Discipline, control, cleanliness and security make for a demanding market niche.

Label production of any kind is challenging and exacting, requiring the manufacturer to explore the new and unusual, to meet thorough standards set by demanding customers. Pharmaceutical labeling, however, just might be the most demanding of all. The discipline required to produce pharmaceutical labels is exceptionally high. Cleanliness is paramount, security is absolute, and quality is pursued with a vengeance. Moreover, the continuing production of innovative pharmaceutical labels means the investment in equipment technology and training.


One of the newest design trends in pharmaceutical labeling is the use of extended content labels. This new design has gained popularity because of the federal Food & Drug Administration (FDA) labeling requirements for over-the-counter (OTC) drugs. Taking effect in 2002, the new regulations require OTC drug packages to display greater amounts of information in standard formats and minimum font sizes. The changes, which will make it easier for consumers to read and understand important product information and use products safely and effectively, will also have an impact on the packaging for each stock-keeping unit (SKU) of every OTC product currently marketed.

To satisfy the new labeling requirements, while preserving space to display logos, colors and other brand-identity elements that facilitate consumer recognition and generate product sales, Mebane Packaging, a Westvaco Packaging Resource, developed the Extended Content Carton (ECC). ECCs are available in a variety of sizes and shapes to house bottles, blister cards and other types of packaging.

Each ECC incorporates a unique design feature that expands the package's total surface area without increasing its size. The different options provide flexibility in balancing FDA information requirements with important product marketing needs. For example, one ECC design incorporates a fold-out panel as part of the carton exterior. Sealed to the carton body during filling, transportation and display, the panel can be opened by consumers to reveal the compliance information underneath, and then re-sealed to maintain brand identity and product promotion. Other ECC designs preserve space for drug-facts copy on the carton exterior by providing interior billboard panels that can be pulled up and out of the carton's top or folded out from its side. The flaps can be designed to be removed or tucked back inside, making them suitable for coupons, dosage regimens, brand identity elements or other information that otherwise would be crowded onto the carton exterior.

Rick Harris, manager of sales and marketing for the packaging business team of FLEXcon, Spencer, MA, says another trend is the increased use of film. ''Clear film one of the top choices of film substrates for the no-label look and for letting the container surface show through. White films are another top choice. A number of applications are replacing paper as it is more durable and is becoming acceptable as an option for container decoration in this market. Film continues to grow in the health and beauty and beverage markets, and we see the trend following for pharmaceutical labels.

Qualifying a converter

Pharmaceutical companies know exactly what they want from the converters they seek out. In most cases, they require that every procedure from beginning to end be in writing. The pharmaceutical label printer must have a Standard Operating Procedures (SOP) book that is tailored for each customer's particular requirements. About 90 percent of the contents of the book are the same for all accounts. There's always a little variation that a customer particularly wants in order to accommodate a desired requirement, so the SOP book is put together after each customer comes in for its audit.

Thomas Handel, executive director of business development at Akorn, Inc./Taylor Pharmaceuticals, Decatur, IL, says, ''One of the first things we look for is if the converter has the SOPs and GMPs (Good Manufacturing Practices) in place to be a pharmaceutical house.''

In addition, overall quality and demonstration of client base is important. Handel says, ''We look at who their clients are and how long have they been in business. We always run a business search on the company, we look for a D&B from them. We also ask if they do any work for any other pharmaceutical companies, have there ever been any recalls that were a function of something they did at their facility, and if so what was it, and how did they correct it. Of course we also look at price per unit. We go out and perform an audit. We run a GMP audit of the facility looking for control, looking for segregation of materials, looking for traceability. If our job comes into their facility, how do they control the job, how it goes out the door according to our specifications, making sure that nothing has changed from the original art work, and that no other materials have inadvertently been diverted into our stock.''

By traceability, Handel means the ability to track everything that goes into a particular run. For example, he explains, ''If you get a complaint back from the field that says that the labels were peeling off, one of the things you're going to have to do as a pharmaceutical manufacturer is to investigate any reserves you have in house, to make sure that you didn't see anything in house to suggest that you're going to have a problem in the field. Then you're going to have to contact the label manufacturers, say, 'Hey, you know we have labels out there for six months, two months, four months,' whatever the case may be, 'and it appears that the adhesive is letting go.' Then they're going to have to do an investigation in their own facility to make sure that the proper adhesives were used, the proper applications were performed to apply the adhesives to the products, and that they didn't see anything in their facility that would suggest that it would be a problem. And if they don't have good traceability, it's very unlikely that they're going to come back and give you a meaningful investigation and with possible suggestions as to the cause of what's happening to these labels in the field. It all comes down to the documentation of the process.''

Tom McGuire, business development manager at Label Graphics, Fairfield, NJ, agrees that pharmaceutical companies have exceptionally high demands. ''Pharmaceutical companies are looking for a facility where the printing process is controlled, a place where standard operating procedures are in place. We train our personnel to a higher level, we follow cGMPs (current good manufacturing practices) that we have in place, we have security standards in place, i.e., destruction of waste, consecutive numbering on the lining for reconciliation. They're looking for the ability to print very small type.'' McGuire says readability can sometimes be a problem when the font size gets too small, but that's where the printing equipment and the experience of the people come into play. Label Graphics has printed as small as three and four point type. McGuire says that kind of fine printing is usually done on a rotary letterpress.

Cleanliness and documentation

Other factors pharmaceutical companies look for while qualifying a converter are security and cleanliness. McGuire says, ''The facility has to be very clean and the employees have to go by certain standards, so that they're not getting anything on the web and so that the web is clean at all times. This is critical because pharmaceutical companies don't want any contamination of their products in the packaging process.''

Arlington Press in Brooklyn, NY is the pharmaceutical division of Impaxx, Schaumburg, IL, and its president, Robin Henfling, confirms the cleanliness of his plant. ''We are a showplace compared with a commercial site. We have to have product separation, maintenance programs, housekeeping programs, test control programs. And everything has to be documented and maintained.

''Sometimes I joke around and say, we're not really selling ink and paper - we're selling procedures and controls. We have complete quality systems - standard operations programs. Everything is documented, from the maintenance programs to how often we change the mouse traps, to counting the flies in the flytrap. We're also audited once every year by the pharmaceutical company. They look at the complete set up, not only the fact that we can print but also maintenance records.''

Handel says, ''It goes without saying that there is high quality in pharmaceuticals, and aesthetics is a big part of that. The visual impression is a good indication, at least in the patient's mind, of quality of the material inside the vial or the syringe. If they get a label that is smeared or is kind of ugly, then that reflects kind of poorly on the product itself.''

This practice seems to hold true even outside the United States. Norberto Fridman, director of Autopack S.A., Pablo Podesta, Argentina, says that pharmaceutical companies in his country have requirements similar to those in the US when they are looking for a converter. Above all, the facility must be extremely clean.

McGuire says pharmaceutical companies are probably the most demanding customers, because they demand that everything comply with their requirements 100 percent.

''Everything needs to be checked as we run step by step to make sure that we're following their specifications. They want to make sure that the proper materials are being used - proper inks, proper varnishes to make sure the labels don't scuff. We have a quality control department that checks as we go along. We do that as soon as the order comes in house; we check the specifications all the way through to prepress, to on-press, to inspection and all the way through shipping.''

Qualifying converters

As the senior purchasing agent of Hoffman-LaRoche Inc., Nutley, NJ, a manufacturer of pharmaceuticals, Gary Penetta says the company looks for a converter who has been in business solely as a pharmaceutical printer.

''We want them to be using SOPs that are strictly for the pharmaceutical industry; so that you don't have a pressman out there thinking, 'Today, I'm doing a drug label, so I can't gang produce - oh, and my next job is an oil job,' because there is the potential of huge mix-ups that way. We don't think it should be as lax as running cosmetic products, or chewing gum labels. We have more rigid requirements. For example we cannot have fish eyes or broken letters or anything that can possibly cause a problem with interpretation of what the label should say.''

Customers and converters agree that quality is paramount. Everything is checked each step of the way. While qualifying a converter a pharmaceutical company will look at the converter's everyday practices as well as past orders. McGuire says, ''They look to see what we have in place and if we are following them in our everyday operation. They'll pull out orders, go through it step by step, and make sure everything is as it should be, as far as making sure we have the correct equipment, the counts are correct. They're looking to make sure we have the control. Order entry must be exact; nothing can be duplicated. No possibility for mix-ups.''

In addition, if a converter has five plants, they can't produce labels for pharmaceuticals in all five plants. They can produce only in the one plant that has been audited and approved by the pharmaceutical company. It is unlikely that a pharmaceutical company will approve two plants of the same converter. Penetta says, ''We pretty much keep them on a tight rope. We tell them what we want and how we want it done. We don't give them a lot of flexibility. In fact, none at all.''

This quality check is critical because there is zero room for error in pharmaceutical labeling. Penetta explains: ''In the industry today, it's required that on a label or the carton a picture of the drug product is on there. And if the color is off and does not meet strictly within our guidelines, it could possibly lead them to take a different drug. Just in case they get a box that has a yellow picture of the drug and the actual drug is green, then they'll have a heads up, so to speak. Quality is not acceptable if it's not 100 percent. Readability must be 100 percent, and it must also be 100 percent scanable. This is especially important because between 85 and 95 percent of all recalls are due to printing errors.''

Joseph Buono, sales manager for US markets, Industrial Printing Tech, Longmont, CO, says color matching and exactness is also very important especially with OTC drugs, because they are required to put a yellow caution label on each box. Industrial Printing Tech is a division of CSAT in Eggstein, Germany.

Plant security

Another important issue with pharmaceutical labeling is security. The disposal of printing waste is critical, because there is a high risk factor involved when dealing with controlled substances. Pharmaceutical companies don't want counterfeiting. Henfling says, ''No one wants to pass a false drug for something else. The label really defines what the drug is for the consumer - so we don't want any mix-ups there.''

''We require that in any facility that we use, any and all waste is sent down mechanically to be destroyed or incinerated,'' says Handel. ''Again, that's important because you don't want the risk of diversion, you don't want the waste to end up anywhere it shouldn't be.''

To avoid any possibility of mix-ups, every single detail of an operation is tracked. For example, the converter must keep track of the precise number of feet on a roll that is printed. The footage that does not total out in printed form is checked for disposal. For example, if the order is for 200,000 feet and they only ship 175,000 feet, the converter must account for the difference.

In addition, the labels are kept under lock and key. When labels go from the press to the inspection department they go in a secured container, one container per order. After the inspection is finished and the labels are packed they go into a secured, locked, wirebound cage system where they are manifested through a check-in, check-out system signed and dated by two people. And they are accounted for daily. This treatment applies equally to all pharmaceutical labels, for both ethical and OTC products.

Another example of security is that after each order is completed, all material pertaining to that order is removed from the press area. All printing plates are immediately stripped from their print cylinders, the work order on the job is packed in a security box with the printed copy to go to a separate rewind and quality control check.

McGuire says that in addition to destroying the waste, they also perform line clearances. ''Say we're printing one copy of a customer's label. When we finish that job and we bring in the next copy, we have to clear the entire area, the whole press, and have it signed off by someone other than the press operator that all materials pertaining to the prior job are out of that area, waste is destroyed, plates are taken out and destroyed.'' This is to ensure that there is no confusion of copy on labels that may be similar as far as layout and colors are concerned.

As far as production precautions are concerned, each press operator must get an OK from the supervisor when the job is set up to run before he can begin. The press is checked for color, position, copy, everything.

When a job is completed, the inspection department, which is enclosed in a secured area, rewinds and checks all print copy from every roll. No more than one or two splices are allowed per roll, depending on the customer's SOP rules. McGuire says ''There is only one copy at the rewind department at one time. The primary issue is that labels don't get mixed up. '' The inspection department and quality control have the last word on the product, and can reject all or any part of any order. Of course, the customer also has its own inspection. And they can reject any order - no questions asked.

Ethical vs. OTC

Although most manufacturers of over-the-counter drugs have stepped up their standards, there still seems to be a difference in labeling and standards between ethical and over-the-counter drugs. ''There is definitely a higher standard for ethical pharmaceuticals,'' says McGuire. ''For those companies that produce both ethical and OTC, they may have different divisions, but they probably inspect both to the level of ethical.''

Another area of difference between ethical and OTC labeling is in the graphics. Henfling says, ''An OTC has to wind up on the shelf where the consumer can see it. It has to have high graphic content and has to appeal to the general population. In ethical labeling, the type is critical. It can make the difference in dosage - for example, .5 or 5 mg. That's critical so you want to make sure that's right.''

Type size is another issue. Because the amount of information required to appear on a label has increased over the years, the point size of the font has decreased. However, Henfling says, ''Labels have to pass FDA inspection before they can be used. Usually if a company uses a small font, they have to justify why. For example, their reasoning might be something like the use of a small vial, so you can't get a large label on there.''

With the use of smaller fonts, the chance of missing incorrect printing increases. That's why some converters have computerized systems to check for spelling and correct information.

''We also use a TVS system -text verification - where we don't rely on the human eye to read a job and see the mistakes,'' Henfling says. ''This system will check electronically and compare it to the label to see if it matches.''

According to Handel, ''When you get these labels in, they are going to go on your products that go out the door. And if it has the wrong product name on it, if it has the wrong strength on it, if there is a critical error on these labels or packaging materials, then you're going to end up recalling the products from the field, and of course no one wants to do that.''

Handel says that the decrease in type size has led the industry toward the new trend of outserts, or extended content cartons. ''Those are developed as a function of two things. One is that the patient typically never sees an insert. The pharmacist throws it away when it comes in or it goes into a file. So if it's part of the physical vial, it's more likely that the patient will actually get the insert. Second, there is so much more information that the companies are putting onto their labels and inserts these days, that outserts are a good way to do that. It expands the area for text, and the patient gets to see the information that would typically be on an insert.''

Yet another security measure is tamper evidence of a product. This applies more to OTC drugs. Harris says, ''You don't want children getting at the products. We have a line of tamper-evident products, including adhesive-coated shrink films, acetate films, destructible polyethylenes, and holograms for authenticity. The objective is to create an ideal medium for tamper evidence on containers.''

Bottom Line

The pharmaceutical label market is intensely competitive. Pharmaceutical companies are looking for only the best converters to produce their labels. As Handel sums up, ''You want to use someone that does a very high level of quality work - not necessarily solely for the pharmaceutical industry, but probably someone who subscribes to ISO practices, or is ISO certified. It is also important that they have excellent documentation and traceability systems. And that they fully understand the significance of mislabeling something, or having an incorrect label going out to the field, having to recall products and the damage that it can cause. They have to have the system in place that will make sure that doesn't happen.

''I don't think the company needs to be an exclusive pharmaceutical printer, but I wouldn't go to a converter who has no experience in pharmaceutical labeling.''