Complying with Track and Trace
Biogen Idec blazes a path to California compliance
By Stephen Barlas
Bob Hamm, executive vice president, pharmaceutical operations & technology, at Biogen Idec (BI), says his company didn't think twice about putting serialized, two-dimensional (2-D) barcodes on containers of Avonex and Tysabri, the two main products manufactured by the Cambridge, MA-based biotechnology company. There is clearly going to be an incremental, per package cost for serializing those cartons, which contain either small pre-filled syringes or vials, and are loaded into cartons at a Catalent Pharma Solutions packaging facility in Philadelphia.
But if cost wasn't an issue, California was. The Golden State had -- up until March 25, 2008 -- a January 1, 2009 deadline for all pharma manufacturers shipping product into the state to put serialized numbers, either in barcodes or radio frequency identification (RFID) tags, on each item package going into each case loaded onto each pallet. California, like Florida before it, established the mandate as a way of keeping counterfeit drugs out of the state. But California went considerably further than Florida by requiring not just a lot number, expiration date and NDC number on both the label and a pedigree -- a shipping document of sorts passed down the distribution line -- but by requiring an electronic (not paper) Pedigree containing a unique serial number stamped on each individual package, such as the BI paperboard containers holding those vials and syringes of Avonex and Tysabri. The Florida test was the equivalent of an eighth grade intro-to-algebra test. California was calculus, and drug manufacturers vehemently protested the nearness of the implementation date.
Today, after the California Board of Pharmacy on March 25 delayed the implementation of its e-pedigree requirement until January 1, 2011, the hearts of drug executives up and down the distribution chain are back in a normal sinus rhythm. But the two-year delay will not provide a lot of breathing room. The complexities of packaging line serialization is still college-level calculus, and those companies that are right now passing the test move front and center in the industry as class leaders over whose shoulders other companies will be intently looking.
"Biogen Idec is the first company to publicly announce item level serialization for its entire product line," said Kamal Mustafa, president of Secure Symbology, (SSI) Inc., the Wayne, NJ-based company that is providing the barcode printing, product aggregation and database operations which were installed at Catalent's (Somerset, N.J.) Philadelphia commercial packaging facility, where both Avonex and Tysabri are packaged. It is that serialization of each item-level package that is the relatively expensive part of the California ePedigree requirement, making past packaging operations, where only the lot number and expiration date were printed in a big linear barcode, look like horse-and-buggy days. Once the serialization is done, integrating the e-Pedigree with downstream partners in the supply chain is the challenging part of the process.
But Biogen Idec, unlike most of the rest of the industry -- both biotechnology and conventional pharmaceutical marketers -- decided not to be paralyzed by California's complexities. "We are treating chronic disease, and to do so we put hundreds of millions of dollars into our manufacturing plants," explained Mr. Hamm. "With the California law coming into view, and other states such as New York likely to follow, we had to look at feasibility more than cost. We didn't debate the cost-to-benefit equation. Any good company would want to insure the quality integrity of its product. And the current lot-trace capability can be duplicated by others with less than noble motives."
If the California Board of Pharmacy was awarding good corporate citizenship medals for prompt e-Pedigree compliance, BI would get one. On March 25, when the board pushed back the e-Pedigree deadline two years, D. Timothy Dazé, a board member and deputy city attorney in Los Angeles, complained, "All I'm getting is 'We can't do it, we can't do it, it's too expensive.' And I ask, 'What value do you folks put on a life?'"
In a sense, compliance with California will be easier for Biogen than for many other companies. First, the company manufactures and distributes only two major products, Avonex and Tysabri, which are approved for multiple sclerosis. (BI does not manufacture its third major product, Rituxan, indicated for non-Hodgkin's lymphoma and rheumatoid arthritis.) Pfizer, GlaxoSmithKline and many of the other bigger companies have many more products, and the complexities of compliance with California by Jan. 1, 2009 were momentous.
But also easing Biogen's path was its long-time relationship with Catalent, one of the biggest contract packagers in the pharmaceutical industry. Biogen had started working with Catalent's predecessor PCI Services in 1995, the year before Avonex was introduced. PCI Services was later acquired by Cardinal PTS, a division that was sold in April 2007 to the Blackstone Group and renamed the Catalent PTS. Avonex has been packaged on a dedicated packaging line at Catalent's Philadelphia facility, since 1996. Tysabri has been packaged at the same facility on its own dedicated line since July 2006.
"When we decided to meet the California deadline of January 1, 2009, we had no reason to look beyond Catalent for a vendor," said Mr. Hamm. Biogen did initiate a formal bid process, however, for suppliers who could provide the serialization technology for Catalent's packaging line and for the e-Pedigree software and data systems that would take the data from the packaging line for each item packaged and store it and then spit out an electronic Pedigree that would follow the package as it made its way to the wholesaler and ultimately a pharmacy (in Biogen's case, a specialty pharmacy).
In the end, Biogen chose Secure Symbology to put 2-D, serialized barcodes on each package of Tysabri and Avonex, with SupplyScape Corp. of Woburn, MA providing the pedigree software. "SSI had a prior relationship with Catalent, so that made our choice a little easier," said Mr. Hamm. "But clearly all the providers in this area are well respected." The major competitor to SSI is SYSTECH International. Besides SupplyScape, rfXcel Corp. (San Ramon, Calif.) and Axway (Scottsdale, AZ) are also certified by EPCglobal for their e-Pedigree systems.
The first decision Biogen Idec had to make was whether it was going to use RFID tags or barcodes to carry the serialization numbers for each product. The RFID tags are much more expensive, costing 7-25 cents per label, depending on volume. A 2-D barcode costs less than a penny to print. The big wholesalers such as Cardinal, AmerisourceBergen and McKesson have all made it clear that they want drug manufacturers to put RFID tags on products. That is because if products are serialized with 2D barcodes, the wholesalers will have to open every carton and read every package -- with a barcode reader--individually. That will take an enormous amount of time. RFID tags, on the other hand, can be read without opening the carton.
However, Biogen Idec didn't really have a choice. While RFID has been approved for solid dose forms by the Food and Drug Administration, it has not been approved for liquids, including biologics like Tysabri and Avonex. In addition, there is a question about whether the frequencies might alter the structure of a biologic products. Moreover, even with regard to solid dosage forms, there is a dispute over whether high frequency (HF) or ultra high frequency (UHF) tags should be used on the item-level package. There is consensus that UHF is the best choice for cartons and pallets, because UHF tags can be read from further away than HF tags; however HF tags cause fewer "misreads."
"RFID is the ultimate solution," stated Mr. Hamm. "However, it is still unproven where biologics are concerned. BI opted for 2-D barcodes based on the information available when we were designing our solution."
The job of working with Biogen's vendors and navigating the technical challenges of applying smaller, 2-D barcodes to Tysabri and Avonex packages fell to Larry Singer, director, global supply chain at Biogen Idec. "2-D barcodes are not a new technology," explained Mr. Singer. "What is new is adopting it onto a package." But that didn't turn out to be too big a problem. "You can get an extremely large amount of information onto a small label footprint when you use a 2-D barcode," said Mr. Singer. "There is plenty of available real estate on the label. And as long as you are able to phase out your old product labels, there really isn't any additional cost to designing the new labels."
The major cost for Biogen Idec is for the use of the SSI technology installed on the Catalent packaging line, and for the validation of the new packaging process once it is completed. Kamal Mustafa of SSI said that each packaging line has slightly different requirements, and neither he nor Mr. Hamm at BI would discuss specific costs. But Mr. Mustafa remarked the cost of installing his "modules" -- there are three on the Biogen lines -- can run anywhere from $100,000-$400,000. In BI's case, it is paying an incremental additional cost for every carton of product printed with a 2-D barcode on the Catalent line, an incremental cost which basically reflects SSI's capital costs.
In the case of Tysabri and Avonex, small vials or syringes are placed in small pre-printed cartons and then placed on the packaging line. As those cartons move down the line to the first module, a 2D datamatrix barcode is printed on each carton, the ink is dried, the barcode is then scanned, the scan quality is graded, and if it is not acceptable that carton is "kicked off" the packaging line. Then the cartons go to the next module where they are stacked in cases. At the third module, the cases are stacked on pallets. All three modules can "talk" to one another, and they all upload data to a database that SSI maintains. Ultimately, that data is used to create the e-Pedigree for each product, which is done with SupplyScape software.
Biogen Idec includes a unique, sequential serial number in the information stored in each 2-D datamatrix barcode. DataMatrix is one of two formats used in 2-D product label barcodes, the other is called RSS. Retailers generally prefer RSS barcodes because they can be read by most pharmacy scanners. But a DataMatrix barcode takes up less space on the carton and can be read even when part of the barcode is obscured. DataMatrix barcodes can store from 1 to about 2,000 characters. The symbol is square and can range from 0.001 inch per side up to 14 inches per side. As an example of density, 500 numeric-only characters can be encoded in a 1-inch square using a 24-pin dot matrix printer.
Because of its early start, Biogen Idec will have its feet up come January 1, 2009 just as nearly every other pharmaceutical company in the U.S. starts to sweat the Golden State's new January 1, 2011 e-Pedigree deadline. "We'll be done easy by 2009," stated Mr. Mustafa. "With our eyes closed."