The full weight of FDA’s regulatory might usually comes down to almost trivially simple elements: the label, insert and related packaging that surround the pharmaceutical product. From black-box warnings, to implementing the new Risk Evaluation and Mitigation Strategies (REMS—see related article), to anticounterfeiting and other brand-protection measures, the physical embodiment of all this attention is slips of paper or film—along with the critically important information printed on them. Thus, a change from the traditional printing technologies, such as offset or flexo printing, to digital printing can shake up many other industry processes.
Digital printing, or print on-demand (POD), is simply the same technology used in printers on most office desks, (usually, ink-jet printing), but in industrial printing, the technology is transforming packaging design, inventory management and, significantly, the ability to respond rapidly to changing regulatory requirements. A growing number of printing suppliers to the pharma industry are making the multi-million-dollar investments in the new systems.
“The benefits are witnessed by the customer as they implement these practices,” declares Barrie O’Brien, co-owner of American Label & Tag (Canton, MI), a manufacturer of custom labels and tags. “Although there is no magic in our technology and success, it is the end result that seems magical.”
Although relatively new to pharma packaging, there is nothing hocus-pocus about POD. These digital systems enable just in-time (JIT) printing that allows for shorter production runs while lowering inventory of printed materials and packaged drugs throughout the supply chain. Digital presses also do not require a significant “make-ready”—which can involve printing hundreds of feet of non-usable material—so there is minimal waste.
“Digital printing works well for many packaging types like labels, cartons, inserts as well as security printing applications,” notes Rob Ryckman, VP, sales & marketing, CCL Label Global Healthcare Group (Hightstown, NJ), a supplier of decorative, informational and promotional labels. CCL reports having installed digital printing systems in four key pharma locations in North America.
Conventional printing processes take as many as 17 steps to complete a given job, from art generation and plate making to printing. By comparison, digital offset print production enables printers to function in as little as three steps, which helps eliminate areas for potential quality-related issues. Files can be changed, saved, and output directly to the printer, and shared for speed and accuracy from labels to inserts/outserts.
“Thousands of files can be saved on the computer or discs and backed up for future use,” O’Brien points out. “Conventional printing plates and negatives are large and cumbersome to store and eventually become brittle and need to be remade.”
What’s more, digital printers have the ability to cut lead times in half for end users who utilize conventional printing systems. “There is now a greater need for economical JIT printing solutions to match new requirements,” observes Victor Dixon, VP and GM, Catalent Printed Components (Somerset, NJ). “Traditional printing assets are typically laden with substantial set-up time and cost, where often the make-ready costs exceed that of the actual production.”
Digital printing is not considered a fad, as it is well established in other industries. For instance, Hewlett-Packard (HP; Palo Alto, CA) reports the volume of labels printed on HP Indigo presses skyrocketed 500% between 2001 and 2006. One of HP’s latest solutions, the HP Indigo WS6000 Digital Press, is utilized for pharma labeling applications by both Nosco and CCL. “We purchased our first Indigo almost five years ago and, since that time, we have two additional presses,” says Gregg Metcalf, industry market manager, strategic initiatives, Nosco (Waukegan, IL).
According to HP, the WS6000 has a faster speed and larger print format than its predecessor, and its speed and size make it more cost-effective than analog printing for 80% of the jobs label converters typically produce. “The press helps eliminate the need to pre-order large quantities of printed material,” explains Retha Petruzates, segment marketing manager of HP’s Graphics Solutions Business. “Labels and packages can be printed as they are ordered and produced quickly on demand.” HP offers a portfolio of high-end digital presses geared for offset-like quality and high-productivity commercial printing applications as well as industrial printing end uses such as labels, packaging and folding cartons.
The need for speed
Digital printing has come a long way since the new millennium, experts say, when the technology posted higher production costs than traditional offset or flexo printing. It was initially positioned as a more appealing for handling shorter production runs (up to about 200,000 copies). Fast forward to 2009, where computer-to-label digital printing is well suited for shorter production runs involving OTC and Rx drugs required for promotions and pre-launch samples.
“Large quantities are still less expensive to print with traditional technologies,” CCL’s Ryckman confirms. “However, depending on the situation, if all true costs are included in the calculation, then digital is a good fit for many products.”
Data collected by Nosco indicate 91% of all Rx drug SKUs ordered are quantities less than 500,000 units and 50% of these orders number between 150,000 and 250,000, an indication there is an increasing number of shorter runs. “We feel this trend is going to continue with the exception of blockbuster drugs, which are declining in favor of ‘niche busters,’” Metcalf says.
Shorter runs and less inventory help create better cash flow for the end user, industry members point out. “Sitting on expensive inventory, or allowing labels to become obsolete due to changes, can be avoided,” says O’Brien of American Label & Tag. “There are also no plates to inventory and keep secured.”
Catalent’s newest digital offset press, the 74 Karat from Koenig & Bauer Group (US HQ: Dallas, TX), offers the flexibility and capability of digital printing with the quality of offset printing. The unit is positioned as a cost-effective option for short to medium runs and said to be a “true” sheet-fed press. “The 74 Karat utilizes standard sheet fed paper and board materials,” Dixon explains. “The press also assures exact register without ghosting, precision color management with color, and accurate, high-quality results.”
The 74 Karat is marketed as a cost-effective, high-quality offset press with fast job throughput. “We go from raster image processing (RIP—the creation of the printing image) to production printing in approximately 17 minutes,” Dixon says. “The press can go from start-up to color match in less than 10 sheets, therefore waste is a minimum and throughput is high.” With high production speeds up to 10,000 sheets per hour, the unit helps ensure on-demand deliveries while an all-digital data transfer allows for on-demand print capabilities.
With digital label presses, POD also eliminates the need for film, plates, and cylinders used by conventional presses, because the image resides in the computer and outputs directly onto the label film or paper using special inks. Resulting labels are typically finished with a topcoat to enhance gloss and protect the printed surface from damages such as abrasions. And, in some cases, color consistency is improved through digital production.
“This is accomplished through our digital front end management,” Nosco’s Metcalf says. “Once a color is dialed in, that color is captured and stored in the press for the next time the job is run.” This allows repeat orders to maintain exact color consistency from one run to the next.
One of the most important aspects of digital printing solutions is machines are compliant with current good manufacturing practices (cGMP), including full-label reconciliation, or accounting for all labels used and unused, to deter label theft and misuse.
“We have to account for every pharmaceutical label used and unused as required by the FDA,” notes Samir Shah, vice president of regulatory affairs at The Harvard Drug Group (Livonia, MI), a secondary supplier of generic and brand pharmaceuticals, major OTCs, and vitamins. “Reverse numbering on the back of each peel-off label, by vendors such as American Label & Tag, helps us to efficiently achieve this. There’s no need to open or rewind the label rolls, and the last label on the roll tells us exactly how many are left by looking at the back of the label.”
Full material traceability, or backtracking the supply chain and handling of a product’s raw materials, can also help prevent or limit potential recall, if there is ever a question of sub-par product, materials or processes. Label barcode testing and verification also ensures all are readable before shipment, which safeguards against potential returns to the manufacturer. “By numbering the labels, the practice of reconciliation is quick and accurate,” O’Brien says. “And this sharp recordkeeping can prevent costly shortages as well as identify mislabeling or wrongful practices.”
Computer control simplifies the addition of variable information, such as sequential or random barcodes. The variable aspect of the press allows images to change form one frame to another, experts say, which is important when the need arises for variable bar coding. “Typically, a conventional press can only print static information base on the images that are on the printing plate,” Nosco’s Metcalf says. “Digital, on the other hand, can load several different images in a particular field and produce these images randomly.”
This is a critical element when using barcodes for serialization, where each label or package carries a unique identifier that enables distribution tracking and helps thwart product diversion and counterfeiting. And, on a broader scale, digital can be a key factor in near-line customization for pharma packaging. “Pharma label and packaging manufacturers can not only meet serialization requirements with digital, they can address different nations’ regulatory demands on a single manufacturing line,” HP’s Petruzates says.
Computerizing the pre-press process results in a lead time of between one and two weeks, thus reducing the production and storage of excess labels stock to ensure a predictable time to market for products. Printing vendors say that it is now economical to purchase only the number of labels and folding cartons needed at a given time, thus reducing inventories and work in progress. Low minimums enable vendors to purchase the exact number of labels and folding cartons, eliminating “over-runs” and “under-runs.”
“If a customer wants to package 543 bottles, they can have 543 labels,” says O’Brien of American Label & Tag. “Beautiful four-color process designs can be printed and sent out the same day.”
This is an important feature considering ever-changing FDA requirements can affect labeling criteria and render pre-printed labels obsolete. “From label design and graphics to plate making, set up, and proofing, relying on a one-stop shop has allowed us to quickly make any necessary changes,” says Shah of The Harvard Drug Group. “When speed is critical, they can deliver labeling within three days. That gives us peace of mind, helps us stay FDA-compliant, and gets our needed medicines in the hands of customers as quickly as possible.”
Indeed, getting the right labels to the manufacturing site is an important part of the job. Nosco counts several customers who have done away with their labeling control rooms due to the JIT benefit of digital printing. “Digital allows for jobs to be changed from one order to the next without incurring the usual round of pre-press charges,” Metcalf says. “We have customers who have saved anywhere from $10,000 to $90,000 a year in prep charges because of the frequency in their copy changes.”
Shorter turnaround times also allow drug makers to react more quickly to changes in market conditions, experts say, enabling faster launches and customization to address requirements of targeted patient populations. “As the market shifts from blockbusters to personalized medicine,” Catalent’s Dixon observes, “we are seeing digital as a good match for low-quantity ‘rest-of-world’ volume, orphan drugs, targeted biotech and med device applications.”
With more specialty pharmaceuticals coming onto the market, and with biopharma researchers progressing in various types of personalized medicine or “targeted therapies,” the trends are toward shorter production runs of drugs, and the need for fast changeover from one product specification to the next. While the biopharma industry is wrestling with these changes, there’s some comfort in knowing that the printed-materials suppliers are already prepared. PC