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?
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.