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Articles from 2015 In December


Tampering, terrorism, and exposure

By Edward R. Arling, Senior Director, Biopharma Quality Assurance, Pharmacia Corp.; Ralph L. Dillon, Director of Quality Engineering, Biopharma Quality Assurance, Pharmacia Corp.; Joseph F. Noferi, Director, Quality Assurance, Compliance and Validation, Biopharma, Pharmacia Corp.

This past October, the pharmaceutical industry marked an important anniversary. Twenty years ago in Chicago, seven innocents, ranging in age from 12 to 31 years, lost their lives to tampering. Someone (there has been no conviction to date) had laced Tylenol capsules with potassium cyanide and left packages containing those tampered capsules on retail shelves for consumers to purchase. Tragically, three victims were from one family and had reached for the same poisoned bottle of analgesic after the first family member died. 


Today, pharmaceutical products are still in danger. This despite Congress's 1983 Federal Anti-Tampering Act, which provides felony penalties for tampering with or threatening to tamper with any product covered by the Food, Drug and Cosmetic Act, and despite FDA's tamper-evident packaging regulations. First, these regulations only affect consumer products, leaving some prescription drugs without any visible evidence of tampering. Second, with some of today's biopharmaceutical products costing in excess of $2000-$3000 per gram (300 times the price of gold) to produce, some criminals (and even pharmacists, in last year's case of the Kansas City pharmacist found guilty of diluting and distributing cancer drugs) are tampering for profit. Finally, since pharmaceuticals are critical to the social, economic, and political stability of the United States, they are vulnerable targets for terrorism. 

The pharmaceutical industry must therefore secure the supply chain using modern technology to protect all stakeholders--patients and manufacturers alike.

The U.S. government recognizes the threat of tampering and counterfeiting. Through nationally commissioned working groups and the Homeland Defense Initiative, proposals are being made for the design and implementation of technologies that can combat and detect tampering. 

As a result of the Bioterrorism bill, FDA has been authorized by Congress to hire an additional 4000 employees in the Office of Regulatory Affairs, more than 880 of whom will be investigators trained to respond to bioterrorism and counterfeiting, and to protect food, drug, and medical device supplies. New enforcement powers have been granted to FDA by Congress that allow immediate seizure and embargo of any regulated item suspected of adulteration, tampering, or counterfeiting. New alliances are being forged with state and local municipalities for enforcement and increasing the size of mobilization forces. Foreign inspections of food will be increased, and routine pharmaceutical plant inspections are being increased. 

But no government can detect every instance of tampering and protect every consumer. The laws and regulations have been in place for the past 20 years, yet evidence of counterfeiting is increasing. In a perfect world, the control of counterfeiting would be through the application of due process of law. But to do so, pharmacists, wholesalers, government agencies, and pharmaceutical companies must all cooperate to ensure that suspected counterfeits are thoroughly investigated and counterfeiters prosecuted. 

Also, there is no unified world authority to promulgate investigations, nor a world tribunal for enforcement. Consequently, pharmaceutical firms themselves must augment legal approaches with alternative ones to protect industry, stakeholders, and consumers. Industry must go beyond the tamper-evident regulations to ensure package integrity. 

The first step is to institute higher security and controls. Solutions must be crossfunctional, affirmative, and proactive. Company personnel from packaging, intellectual property, marketing and sales, regulatory affairs, quality, operations, and corporate security must be involved. Manufacturers must make it easy to recognize product authenticity and tampering. A specific "fingerprint" is needed for each vial, drum, shipping container, and label. Unique identifiers, like bar codes, for each and every SKU coming out of the plant shipping dock should be in place, revealing site of manufacture, packaging, storage, distribution, repackaging, handling, testing, etc.

Products also should include multiple layers of tamper evidence. These may include seals that need to be removed, features that must be broken, or permanent measures such as color, taste, and fragrance that are part of the product itself. All these measures need to be integrated together to provide protection at each of three levels: overt, covert, and reserved.

Overt tamper-evidence features are those that a consumer or stock clerk would notice, like the foil/plastic seal on a blister package of tablets. If the features are compromised, typically a stock person will set the product aside, and if consumers see it on the shelf, they will not buy it. Covert tamper-evidence features are those that are not published or are typically unknown beyond select groups of employees. For instance, lot numbers could show that a product does not fit the appropriate pattern for legitimately distributed product. Other tools include codes whose color spectrum is only visible under UV light, or special-coded label words/symbols visible only with special viewing devices. Finally, reserved features are those that are unveiled only on a need-to-know basis. Typically they are not discussed beyond a small, select group of people and are not written into product specifications in an obvious way. A reserved feature may be something as simple as a process-inherent trace compound that would normally not be present should another pharmaceutical ingredient supplier be used. The important concept to understand is that there should be multiple defensive layers in each of the three areas of tamper evidence. A bottle with a breakaway tamper-evident cap might also have a glue-sealed carton and contents with a unique, difficult-to-duplicate fragrance.

Tamper evidence needs to be applied at every level of packaging or containment because every level offers an introduction point for tampered product. The levels for tamper evidence start with the largest unit (the warehouse building) and need to be applied at each package configuration level down to the dosage itself.

Form-fill-seal: Making the switch

Can quick-change tooling ease and speed up your changeover?

by Daphne Allen, Editor

For many companies, horizontal form-fill-seal (FFS) equipment is a significant investment. Such equipment can be the most expensive machine on the packaging line. To make the most of that investment, companies often use that one machine for packaging a range of products. Changeover is therefore part of their routine. Merit Medical Systems (South Jordan, UT), for instance, is one such medical device manufacturer interested in quick changeover. (See the side bar on page 42 for more on Merit Medical’s story.)

Over the last few years, manufacturers of FFS equipment have worked to ease changeover. “We have to factor ease of changeover into the machine design,” says Marty Moscowitz, regional sales manager, medical consumer, and industrial division, Multivac Inc. (Kansas City, MO). In the past, “changeover was too long and too complicated. People have been looking for ways to make it more efficient.”

John Merritt, director, medical business development for ALKAR-RapidPak (Lodi, WI), explains the ease of changeover “often revolves around how easy it is to get tools in and out. Tools are often heavy and require a lot of muscle to remove and replace. This can result in health risks, such as strained backs, busted knuckles, etc. There is also a risk of damaging tools.”

To ease changeover, many FFS manufacturers now offer what they call “toolless changeover.” Quite simply, “Toolless changeovers are accomplished by a number of means, such as knurled knobs as opposed to nuts and bolts requiring a wrench,” explains Merritt. “Hoses are connected with integral quick-connect mechanisms, as opposed to clamps that are tightened with screwdrivers.”
Adds Moscowitz: “You can either turn a knob or flip a lever, or even just push a button.” To help Merit Medical with changeover and other tasks, Multivac designed a customized R530 thermoform-fill-seal solution for creating specialized medical kits.

Still, as easy as machinery manufacturers are making changeover, Donald S. Barcan, president and CEO of Donbar Industries Inc. (Long Valley, NJ), advises users to approach quick changeover “with a careful eye on all the issues, including validation and process control.”

CHANGES

Changeover ranges in complexity. The change may simply be to the packaging material, maintaining the same packaging footprint. Or, an entirely new package size or style may be needed. The amount of tooling changes depends on the degree of packaging change.

Tooling that can be changed includes forming dies, sealing platens, and cutting knives. Merritt adds that there are control issues that may need to be changed to accommodate different packages, such as “changing temperature, pressure, and index length.” Also, “there are peripheral issues associated with things like lot coders and in-line printers to changeover.”

Simple changes can often be made in seconds, while complex changes take longer. When changing materials, sealing parameters such as temperature and dwell-time may need to be changed. “When changing the material it would most likely be only a program change,” explains Vin Faherty, product manager, packaging, for Harpak/Hooper Engineering (Easton, MA). “This takes only seconds to change.”

Merritt offers the following range of changeover scenarios:

• When multiple product codes are being run on the same machine with the same packaging materials and configurations, changeover can be performed by replacing one printing plate with another and inputting a new lot code. (For more on this scenario, see the sidebar on page 44.)

• When package shape is being changed but the sealing pattern remains the same, the forming tools will have to be changed, probably requiring a change in forming parameters. Lot code and printing plate changes will also be likely.

• When package shape and sealing pattern are being changed, tools will have to be removed and replaced at both forming and sealing stations. Cutting systems may need to be replaced, and lot code and printing plate changes will also be likely.

Other changes involve adjusting forming depth, says Moscowitz. The depth of the forming die may only need to be adjusted, or for plug assist operations, the stroke of the plug may need to be shortened or lengthened.

In the case of RapidPak’s patented servo-driven plugs, the speed of plugs may need to be adjusted.

SHELVING THE TOOLBOX

Can all these changes now be made without tools? Most can, say FFS machine manufacturers. As Merritt and Moscowitz explain above, many tooling units have quick-change components and require just a bit of elbow grease to undo, change, or adjust.

Merritt says that in the past, changes in forming and sealing tools required that the tooling be removed and replaced, upward out through the top of the machine, which required that film be cut. “RapidPak is excited about its side extractable systems where tools are removed horizontally. It is easier to get to the tools, so there is less risk of injury as well as less damage to tools. Because these systems do not require that the film be cut and then rethreaded, start up after the tools have been changed is faster.”

Moscowitz says that one of the most important developments in the last three years is the addition of multiple tooling stations on one machine that can be changed with the push of a button. “On most of our machines, we can add two to three complete forming and sealing stations that can be called up using a human-machine interface,” he explains. “Each package format to be run on the machine is assigned a code number. Machine settings and parameters are stored as recipes that can be programmed by an authorized user.” Multivac’s onboard processor can store up to 50 recipes.

Hooper Engineering offers dual forming stations and dual seal stations, so changeover is just a flip of the switch, says Faherty. “As an option, the N2500 can be built to hold multiple sets of tooling in-line.” He says that Hooper is the only manufacturer to incorporate dividable tooling with different index lengths. “If the changeover involves a different index length, other firms sell another complete form set. The N2500 can also be equipped with servo-driven form station adjustment that alters the form station by the flip of a switch.”

Moscowitz says that storing multiple stations on one machine can add cost to the machine. “The loading area on these machines is longer, and therefore the machine is more expensive. In addition, die-lifting systems are needed for each forming die.”

The expense may be worth it, he says. “If firms are changing over more than once a day, they can justify this expense. It maximizes the efficiency of the machine. Also, larger tooling needed for bigger packages is harder for machine mechanics to handle,” so there are ergonomic benefits as well.

Future improvements will involve electronics. “The more changes that can be made with the programmable logic controller (PLC), the better. PLC changes are quick, they are verifiable, and history can be archived,” Moscowitz says. In addition, “more centralized control of peripherals can also be accomplished.”
Merritt adds that one of the major advantages of RapidPak’s servo-driven plugs, as opposed to pneumatic-driven plugs, is that they come totally under the control of the PLC.

Multivac is using more electronics, says Moscowitz. “We are using it to make adjustments, like for the depth of a die or the parameters of the longitudinal cutting systems.”

DON’T EVER CHANGE?

Barcan says that many companies that employ FFS machinery “do so because they want higher productivities and a lower per-unit cost for the package.” Higher volumes may justify a dedicated packaging line, thus obviating the need for routine changeover. “In my experience,” Barcan adds, “a daily production on FFS could be more than 100,000 packages, obviously dependent upon the devices being manufactured. Thus the goal is generally not to change out tooling.”

But there may be other reasons for foregoing changeover. Barcan points out that “validation of FFS is directly tied into forming tooling, loading, printing, sealing, and cutting. This process, when properly done, can take up to a week or more per tooling set. Once this activity is successfully completed, manufacturers would not want to ‘upset the applecart’ by making changes. This is also reinforced by the fact that FFS runs are generally three shifts for many weeks, if not months.”

In Barcan’s opinion, a partial if not complete validation would be required every time tooling is changed out. “Depending upon the actual situation, I think the cost of the revalidation could exceed the potential cost savings of ‘quick-change’ tooling. I’m not saying that quick change or ‘toolless’ tooling would not be an asset, but at what additional cost and at what compromise to process control and validation?”

But Merritt says that after changeover, “one merely has to confirm that the process is running within the acceptable parameters established by a prior formal validation/qualification process. Of course, all of this has to be documented,” he advises.

Quality in packaging

Members of PMP News's Editorial Advisory Board focus on trends in package quality assurance.

Inspection technology and supply chain controls are helping to ensure packaging quality and product protection, as pharmaceutical and medical device manufacturers face demands for user-friendly packaging. Speaking on the issue for this year’s Industry Outlook are the following members from PMP News’s Editorial Advisory Board: John Bitner, director of packaging development, Watson Pharmaceuticals; D. Bruce Cohen, principal,

PackTechPlus LLC; Michael L. Forehand, principal packaging engineer, global engineering and technology,

AstraZeneca; Curtis L. Larsen, principal, Spartan Design Group; Michael H. Scholla, global director, regulatory and standards, DuPont Medical and Pharmaceutical Protection; Laura Bix, assistant professor, Michigan State University School of Packaging; and Nick Fotis, director, R&D–surgical drapes, gowns, & custom sterile kits, Packaging Technology Center, Cardinal Health. Karen Polkinghorne, packaging engineer and MDM specialist, DuPont Medical Packaging, joined the discussion at the invitation of Dr. Scholla. In this roundtable with PMP News senior editor David Vaczek, the panel discusses challenges of managing quality and cost.

Investment in advanced inspection technology has grown considerably. What impact is automated inspection having on quality?

Forehand: Traditionally, automated inspection systems were put in place in response to GMP requirements, such as for 100% inspection of labels to prevent mislabeling. However, we are expanding the use of vision systems in other ways to catch problems earlier on in the manufacturing process and correct them at the source. The emerging enhanced speed and capabilities of today’s inspection systems are enabling this. We are actively engaging our suppliers in increasing their use of automated vision inspection to support defect-free supply. We prefer to have automated inspection as far upstream with suppliers as you can get it because defects there find their way down to our lines and impact our efficiency.

Cohen: I’ve heard that FDA is looking to implement 100% inspection on a number of processes. Their thinking at this point is that it would eliminate rogue events on a line that you wouldn’t catch with periodic in-

process inspections. I don’t think it fits every single thing you do, but there are places for it where it is beneficial.

Bitner: It is component specific. There are a number of areas such as Bruce said where it is very relevant. We have sequentially numbered labels where the roll can be taken off the floor, put back in inventory, and returned to the floor very quickly by checking the last label number. So we have complete reconciliation of how many labels were used, how much product throughput was achieved, and how much waste is involved in the process. Visual inspection systems can detect a 2-mm difference in the height of a bottle closure. This capability allows 100% nondestructive in-line inspection. Off-line manual inspection is an albatross from the past. Results were always subject to variance based on inspector fatigue regardless of tightly controlled inspector rotation.

Fotis: I have been on both sides of the medical device supply chain, and when I worked for a medical films manufacturer, we looked at automatic detection of films for gels and cinders. The technology was available, but expensive more than 10 years ago. The biggest issue was whether the customers would understand the level of “defects” that would be acceptable, or would want to dial down the instrument to detect the smallest possible gel in the film. These small gels would never pose a functional problem, or even a cosmetic issue, but the concern was that many audits take place when medical device manufacturers send their quality folks out to assess the film supplier’s capabilities. Some of these folks don’t always understand that there may be such a thing as “a threshold defect”—one that has no bearing on functionality or cosmetics.

Scholla: There are some things automated inspection is perfectly applicable for and can be used with relative ease, but others where it becomes much more difficult. It is pretty easy to detect coating skip in the application of coatings. [But] automated inspection of material supplies can become very complicated in that sometimes the machinery gets more sensitive than you really want it to be. It can’t figure out what is normal and what is not.

Larsen: People are looking at this as a way of saving money. You have to take the time to understand what it can and cannot do, and properly validate it.

Scholla: When somebody tells you to do it on a process that it really isn’t suitable for, it only creates problems and there will be no cost savings, only a cost increase. You are dealing with inspection reports on a process where the automated inspection is not really appropriate.

Do increased rejects become an issue?

Bitner: This goes back to the definition of a defect. We have leak detection systems now that can detect to five microns but that may not be of value based on stability of a given product. Tolerances are calibrated at a level compatible with protecting the safety and efficacy of the product. Mass extraction with micro-flow technology enables more blisters to be inspected without related cost of product/blister destruction.

Cohen: You can’t have one test for all things. You cause yourself a lot of undue work. The pass/fail requirements won’t be the same for a PVC blister with a product that is not moisture sensitive as with a cold form foil blister.

Larsen: Now that we can find more anomalies, we have to ask whether those anomalies are really a failure. Are the pass/fail requirements changing because of the sensitivity of the equipment? We see films that are widely used that fail quite often in testing. Are you going to tell people they can’t use the film? There may be a flaw in how they are testing or setting their pass/fail requirements.

Is the scope of quality requirements on suppliers increasing?

Polkinghorne: A common issue with medical device manufacturers and their suppliers is misalignment of specifications. The end customer would like zero defects, but the supplier’s process produces a certain percentage of defects. Once an MDM and supplier reach agreement or alignment of specification values, both parties are better served. A best practice is for MDMs to use a collaborative approach with

suppliers when writing or revising packaging material specifications.

Cohen: I agree. Your wants and needs as a manufacturer of products doesn’t necessarily translate as the same needs of the supplier. Some time ago, I had a head of manufacturing who wanted no splices on label rolls coming to the packaging line. We said we can do that but it will change the price of the labels and you will never have a roll of labels the same size. We agreed on a specification of no more than three splices. That gave everybody buy in as to what would happen on the production line. There has to be a conversation to make sure that the supplier can produce what you need at a reasonable cost to keep you in production and keep your products on the market. Certainly, we as manufacturers have been pushing our suppliers to be more proactive in understanding their processes and control of what they manufacture in order to give us as close to zero defects as possible.

Larsen: Understanding the capabilities of the supplier’s process is extremely important, but also you both have to be singing off the same page on how you test for an attribute. Are you both doing the testing the same way using the same methodologies? If one uses an in-house method, the other an ASTM test method, the two will never meet. There is a lot of built-in noise with many of these tests. We see it all the time with ASTM F88 seal-strength tensile testing There are three different methods within the standard that you can use. You have to collaborate when putting together the specs and setting the pass/fail requirements to avoid miscommunication.

Cohen: The testing is a good point. I’ve gone through that with flow-through testing on aerosol actuators. The manufacturer was doing it one way and we were doing it a different way on incoming inspection. And never the two shall meet.

Scholla: Another consideration is regional differences and expectations. There are four very distinct expectations around packaging suppliers in the United States, Europe, Japan, and China. In facilities that supply packaging in China today, almost every one of their pouching rooms is a cleanroom environment with everybody looking like they are working in a controlled environment. You won’t find that very often in the United States except with pharma suppliers.

Fotis: I think that the expectation from medical device manufacturers has always been very high for medical packaging suppliers. The amount of added value that is put into the package mandates that packaging reliability be very high. The increasing expectation is that suppliers are not only running a validated production system, but that they have a handle on their variability and are taking active steps to reduce it. One example would be variability in film thickness. Tolerances that were acceptable to the industry several years ago are no longer OK. The more suppliers fine tune their processes and reduce their variability, the less our packaging equipment and process windows need to compensate for what might come in the door.

Forehand: Getting defect-free materials is critical to a lean manufacturing system. The more variability we receive in supplied materials, the less efficient our operations will be. The use of “AQLs” to “allow” a certain level of defects is seen as counter-productive. All defects should be corrected immediately at the source.

What is the progress in defining an allowable minimum hole size for maintaining packaging sterility?

Bix: The testing that we have done suggests that microbes can penetrate extremely small holes, sometimes even in the absence of pressure but certainly pressure, as you would expect, has an effect, as do myriad other factors. When reading anything that we put out regarding Ondrea Kassarjian’s or Jane Severin’s work [on hole studies], you have to put it in the framework of the testing that we did. We used extreme conditions. Another presumably worst-case aspect of the testing was the use of non-porous lid stock so the pressure differential has to be entirely relieved through the defect. We were trying to answer the question: Can microbes penetrate, not, do they penetrate. You have to view and interpret the findings in that context.

Polkinghorne: How did you quantify how dirty to make that environment? Is it based on a hospital central service or distribution environments?

Bix: It would be really valuable if we could characterize what is realistic in terms of the distribution channels and the hospital environments. We relied on other people’s literature in microbial challenge, and used an extreme load of microbes as our starting burden.

Scholla: A lot of work has been done on microbial concentrations in various environments but it is all published mostly in places you wouldn’t go to look for it, like building and cleaning magazines. A recent published study looked at the efficiency of vacuum cleaner bags and the impact of microbial burden in the air when you run a vacuum cleaner. OSHA has established that acceptable in-door air quality has to be below 1000 cfu per cubic meter. There is information out there, but many of these studies go back years and are hard to dig up. Recent literature has looked at the effect of new construction or renovation in a hospital on microbial load in the air in the rest of the hospital.

Bix: This work could eventually go in the direction of modeling probabilities to understand how factors impact a probability.

As Overall Equipment Effectiveness (OEE) is more often used by pharma, quality is a component of the evaluation. Is OEE being driven at the plant or corporate level?

Cohen: When you have multiple plant sites vying for more work, plants want to be seen as the most-efficient and most-cost-effective production center in the group, otherwise they may be in jeopardy. Generally, OEE is a plant-level decision as plant teams are trying to attract the new product work and keep their plant work from dropping off.

Forehand: At AstraZeneca, company-wide, lean manufacturing objectives are driven at the corporate level. Our company chooses to use OEE as one measure of lean plant practices and line efficiency. OEE is measured and monitored at the plant level. We have OEE targets for different types of packaging lines across the AstraZeneca network. We feel suppliers should also be using the same lean programs we use to put out a quality product, including OEE evaluations and enhanced automated inspection on their production equipment. As an example, one of our suppliers determined that if they doubled the frequency of preventive maintenance recommended by the equipment supplier, they ended up with less machine downtime and a higher quality product. These kinds of improvements have a big impact downstream. Automated inspection may initially decrease OEE at the supplier level, but in the longer term OEE should improve as problems are identified and corrected earlier.

FDA is focusing on packaging and labeling guidance to reduce medical errors. How can package redesign help minimize end-user confusion?

Cohen: Avoiding confusing labeling and packaging sounds good with one exception you don’t control. People don’t read labels.

Bitner: Exactly. I think there is an inordinate amount of information in the literature that is neither pertinent or relevant to the patient. The drug manufacturer is mandated to provide a road map–sized amount of literature folded multiple times and wadded up into a one-inch square. What begins as a massive insert becomes nothing more than a single sheet of paper when delivered to the patient at the pharmacy.

Cohen: Labels have to be clear and concise. You certainly have to be able to tell one strength of product from another. However, it requires people to read. For a long time, the ophthalmic industry had color coding of caps to denote what type product you have. Color coding of caps can be ineffective if another manufacturer is using a similar color. It has happened many times when people standardize on labels where you wind up looking at me-too’s on the shelf and people grab the wrong one. Also in the operating room, you want things clearly marked so dose strength is clearly visible and easy to read in a quick moment when someone has to grab something.

Forehand: Standardization of packaging components across our packaging network is seen as an efficiency enabler for us and our suppliers. However, you have to be careful if you are standardizing packaging across the pharma industry too much as you are increasing the ability for counterfeiting to take place. Also, you want packaging and labeling that differentiates products from each other so pharmacists won’t confuse them. Years ago, we had a drive at one of our sites for different color labels across all products and strengths as a way to help operators distinguish one product from another. The problem we ran into was we ran out of truly distinct colors. Today, we use different colors to differentiate between strengths of a product, but we use product name logos with differing fonts to distinguish between different products.

Bix: I think there’s a huge opportunity for standardization of labeling. It helps in that people could look for the information they need that’s most

germane to them in the same place. We are using an information processing model from the discipline of cognitive psychology to guide tests which we can use to actually measure perceptual and cognitive behaviors. Our goal is the creation of designs that are based on science so that we can enable people to easily encode and comprehend things, even in very chaotic environments. I think there are a lot of opportunities for quantified decisions in this space and hope the standards that emerge will be based on data.

Cohen: In a lengthy study some years ago with another university, we submitted an exhaustive amount of samples to people to see what they could read. We came up with a conclusion as to what colors worked best on the packaging and changed one whole marketing division’s graphics. Then new marketing people came in with a whole different concept as to what they wanted their packs to look like. That standard went right out the window.

Larsen: I’m working with subcommittee F04.22.28 “Formatting and Labeling” of ASTM International Committee F04 Medical and Surgical Materials and Devices. They are attempting to standardize a master label template for arthroplasty implant products. It’s a heroic effort chaired by an orthopedic surgeon from Wisconsin. You can’t argue with the premise: If you’re standing on one side of the room and you know you need a 12-cm hip stem, for example, the nurse can pick it out on the other side right away. The trouble is different companies feel their format is the perfect label and they know what their customers want. There is conflict, and different companies are hesitant in making changes or agreeing to a standard way if it doesn’t match what they are doing. This would be a voluntary standard, so how do you get people to agree? Be careful of voluntary standards. There have been occasions where, over time, they have “morphed” into requirements.

Fotis: Medical packaging departments have been validating the functionality of their packaging for many years. There are seal-strength tests, accelerated aging, simulated distribution, and visual inspection. A next step for the industry is validating the label copy of the package. By obtaining test data via voice of the customer research, a company can determine whether the “open here” arrows are quick to find and easy to understand. Surveys of simulated or actual users could determine how long a nurse takes to preinspect a package before opening it. How long does it take to properly orient it, to find the expiration date, and to confirm the product is usable, and then how long to actually access the device? Cardinal Health, like several other medical device manufacturers, has taken candidate packaging out to the field in facilitated focus groups to determine how actual users not only react to the functionality, size, and shape of the package, but also the labeling.

Scholla: FDA in a recent meeting and AAMI in an upcoming conference are focusing on human factors in medical devices that are intended to be reprocessed in the hospital. FDA is clearly concerned about instructions around reusable medical devices: how to disinfect them, how to take them apart and clean them, how to put them back together again, how to sterilize them. If I look down the road, I think that we will start seeing application across additional areas that FDA is concerned about related to the human factor element.

Are there advantages for manufacturers with the proposed One-Document approach where elements such as the package insert, Med Guide, and the pharmacies’ printed material would be combined?

Bitner: I’m not so sure about that. If all that information is in a single document, how do we print it, how do we assemble it to the package, how do we assure ourselves that the patient gets that wad of literature, and how can we as the drug manufacturer ensure that they are going to read and comprehend everything provided. The right people are more likely to get the information intended for them with separate pieces of literature. It is way too cumbersome to squeeze all the copy, graphs, and drawings required into a single document. My view is combining all the literature into a single document is heading in the wrong direction.

Cohen: I worked with a PhRMA task force for over ten years with FDA trying to get them to approve an electronic package insert, to get it off the package, get the paper out of the way, and get it electronically available where it needs to be in the dispensing pharmacies. There is something currently in the works at FDA to prepare a proposed rule change to allow that to happen for manufacturers. At the same time, there is another industry group working with FDA to place the Med Guides, the wallet cards, all the laymen’s information that’s given to the patient when they receive the script off the package and into the same software at the pharmacy that prints the label. That’s all well meaning, but if somebody doesn’t have the conversation with the patient, there is a disconnect. The interaction with the pharmacist who is giving you that bag is the last chance you have. Sticking it on the vial doesn’t mean it will be read. As John has said, we used to have to put two or three Med Guides attached to a leaflet attached to the bottle, and I can almost guarantee you that none of the patients got any of the information at the pharmacy. I have yet to receive a Med Guide in unit-of-dispense packaging from mail order. There are two glue spots where they ripped off the leaflet. It is replaced by a printed version that is not exactly the same level of information.

Bix: Studies have suggested that when people are inundated by information it can become overwhelming. As such, I would support the idea of concise and standardized information that enables providers and patients to access information that is critical to their needs. That said, I think it is important to carefully consider design decisions. For instance, we recently did a study that investigated the effect of color on the ability of patients to notice the prescription warning labels placed on vials at the pharmacies’ discretion. An eye-tracking device was used to gauge patients’ ability to notice these colored strips. We compared the behavior of a panel of college-age students with a 50-plus age group. The differences in their behaviors were quite startling. The older population just sat on the white pharma label, where the younger people very actively rotated the vials and looked at the warning labels. Possibly the Internet generation is less linear in their processing. I think that it is very important to understand the needs and behaviors of the patient in order to make informed decisions.

Cohen: Back in the 1980s, the Giant Food chain put in a new—and costly—labeling scheme for their OTC product lines with pictorial information on the labels and signs on the shelves. It drew attention to the things they needed to find on the label, and helped non-

English-speaking people. Unfortunately, it didn’t get picked up by anybody else.

How is downstream quality being addressed, such as when manufacturers’ qualified packaging is cast off in the “last mile”?

Larsen: What makes me cringe as a medical device packaging engineer is there are times when we do not know what happens to the product once it gets into a large distribution warehouse. They may be grabbing sterile packaged units from a multipack box and combining them in a distribution box with other product for a specific point-of-use. We need to understand when the original packaging system is no longer in place and if or how package protection might be

compromised.

Scholla: One of the questions I always ask at our seminars is how many of our packaging engineers have actually gone to a hospital and watched their product arrive. Usually, one or two out of 40 or 50 say they have done this. And I ask: What did you learn? No cardboard goes upstairs. People design shelf packs for shelves, but in many instances the shelf pack never makes it to the shelf. It is dumped into a plastic bin that fits perfectly on the hospital’s organization shelves. While we wouldn’t like that to happen, there is another viewpoint. If this is what normally happens, you have to design your sterile barrier system to meet those challenges. Also, you will have one-off situations. A box is left on a loading dock in Spain over the weekend, and it rains. By Tuesday morning it has mold spots on it. The label says sterile unless opened or damaged. Is it still OK?

Larsen: Often times we do not understand our distribution cycle. We will do a particular ASTM D4169 Distribution Cycle stress test on our packaging system to judge its design performance. In reality, it may not represent what it will be exposed to once it goes out the door. There is not nearly enough thought, money, and time devoted to address these unknown downstream issues, and it is frustrating because it is a significant concern; they can and do cause damage in the field. There is very little control of the packaging system once it leaves your finished goods.

Package coding requirements to support package traceability are in place in France and Turkey and coming in the United States. How active are companies in deploying in-line coding at this point?

Cohen: When somebody comes forth with a set of standards that the industry can live with on both the manufacturing side and consumption side, this thing will happen. As the rest of the world leaves the United States behind, it is going to be a form of catch up and then you will have more than one type of system being used globally. Hopefully, we will not have to live with that. It would be nice to have a standard system that all of us could use. Standards development is taking way too long.

Efficient packaging for global markets

Members of PMP News’s Editorial Advisory Board focus on low-volume packaging trends.

Companies are challenged to maintain production efficiency as trends from new global markets to personalized medicine lead to smaller lot sizes. Against the back drop of a changing business model for pharmaceuticals and regulatory expectations, a Quality by Design approach by pharma and medical device firms can yield a deeper understanding of product needs and packaging requirements, leading to more options in materials and processes.

Speaking on the issue for this year’s Industry Outlook are the following members from PMP News’s Editorial Advisory Board: Jordan Montgomery, technical fellow, Medtronic CRDM Package Engineering; Dan Penny, director of packaging engineering, Cardinal Health; Laura Bix, assistant professor, Michigan State University School of Packaging; Rich Hollander, vice president, packaging services, Pfizer, Inc.; Michael Forehand, principal packaging engineer, global engineering and technology, AstraZeneca Pharmaceuticals; Michael H. Scholla, global director, regulatory and standards, Dupont Medical and Pharmaceutical Protection; D. Bruce Cohen, principal, PackTechPlus LLC; and Curtis L. Larsen, principal, Spartan Design Group. The roundtable is moderated by PMP News senior editor Dave Vaczek.

Q. Is low volume packaging comprising a larger part of companies’ product mix?

Larsen: Low volume packaging will always be there especially with new start up products. You are always starting with low volume and if marketing hits a home run you are up and running on high-speed form-fill-seal (FFS). But you have to have ways of handling these low volume, limited-distribution type products that we all deal with in a regulated industry.

Penny: There will always be a certain portion of the product line or the startup codes that will be low volume. We tend to do many more high volume products, but there will always be a need for low volume packaging.

Forehand: What we see is a lot more growth in some of the global emerging markets that are lower volumes. We want to be able to provide these markets with packs in their local language which meet local requirements. There are opportunities there that create challenges in the packaging space.

Larsen: Low volume packaging is all in the eyes of the beholder. If an OEM with a $100,000 defibrillator sells 100,000, that’s huge. If you are selling an experimental LVAD device that costs $1.4 million to put in and monitor-- 20 of those a year is pretty good.

Q. Low volume packaging could comprise new product for which demand is uncertain. You also have low volumes when drugs lose patent.

Hollander: That might not translate directly to small lot sizes; rather that might translate to a decrease in the frequency of runs. It will depend on a multitude of variables-- manufacturing lot size, inventory carrying costs, etc.
Scholla: As devices or pharmaceuticals come out you have the low volume part at the beginning but you also have companies that make high volume products. How do you make those material choices and packaging form choices? Do you start with pouches and eventually switch over to FFS? Do you use the same materials?

Penny: In some cases it depends on capital. If we have capital sitting on the floor in FFS machines and we have capacity, we may choose to purchase a die that will make that other size of package. If we don’t have capital on the floor it might be more likely we make a decision to go to a pre-formed package early on until we can justify the capital. Capital often helps drive that decision.

Scholla: And your choice of materials? When you are coming out with something new and you know it will be low volume, do you pick new packaging materials or do you go with the old standbys?

Penny: If time-to-market is urgent and we have aging on a material combination, that would receive a logical preference. We can use an existing aging study and not have to repeat that before launch. We have Tyvek pouches that we have accelerated real time on that would improve our time to market. If there is a requirement for the product that would preempt us from doing that we would be forced to look at a new material even if it was a pre-formed package.

Larsen: You hit the nail on the head. If you can use something that is pre-existing and you don’t have new device fragility requirements that you need to address you are going to go with what is proven, what works, and what you have specifications on--toxicity, biocompatibility, and stability data. Until something pushes you out of that area, why wouldn’t you use the data you already have.

Montgomery: We would do that whether it was going to be a high volume product or a low volume product. We focus on the requirements of the product first. From a production efficiency standpoint it is exactly the same thing. We would have our process capabilities and production efficiencies set for high volume or low volume products with the same criteria in mind.

Penny: The only thing that we would maybe do a bit differently is if we come out with a new product line that we know is going to be high volume. We may be looking at what kind of cost savings we might be able to get. If we have to put in a new FFS line, does the product have characteristics that would allow us to come right in with a less expensive material. Or maybe we go in with the standard material as you said and we are already working on something that is lower cost, because we know it is going to be a real high volume product.

Larsen: You are absolutely right. If you know that this is going to be a home run, and you have to tool up, start ordering FFS way ahead of time for your off shore plants.

Penny: Absolutely correct. If it is low volume we are probably mostly looking at time-to-market and something that will meet the requirements and not try to drive cost efficiency right up front.

Cohen: People have different definitions of low volume. If you are putting out a cancer drug the number of units you may sell would be classified as low volume but the dollars you generate in sales would not be and that may have an impact on the decision you make on how to put that pack out on the market. A lot of my clients are small-to-medium size with volumes you might consider low; they would not. In some cases they don’t have the wherewithal to do it so they are going outside to CMOs. That has an impact on their packaging decisions.

Forehand: It depends on your packaging process too. When we talk about low volume, we are talking about production order sizes where changeover time begins to creep into your conversion costs to a higher extent than you would like. That’s when we begin to think about new ways of working.

Hollander: That’s how Pfizer views it as well. A simple rule of thumb is when change over time exceeds your run time. And quite frankly we find that less in the US and more in emerging and our European markets.

Forehand: You might have a similar pack you make for the US market as you might make for an emerging market but if you try to run the emerging market’s volume on the same asset the changeover time between product strengths gets to be longer than your run time. For the US market you never really have that problem.

Hollander: What you are alluding to is our business has been evolving to require an increasingly higher proportion of lots that are low volume. This brings the equipment mix that we have in our sites into the spotlight. Do we have the right type of equipment for today’s demand versus the demand that we had in place when we originally purchased the equipment.

Penny: For international markets, the question for us is are we creating a separate international code because the product is different. For us in many cases it has been because of the labeling requirements. In some cases to minimize running the low volume codes we have gone to a global print where the same product we sell in the US has full global labeling on it. We have tried to minimize some of the lower volume runs with this approach. That is different than if it is a different product requirement for the international market.

Hollander: Most of us have similar strategies in place where we try to maximize a particular platform, for example, common blister card footprints or bottle sizes to minimize changeovers. We can further minimize the impact of small lot sizes by being clever about how we label product by looking for the opportunities to leverage common labeling—same package for multiple markets where we list all required languages on the same pack.

Forehand: That requires some standardization in your packaging as well. You need those (multiple) markets to take the same blister design or number of tabs in a bottle.

Penny: In some cases you run into geography issues where you don’t have enough room to do that. You then wind up with the lower volume codes due to the print requirement.

Hollander: We have been fairly successful as a company knowing where and how to leverage both shared and common packs, particularly in Europe and Latin America to help offset some of these smaller lot sizes in particular markets. We are doing what we can but we are concerned as to where things are headed with respect to serialization and the lack of uniformity in the coding standards. Technology does not allow you to put more than one serial number on a pack. If you have three different codes for product identification on the pack required by the health authority for the three respective markets we are sharing the pack with, and they also start requiring to tie a serial number to the product code in the three barcodes carrying the product code, we will need to revert back to individual packs and have even more smaller lot sizes.

Q. What is the opportunity to consolidate products on lines that may be partly idle?

Hollander: There is no easy answer to that. I think it is safe to presume that all companies are looking to optimize their asset base so if we have under-utilized equipment within a site or across our network, we consolidate volume to increase the asset’s utilization. This sometimes means moving products between lines, sometimes across sites, and sometimes if it makes sense replacing/augmenting the equipment we have to better match the demand profiles of our products. There are a lot of different ways to make more effective use of your assets.

Forehand: Our equipment manufacturers for blister machines for solid oral dose packaging have done a really good job in improving the design of their equipment to support faster and faster changeovers, and I am sure this holds true in other types of packaging equipment as well. But what we see today is a lot of times equipment changeover becomes faster than the actual procedural changeover. It doesn’t take an hour-and-a-half any more to clean a blister machine feeder and change the tooling. They have automated the process to make it simpler and faster. Now the challenge for us becomes to change our procedural ways of working to match how quickly we can mechanically change lines. We need to continuously improve how we should operate with low volume.

Q. Can existing equipment be upgraded for more efficient for low volume production?

Forehand: There is a certain level of improvement you can make to equipment to make it changeover faster. That is something you are going to do regardless of what your order size is. Improving overall equipment effectiveness is constant across the entire volume spectrum; you will work on improving changeover as much as you can. The point here is that even our best efforts haven’t got it into the range where we are satisfied with how changeover time impacts our conversion costs for low volume.

Penny: I would agree with the procedural issue. We took a look across all of our plants where we had FFS lines and did a time mapping from shut down to start back up of the next order. We did this because we were looking to lower our order quantities to reduce inventory levels as part of our lean manufacturing efforts. Certainly there is more opportunity with the new technologies for faster changeover of the machine, but I would agree that we found that there was a lot more procedural downtime from shut down of one order to start up of the next than there was actual mechanical change over. By using a pit crew-type of approach where people were doing things concurrently--clearing paper, changing ink colors--we were able in some cases to reduce our downtime by 60 to 70% just by changing the way we worked, without changing any capital.

Q Does the trend to lower volume make outsourcing more attractive?

Cohen: The majority of the small-to-medium size companies I deal with do very little of their own manufacturing and packaging. For one client with a new product the CMO did everything for them—manufactured it, packed and labeled it, and shipped it out. They had an emerging market order where they wanted 500 units for an annual usage in that market. It was a problem getting those made without losing your shirt because they couldn’t take 500 units out of their US stock and re-label it. Do you do a separate order, do you go to bright stock and have someone else do the packaging and labeling. Many of these new products for emerging markets tend to be very small orders for the first couple of years until you establish yourself and actually have a product line with increased sales. It is not a Pfizer world or Merck world where with some products out of the box you have hundreds of thousands or millions of units you are selling.

Hollander: That is not really the case these days any more Bruce. We don’t have many blockbusters these days. In terms of the direction of big pharma, we see an increase in precision medicine targeting populations with certain genetic profiles for which we our products will be most successful. The lot sizes tend to be very small and the overall volumes tend to be very small as well. We are learning how to manage the complexity that comes from these types of products as the volumes are comparatively smaller and for all markets, US included.

Cohen: I’m dealing with volumes now where less than 25,000 units is a production lot.

Hollander: Yes, we are talking about the same thing, as many lot sizes are well less than 3000 packs. A point I would like to make is we need more of our OEMs to start understanding that the business model for pharma has changed. I think there are a lot of technologies they need to embrace faster that will help us with managing these small lots, such as making use of our digital assets when it comes to printing, quick change machines, and machines that will allow us to postpone production as late in the process as possible and allow us to get it to the intended market/patient quickly. It is not just that there are small lot sizes; ideally what we would like is to delay the packaging, not just the labeling, until we actually have a demand for the product from a particular market. If we package product even as bright stock we are tying up money in inventory; we are only buying ourselves flexibility in which market we will target the filled package. When dealing with such small volumes and expensive products, it is optimal to fill/label/pack to a specific market demand if at all possible.

Q. Digital printing becomes more cost effective when dealing with lower volumes?

Hollander: There are a lot of technologies in the area of digital printing. We have been leveraging digital print technology for 15 years on lid stock and 20 years for shipping case labels! Over those years technologies have evolved in this space very well so now we can digitally print tiny bar codes as well as six-point font on knurled blister packs and have it readable. When we move to cartons, are we talking about digitally printing cartons on line, at/near line, or having the carton supplier digitally print in their own site to match our small lot size demands. The same thought process applies to leaflets. There are a lot of different ways to skin it and each one of them with different potential technologies to support it and different points where one method makes more sense financially from a total cost perspective than another. Each company needs to define how it wants to leverage the technology based on their demand profiles, printed component type/sizes, equipment base, and capital plans.

Larsen: Last year during the HealthPack 2012 conference we visited Ethicon Endo Surgery in Albuquerque where they have print-on-demand set up for all their instructions for use. It was simply amazing—a truly versatile system. They ran what they needed for each job individually. You can make changes on the fly for each lot and you don’t have a lot of waste.

Q. Are companies adopting a Quality by Design approach for new products?

Montgomery: Very much so for our organization. We are designing for liability of products and designing for manufacturability of products. QbD is being pulled into product development at the earliest levels.

Larsen: This has always been a part of any good engineer’s process--coming up with the most effective, safe, and functional package. It is getting a lot of focus now and that is a good thing, but if you were an engineer worth your salt you were doing this 30 years ago.

Penny: I agree with you Curt. We’ve always done it. In some cases, we have formalized doing FMEAs (failure mode and effects analyses) as a part of any packaging project. So we have put in more formal techniques but we always would be looking up front at potential risks and building in the controls for those.

Larsen: We have formalized tools of measurement and that is all good. But I think it has always been a part of industry.

Hollander: We design our container/closure system to be fit for use; namely to protect our products for the environment, be able to deliver the right dose and not interact with the product. In pharmaceuticals, most companies are now working to better understand the specific protection needs of a product so they can optimize what type of container closure system is to be used and leverage that product understanding to use good judgment in pursuing post approval packaging changes to minimize unnecessary stability programs.

Forehand: Our thinking is right in line with that. We are looking for the opportunity to understand the product better and that will allow us to optimize our packaging. As a conservative industry, pharma has probably over packaged in a lot of cases. 
We are trying to think creatively about how to best protect the product keeping in mind the product characteristics and risks. This allows us to advance objectives like sustainability, reducing pack materials by weight, and reducing the amount of material we buy to provide cost savings.

Bix: I had the opportunity to attend a conference earlier this summer where Dr. (Janet) Woodcock spoke and touched briefly on QbD. The thing that struck me that was maybe different from traditional approaches is they are starting to engage the end-user behavior more than they have historically. Where it has always been about product protection, product efficacy, product safety; they are talking about the user being a part of the risks and the user being part of the benefits, and how can the system deliver not only from a product protection standpoint, but how does the system interact with the people to deliver what it is supposed to do. My spin on that is that FDA is moving toward a more inclusive model in terms of what the system needs to deliver. How will people use it, how will they interact with it, and will it deliver from that end of the spectrum as well as what we have traditionally focused on.

Larsen: Is this the human factors part of the equation that is certainly getting more and more focus, with the new human factors standard that has been written? This is really important.

Bix: Yes, I think they are rolling it up into QbD and saying safety and efficacy is not just about the interaction of the product and the package. But the package also has to be used in the way it was intended to be used. You are looking more at total system risk and total system benefit and testing or evidence that will be more robust than it has been in the past.

Montgomery: Laura, what you have said regarding the user very much aligns with FDA’s whole design control philosophy in Part 820. You need to establish your users’ needs and the intended uses of the product and that has to flow down through each level of design via design inputs and design outputs. It is very clear that is the expectation of FDA and it is how you conduct design validation. You need to show that your final product including packaging is mapping back to your users’ uses of the product.

Q. As you derive a better understanding of risk, or the edge of failure with QbD, this creates more options for packaging and processes?

Larsen: Yes. What is the fragility level of this new artificial brain? What do I need to do to package it most efficiently so it will get there but won’t cost me an arm and a leg. We often times don’t know what that fragility level is. As a result, we’ll over package it. So we’re not doing our very best as an engineer in optimizing the cost and maximizing the protection because we don’t know what it takes, how much protection the package contents need.

Hollander: If we can deepen our understanding of our product packaging needs we can further optimize our packaging to use less packaging--lightweight bottles, down gauge film thicknesses, etc. One thing we are progressing internally is a modeling tool which helps us predict how our product will react at various temperature and humidity conditions over time with any known container/closure system we have qualified. The tool leverages data generated from experiments where we look to determine how long the product can withstand extremely aggressive temperature and humidity conditions for relatively short timeframes. With this knowledge, we can accurately predict what container closure systems we need to use in order to obtain a target expiration date for a specific ICH climactic zone.

Scholla: QbD is not a new concept, it has been around for ever, right? For me this comes down to two questions: How much more time do we spend documenting for appropriate regulatory agencies around the world that we design quality in? And, though we may be over packaging as has been discussed, is it really worth financially redesigning packages that then under go additional scrutiny because they are new and different?

Forehand: In understanding your product needs you are gaining flexibility for post approval changes, where you are lowering the cost and complexity of those changes.

Q. Pack-to-order is an approach to the small lot size trend for global markets. What is the outlook for medium-speed, high-flexibility machines?

Hollander: The need is definitely there and the equipment manufacturer base has certainly stepped up their offerings in recent years. I would say they are still all in the low single digit serial numbers in terms of number of pieces of equipment delivered to customers at this point. We are at the very beginning of the life cycle for this type of equipment.

Penny: We are seeing the need for some of the newer lower capacity lines and we have in some cases invested in Multivac FFS machines for more flexible production.

Forehand: One of the challenges is getting the equipment manufacturers to extend the reach of their technical support around the world, especially in the Asia and the South America regions.

Q. Are new markets prompting evaluation of new primary packaging materials?

Hollander: ICH Climatic Zones IV A and B have certainly required pharmaceutical companies to increase barrier protection for some products. These increased barriers are expensive and do impact cost of goods. Pfizer would like to see a new generation of high barrier films come to market with a lower cost.

Forehand: As with the equipment tech support, we would like to have more global supply sites from the pack material vendors.

Penny: There has been a move in that direction with some of the major global packaging suppliers who are more active in Asia. But I would agree; it is not enough and it needs to continue. We are looking at regional suppliers as opposed to counting on the global suppliers for Asia markets.

Q. Are extended cold chains promoting reevaluation of tertiary packaging and supply chain logistics?

Cohen: It is a question partially of economics. For domestic cold chain shipping we are usually working 2 to 5 days maximum. Depending on what you are packing, you can sometimes get two-day delivery and it usually works very well. If you are going outside the borders, you really have very little control of the pack after its leaves your door. Even if you use a special carrier, customs can hold you for weeks or longer. If you have a non-mechanical environment (cool packs) and you get stuck in a customs location, there goes your product. There is always an economic decision to be made: do you spend the money for a self-contained pallet load container that in worst case can be plugged in if there is a delay or that runs on its own fuel or do you cut that price and go to something that you build around a pallet in the hope that it makes a certain time delivery. Where do you justify spending $10 grand for an active unit or something under $5 grand for a pack around a pallet. The passive works well, until it doesn’t, then you wind up losing that shipment and what does that cost you?

Scholla: You bring up a very good point. You qualify your packaging based upon your distribution. The moment you move outside the US and Europe it is pretty hard to define that distribution cycle. There are so many idiosyncrasies that can occur. So it is very difficult to go to something cheaper because you don’t know what’s going to happen when its gets to Penang, Malaysia or Shanghai.

Cohen: One of my clients is shipping a pallet load of refrigerated product that is upwards of $800 to $1,000 a vial. I’ve got significant dollars invested in that product. Most of the time an active container will be reliable even if you are delayed. That is more insurance than a passive solution packed for a specific time period. Where I used to work we had a truck that crossed the Canadian border and sat in traffic because of a storm, froze up totally, and we lost the whole truck.

Scholla: The whole issue ends up being you are qualifying the packaging based on a distribution cycle that is not definable. There are way too many variables.

Exclusive Roundtable: Pharmaceutical Packagers: Compete through Innovation

Pharmaceutical packaging–focused members of PMP News’s Editorial Advisory Board discuss competition in a changing industry.

For this year’s pharmaceutical packaging roundtable, PMP News has brought together members of its Editorial Advisory Board with extensive experience in pharmaceutical packaging: John Bitner, director of packaging development, Watson Pharmaceuticals; Laura Bix, assistant professor, Michigan State University, School of Packaging; D. Bruce Cohen, principal, PackTechPlus LLC; Rich Hollander, vice president, packaging services, Pfizer Inc.; and Steve Hess, executive director of packaging technology, Merck and Co., Inc.

In this roundtable with PMP News editor Daphne Allen, they discuss the future of pharma packaging.

(Questions in bold are posed by Allen.)

How is the role of pharma packaging changing given the current economic climate? Downgauging or other packaging changes to reduce cost have been around for some time, but are there new pressures? Do these tie into lean manufacturing and sustainability initiatives?

Hollander:
 The pharmaceutical industry as a whole was suffering long before the global financial crisis. The crisis just exacerbated an already difficult situation. Product pipelines are not what they were 10 years ago, and there are stronger requirements for clinical studies to support a drug’s approval. The economic downturn affects people’s discretionary spending, and as out of pocket expenses for medicine fall into that category, many patients do not take their medicine as prescribed.  In order to continue topline growth, companies are pursuing more new chemical entities (NCEs) through in-licensing, partnerships, or outright acquisition as well as establishing strategies to grow sales from their own off-patent molecules. These approaches have changed our business model. Manufacturing organizations have had to work differently, with an increased focus on managing costs.

In the packaging area, this translates to a higher number of lots with much smaller lot sizes than what we saw 10 years ago. Within our operations, we utilize Lean manufacturing concepts to reduce overall lead times, while minimizing work-in-process inventory. Our packaging operations have put a significant effort into establishing the right metrics to measure overall equipment effectiveness (OEE) and have made great progress. Within package technology, we look to manage cost in a variety of ways. Examples include focusing on things we can control, such as downgauging materials with a “test-to-failure approach” to optimize material usage while ensuring sufficient product protection or partnering with suppliers to advance new technologies for component manufacturing, which would lower costs.
  
Cohen: There is a big push to reduce the number of SKUs globally. Many products have grown into multiple SKUs—I know of one product that has 400 SKUs alone. The sheer number makes it difficult and more costly to package. As Rich says, there has been an increase in smaller lots. The question is, can the products be packaged for global use in ways that use the same design and simply update the language, or can you combine languages?

Bitner: Of course, more SKUs infer a number of SKU’s having lower quantities, which tend to increase piece price and manufacturing costs. Many times, SKUs must remain so that patient needs are met as well as to fulfill our commitment to the franchise. Again, operational excellence is where efficiencies are discovered and consequently implemented.

Do you see any preferences for a global pack or regional packs?


Cohen:
 In some cases you can run a medium to large manufacturing lot and break it up into smaller packaging lots for regional packs. You can begin by packaging the solid dose in a blister with a single language or a bar code for identification and then at the time of the order packing add market-specific information and identification. The goal is to reduce the number of different-sized packages and SKUs. 

Hess:
 This is one area where packaging suppliers and equipment manufacturers can really help us. All of us are looking for opportunities to combine packaging for multiple markets. But when we do that, the literature gets larger and larger, and it can be a rate-limiting step. Helping us manage longer and longer product circulars is important until we get to paperless labeling.

Cohen: You have touched my soapbox, Steve! (Editors’ note: Bruce recently led PhRMA’s Paperless Labeling Task Force, and a few EAB members report anxiously awaiting FDA guidance in this area. )

This sounds like late-stage customization. Are today’s lines prepared?


Hess: Our packaging lines will need to be reengineered. Most of our lines are not currently equipped for late-stage customization. We do some digital printing, but only in isolated cases as we learn more about technology capabilities and market needs. 

Hollander:
 We have a multifaceted strategy for dealing with small lot sizes.  In addition to our focus on OEE, we leverage common pack labeling and also partner with suppliers to improve their ability to support the printed component requirements. Some suppliers are utilizing digital printing to meet these needs. 

Is technology the answer to competing in this new economy?

Hollander: Yes, technology will play a huge role in our ability to compete. Our industry has been spoiled with great products with large volumes and invested large amounts of capital in packaging equipment without understanding how we would use that equipment should the number of SKUs increase and the lot sizes decrease.  While our equipment suppliers offer equipment today that minimizes changeover time, that equipment is still expensive. Industry doesn’t have a lot of money to invest in new equipment while we have not yet depreciated our existing equipment base. We need smaller, more agile machines that are less capital intensive to ensure an attractive return on investment.

Bitner:
 We have placed emphasis on every facet of efficiency from management of vendors to monitoring of each packaging line activity. State-of-the-art awareness, and technology that even precedes state-of-the-art awareness, continues to provide a significant advantage to competitive strategy. Time studies and enacting the lessons learned from those time studies are significant factors in gaining efficiencies that translate to higher quality, expedient delivery, and lower costs.

Hollander:
 Pfizer has a strategy called “Capturing Our Global Advantage,” which aims to supply our marketing organization product at a competitive cost. We look to leverage Pfizer’s global network, which does include external suppliers. 
 
Hess: We are the same way. We are focusing on identifying the value proposition. Five or 10 years ago, we felt it was our right to package something coming out of R&D. We no longer have that right. We have to ensure we can provide the same value the external market can. If a contract packager is more efficient than we are or has unique capabilities that are not core to our operations, we will select that contract packager. This is a significant step change.

Cohen: Over time, manufacturers have been looking at going to other operations in countries with lower costs. Companies focus on getting those operations up to FDA standards so they can take advantage of the lower cost basis. They can then deliver the value promised to their customers.

So FDA’s increase in foreign inspections will support this trend?

Cohen: Yes.

Bix: And there is a lot of potential technology to track and trace products through the global supply chain.

Are manufacturers utilizing this technology now?

Bix: The drug side has been much more aware and proactive in tracking and tracing. But the sense I get from the medical device side is, “it hasn’t happened to us,” and that is naive.

How are initiatives such as Quality by Design (QbD) and Process Analytical Technology (PAT) influencing pharma packaging decisions?

Hollander: 
Our strategy to provide our marketing organization with competitive cost and quality forces a few things to happen. Our own internal sites now need to compete with low-cost locations, which include contract packagers. With appropriate automation and innovative technology, competitive sites could exist in the United States or other higher-cost locations. As a result, our internal operations have embraced technology and innovation as they realize that is their path to competitiveness.

Many manufacturers today are citing lean manufacturing and sustainability initiatives to run more efficiently. Is this driven by the economy?

Hess: We have certainly implemented many of the same approaches and have been operating in a lean mode for many years now. With smaller batch sizes, clean up and changeover become critical processes. We need technology to be more flexible. But I don’t want to focus completely on cost. There is opportunity for us as packaging engineers to add value. As products become more and more similar because claims are similar, there may be the chance for differentiation through packaging. Packaging can help payers, prescribers, and patients make their buying decisions. We have to figure out what they need and leverage them.

Bitner:
  Our clients drive a number of our packaging initiatives. They welcome our willingness and creative ability to 
differentiate. It is all about reason and logic and the courage to change. In the past, most resisted innovation because they could. Today, the competition is fierce. For instance, removing utility knives from the distribution center addresses the number one reason for downtime, personal injury, and damage to the product. A simple perforation around the perimeter of the shipper answered that challenge. 

Cohen: If you are the innovator, you have no competition. But if you are the third or fourth product, you have to differentiate your product.

Hess:
 It could be as easy as adding data elements such as bar codes to your packaging to facilitate the process for end-users to capture data more efficiently. It could be a recycling program to reduce waste in a doctor’s office.

Bix:
 In one of our classes, we had a surgical team from the National Center for Patient Safety set up a mock surgical room. We had gowned students present a number of medical devices and drugs to the aseptic fields, and the team took our students to task on some of the designs. It was quite enlightening in terms of the challenges. There is a lot we can do to deliver value through packaging. As patient outcomes drive the system through the Centers for Medicare and Medicaid Services, things that can improve value delivered to the patient will catch on.


How is packaging being used today to increase patient safety and reduce medical errors? What improvements need to be made?

Cohen: One thing that is relatively mundane is marking lot and expiration in a manner so that consumers can read it in the store. In other words, print it and not deboss it. I have on a number of occasions bought items that were expired, and I could not read that date in the store.

Bitner: Is that not the problem? Not whether lot and expiry are debossed or printed, but that expired product is on the store shelf?

Given the economy, can pharmaceutical companies afford to invest in making packaging a solution solver? 


Hollander:
 I cannot think of any company in our industry that would not pursue patient safety because of cost concerns. Our struggle is the need for standardization of the technical requirements to meet the business requirements for all markets, not just the larger ones, as our packaging lines do not differentiate between markets.

Bix:
 In terms of human factors, there’s a lack of understanding of prominence, conspicuousness, and legibility. We are trying to understand how perception and cognition help us develop tools in place to test designs for usability. We are trying to put science behind behavior so we can make more educated decisions behind design to mitigate and prevent error.

Hess: Rich hit on it with the need for harmonized requirements. Once we harmonize the requirements it will then be much easier for us as suppliers to comply with those requirements. Once we understand those requirements, we then have to drive adoption. Using the tools can help—such as the data in bar codes on packages—but the rate of bar code reading is still pretty low. We definitely need to get the adoption rate up and then we will find more useful ways of incorporating more data into our packaging to prevent medication errors.

Cohen:
 Companies want to use new technologies. But one company switched to soy-based ink for the environment, and most of the time its bar codes wouldn’t read because there wasn’t enough contrast and density in that ink. It will fall on packaging folks at manufacturers to look at the end-user and the supply chain to see how the product and package are used in the field.

Bitner:
 Packaging must be a solution solver. Failures are often the result of change for change sake. Collaboration is essential as long as the correct corrective actions are identified and agreed upon. We as packaging engineers should not only suggest that science be used to justify differentiation, but insist on it. Major supply side companies actually see a need, but then introduce a resolution with distorted promotions absent of technical foundation. Collaborate with vendors as a partnership . . . and then show me the data. Trade offs for immediate solutions could be devastating. As just one example, the market strives so hard for compliant packages that while handing out awards for sustainability, we load the landfills with resins not feasible for recycling.

How do we drive harmonization? Through the Sustainable Packaging Coalition? FDA? GS1 Healthcare?

Hess: GS1 is one area in which we can bring the entire supply chain together—industry, manufacturers, distributors, and providers—we need more opportunities like that to drive common requirements. There’s not enough of them right now.

Is there a need to revisit any attempts to make pharmaceutical use a more risk-aware, more-compliant experience? 

Cohen: 
You need to introduce packaging that is better for the customer and improves their access to the product and still meets your regulatory requirements.

Hess: 
That is what I was saying earlier. We have to demonstrate value and not focus on the cheapest package. It is about meeting their value proposition. Otherwise we will lose in the marketplace. The value has to be in the eyes of your patient.

Bitner: Our number one focus should be to educate patients. A package cannot do that alone, but as learned with direct-to-patient advertising, packaging can have a mighty impact. We must retain our focus for saving the lives of children and improving the quality of life for our seniors. It does not take a fortune to design an effective package. Packaging supply side seems eager today to collaborate with customers in meshing creativity and ingenuity with manufacturing prowess. Only through an all-inclusive cross-functional effort from cradle to grave will a productive package be possible without trade off or sacrifice to a key element. 

Cohen:
 You don’t want to put any barriers in between the patient and your product. If you have the best pack you will have a satisfied customer.

So perception justifies investment?

Hess: The iPod isn’t the cheapest MP3 player, right?

What challenges does compliance packaging face?


Bix: We continue to study child resistance and senior friendliness. There is a lot of variability that overlaps, so segregating those two populations into two neat silos is very difficult. One thesis found little difference between disabled patients and children in terms of strength and hand-to-eye coordination. The only real difference was the size of their hands. 

Bitner:
  Anthropometrics has identified that a small female hand is about the same size as a larger four-year-old’s hand. True, the introduction of computers to three-year-olds has accelerated eye/hand coordination. The unmitigated strength of an innocent, shy little child is amazing when she is committed to opening that package. What children lack is the wisdom of experience that comes with age. We can still out smart them. Therein lies the difference.

Cohen: In some patient focus groups we held on design, we found a love-hate relationship with no middle ground. We often had to decide who we would end up isolating when selecting one design.

Hollander:
 Speaking specifically about the U.S. market, I’m often asked for examples where we have designed innovative packaging to help patients. I can point to a variety of specific examples where we have designed compliance packages that were received very well by physicians, pharmacists, and patients. But overall I do not believe Pfizer or the industry have addressed the larger need here. There are a variety of factors to be considered when trying to understand why. For example, is the drug for acute or chronic use? If acute, is it approved for a variety of indications, each with a potentially different dosing regimen? How is the product likely to be dispensed to the patient, as it needs to be child resistant—how toxic to a 25-lb child is it? We also need to consider the pharmacist and how reimbursement programs may influence dispensing habits for the product.  All of that is considered when we sit with our marketing teams and discuss design.

Bitner: The number one reason for nursing home admittance is the inability to manage one’s medication regimen. That said, everyone should want to support every aspect of compliant packaging. Designers and engineers who are not aware of a child’s thought process or are not intimate with the daily struggles of the elderly are an impediment to their own initiative. Technical intellect exists within the realm of the multitude of packaging industries. It is their willingness to unleash it that drives success. 

Bix: Do you have concerns for the efficacy of your products in vials and in automated pharmacy packaging systems?

Cohen:
 I absolutely want the manufacturer’s bottle. Brand manufacturers do a 30-day and a 90-day package. Hopefully, that gets dispensed.

Hollander: 
Whether or not the manufacturer’s package is the dispensed package varies based on pharmacy type: mail order, retail, or hospital. Also, at the pharmacy, reimbursement plan polices, inventory carrying costs, and the level of automation factor into the decision of which package goes to the patient—the original manufacturer’s or the pharmacy’s repackaged vial. 

Bix: 
There is a big question lingering out there—all the safety and efficacy data is on the manufacturer’s package. It is somewhat of a mystery what is going on in vials, at 30 days as well as at 90 days.

Do packaging professionals need to get involved to change the trend toward manufacturers’ packages or is it an issue that FDA or state boards of pharmacy change? If everything goes to an automated-pharmacy, mail-order environment, what will the role of the packaging professional then be?


Hollander: Repackaging happens at three levels: large-scale repackaging for resale, which is regulated by FDA, mail-order pharmacy repackaging pursuant to a prescription, and retail pharmacy repackaging pursuant to a prescription. The latter two are governed by the State Boards of Pharmacy. The regulations on container closure systems are fairly consistent in that the repackaged product must not have an expiration date longer than 12 months (less if the remaining expiration date is less than that) unless they can provide stability data supporting the new package. 

Cohen:
 The barrier of a typical pharmacy vial is far less than what manufacturers have developed for shipping and shelf life. But in most cases, expiration dates are reasonable dates and the product is viable past that.

Where should packaging professionals focus their efforts?

Hollander: The purpose of the package is to protect the product and not interact with it. Throughout a product’s life cycle, we look to better understand our product’s needs and use that to optimize barriers required. Another area of focus for us is in the manufacturing of the components themselves. While we are driving forward toward new technologies to produce our components, we are also defining our critical-to-quality attributes, and in turn ensuring we understand our suppliers’ process parameters that control those attributes. We want not only to  achieve financial savings with these technologies, but also to improve the overall quality of the components themselves, which will lower total cost even further.

Hess: 
Life cycle management is an issue. The package may take on different roles throughout the product’s life cycle. Trying to maximize the product’s value through packaging is one of the new roles we’ve taken on. At the beginning, you need to communicate the product’s use and effectiveness, but later on the package may have a different role.

Cohen:
 Innovative packaging is for the beginning of the product’s life. But if you are on the down slope toward generic introduction, you’re looking to reduce cost basis. So if you are in innovative packaging at launch, you may not be at the end.

Bitner:
 The role of the package engineer begins on the side of the formulator. The role is to meet safety and efficacy needs from inception to the recycling bin. Packaging engineers cannot always depend on all those needs to be identified for them. We must assertively pursue some of those needs from wherever they may emanate. It is to deliver that packaged product to the patient as an intuitive tool for product access through the life of the script. That role includes not necessarily following, but guiding and supporting those packaging components from vendor to commercial availability through the pharmacy and into the patient’s hand.

Hollander:
 A perfect example is the evolution of our Z-Pak. We originally launched Zithromax (azythromycin) in a bottle of 50 capsules. But this product had a novel dosing regimen for an antibiotic: take two capsules on the first day, and one for each of the next four days. Physicians didn’t always prescribe the dosing regimen correctly; patients were confused when they got home. Prescription growth was slow. We then packaged it in a blister card with simple instructions on how to take the product and placed it in a carton with literature about why the dosing regimen was different. Packaging the product as a single course of therapy made it easier for the pharmacist to dispense. Our marketing team came up with the idea to trademark the name Z-Pak and have it represent a single course of therapy, so that it could be written as the prescription itself, making it easier for the physician to prescribe. The product sales started to increase at this point. Subsequent market research showed that while patients were now complying with the dosing regimen better, they weren’t reading the literature. So we came up with a wallet-style pack, and sales improved further. For such a highly successful product, we invested heavily in the equipment to package, which leveraged a lot of innovative technology in order to manage our cost. Twelve years after we introduced the wallet-style package, we realized the Z-Pak is a household name, and the need to educate the patient on its dosing regimen is not what it once was, so we have gone back to the original blister card and literature in a carton in order to further manage our costs.

Hess:
 Packaging professionals want to be part of the solution. If we can identify needs and harmonize them, we can then start to meet them.

On the path toward sustainability

Pharmaceutical and medical packaging professionals are finding new ways to help the supply chain reduce and recycle packaging waste.

Sustainability has become a priority for many companies throughout the pharmaceutical and medical device industries. Pat Bartholomew, Director, Environment, Health and Safety, at Baxter, tells PMP News: “Product environmental performance is an issue of growing importance in the healthcare sector, including the responsible treatment of healthcare products at the end of their useful life. Because the appropriate approach varies by type of product, companies can have a range of initiatives.

“For example, at Baxter, some of the electronic medical devices the company sells can be repaired and refurbished. Other products, such as intravenous (IV) bags, cannot be reused due to regulatory, quality, and safety reasons. However, they may be responsibly recycled to recover energy and materials for other uses.”

Therefore it’s no coincidence that many winners in this year’s AmeriStar awards program have achieved some measure of sustainability. IoPP’s AmeriStar winners this year have reduced package weight and footprint and have increased the use of recyclable materials, among other accomplishments. For instance, Ecoslide-RX from Keystone Folding Box Co., which won in the Drug & Pharmaceutical category, contains no plastic in its secondary packaging and requires minimal film and foil, Keystone reports. Dividella’s NeoTop top-load syringe carton for Sanofi Pasteur’s flu vaccine franchise is made from 100% recyclable paperboard material. A reduction in volume cut shipping and storage costs in half.

And in AmeriStar’s medical device packaging category, winners included the TKA Femoral Packaging System for Arthrex from Perfecseal and the CardioFocus HeartLight Cardiac Ablation System Balloon Catheter Die-Cut Tray by Beacon Converters Inc. For Arthrex, Perfecseal employed its new PerfecForm OrthoSecure, a new material combining both polyurethane and PETG in one two-layer formable film, instead of using a separate PU insert, reducing the number of packaging components. For CardioFocus, Beacon developed a die-cut tray made from 100% recyclable HDPE that uses 32% less packaging material and weighs 50% less than a thermoformed tray.

Packaging professionals are demonstrating they are key partners in sustainability. “Packaging teams are being called to help reduce energy consumption, material usage, and costs throughout the entire life cycle of the package without sacrificing the performance of their packaging,” explains Matt L. Doornink, packaging engineer/project manager for DDL Inc. “Although packaging is only a part of a product’s overall carbon footprint, it is often the most visible. Once a package has fulfilled its purpose, it is often found filling space in the environment.”

Manufacturers of life-saving products continue to proceed conservatively, however. “Medical device companies are struggling to create opportunities for sustainable practices as their paramount objective is to produce a quality, reliable, and effective product 100% of the time; and to deliver it to the end user in that same condition 100% of the time,” adds Pat Nolan, DDL’s president. “With this objective, MDMs will use whatever materials and processes necessary to ensure the products’ efficacy. However, sustainable practices are being used to reduce packaging materials through downgauging, using plastic materials that are more sustainable in their manufacture and use of raw materials, and optimizing the package design with sustainability in mind at the start.”

Supply-chain partners are eager for assistance with packaging waste. “Medical device packaging waste is a big problem for hospitals and clinics. Packaging waste for hospitals is a big cost to dispose of,” notes Nolan. While “some of the waste is considered infectious and must be disposed of properly through incineration, most of the medical waste is non-infectious. This packaging waste is often placed in regular trash bins and is land filled. There are few systems for recovering the medical device packaging waste for reuse or recycling. Some devices may lend themselves to be packaged in reusable packages. MDMs can develop closed loop systems to facilitate reclamation. Hospitals can request package materials that are more recyclable with training on the materials that can be segregated into special bins.”

Groups such as Healthcare Plastics Recycling Council (www.hprc.org.) and PracticeGreenhealth are stepping up to help hospitals and practitioners tackle waste, but they need help from healthcare products manufacturers. Medical device manufacturers in particular are getting direct requests from U.S. hospitals to help them reduce, reuse, recycle, or divert waste, reports Roseann Salasin, global marketing director, DuPont Medical and Pharmaceutical Protection, a company among HPRC’s founding members. The driver behind interest is regulation, she says. “Certain counties are restricting the amount of waste that can go to landfills,” she says.

HPRC continues to move forward with several initiatives to increase plastics recycling in hospitals, including plastic packaging. The group has organized pilots, developed guidelines to help product and package designers improve recyclability of disposable plastic products, and recently released a recycling tutorial for hospitals. HPRC members include Baxter, BD, Cardinal Health, Covidien, DuPont, Eastman, Johnson & Johnson, Kimberly Clark, Perfecseal, and SABIC.

Baxter reports that it is training its product engineers on HPRC’s Design for Recycling Guidelines. “Each HPRC member company is implementing them in various ways,” Bartholomew says.

“Companies can seek other opportunities to partner with waste management and recycling firms to test the economic and logistical feasibility of more efficient management of wastes generated from hospital products,” she adds. “This includes value stream mapping of hospital wastes to identify where and how the waste is generated.”

To increase awareness of the potential for plastics recycling, HPRC recently presented its hospital tutorial, HospiCycle, at CleanMed 2013, generating a lot of interest among hospital professionals, reports Salasin. “Recycling is now moving from a ‘nice-to-have’ to a ‘must-do,’ ” says Salasin. “We are also seeing efforts to monetize recycling. Hospitals are asking for help on what to do and how to get started.”

HospiCycle was developed with the help of HPRC’s Healthcare Facility Advisory Board, whose members, Kaiser Permanente and Stanford University Medical Center, contributed data, lessons learned, and insight from plastic recycling pilot studies carried out at their facilities. It was also based on findings from an early HPRC pilot study involving Cleveland Clinic, Engineered Plastics, and Waste Management. The tutorial helps hospitals begin to identify recyclable plastic waste, assess existing infrastructure to support recycling programs, look for recycling partners, and develop and audit recycling programs, among other activities.

Another HPRC-organized pilot study set to wrap up shortly with Stanford will provide further guidance. Tod Christenson, HPRC’s executive director, says that this pilot is enabling HPRC to identify the types and volumes of plastics that are typically seen in ten different areas of the hospital in order to understand the opportunities for plastics recycling. “We set out to identify points of aggregation and collection or interception,” he says. “This pilot demonstrates several considerations that must be made when managing waste and ordering supplies. It helps illustrate the variety of factors needing consideration when designing a plastics recycling program such as which departments represent the greatest opportunities, building/space logistic needs, internal stakeholder engagement requirements, union participation, hospital aesthetics, etc., that hospital professionals must consider.” 

According to Christenson, the pilot identified more than 70 tons per year of plastic currently generated by Stanford’s main operating room and eight other departments that have the potential to be diverted to the recycling stream, representing a 29% diversion rate. About 85% of such plastic is flexible, and about 15% is rigid.

In addition to helping Stanford with its own programs, the pilot will enable "HPRC to use such data to develop an additional worksheet for HospiCycle that can help other hospitals establish targets and goals," says Christenson. "We will also be able to make recommendations for hospitals on where to start and what to pursue as well as how to train employees, raise awareness, and monitor progress."

Hospitals are also beginning to look for ways to “monetize sustainability,” Salasin adds. “Sustainability has a positive impact on business profitability because the money spent on waste can be reduced. There are a number of ways to measure it, in terms of costs and space. The ultimate goal is to show the positive bottom line impact to business.”

Christenson agrees, and he believes that pilot programs such as Stanford’s will help HPRC develop data on the actual costs behind traditional waste disposal versus diversion to recycling streams. “It will help us flesh out the business costs and show hospitals the disposal costs that wouldn’t be incurred if waste were to be diverted,” he says.

Salasin will present HPRC’s programs at the upcoming Healthcare Packaging Immersion Experience (https://www.msu.edu/~hcpie/index.html) organized by Michigan State University’s School of Packaging. This event allows the audience to experience how their packaging impacts the clinician’s ability to provide care to the patient. This year, MSU is extending the experience to also include the impact of packaging waste and respective issues clinicians face with the intent to engage industry to help.

Salary survey: Healthy compensation, cautious outlook

Despite a pretty stable job market and growing compensation, survey respondents worry about downsizing and overseas outsourcing.

By Daphne Allen, Editor

The average salary for respondents in PMP News’ eighth annual salary survey is a healthy one—$89,200. More than half make $75,000 or more per year, and only 6% earn less than $50,000. On average, raises are healthy, with a mean raise of 5.1%. Only 8% did not receive a raise.

Given this job climate, most survey respondents are satisfied with their positions—less than 10% are actively looking for a new job. They have spent considerable time in the industry. The median number of years spent working in the healthcare product packaging industry is 13 years, with respondents working for their present employers an average of 10 years.

Despite such stability, respondents are concerned about market conditions such as consolidation and downsizing. Others fear anticipated threats from competitors, such as overseas operations or generics companies.

Perhaps driven by such competition, packaging professionals are keeping an eye on the bottom line. One respondent sums up the packager’s role in this way: “[My compensation] is directly affected by [my] ability to provide low-cost, high-quality products to the customer quickly.” Another writes that “adapting to new technologies and staying current with market direction” affects his compensation. Another notes that today’s packaging realities—“increasing materials cost”—can directly affect wages: “It is very hard to achieve your cost savings objective when everything is going up in price. This reflects badly on yearly review.”

Several respondents appear troubled over consolidations and cost cutting within the industry. Competition and outsourcing work overseas are other concerns. “Cost-saving initiatives and outsourcing increase shareholder value, but keep salaries down,” writes a respondent. “Downsizing puts added burden on survivors.”

“Possible price controls on products” will play a role, reports another. 
Others spoke of increased costs of oil and plastic resin as affecting wages.
Such market conditions appear to be driving lean manufacturing, which may present compensation opportunities for those professionals who can implement successful programs. “Lean manufacturing and cost-improvement progress” will affect compensation, writes one respondent. Others spoke of Kaizen programs. 
Many see value in their efforts. “Validation of package systems requires expertise in package development, qualification, risk assessment, and process control.” Wrote another: “RFID and other logistical technologies will possibly increase my compensation value because of my technical skills.”

Skills may pay off. “I believe my own performance level and utilizing the tools currently available to me will have a much greater affect on my personal compensation.”

METHODOLOGY

The data for this year’s survey were obtained during a mail survey of PMP News subscribers. The survey was designed jointly by PMP News and Readex Inc. (St. Paul, MN) and conducted June through July of this year. Surveys were mailed to 1200 domestic subscribers, representing 10,001 packaging professionals who work for manufacturers of medical devices, pharmaceuticals, in vitro diagnostics, and nutritional supplements.

The sample was limited to only those with one of these job functions: engineering, packaging design, production/manufacturing, QA/QC, and research and development.

Of the 1200 mailed surveys, 443 usable responses were returned, representing a 37% response rate. Because usable responses were received from less than half the survey sample, the possibility exists that those who did not respond might have answered differently than those who did.

The results in this article are based on the responses of 356 respondents who indicated that they are involved with healthcare product packaging and work full time. Statistically speaking, these 356 individuals represent an estimated 8000 industry professionals. The margin of error for percentages based on 356 usable responses is ±5% at the 95% confidence level. The margin of error for percentages based on smaller sample sizes—males or females, for example—will be larger.

The survey was conducted by Readex in accordance with accepted research standards and practices.

Three times for three lives

For years, Baxter has publicized its fight against medication errors. In 2002, Baxter set an aggressive deadline for bar coding all of its injectable and IV-solution products. In 2003, the Institute for Safe Medication Practices (ISMP; Huntingdon Valley, PA) recognized Baxter along with Alaris Medical Systems and B. Braun Medical with a Cheers Award for “furthering development of smart pump technology.” Soon after, the company would promote its Enlightened HRBC technology for bar coding IV-solution bags.

With this track record, it’s hard to believe that any of the firm’s products would be involved in a medication error. But according to CNN reports, D’myia Alexander Nelson, Emmery Miller, and Thursday Dawn Jeffers, all premature newborns, died in September from heparin overdoses. Instead of receiving Hep-lock U/P (preservative-free heparin lock flush solution, USP 10 USP units per ml), they received Heparin sodium INJ injection, USP (10,000 USP units per ml). Single-dose vials of Heparin sodium INJ injection intended for adult patients were somehow loaded into a neonatal drug-dispensing cart. Nurses obtained the typically adult-dose vials and injected heparin 1000 times stronger than prescribed into the premies’ IV lines.

Baxter believed it had taken several steps to prevent such errors. According to Baxter spokeswoman Erin Gardiner, the products in question featured different-colored labels (dark blue versus light blue), different bar codes, different-colored caps (one is gray and one is bright green), and different type styles.

Gardiner says that, “Prior to these unfortunate incidents at Methodist, Baxter had not received any customer complaints about perceived similarity of labeling between Heparin and Hep-lock U/P.”

Michael R. Cohen, RPh, MS, ScD, and ISMP president, says that, “when errors like this one happen, there are always multiple factors that contribute. These particular vials are not labeled all that poorly but do look somewhat alike because they are same color, size, have same drug name, etc.”

One culprit may be “at-risk behavior,” as described in ISMP’s September 21 newsletter, Medication Safety Alert. “When the nurses requested 10-unit vials, the automated device pointed them to the 10-unit storage location,” says Cohen. “Probably a thousand times in the past, the nurses stuck their hands in that bin and got 10 units/ml. They did same thing they always did—picked it up—it must be 10, they thought. But this time it wasn’t. Shouldn’t they have read the label? They probably thought they did when they saw the automated dispensing unit screen. But they should have read the label three times.”

Human nature may be at fault. ISMP points out that, “Behavioral research shows that we are programmed to drift into unsafe habits, to lose perception of the risk attached to everyday behaviors, or mistakenly believe the risk to be justified,” it writes. “Over time, as perceptions of risk fade away, they take shortcuts and drift away from behaviors they know are safer.” For example, a nurse who takes the time to practice safe habits may be criticized. But a nurse who speeds care for several patients in one shift may be admired, and others may follow her example. “Therein lies the problem,” ISMP argues.

Perhaps at-risk behavior should just be assumed and prepared for. That’s precisely how packagers can make a difference. Packaging and labeling cues could play a role in forcing practitioners to pay attention to product differences.

Daphne Allen
Editor

Reducing packaging time of surgical saw blades—safely

A new system makes changing heat blocks for blister sealing safer, while improving heat transfer and sealing-time efficiency.
The Aergo 2 Plus features the ATEX (automatic heat-plate tool exchange) system, which allows operators to change hot and heavy heat plates safely.

Synvasive Technology Inc. (El Dorado Hills, CA) has carved out a niche in the medical device market by making surgical-steel saw blades for orthopedic surgeons to use when reconstructing bones and preparing joints for implants. Synvasive’s blades include a patented tooth design known as Stablecut, which is intended to cut more accurately and more coolly than competitive blades.

Synvasive packages the blades using a new Aergo 2 Plus sealing machine from SCA Consumer Packaging (DeKalb, IL; formerly Alloyd Co.). Operators at the machine’s two stations place blades into secure, easy-to-open trays at the rate of 16 per cycle.

According to Allen Culuris, manufacturing process engineer at Synvasive, the company ordered the new Aergo 2 Plus because increased demand was requiring more packaging capacity. The new Aergo 2 Plus is now the primary sealer.

The Aergo 2 Plus medical tray sealer is the latest version of SCA Consumer Packaging’s ergonomic line of medical tray and retail blister sealing machines, incorporating design changes intended to make operation less stressful for both operators and trays. The unit is a front-to-back shuttle sealer that includes two load-and-unload stations, each with a shuttle-bed apparatus to slide the trays under the press-and-seal station located in the center of the machine. Depending on workload, either one or two operators can load trays, products, and lid stock, in that order, into cutout areas in the nesting tray that rides on the shuttle apparatus. Because the machine’s operation is largely based on the operator’s pace, any ergonomic enhancements can increase productivity.

Improvements incorporated in the newer Aergo 2 Plus have made the shuttle smoother and ergonomically easier on operators’ hands. The table is 40 in. high—a height recommended by industrial designers for maximum comfort—and a footrest has been added.

The newer sealer also features SCA Consumer Packaging’s patented ATEX (automatic heat-plate tool exchange) system for changing heat plates during package changeovers. The system enables operators to change hot (up to 500°F) and heavy (up to 12 lb) heat plates safely and more easily, without having to call for additional help.

Synvasive Technology uses the front-to-back shuttle sealer to package its surgical-steel saw blades.

Heat plates are changed using transfer trays. The operator places an empty tray on the shuttle bed and then turns the ATEX system key to the “unlock” position. The Aergo 2 Plus automatically lowers the hot heat plate onto the tray and releases the positioning cones that keep it aligned. The operator then moves the tray to a holding cart and positions another tray holding the new heat plate on the shuttle bed. The ATEX key is turned to the “load” position, and the Aergo 2 Plus automatically activates clamps that grip and hold the positioning cones, securing the heat plate in position. The connection is positive, and alignment is perfect each time.

“The ATEX system really cuts changeover time,” says Culuris. “We now change over in 25% of the time it took on the older system without ATEX.”

While SCA engineers were developing the patented ATEX system, they also studied the transfer of heat from the machine’s heat platen to the heat block that does the sealing. The heat block is a custom-machined tool, the contour of which perfectly matches the geometry of the tray flange to which the package lid is to be sealed, focusing heat and pressure during the sealing process to the precise points on the package where they are most needed.

What the engineers found was that, because the ATEX system seats the heat block to the machine’s platen perfectly each time and locks it in place securely at three points, heat transfer between the two parts meets less resistance than it does in machines where the installation is done by hand.

In practical terms, the increased heat reaching the blister means less dwell time is required for each seal, increasing the number of blisters that can be sealed per hour.

The ATEX system seats the heat block to the machine's platen perfectly each time and locks it in place securely at three points.

“Our study showed an increase in transferred temperature of 4%,” says Ken Sullivan, director of marketing for SCA Packaging. “Small as that seems, it was enough to increase the productivity of the machine we studied by one cycle per minute. That amount of increase adds up very quickly.”

For Synvasive, the new Aergo 2 Plus with ATEX produces approximately 32 blisters per minute, while the older SCA sealer that the company had used delivered about 18. When time needed to load and unload twice as many blisters and blades per cycle is taken into account, the gain is significant.

The newer heat blocks also feature an Alloyd Armor coating, a codeposit of Teflon and electroless nickel to separate the block from the blister tray. Earlier blocks used a Teflon-impregnated fiberglass membrane that could be a source of contaminating particulates and had to be replaced when it wore with use.

“These coated blocks have yielded more-consistent seals and better process capability (Cpk),” says Culuris.

SCA Packaging also aimed to make machine validation less time-consuming. A validation port on the Aergo 2 Plus enables Culuris to continuously check the time, temperature, and pressure settings of the sealer while it is running, letting him keep a running record of those numbers.

“I attached a data logger to the port,” he says, “which collects temperature data every 2 seconds and continuously charts dwell time and air- pressure figures. Since it went into operation, temperature in the Aergo 2 Plus heat platen has varied only about 3°F, which is acceptable.”

Synvasive’s Aergo 2 Plus was validated and placed in production in June 2006. As new tools and heat blocks are delivered, Culuris needs only to run a few hundred blisters from each one to demonstrate that they work as described. Then they, too, can play their role in streamlining the company’s production schedule.

Salary survey: Innovation adds to compensation

Amid outsourcing and consolidation fears, packaging professionals find that advancing their companies' operations may also advance their careers.
 
By Daphne Allen, Editor
 

According to Wikipedia, outsourcing “is often defined as the delegation of noncore operations or jobs from internal production within a business to an external entity which specializes in that operation.”

Outsourcing has respondents to PMP News’s 2006 salary survey a bit concerned. “Trending of outsourcing labor to Far East and Mideast countries is reducing the number of local U.S. companies,” writes one respondent. “This will negatively impact the amount of job opportunities as well as the potential of salary increases due to the lack of competition for professionals.” Several other respondents specifically identify outsourcing as a trend that will affect their personal compensation in the next year.

Respondents are also concerned about downsizing and cost constraints, rising costs of raw materials and energy, generic competitors, and patent losses.

For now, though, salaries aren’t suffering. On average, respondents to our survey earn $90,400 annually. Half make $88,000 or more. The average raise was 5.2%. Only 9% state that they did not receive a raise from their employer. Last year’s average annual salary, which was based on a different group of respondents, was $89,200.

More than three-fourths (76%) of key respondents are satisfied with their current position, and only one-third are either actively looking (8%) or strongly considering (25%) a new job search.

Some respondents even speak of a shrinking workforce. “I think a shortage of experienced professionals in pharmaceutical manufacturing contract outsourcing will keep salaries high.”

Despite their worries, many respondents speak enthusiastically about the products they are packaging and the emerging technologies they are employing. For instance, one respondent describes healthcare products that use “different areas of body access.” Such projects have led the respondent to “create new business models with a new product platform that is not as mainstream to ease body entrance.”

OUTSOURCING, CONSOLIDATION FEARS

A significant number of respondents are worried about outsourcing. One is “concerned about outsourcing engineering to China and India,” but doesn’t “know how that might affect medical device engineers over the short term” in terms of job stability and pay. Another respondent paints an even bleaker picture: “I see the single most (sic) event that will affect domestic (USA) employees will be the continued outsourcing to China, and soon to be on the same level will be India.”

“Products moving offshore into India, China, [and the] Far East will reduce opportunities in the United States,” predicts a respondent.

One respondent links “lean” operations with outsourcing. Another offers an explanation: When “outsourcing to low-cost countries . . . cost is not a function of labor cost but of total cost, including tax rates on revenue.”

Also concerning respondents are consolidation and mergers between companies. “Consolidation/sale of division will remove potential for any promotions,” laments one survey respondent.

“Downsizing is encouraging me to retire,” writes another.

The merger with Boston Scientific and Abbott, for instance, is affecting at least one respondent’s compensation.

MONEY, MONEY, MONEY

As their employers seek to control expenses through outsourcing and other transactions, packaging professionals, too, are keeping an eye on costs. They may be rewarded for driving costs down, or they simply may be losing opportunities for compensation increases.

“Scale-up of batch sizes will lower conversion costs,” explains one respondent. “If this is achieved, all marketing receives a 10% bonus.”

Another respondent speaks of trends toward “automation and [the] ability to apply and save packaging costs.”

Virtually all (96%) respondents have some influence on packaging decisions: 37% authorize or approve purchases, 28% recommend purchases, and 20% are part of decision-making committees. Eighty-six percent use the Internet to research suppliers, and 56% have used the Internet to purchase materials or equipment.

The state of the U.S. economy is influencing these purchasers’ compensation, and therefore may be influencing their decisions. “Fuel costs [are] impacting our prices, sales, and ultimately compensation (e.g., raises and bonuses).” Writes another: “Cost of materials (inflation) eats up margin.”

Other respondents report that the loss of patents as well as increased competition from generics will affect compensation. “BMS products coming off patent protection” will affect at least one respondent.

BRIGHT SPOTS

These economic woes haven’t dampened hopes, however. Respondents speak of advancing technologies and products influencing compensation. “Automation and process history impacts quality,” writes a respondent. “Scientific understanding and engineering know-how should help,” says another.

The implementation of “lean and Six Sigma” and “new technology” and “robotics” as well as improvements in “technical skills” and “increased efficiencies” will also affect compensation.

Packaging professionals are looking for the latest innovations. “Diverse packaging involves more testing,” writes one respondent. Another points to “medical moisture-barrier packaging. Five new packaging projects all need this.”

Demand for healthcare-related products may also add to salaries. “Baby boomers are starting to retire,” notes a respondent. Another points to “the general aging of the population.”

Perhaps resulting from such aging, many trends pointed out by respondents are emerging: “Growth of the orthopedics segment;” “Diabetes treatment, such as insulin pumps and smaller, more precise devices;” “Increased positive indications for the use of implantable devices to treat heart conditions;” “New products and combination products (drugs and devices);” “New medical devices for therapy and diagnosis.” Many respondents are awaiting the completion of clinical trials or the launch of new products to see a change in market demand—as well as in their salaries.

METHODOLOGY

The data for this year’s survey were obtained during a mail survey of PMP News subscribers. The survey was designed jointly by PMP News and Readex Research (St.Paul, MN) and conducted June through July of this year. Surveys were mailed to 1200 domestic subscribers, representing 11,313 packaging professionals who work for manufacturers of medical devices, pharmaceuticals, in vitro diagnostics, and nutritional supplements.

The sample was limited to only those with one of these job functions: engineering, packaging design, production/manufacturing, QA/QC, and research and development. Known suppliers to the industry and those with job titles of administrative assistant, attorney, buyer, CEO, CFO, consultant, owner, president, purchaser, or secretary were manually omitted from the sample by the editors before the surveys were mailed.

Of the 1200 mailed surveys, 416 usable responses were returned, representing a 35% response rate. Because usable responses were received from less than half the survey sample, the possibility exists that those who did not respond might have answered differently than those who did. Survey results should be interpreted with this in mind.

The results in this article are based on the responses of 317 respondents who indicated that they are involved with healthcare product packaging and work full time for a medical device manufacturer, in vitro diagnostic manufacturer, pharmaceutical manufacturer, and/or nutritional supplement manufacturer. Statistically speaking, these 317 individuals represent an estimated 8600 industry professionals. The margin of error for percentages based on 317 usable responses is ±5.4% at the 95% confidence level. The margin of error for percentages based on smaller sample sizes—males or females, for example—will be larger.

The survey was conducted by Readex Research in accordance with accepted research standards and practices.