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Articles from 2015 In November


"World of Cups 2015" and Launch of the New Large IC-RDM 76K

Heilbronn, June 2015. –  „World of Cups 2015“in line with this motto ILLIG, manufacturer of thermoforming lines, welcomed almost 200 participants from the whole European economic region and even from South America and India to their RDM-K Open House in Heilbronn, April 21 and 22. Presentations on state-of-the-art automatic pressure forming machines of the RDM-K series for combined forming and punching were supplemented by different practical machine demonstrations. Serial production of samples of different shapes and sizes was demonstrated on a total of six state-of-the-art high-performance thermoforming lines. The participants were particularly interested in two exhibits: The new large IC-RDM 76K which was presented to the public for the first time as well as an IC-RDM 70K, interlinked with a newly developed RDML 70b IML-T unit.

Cups with sealed rims were produced on the new, large IC-RDM 76K out of PP using a 60-up mold, cup diameter 75 mm, height 100 mm – with an hourly output of about 126,000 cups. The higher productivity of the IC-RDM 76K can be attributed to its even larger forming area (760 mm x 530 mm) compared to the forming area of the well-known IC-RDM 75K (700 mm x 450 mm) which is already considered “large”. The lower table in lightweight design is also a new feature which still allows high movement speeds in spite of the enlarged forming area, such as achieved by the IC-RDM 75K. Very precise movement sequencing is achieved together with very high running smoothness and in conjunction with an innovative gear for the main drive this last but not least also results in an extended service life of the mold. Further performance features such as calculation of basic setting for all heater and machine parameters, process monitoring to detect possible material tears, visualization of process data for analysis and optimization of the thermoforming process, optimized mold change, etc., allow a very high productivity of the IC-RDM 76K with high process reliability and high product quality at the same time.

Decorated rectangular polypropylene tubs were manufactured on the IC-RDM 70K production line with RDML 70b, forming area 680 mm x 300 mm, using an 18-up mold, at a speed of 16 cycles/min resulting in an hourly output of 17,280 tubs. The tubs were decorated on all four side walls and the bottom in brilliant photo quality directly during forming.
An IML unit especially designed for this task removes the printed labels from a magazine and places them into the mold’s cavities in the forming station of the thermoformer. During the subsequent forming process the label bonds permanently and true to contour with the part’s walls. The large decoration area is a special benefit contributed by the IML-T technology which, among other purposes, can also be utilized to comply with the new legal obligation to provide nutritional information. Moreover, the label can even add to increased pack rigidity – subject to geometry and quality. As a result, the material thickness can be reduced (saving of material costs) and the pack’s top load is still maintained. The fact that every cavity in a mold can be loaded with an individually printed label is a further advantage provided by the IM-T technology developed by ILLIG. This also allows product changes to be performed fast and with little effort. Labels made of all conventional materials can be processed as well as labels made of PS and PP even through to paper labels.

ILLIG is a global leading supplier of high-performance production lines and molds for thermoforming plastic materials as well as of solutions for the packaging industry. The company's product and services portfolio comprises the development, design, fabrication, installation and start-up of complex manufacturing lines and individual components. With branch establishments and agencies in over 80 countries, ILLIG is locally present in all markets around the globe. For more than 65 years, this owner-managed enterprise has been serving its worldwide clientele as a reliable partner in cost-efficient thermoplastic molding of sophisticated precision parts backed by innovative technology of unsurpassed quality and a comprehensive worldwide after-sales support.

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Further information:

Wolfgang Konrad, Director Public Relations

ILLIG Maschinenbau GmbH & Co. KG, Robert-Bosch-Straße 10, D-74081 Heilbronn

Phone: +49 (0) 71 31 / 5 05 – 2 36, Fax: - 12 36,  E-Mail: [email protected]

 

Editorial contact and voucher copies:

Dr. Georg Krassowski, Konsens PR GmbH & Co. KG,

Hans-Kudlich-Straße 25,  D-64823 Groß-Umstadt – www.konsens.de

Phone: +49 (0) 60 78 / 93 63 - 0,  Fax: - 20,  E-Mail: [email protected]

Combination products: What role does packaging play?

For the last few years there’s been a steady stream of new combination products, and deepening trends toward self care appear to be encouraging even more. Home healthcare is growing just as healthcare systems are being encouraged to improve patient outcomes, so devices that ease drug administration and encourage compliance continue to be in demand. And as healthcare systems look to reduce the length of hospital stays and prevent readmissions, pharmaceutical-enabled devices are being employed to shorten procedure times and promote recovery while minimizing the chance for practitioner errors.

Hence the increase in the number of prefilled syringes, pen injectors, inhalers, and drug-eluting stents. Other combination products include orthopedic products, infusion pumps, wound care products, transdermal patches, and more, reports Allied Market Research in “Global Drug-Device Combination Products Market (Product types, Application, and Geography) - Size, Share, Trends, Company Profiles, Demand, Insights, Analysis, Research, Report, Opportunities, Segmentation and Forecast, 2014 – 2020. The firm divides applications for combination products into the following categories: Cardiovascular, Non-Cardiovascular, Urological, Bone Treatment, Antimicrobial Treatment, Cancer Treatment, Ophthalmic Treatment, and Diabetes Treatment.

And it is a growing market indeed. Transparency Market Research (TMR) predicts that the global drug device combination products market will grow at a CAGR of 7.9% between the years 2013 to 2019. It valued the 2012 market at US$66 billion and expects it will reach US$115 billion by 2019. The report is titled “Drug Device Combination Products Market - Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2013 - 2019.”

WHAT FDA IS SEEING

Anya Harry, M.D., Ph.D. Medical Director for Voisin Consulting Life Sciences (and former FDA medical officer and branch chief), reports that a total of 330 combination products were submitted to the FDA Office of Combination Products for review in FY330, compared with 264 in FY2012. And there were 828 inter-center consulting requests in FY2013, compared with 660 in FY2012.

When asked to explain the difference between total combination products submitted for review and total inter-center consult requests, Harry, who gave an overview of combination products during Pharmapack North America in June, says that the “total combination products submitted are the numbers of applications sent to the FDA for review, while the number of total inter center consult requests are the numbers of requests from one center to the next for consultation. For example, if the combination product is a part of a New Drug Application, then the Center for Drug Evaluation and Research will consult the Center for Devices and Radiological Health to provide input regarding the delivery aspect/component of the application and vice versa.”

Harry says these totals “show there is more interaction between the different centers at FDA for review of these applications,” Harry says. “Not all combination product applications are reviewed necessarily by two centers. If [an application is] very straightforward, one center may review the whole application without consulting another. For example, heparin lock flush solutions are combination products; however, CDRH reviews the application without consulting CDER unless there is a complex or new issue.”

PACKAGING'S ROLE

So what role should packaging play in this burgeoning market? The packaging for combination products can be just as complex as the products themselves. Designers need to identify specific product and user requirements for both primary and secondary packaging. And not only must packaging serve the traditional roles of maintaining product integrity, efficacy, and perhaps even sterility, it may also need to be patient friendly by promoting user convenience, safety, and compliance. Package design should therefore be built around both product and end-user needs.

When it comes to designing primary packaging for combination products, Eric Schmohl, Customer & Application Support Manager for DuPont Medical & Pharmaceutical Packaging, explains that considerations depend upon the risk analysis of a product and the applicable standards.

“With regards to vials and syringes, [designers must] protect liquids from any contaminants, visible or nonvisible, as well as [promote safe] handling both by the nurse and the patient,” Schmohl says. Considerations therefore include “usability, biocompatibility, extractables and leachables, and potential sterilization of the content.” In addition, the prevalence of automated filling lines adds “easy processability” to the list of needs, he says.

Inhaler canisters and cartridges for pens need to be easy to handle for patients of varying age and capabilities, says Schmohl, calling it “a very special consideration that rarely applies to a primary package of a mere medical device."

Immediate plastic packaging for drug products requires different levels of documentation, depending on whether they are for oral or topical products, for inhalation, or for parenteral or ophthalmic administration, adds Schmohl. "And there is further differentiation on whether it concerns a solid or a non-solid dosage form. In essence, the requirements for plastics that are in direct contact with a drug are higher in terms of documentation of chemical interaction, extraction, and toxicological information than compared with a mere medical device. As a rule of thumb, primary packaging of a combination device requires more-sophisticated packaging design and validation than that of a typical medical device. Adding a drug functionality to a standard product such as an intravascular catheter will turn this product’s packaging development into a different story. The different standards for medical devices and medicinal products need to be consolidated, and this results also in different solutions and total costs of packaging."

In addition, "particles and particle burden is of high interest, especially to those manufacturers who handle non-solid drugs. This is less of a concern for a majority of medical devices,” he says.

For combination products that are required to use a sterile barrier system, the sterilization method drives packaging materials selection and design. In some cases, the secondary packaging serves as the sterile barrier. “For pharmaceutical products as well as for products to be used in the operating room, secondary packaging can serve as ‘dust’ protection to allow for moving product from the gray to the white zone,” Schmohl says. “But it can also be a sterile barrier to allow for protection of a product such as a prefilled syringe for use in an ophthalmic surgery, which needs to be sterile on the outside for immediate use.”

If a combination product requires both sterilization and a moisture barrier, the secondary package (e.g., aluminum pouch) can encapsulate the porous primary packaged unit after steam or gas sterilization, Schmohl says. “In this case, secondary packaging serves a need that is in conflict with the sterilization required, but there are solutions where just another conversion step of the sterile barrier system after sterilization can turn a porous package to a non-porous package, too (e.g., vented aluminum bags with a second seal to close the vented area).”

Secondary packaging for combination products may serve as the sellable unit, says Schmohl. As a result, it must support visual needs and labeling requirements such as Unique Device Identification and instructions for use (IFU), which should fit within or be printed on the surface, says Schmohl.

The secondary pack may also include several units.

Unless marketing and the look of a packaged unit play an important role, the protection needs will define the least costly configuration in most cases, Schmohl says. “Functionality of primary and secondary can vary or be exactly the same depending on the case. Unit cost per packaging will usually decrease from primary to secondary and so further as protection requirements do,” he says.

A special function of a secondary or perhaps a tertiary shell can be protection against temperature variations, Schmohl adds. “It can start with a white or reflective box versus a dark-colored one and end up in a box made of insulation material,” he says.

KEEPING THE USER IN MIND

Packaging professionals responsible for developing solutions for combination products should also consider human factors for increased acceptability of the product by patients as well as treatment compliance for better clinical outcomes, says the team at Voisin Consulting Life Sciences.

Some of the market’s best growth opportunities include biotech drugs and advanced therapies with associated devices for a number of user-focused functions. Challenges in design and development arise from the need to ensure completion of such complex tasks as the accuracy of doses delivered and the need to support repeated use and/or cleaning processes, say Harry and her team at Voisin.

In keeping with design control practices commonly used for traditional medical devices, Voisin Consulting Life Sciences advises considering the following:

Develop and Document Input Data: Consider both client requirements for packaging and labeling as well as regulatory requirements along with any such data from previous similar product development and risk analysis. Should also include functional specifications for packaging as well as safety and performance specifications as expected for the intended product use.

Conduct Design Reviews: Meetings should include an interdisciplinary group of professionals (including packaging professionals) and should be held periodically and documented. The reviews should cover package and drug-delivery device design and all development studies. Any deviations and solutions should be identified and documented.

Perform Design Verification: Professionals should evaluate whether output data complies with input data in terms of package and drug-delivery device function and safety.

Perform Design Validation: Professionals should evaluate whether the performance of the package or drug-delivery device design satisfies the requirements of the intended product application.

Document Output Data: Professionals should demonstrate and document conformity to input data and approve the design specifications, ensuring that the package or drug-delivery device design is inline with production and control capabilities. Should consider key features for safe use such as leaflets, labeling, and all marketing and training tools.

When following design control practices as well as working to meet any special circumstances or needs, Harry and her team advise packaging manufacturers and suppliers as well as contract manufacturers to recognize that the drug-delivery device is both a container closure and a device with specific functionality affecting both safety and efficacy of the contained drug. “This should be fully taken into account during development by device manufacturer,” she says. “A close relationship between drug and device developers is highly recommended.”

The Medical Packaging Community is tracking the growth of the combination products market, and we are curious about the role packaging plays. Please join our community and complete our short anonymous survey to help us better characterize the market and associated packaging. (The survey link can be found in the community lounge's message board.)

We’ll share the results with you just as soon as we can.

ISO 11607 to be revised

Get ready for a pretty different ISO 11607.

Nick Fotis, global packaging director for Cardinal Health, tells PMP News that ISO 11607 Parts 1 and 2 have begun to go through the revision process. Fotis recently joined David Johnson from Halyard Health as co-chairs of AAMI Working Group 7 to succeed Jackie Daly Johnson, president of Beacon Converters. Additionally they will be on the U.S. delegation to the ISO Technical Committee (TC) 198/Working Group (WG) 7 Packaging when it meets in December. 

At AAMI’s April meeting, Jackie Daly Johnson was thanked for her work in leading the committee, particularly her efforts in taking ISO TS 16775:2014 through drafts, revisions, and publication.  “ISO 16775 is the ISO guidance on the application of 11607,” explains Fotis. “It is not a standard itself, but a guidance on 11607.  In the United States, it replaces AAMI TIR (Technical Information Report) 22 and is also known as ANSI/AAMI/ISO TIR 16775:2014.”

Fotis reports that a total of 58 comments have been received from all over the world regarding proposed changes to ISO 11607. Jordan Montgomery, technical fellow for Medtronic CRDM Package Engineering, working on behalf of the AAMI TC198/WG 7, suggested that the document be reorganized to flow better, Fotis reports. “Currently, the document starts off with the materials section, but that’s really not how package engineering starts. Instead, the document would start with methods to determine customer and device use requirements. Material selection really flows out of packaging format and sterilization decisions,” Fotis explains.

The U.S. group proposed that “the requirements of the current document be maintained, but the current sections 5 and 6 would be reorganized into sections 5, 6, and 7. This proposed revision came out of a task group from the AAMI WG 7 lead by Montgomery and Jane Severin with David Johnson and Brad Bushman of Standard Textile, as well as input from Patrick Polito of Moog, Miraj Sheth of G.E., and Carol Smith of BSCI,” Fotis continues.

Other revisions were also suggested. “Many are editorial or updates to test standards, but there are also several technical comments,” he says. “These comments were reviewed at the meeting and the United States established a position on these comments to be discussed at the ISO meeting in Berlin in December.” 

In December in Berlin, all members of TC198/WG 7 (representing as many as 28 countries) will be meeting to discuss and prepare the committee draft for revising ISO 11607. All 58 comments will be considered, including the U.S. delegation’s suggestion to reorganize the document’s flow.  “We expect a lot of discussion on the format change,” says Fotis.

The committee draft revision proposal is expected to be available to committee members in early February 2016, after which the AAMI committee will vote and prepare comments. The next steps would include discussing all comments at another TC198/WG 7 meeting and then producing a Draft International Standard, then a vote and comment period on the DIS, then preparation of an Final Draft International Standard for voting only.

Fotis hopes to see more industry engagement. “More people from medical device manufacturers and converters should get involved in AAMI. In general, AAMI members can participate by providing comments that can be incorporated into future documents and help influence the way those documents are structured,” says Fotis.

Fotis adds that once ISO 11607 is revised, ISO 16775 will be reviewed to determine whether changes to ISO 11607 are substantial enough to warrant changes to ISO 16775.

Fotis, Montgomery, and Scholla all serve on PMP News’s Editorial Advisory Board.

4 ways inserts could help medical device manufacturers reduce costs

Medical device packaging teams may be asked to take a certain percentage of costs out of a given product each year. It may surprise you, but redesigning one component—the insert, often called the IFU (instructions for use)—may help.

Material
“The easiest way to save money on your IFUs is by finding less expensive materials, such as moving from 40# to 27# stock,” explains Lori Robinson, who handles communications for Robinson Printing. The company recently hosted a tour for the Institute of Packaging Professionals’ Southern California Chapter.

“As an example, we have made a suggestion to one of our customers to change a material in their In-Sheet product. We have found a better-looking, less-expensive material that will save them 5%,” she says. “The challenge is that the customer will need to change its specification.”

The very thinnest paper Robinson Printing uses is a medical-grade, 27# white opaque offset. “We print black ink on this very thin paper and see-through (of the ink) just simply isn't an issue. However, if our customers have a concern about this, we suggest using a special Pantone grey ink. This ink is still very legible, but eliminates any problem with show through on a thin sheet.” Many customers do want to continue using only black ink, and Robinson says that “it really has never been a problem.”

Particulates from the inserts have never been a concern or an issue either, she adds. “The paper is medical grade and this ensures very clean, fuzz-free paper,” she says.

Layout
A company can also save quite bit by reviewing its current IFU program, says Robinson. “We can often make suggestions for better layouts and sizes that will save the customer on material costs and more efficient layouts. For example, a better fold can get an IFU through a folder much more quickly saving valuable time and money.”

Robinson encourages medical device manufacturers to get in touch during the planning process so the final IFU is the most cost-efficient design possible, she says. “Our customer provides us with a final desired folded size for their IFU (based on product /package dimensions) along with the text. Based on this information our Graphic Designers will layout the IFU (including all the folds) to fit the final desired size. This ensures the final IFU is not obtrusive to the already planned packaging design. At this point we provide a folding sample so the customer can ‘play with it’ in the product's packaging and make any final tweaks to the design.”

In the case of a language expansion or other addendum to be added to an already existing IFU, Robinson says that her company can augment an existing IFU with an added panel or two by simply expanding the paper size. “This process is tricky, though, because there are certain folds that are optimal for speed through the equipment and for a nice, clean finished look,” she says. “When expanding an existing IFU to accommodate extra information, it’s important to use an expert in designing IFUs so your new design is as cost efficient and professional-looking as possible.” 

Quantity
Another way to save money is simply to order in higher quantities, Robinson says. “Simply taking the time to plan your orders for six months to a year can save a company significantly,” she says.

Format
There are alternatives to the traditional insert. Robinson Printing offers InSheet, an insert or booklet that can be attached directly to a pouch or carton. The format can be used to streamline labeling practices and be customized in terms of layout for maximum space and lower pricing, reports Robinson Printing. “If the IFU is placed on the pouch, then multiple pouches can be placed in a carton ensuring the instructions do not get separated from the device,” she says.

There are also user benefits. “This would ensure the instructions stay with the device until it is removed from the pouch in a sterile operating room setting,” says Robinson.

Robinson Printing can also print on the liner of In-Sheet. “One customer prints important regulation symbols onto the adhesive liner. They like this option because the liner is permanently adhered to the packaging so symbols remain with the packaging," Robinson says. "Currently, we only have used black ink for this process, but we have the ability to print up to 2-colors on the liner. If someone wanted full, 4-color process, we could pretty easily retrofit our machinery to accommodate them.”

One customer had subjected to a drop test Robinson Printing’s In-Sheet holding a booklet, she reports. “They had an issue with the front cover of the booklet ripping off from the adhesive. This was solved by providing a thicker outer cover for the booklet. We are often closely involved in our customers' testing and validation practices and look to provide solutions both for quality and cost savings to the problems they encounter.” 

Focused on medical packaging design and technology?

Standardizing labeling

ISPE seeks to improve clinical trial personnel understanding and practitioner patient compliance through standardized booklet labels.

ISPE (www.ispe.org) has developed industry guidance to help companies conducting global clinical trials standardize booklet labels. Available for purchase on the group’s Web site (http://www.ispe.org/ispe-good-practice-guides/booklet-labels), the ISPE Good Practice Guide: Booklet Labels was developed to help train clinical trial personnel on proper booklet label use.

“ISPE is pleased to introduce its first Guide to support standardization of booklet labeling requirements globally,” said ISPE President and CEO Nancy S. Berg, in a statement. “Companies involved in clinical trials now have a resource that provides guidance on how to design and structure a booklet label and how to standardize the use and application of booklet labels for global clinical trials. By following the recommendations presented in the Guide, companies can feel confident that their booklet label strategy is supported by a scientific, risk-based methodology and that patients will receive accurate, complete, and compliant instructions in their local language.”

ISPE was particularly interested in “standardizing label information, proper use of the booklet label, ensuring compliance with applicable country regulations and enhancing site and patient understanding and compliance with label instructions,” explains Michael A. Arnold, R.Ph., senior director strategic relationships and investigational products business process owner at Pfizer, who served as mentor to the Guide task team.

“Labels are an important component of a clinical trial supply package,” he explains. “Among other information, they are a source of communication to the study sites and patients regarding proper use and storage of the product. Most people are used to seeing a single label on their medication provided by the local pharmacist. In clinical trial materials (CTM), we need to provide investigational product information to patients around the world and in multiple languages. The booklet label allows the pharmaceutical industry to prepare large volumes of required supplies efficiently and cost effectively. Benchmarking showed clearly that the pharmaceutical industry uses booklet labels in several different ways and standardization could be of value for investigators, patients, and global regulatory authorities.”

Standardization could also help promote patient compliance. “It is important to understand that in the clinical study space, label purpose and content is often very different than what most patients see when receiving a medication from their local pharmacy,” says Arnold. “In clinical studies, by nature of study design, the placebo and active components of a study look identical and are not discernible to the investigator, study personnel, or the patient. Therefore, label information is extremely critical, and any improvement or simplification of its use can lead to greater accuracy in dispensing and overall patient compliance. Important label attributes include: container identification, patient identification (patient number), storage instructions, dosing instructions and, where appropriate, emergency contact information. Each country-specific label must meet applicable country regulations, and for the most part, these are not standardized and can lead to potential compliance errors as well.”

ISPE also sees potential to increase operational efficiency. “Operational efficiency is important for a number of reasons, which can include containing costs, timely preparation of supplies to ensure no interruption in patient supply, compliance with applicable local regulations, and simplification of patient use and ultimately enhancing patient medication compliance,” explains Arnold.

It could also reduce relabeling. “Labels are very high on the list of reasons for audit citations,” says Arnold. “The purpose of this guide is to take the learnings and feedback from regulatory inspectors and industry experts and develop a guide that will minimize the chance of these issues reoccurring and to drive toward a more optimal, business-efficient, patient-focused and regulatory-compliant process within our industry. I think the authors and contributors of this guide have produced a very valuable document for our industry.”

During development of the guidance, “feedback was obtained from a number of pharmaceutical companies who routinely conduct clinical trials and have received study site feedback,” he says. “An inspector from European MHRA also provided some experiential feedback as well. Obtaining direct feedback from patients is complicated due to legal and confidentiality requirements.”

Lori Robinson of Robinson Printing (Temecula, CA), which prints clinical trial labeling but was not involved in development of the guidance, says that “My first reaction is that standardized instructions is a very good thing. I would imagine doctors, nurses, and patients would appreciate being able to immediately find product information because every IFU [instructions for use] looks similar. The standardization of product instructions can only improve their effectiveness.”

Robinson Printing hits 90th anniversary in printing

Dave Robinson was just two years old when his father Mike became owner of Robinson Printing, so he has long witnessed—and now helps guide—the family-owned company’s ongoing growth. Celebrating its 90th year in business in 2014, Robinson Printing continues to evolve in terms of technology and capability, offering labeling innovations to solve real-life customer challenges. The company will exhibit at Medical Design & Manufacturing Westin Anaheim February 11-13 at Booth 5375.

“You’ve got to keep your ear to the ground to identify what the next customer need might be,” Dave says. And, over the years, “we have been fortunate to be able to invest in equipment. Today we are using faster, more accurate, automated equipment that has allowed us to innovate. If you cannot upgrade to meet customer needs, you could be left behind."

Evidence of the company’s equipment investments is one of the original presses purchased second-hand by founder Joseph Robinson in 1924, now sitting in the front office. “Since my great-grandfather Joseph opened his stationery and printing shop in downtown Long Beach, we have strived to find our niche in order to keep us competitive and relevant,” continues Dave. The company began by offering letterpress printing, and as the technology increased, “so did we.”

Joseph was able to guide his new company through the Depression (and later a World War and war rationing). “The challenges he faced are not unlike those we face today,” says Dave.

In the 1930s, Joseph’s son Norman studied printing at Long Beach Poly, and given his experience in the family business, helped teach a few classes, explains Dave. Shortly after, Norman took over the business, adding greeting cards to its offerings, and later automation in the 1950s. “Our first Heidelberg press was installed in the 1950s, and it was one color,” says Dave.

Norman’s son Mike was born in the 1940s, and at a young age became a printer’s apprentice. Mike did venture off to pursue a sports writing career, but given that “printing was his second nature” and he preferred the environment of the family business, he rejoined in the 1960s.

Mike ended up leading the business after one day in 1969 suddenly claimed the lives of both Mike’s father, Norman, and grandfather, Joseph. “My dad went from being an employee one day to the owner the next. It was a trying time,” says Dave.

“Without our tight-knit family of highly skilled and caring employees we would not be where we are today,” Dave’s brother Steve adds.

In the 1970s, Robinson Printing was working with Pacific Christian College, which would later become Hope International University, which had asked the printer to move along with the college to Fullerton, so the company started a new chapter in a new location. Mike later took on a partner savvy in electronic prepress processing, eventually buying him out. He then sold the Fullerton business and purchased a new one in Temecula, switching the family name to the new business and entering the world of medical printing in 1981.

“We worked with a small medical device manufacturer in the area, and we grew along with them,” says Dave. “For more than 30 years [our] specialty has been medical instruction printing. While we also produce full-color commercial work, our main focus is this high-quality, incredibly accurate printing that accompanies medical devices, pharmaceuticals, and other complicated products.”

In the 1990s, the printer saw demand increase for medical device labeling solutions that could fit in a lot of text in smaller and smaller footprints, says Dave. “Demand for multiple-language instructions grew, so we developed labeling solutions for map-fold designs and booklets. In the beginning, it was around 8 languages, and now is up to 32.” To support such map-fold and booklet designs, Robinson Printing invested in miniaturized folding equipment that could work with unique paperstocks.

Medical device manufacturers still use booklets, but map-folded options are increasingly popular. Dave says that “packaging requirements are changing, and the package size drives the size of the insert, so companies are selecting map-folded designs folded to specs.” The printer was also being asked for smaller and smaller footprints, so it worked its way down to 1 1/8 x 1 1/8 in. and now is adding new equipment to get down to 7/8 x 7/8 in. The equipment will be dedicated to such applications, reducing set up time.

Robinson Printing also developed new adhesive-backed instructions for use (IFUs). “When a customer approached us to develop a way to provide an adhesive backer to their thick, map-fold IFUs, we devised and customized machinery that uniquely would meet this need. Today, Robinson Printing’s In-Sheet is a one-of-a-kind adhesive IFU used frequently by our customer base throughout the medical device industry,” explains Mike. The design also allows medical device manufacturers to avoid having to include such an insert inside a package subjected to sterilization.

The company has built equipment that can produce large-format In-Sheet IFUs. It has even moved 192-page booklets to the In-Sheet format. “It really is designed for larger IFUs, not minifolds, because glue dots typically work in those cases,” says Dave. “But we can customize the equipment to fit what we are doing.”

Robinson Printing now employs the family’s fifth generation, Dave’s twin sons, Tyler and Aaron Robinson. “We appreciate the uniqueness that comes with being a fifth generation business owner,” stated Tyler. “It’s our desire to see the company continue to grow, meet our customer’s needs, and to provide employment for others in our community.”

Robinson Printing is certified to the ISO9001:2008 standard for quality and compliant with cGMP standards. It maintains complete control of the product in their specially equipped, quality managed facility—from prepress to printing to folding to inspections to delivery.

Consolidating, in more ways than one

Employing universal packaging for one medical device manufacturer resulted in a savings of at least 30%, claims one thermoformer.
 
While trends toward cost cutting are nothing new in the medical device packaging industry, prolonged economic recovery may be prompting more aggressive approaches.

Traditionally, MDMs have sought to reduce costs through downgauging the materials used for thermoforming trays. But given performance requirements and remaining inventory volumes, downgauging may only get MDMs part of the way.

Instead, consolidating multiple SKUs in universal packaging could give MDMs “the biggest bang for their buck,” explains Jason Crosby, medical business manager for Plastic Ingenuity Inc. (Cross Plains, WI; www.plasticingenuity.com). “There are limited opportunities in downgauging. But if companies can move from 20 different trays into just five, the savings can be substantial. More companies should look at consolidation.”

Crosby reports that last year his company helped one customer consolidate some of its products into universal packaging, realizing a savings of at least 30%.

Downgauging may be slightly “easier,” admits Crosby, because MDMs typically “do not need to retool unless the downgauging is significant.”

In addition, depending on the changes made to the sterile barrier system, the revalidation requirements associated with a new design could be perceived as “burdensome,” Crosby says.

Nonetheless, nearly every consolidation project that Crosby has been involved with has had a “positive outcome,” he states. “Not only were there cost savings and fewer items to inventory, but the MDMs have improved operational efficiencies and throughput.”

DO THE MATH
Over the years, the number of medical devices a given company may market multiplies through product line extensions and company acquisitions. “These MDMs could have 20 SKUs, each requiring unique trays,” says Crosby. Many of these could be in small volumes, he has observed, so these companies could be paying for a series of short thermoforming runs as well as spending internal resources to manage all that inventory. “If companies change their ordering volumes from five separate runs of 20,000 to one universal run of 100,000 parts, for instance, they could see some savings,” he reports.

And these MDMs could be inventorying much more than different-sized thermoformed trays. “They have multiple sizes of Tyvek lids, different-sized cartons, and even different sealing nests to inventory,” he adds. “MDMs could streamline inventory throughout their packaging systems, and they may even be able to consolidate some suppliers.”

In addition, MDMs may be spending significant resources on frequent heat-sealer changeover. “If MDMs were to consolidate product lines into the same tray design, they would have fewer parameter changes and therefore have faster set ups. They could batch their orders together and gain efficiencies.”

DO THE HISTORY
When consolidating several SKUs into a new universal design, MDMs will need to ensure that the new design meets the design requirements of each SKU. “Revalidation can be painful,” says Crosby. “And some companies simply just don’t have the resources. Some companies do not have engineers working on existing designs because they are charged with new projects.”

Crosby says that thermoformers “can help in some ways, but MDMs still need to run the new tray designs on their own equipment so they can validate their own processes on their own lines.”

To determine whether consolidation makes sense, MDMs should weigh the costs of revalidation versus the potential cost savings, Crosby explains. When asked whether there is a “magic number in savings” at which a revalidation makes sense, Crosby says that it depends on the company.

“In some cases, you can leverage existing historical data, utilize that data for new designs and processes, and even cross reference from one product line to another,” he says. “But MDMs need to make those decisions based on the level of risk.”

DO THE NETWORKING
Crosby advises MDMS to consult their suppliers for cost-cutting ideas. “Many times MDMs don’t utilize their suppliers enough. Internally, they may just go after the low-hanging fruit, but they should engage their suppliers. Utilize your suppliers’ design expertise to assist with the design consolidation. There is value that the supplier base can add, if MDMs are willing to be transparent about their product requirements.”

ISPE provides guide on design of packaging facilities

The comprehensive guide emphasizes risk-based evaluation for complying with FDA cGMP regulations.
 
ISPE, the International Society for Pharmaceutical Engineering, has released new guidance on design, construction, commissioning, and qualification of packaging, labeling, and warehousing (PACLAW) facilities.
 
In presenting the first comprehensive guidance for PACLAW facilities for meeting FDA cGMP requirements, “ISPE Good Practice Guide: Packaging Labeling, and Warehousing Facilities” addresses Quality by Design, with directions on how to comply with FDA’s systems-based approach with a risk-based inspection model.
 
The guide uses a risk-based approach as described in ICH Q9  “Quality Risk Management,” and in ASTM E2500-7 Standard Guide For Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment—guides that apply the concepts introduced by FDA’s “Pharmaceutical cGMPs for the 21st Century—A Risk-Based Approach.”
 
A guide for a risk-based approach to automated equipment following GAMP 5 (Good Automated Manufacturing Practice) is referenced. A collaboration between JETT (Joint Equipment Transition Team), a consortium of healthcare industry equipment users, suppliers, and consultants, and ISPE’s Risk Management special interest group on GAMP 5, the Practical Application of Risk Management Process guide defines the key process steps involved in risk assessment preparation and testing. [See chart below]
 
“What is really valuable about GAMP 5 and the risk-based approach is you concentrate and test on those areas that are quality critical to the product. This can save a huge amount of time in validation,” says Mel Bahr, founder of MGS Machine Corp, and a team leader on the “JETT Risk-Based Approach to Automated Equipment” guide.
 
“We are not seeing as many pharmaceutical companies as we expected embracing the risk-based approach [for packaging operations]. It is difficult for the large companies to change,” Bahr says.
 
“We have held training sessions in the last year with some generic manufacturers to help get them started using this approach for secondary packaging,” Bahr adds.
 
The risk-based inspection model has gained the most traction on the drug manufacturing side, agrees Nancy St. Laurent, chairman of the ISPE group that developed the PACLAW guide.
 
“When it comes to the ICH Q9 risk-based approach, packaging is usually a step child. All the thought and planning for QbD seems to surround the upstream manufacturing operations,” St. Laurent says.
 
“This is a guide on how to design and build and operate the packaging, labeling, and warehousing operations. We are asking people to think through each step along the way—from ground-up design to validation. That is a manifestation of QbD,” St. Laurent adds.
 
St. Laurent and her PACLAW team commenced the Guide process in 2004. The Packaging Machinery Manufacturers Institute (PMMI), Weiler Engineering, and Omori Machinery Co., besides MGS Machine, represented equipment manufacturers. Pharmaceutical companies and consultants assisted in the guide’s development. FDA provided review and technical guidance on each chapter, St. Laurent says.
 
Areas covered include architecture, utilities, temperature mapping, and flow of people, materials, equipment, and product.
 
“Pharma manufacturers often don’t have the space to adequately segregate materials. The most common FDA recalls have continued to involve labeling issues. The guide describes what the spacial and physical arrangements should be for the different operations to prevent cross-contamination and avoid these mix ups,” St. Laurent says.
 
MONITORING AND CONTROL
Control and monitoring is addressed for both packaging equipment automation and building management systems. In packaging operations there will be two types of controls: machine controls and SOPs.
 
“Assuming the appropriate SOPs are in place, a risk-based approach to the design of the controls and verification systems on machines is the best strategy to eliminate mix ups, Bahr says.
 
“Automation—with such devices as vision systems (for print verification) and bar code scanners integrated with properly designed controls—can virtually eliminate product mix up 
problems. Control systems have to be fail safe as part of a verified system—if a problem is detected, the line should shut down automatically,” Bahr says.
 
Adds St. Laurent: “The implementation of systems with controls for sequential bar coding should help improve control on packaging and labeling processes where you have total control of printed label material.”
 
The guide covers good commissioning and verification practices with specific monitoring strategies—such as Process Analytical Technology (PAT)—applied to critical parameters and processes.
 
A key concept in facility design and related to QbD and risk evaluation is cGMP critical parameters. “The cGMP critical parameters can be prioritized through a risk-based evaluation. For example, where hygroscopic, light-sensitive, or temperature-sensitive materials are being packaged, the product sensitivities will define critical design parameters that will need adequate control in order to maintain product quality,” the guide reads.
 
A systematic process where individual hazards are identified, analyzed, and evaluated, risk assessment is a continual/ongoing process throughout the life cycle of an automation solution, as described in the “JETT Risk-Based Approach to Automated Equipment.”
 
The amount of effort invested in risk management should be commensurate with the level of risks of the function(s) being automated, as incremental iterations of risk management activities are performed throughout the system life, the JETT guide says.
 
Various methods are available for risk management, depending on the risk category, the JETT guide describes. FMEA (Failure Mode and Effects Analysis) is used in the pharma industry to assess machine component meantime between failures.
 
Other methods include HAZOP (Hazard and Operability Analysis) for analysis of continuously operating equipment where there is a single operating state, and OHA (Operating Hazard Analysis), which looks at each step in the production process and is useful for analyzing batch processes for potential hazards, the guide states.
 
FTA (Fault Tree Analysis) provides a graphical depiction of all causal chains of failure of a system or subsystem.
 
“It is recognized that while these methods are well known throughout all sectors of industry, practical application of these methods within the life science industry is not well developed,” the guide says.
 
Using the “JETT Risk-Based Approach to Automated Equipment” in the risk assessment process, you apply a structured analysis to the system to determine what business processes, system activities, and human control activities need to be assessed. The JETT guidance then provides a step-by-step example of a risk assessment process. Items requiring rigorous testing are then subjected to a FMEA-type approach.
 
“For machinery manufacturers, validation requirements can vary widely. [With a risk-based approach] you decide what is critical to quality and focus on that,” says Bahr.
 
“Without using a risk-based approach, as much attention was given to an annunciator sensor (indicating a low magazine on a cartoner) as to test a bar code scanner that verifies you have the right carton and right bottle going in the carton.
 
“I also like to promote an output-based approach. For example, [take]a cartoner after the product is loaded and the carton is to be printed with the lot and date code, which needs verification. The vision system is rigorously tested, the print unit need not be subjected to the same rigor. The printing system is commissioned, the vision system is validated,” Bahr says.
 
In a trial with a pharmaceutical customer, MGS Machine assisted in slashing the validation time with the risk-based approach.
 
“After the FAT process, the equipment was put under change control at our plant. The documentation was rolled over and the line was validated after two weeks in their plant and turned over in four. They would typically allow 12 to 14 weeks after delivery of equipment to finalize validation and turn over to production.” 
 
The ISPE Good Practice Guide is described as an approach to satisfying cGMPs, while providing realistic solutions to business and operational concerns.
 
“PACLAW facilities are very different from other types of pharmaceutical facilities, and up to this point, there has been no consistent guidance available to help companies ensure compliance,” says Guide author Nick Davies.
 
“With this (Guide) the industry finally has tools to ensure their PACLAW processes are efficient, compare their processes to established best practices, and demonstrate compliance to regulatory agencies.”

Unique coding, over the years

Over the years, PMP News has been tracking the need for product coding at item levels. In “Cutting Edge Coders” from the October 1995 issue, for instance, then features editor Jennifer Reid Holman wrote that “the latest computer-operated printers—including new models of thermal-transfer coders, ink jets, and laser coders—offer more variability. That means you can automatically print real-time or an individual number on each package.”
 
And in “Booming Bar Code Systems” from the November 1995 issue of PMP News, it was observed that “Market-specific requirements and the introduction of advanced 2D symbologies has further expanded the capabilities of bar coding. With the technological advances, the limitations of bar code systems are disappearing. New radio-frequency and semiconductor chips allow bar code applications to employ denser information content and read-write capabilities.” The article went on to discuss several systems for bar code printing and for bar code inspection, some of which could be used on packaging lines. Such technology would continue to advance over the next two decades, striving to meet industry’s requirements for accuracy, repeatability, reliability, and line speed.
 
In May 2002’s “Marking Medical Packages with Serial Codes,” editor Daphne Allen explored the potential of serial codes. “One method of printing directly onto medical packages as they are being formed, filled, and sealed offers the ultimate in product identification and protection—serial coding,” Allen wrote. “In addition to carrying a lot code and an expiration date, each product is marked with a unique number that is part of a series. The numbering system can be downloaded from a database, which can be easily accessed with today’s programmable printers. Serial coding facilitates responses to two unfortunate realities often facing the medical device manufacturer: recalls and unauthorized product distribution, also know as diversion.”
 
And when PMP News marked its 10th anniversary in the November 2003 issue, one packaging professional predicted the following developments over the subsequent decade:
 
• Visible bar codes on all products.
• Invisible bar codes on components and semifinished goods to facilitate supply-chain tracking.
• RFID on all pallets.
• Quality inpsections of single units versus lots.
• Increased level of in-line printing: not just variable-information printing, but also package inserts and label copy printing.
• Increased supply-chain security against economic and sociopolitical terrorists.
 
Now, 10 years later, many of these predictions or approaches have yet to be fully realized. Industry pioneers have invested in the development of item-level serialization, developing packaging lines that utilize state-of-the-art printing, inspection, and verification. But wide-scale changes in product serialization have yet to transform pharmaceutical distribution. Industry has largely been awaiting regulatory action and supply-chain support before making sweeping changes to product identification. FDA did release its guidance on Standardized Numerical Identification (SNI) for prescription drugs in 2010, but industry has still been concerned about the lack of federal regulation. California’s electronic pedigree law appeared to be in-line in with FDA’s SNI guidance, and vice versa, but industry still feared the emergence of other states’ requirements that could complicate regulatory compliance.
 
The passage of H.R. 3204, the Drug Quality and Security Act (DQSA), appears to put such fears to rest, and gives industry more time for compliance. So, within the next 10 years, will SNI enable stakeholders to pinpoint the exact location, custody, and status of a single pharmaceutical package? Will such information have already transformed the supply chain, leading to more-efficient distribution and minimal or nearly nonexistent counterfeiting and diversion? And will it have yielded robust patient outcomes data through electronic health records capture, leading to more-effective, more-cost-efficient health care?

Discuss packaging options early, especially when it comes to sterilization

Packaging considerations should be made early during the product development process, advises members of the Sterilization Packaging Manufacturers Council (SPMC) of the Flexible Packaging Association. Members of the SPMC’s Technical Group spoke during the Webcast, “Sterilization: A Sterile Packaging Perspective,” covering the impacts that different sterilization methods have on medical packaging materials and what to consider when developing such packaging.

For engineers to begin to understand how packaging materials respond to sterilization, Marie Tkacik, Director of Product Development and Optimization of Beacon Converters, urged attendees to start with AAMI TIR 17 and its annexes as well as ISO 11607 and AAMI TIR 22 currently under development as ISO 16775, which lists 11 different sterilization methods.

“These standards are important references to help start the decision-making process, but they are not the end point,” Tkacik explained. “Including your packaging supplier early, such as during the developmental stages of your product, can improve the process and create a list of options to enable sterilization and the maintenance of sterility.”

Tkacik spoke along with fellow members of SPMC’s Technical Group who discussed specific sterilization methods. Geoff Pavey, Sr. Principal Engineer, Packaging Development, Oliver-Tolas Healthcare Packaging, spoke about EtO; Dr. Henk Blom, Director of Technical Services, Rollprint Packaging Products Inc., spoke on radiation; and Christopher Osborn, Vice President of Research & Development, Perfecseal Division of the Bemis Company, spoke about autoclave, steam, dry heat, and alternative methods such as pulsed white light, chlorine dioxide, x-ray, ozone, and Vaporized Hydrogen Peroxide.

Interestingly, many Webcast attendees who responded to a live poll during the event already appear to be following SPMC’s advice to start early. When asked at what point in the medical device development process they consider package design and materials, half of the respondents reported they do so “during the prototyping/development process.” And 36% are considering packaging even earlier, “when gathering inputs/requirements” during “Voice of the Customer” activities. Just 10% are doing so “at the time of design verification/validation,” and only 4% are doing so just “prior to launch.”

Tkacik says that "it is encouraging to see the polling result. The earlier we are involved in the developmental process, the better. A package designed well provides a high degree of value to the finished product. We need to be available to that 4% and encourage them to include their packaging and material suppliers, too."

Engineers should consider packaging early, because as Osborn stated during the Webcast, the “sterilization method is critical to quality requirements for packaging design and material selection.” Consequently, packaging engineers should work closely with material and packaging suppliers throughout the design process,” he added. “Make sure materials are fit for and compatible with sterilization methods, and protocols should be designed to assess the effects of sterilization on packaging materials. You really want to be able to document what happens to material through sterilization process.”

The group also addressed several questions during the live event, and they will share those answers as well as tackle unaddressed questions under the FAQ section of its Web sitewww.sterilizationpackaging.org