product lines coded with RSS, and he says that another six or so firms are now piloting RSS or RSS/Composite codes. 

George Wright IV says that RSS/Composite is becoming the de facto standard. Vice president of Product Identification & Processing Systems Inc. (PIPS; New York City), Wright says that RSS/Composite was developed by UCC as “a technically robust, compact linear-scannable symbology compatible with its fundamental EAN/UCC 14-digit Global Trade Item Number (GTIN) coding structure.” That structure incorporates the NDC (or a Universal Product Code [UPC] for nondrug products), a one-digit packaging-level indicator, a one-digit check-level digit, and pad or flag digits as specified by the standard. 

“RSS works for the pharmaceutical industry precisely because it encodes the EAN/UCC 14-digit GTIN on unit-dose packages with limited real estate, like hospital unit-dose [HUD] blister packaging, and its Composite code can be used for encoding lot codes and expiration dates,” adds 

Rich Davis, president of Quint Co. (Philadelphia), a manufacturer of printing plates. 

Code 128 has been used successfully on HUDs by companies like Merck and UDL Laboratories to encode NDCs. In such applications, the Code 128 symbol encodes data in a 12-digit UCC-12 UPC format but not in the UPC symbology. 

But since this coding structure does not include the packaging-level indicator, using it to identify unit-dose packages may no longer be appropriate. The code identifying a multipack carton would be the same as the code identifying a single dose for those drugs that do not have a separate NDC assigned to the unit-dose level. 

And Davis says that one of the most important things to keep in mind when determining the content of a bar code’s data structure is that each packaging level must be assigned its own unique identification number. “There seems to be some confusion, or it may be that some are just not aware of this fact. The GTIN data structure and the RSS bar code address this issue.” 

The Code 128 format reserved for worldwide EAN/UCC system use, called UCC/EAN-128, does include the packaging-level indicator digit and can encode lot codes and expiration dates should FDA require them, but the expanded symbol is almost always too long to fit on most if not all HUDs, says Davis. 

For Rich Hollander, senior director of packaging services for Pfizer, RSS’s selling points are that it encodes the GTIN (including the packaging-level indicator) and that its Composite component encodes the lot and expiration date, all in a relatively small amount of real estate that can be read by conventional laser scanners and that does not require imaging systems. “Encoding the packaging level in the GTIN negates the need to assign a new NDC to the unit-dose package. Further, using the GTIN at the unit-of-use level and eventually at other packaging levels will enable manufacturers, wholesalers, and retailers to have a common way to view inventory. ”

Some drug companies, though, have obtained or are considering obtaining new or multiple NDCs from FDA to represent the unit-dose versions of their drugs. Merck currently uses the last two digits of the NDC to indicate packaging size. In this scenario, companies need to notify FDA of changes to the NDCs and keep track of multiple NDCs for one drug. 

Robert A. Hankin, president and CEO of the Health Industry Business Communications Council (HIBCC), the organization responsible for developing the Health Industry Bar Code (HIBC) Supplier Labeling and Provider Application Standards, believes that government regulations for labeling of pharmaceuticals down to the unit-of-use level may eventually carry over into medical and surgical supplies. “There are very clear benefits that can be derived from precise identification of individual items,” he says. “Patient safety is obviously the primary concern, but cost containment is another serious topic when discussing healthcare reform. Specific billing of actual items used can be a key enabler in managing rising healthcare costs.”

The HIBC Supplier Labeling Standard has recently been revised to update specifications for small-package labeling. HIBCC believes that for items with minimal real estate, like unit-of-use packages, symbologies such as PDF-417 and Data Matrix are preferred. Hankin notes that the imaging technology used to read symbols like Data Matrix are broader in their applicability to multiple clinical tasks, such as reading and recording signatures, text, and faces and are now reaching the market cost-effectively.

Wright calls Data Matrix a “reliable, well-established 2-D code that has been proven appropriate in other applications.” But, he notes, “It has not yet been formally adopted for use in any healthcare bar coding standard, although the proposed revision to the HIBC Supplier Labeling Standard would codify its use for manufacturers that follow this standard. They tend to be medical/surgical device manufacturers, however, not drug companies.”

Wright hopes that EAN/UCC will eventually adopt Data Matrix as a data carrier for GTIN marking in circumstances where RSS/Composite codes are too large for the available space. “Data Matrix complements RSS/Composite symbology. But the choice of a data carrier is secondary to the choice of a data structure. FDA must not only mandate the data content for bar coding unit doses (NDC, lot and expiration date), but must also specify the data format in which these elements are to be encoded. Otherwise, clinical software and materials management systems will have no idea how to handle the data stream coming from the scanner. Without such specificity in an FDA mandate, the healthcare supply chain will be thrown into utter disarray, with some companies putting the NDC followed by the lot and then expiration and others putting the data in some other order or format.”

At a minimum, Wright says that FDA should mandate the EAN/UCC coding structure, starting with the 14-digit GTIN format to encode the NDC for unit-dose bar coding on pharmaceuticals. “The U.S. pharmaceutical industry has adhered to this EAN/UCC standard since the early 1970s when, in a cooperative effort between UCC and FDA, the NDC was first embedded within the UPC data structure. Moreover, the EAN/UCC system clearly codifies the format for additional data, including lot and expiration date.” 

Hospital unit-dose symbology comparison chart courtesy Quint Co.

For very small packages or in cases like vaccines where even more data may be needed, Wright believes the global EAN/UCC system should adopt Data Matrix as a data carrier with a sunrise date of 3 to 5 years in the future. “This would serve as notice to the supply chain that at a certain point in time, the use of 2-D imaging scanners would be required in certain applications, like medication administration,” Wright continues. “Without this guidance, hospitals and clinics will purchase less-expensive laser and linear CCD scanners and then find that 2-D codes that cannot be scanned with these tools are in the supply chain, and no one told them they were coming.”

According to UCC’s Roberts, a drug firm has already requested that EAN/UCC adopt Data Matrix. 

PRINTING

When FDA announced its forthcoming unit-dose bar coding rule 15 months ago, several drug packagers bristled at the idea. Many doubted that such codes could be produced in-line at typical blister line speeds. They also wondered how to maintain registration when printing human-readable information and bar codes in small areas. Finally, they worried that if they decided to use a new code, like Data Matrix or RSS/Composite, they would need new equipment and tooling. 

In Pfizer’s case, Hollander and his team were able to apply RSS/Composite codes without significant investments in new printing equipment. Before going into commercial production, Pfizer performed extensive trials off-line at Adolph Gottscho’s Union, NJ facility, since Gottscho’s flexographic platen printer was widely used on Pfizer’s packaging lines for hospital unit-dose blisters. Pfizer also worked closely with Quint’s Davis to evaluate many different printing options for the RSS/Composite codes. Once these trials were complete, Hollander says the team then performed trials at each of its three sites in Puerto Rico that package these blisters. “The challenge was not in the technology used in printing but in learning how to use the available technology better. We needed to better understand the type of substrate we were printing onto, the inks used, the mat material, roller type, bar width reductions, and many other parameters to ensure that we had ANSI grades of C or better when verifying the codes on each blister.

“Further, once we concluded that the RSS/Composite code was the symbology to use to achieve our goal of encoding GTIN (NDC), lot number, and expiration date, we wanted to minimize time to begin doing this commercially. This meant we would need to do so with our existing blister card sizes to mitigate the need for purchasing new tooling, which is not only relatively costly, but has a significant lead time. In the end, we were able to meet these challenges. In doing so, we were also able to ensure that our line throughputs were not affected due to the production losses associated with larger blister cards.” 

As far as machine speed is concerned, John Soporowski of Annuity Packaging Systems says that in-line printing “really has no effect on cycle rates. Modern printing systems are quite capable of producing extremely high-quality print on either continuous- or intermittent-motion thermoformers. Registration of the printed web is simple on an intermittent thermoformer, as most printers print in the dwell cycle of the machine, so registration is always correct.”

Jim Umbdenstock of Griffin-Rutgers Inc. (Ronkonkoma, NY) adds that many printers can control the movement of a web. Marketing Metronic rotary flexo printers, he points to the ability of these printers to speed up or slow down a web for printing as needed.
Soporowski adds that Greydon (York, PA) offers the Servo Max flexographic printer, which automatically phases the print cylinder in relation to the index length of the machine. “This printer can be used on either continuous or intermittent machines without any further modification.”

Other printing technologies can be used to print variable bar codes, says Hollander, like thermal-transfer printing, ink-jet printing, and even steered-beam laser etching. “The technology is available for these codes today. Companies will need to invest in the equipment, qualify their equipment properly, and begin printing,” he says. “It should not be overlooked, however, that some of the technologies that are available today are different from what is presently used on pharmaceutical packaging lines, since they were not configured for variable bar codes. This may slow overall progress in this area, but as new equipment is required, its ability to reliably print variable bar codes will be a key requirement.”

SUPPLIER OFFERINGS

Umbdenstock of Griffin-Rutgers says that when it comes to printing unit-dose packages, flexography is the best. “Gutenberg got it right—applying ink to a plate that applies it to a substrate is still the best way to print—it gives you the best quality.” Umbdenstock says that systems that use UV curable inks result in the best bar codes, because the ink formulation is laid on and cured by a UV lamp. “Solvent- and water-based inks need part of the formulation to evaporate or to be absorbed by the substrate, so the ink that is laid down isn’t always what you get.” In addition, over the course of a printing run, black ink can fade to shades of gray due to evaporation and replenishment issues.

Greydon also sells the Micromax printer, a rotary flexo printer that president Greg Rochon says doesn’t need as much ink and pressure as a platen flexo. Greydon is currently helping a pharmaceutical firm in Puerto Rico evaluate the printer for producing RSS/Composite codes on paper-backed blister foil. The operation is producing 10–12 blister packages at a time on a Klöckner CP-3. “The firm has a local printing plate maker provide new plates daily for printing lot numbers and expiry dates,” he says. 

In case companies don’t want to pay for new plates daily for new lots, Greydon is negotiating with a couple of other companies in order to provide a system that can produce plates in-house. “Such a system will make flexography programmable,” he says.

Flexographic printers by definition, though, are not programmable, nor what Umbdenstock calls “intelligent.” For that, he says, you may want to consider digital printers, like Hapa digital printers. These programmable printers can generate new codes on demand and print in resolutions up to 600 dpi at 19.2 meters/min. Romaco (Pompton Plains, NJ) offers them for in-line printing of RSS on blister lines. 

Uhlmann Packaging Systems LP (Towaco, NJ) is also offering digital printers for its blister thermoforming lines, explains Christopher Anderson, aftermarket sales engineer for Uhlmann’s vision inspection and printing solutions. “Our solution for printing RSS and Data Matrix is VisioPrint, a digital printer manufactured by our strategic partner CSAT (Longmont, CO). We use a Windows-based program called TASC that allows users to create blister layouts and import files into TASC to send the print images to our digital printer for immediate 
production. This software would reside on a laptop near the printer or over a LAN or WAN with a desktop PC for easy approval and production.” 

Rochon and Glenn Breslauer, director of IT marketing for Bell-Mark (Pine Brook, NJ), however, suggest programmable thermal-transfer printing as an option. “In March we will have the software for our line of thermal-transfer printers ready for unit-dose RSS code printing,” says Rochon.

Breslauer says Bell-Mark’s thermal transfer printers will also be ready to print RSS. Its EasyPrint II MLP (multiple-lane printer) is designed to print many two-dimensional codes, like Data Matrix, PDF-417, Maxicode, and soon, RSS. “Our 5-in. printhead, which is the largest in the industry, can print the entire package in one pass, at speeds up to 500 mm/sec, which is well above the requirements for blister lines,” he says. He adds that while many applications require narrow-web (from 240 mm) or wide-web printers (up to 630 mm), “our printers can meet all specifications, and our 5-in. printhead should eliminate the need for multiple print stations.” 

Videojet (Wood Dale, IL) also offers a range of products that can print RSS/Composite symbology on many substrates. At Interphex the firm will show several technologies, including continuous ink-jet and laser, that can print these symbols. “We also plan to add the symbols to our Dataflex thermal-transfer overprinter and to our PrintPro binary-array printer later this year,” says Videojet’s Scott Liniger. “We can also print Data Matrix symbols with our range of products.”

CODE VERIFICATION
 
Printer suppliers like Bell-Mark report that high-resolution printing is already a reality, and Breslauer foresees few problems with achieving the bar code quality necessary for verification. “Our 300-dpi printheads produce bar codes that are easily verifiable and scannable,” he says.
Verification, however, can be tricky. Davis of Quint says verifying a bar code means grading its quality according to worldwide standards adopted by ANSI/ISO. “Nine bar code parameters must be evaluated: edge determination, minimum reflectance, minimum edge contrast, symbol contrast, modulation, defects, decodability, decode, and quiet zone. The code must receive an overall grade of C or better to pass evaluation.”

Webscan Inc. (Brentwood, NY) offers what it calls the industry’s only print-quality verifier for RSS/Composite codes. The firm’s TruCheck product line meets ANSI/ISO standards for 2-D bar code print quality. Webscan’s president Glenn Spitz says that the TruCheck product line is being used to verify RSS/Composite symbols by virtually all of the major pharmaceutical firms that are now putting RSS on their products or are currently in the testing and implementation phase of unit-dose bar coding. Spitz emphasizes the importance of true verification of print quality as required by worldwide industry standards, which ensures that the printed codes will be readable no matter where or by whom they are scanned. 

Hollander, though, believes the grading system is too rigid for hospital unit-dose blisters, as it does not take into consideration the conditions under which the bar codes are created. “They are printed on paper with a platen, and the web is stretched and sealed under high temperature and pressure and then punched from the sealed web. With all that processing, what is the best method to judge the quality of the bar code that is delivered to the end-user?” he asks. “The approach the present algorithms use in the commercially available verifiers for RSS/Composite codes does not work with this issue well. Poor verification grades, e.g., an ANSI ‘F,’ will often read accurate the first time with a simple handheld scanner, despite their poor grade. The verification algorithms do not compensate for uneven printing surfaces, such as those for HUD blisters, and often give readings that while accurate based on what the verifier is designed to do, are misleading in practice. Often, if you scan a second or third time, you will get different, and often improved grades. We are still learning about printing these codes, and the hardware used to scan and verify is still being improved. It will take a little more time before things have stabilized.”