Muttenz, Switzerland – Borrowing from successful consumer marketing strategies, specialty chemical maker Clariant hopes to boost patient adherence to treatment by making inhalers and other drug-delivery devices more attractive and appealing.
To do so, new special-effect colors were recently introduced into the company’s MEVOPUR line of masterbatches and pre-colored compounds.
“If this technology has been used successfully in consumer goods, why not in medical devices?” said Steve Duckworth, Clariant’s Global Head, Healthcare Polymer Solutions. “We believe that, by making pens and other personal medical devices more like consumer products, patients may be more inclined to carry them and use them.”
While similar effects have been created using paint and other decorative processes in the past, they tend to lack durability and can severely impact the cost of the plastic component, according to the company. Special-effect pigments, on the other hand, are compounded into the plastic and cannot chip, scratch, or peel off.
“Diseases such as COPD and diabetes are rapidly increasing and self-administered medication via auto injector or inhaler is becoming the norm,” said Duckworth, pointing to U.S. studies that indicate patient adherence to treatment programs is only 28 percent, wasting medication and billions of dollars.
Manufacturers are looking for ways to make their devices more attractive and easier to use, creating standard ‘device platforms’ that can be customized with color and special effects, he said.
When added to plastics, special effect pigments create a singular impression like pearlescence, sparkle, or a metallic look. Such materials have been used for many years to enhance the look and market appeal of personal care and consumer goods, where less regulatory documentation is required.
Clariant completed testing to confirm that the ingredients of the new special-effect master batches and compounded materials conform to medical and pharmaceutical norms.
The MEVOPUR branded products are aligned with USP parts 87 and 88 (Class VI devices) and ISO10993. Manufacturing takes place at three ISO 13485 certified and dedicated production facilities located in the U.S., Europe, and Asia.
The products were recently featured at MD&M West 2016, in Anaheim, CA and at Pharmapack Europe 2016 in Paris.
Pharmaceutical Processing asked Clariant executives Steve Duckworth, Global Head, Healthcare Polymer Solutions, and Mayendran Pillay, Global Marketing Head, to describe the new special-effect pigments and the company’s unique approach to improving patient adherence to medication.
The following are edited excerpts of their responses.
Q: How did the idea for MEVOPUR come about? When was it officially launched and when did it surface for use in the U.S. pharmaceutical market?
Clariant: The concept of a specific product line for medical and pharmaceutical applications was created in 2008-2009. We had long-standing business in the sector, but noted that we needed to adapt our approach and commissioned a customer study. It became clear that views expressed coincided with a plan we called ‘Controlled Consistent Compliant.’ We then identified sites on each major continent, including one in Lewiston ME, to focus our efforts and knowledge, and we put in place the cGMP quality system ISO13485 across the sites. Certification was gained at all sites during 2010, and when the final certification was completed in September 2010 we launched the brand MEVOPUR globally.
In 2015 we also introduced a specific range of white polyolefin concentrates and compounds for pharmaceutical packaging under the brand REMAFIN-EP, which offers the same features and benefits as MEVOPUR, along with some specific regulatory pre-testing for pharmaceutical packaging applications, including European Pharmacopeia 3.1 and U.S. Pharmacopeia <661>. That product line, manufactured in both Europe and the U.S., also is available globally.
Q: What are some of the longstanding competitive products in the market that MEVOPUR might replace going forward and in what specific applications?
Clariant: Most concentrates and compounds, including our own ‘historical’ products, where the risk of changes in raw materials must be reduced for medical or pharmaceutical applications, or they do not meet tougher regulatory controls. The product has a different level of controls that start at the ingredient level with the pre-evaluation to regulatory standards applicable to the sector, and then through the manufacturing process. It is not possible to do this unless you start at the initial formulation of the concentrates or compounds.
Q: What specific color and additive concentrates and compounds under the MEVOPUR brand are designed for pharmaceutical use?
Clariant: We created a range of standard and custom colors based on pre-testing ingredients to USP <87>, <88> class VI, and ISO10993 and are available with the regulatory declarations, Drug Master File, and full change control. We created these in the polymer resins typically used in the healthcare sector, for example, PE, PP, PC, cyclic olefins, PEBA, and TPU. Some of the colors were developed to established color standards, such as the ISO6009 colors for needles and IV cannula, and the American Academy of Ophthalmology (AAO) colors for closures for eye medicine. In addition, we created a range of MEVOPUR ‘pre-tested’ functional additive compounds and concentrates that enhance the polymer performance or aid downstream processing, including friction reduction, permanent marking via laser, permanent antistatic for films used in API handling, and protection of the polymer during radiation/e-beam sterilization. The pre-testing opens the door to use technologies that are used in other ‘industrial/consumer’ applications, but relevant declarations for the substance still must be obtained for the healthcare sector.
Q: What interaction, if any, takes place between the colors and the medicine? Did other colors leave Extractables and Leachables (E&L) in the drug? How was this approached in the past?
Clariant: E&L into the medicine or in the case of device interaction with the body is getting very high attention, although it is a highly-complex subject. There are many examples where even though materials were evaluated during the development and validation phase, due to a change somewhere in the polymer/colorant/additive ingredient supply chain, a leachable issue occurs. The regulators are paying particular attention to this. The problem manifests itself because there is not a good understanding of where the ‘potential leachable’ comes from. The sector has tended to think that if you have a food contact declaration for a material, and a one-time test, that everything remains the same. In reality, ‘change’ at the start of the supply chain is a high-frequency occurrence. There are some general rules we developed with an understanding of what types of ingredients can extract. But that is exactly why we do the pre-evaluation/qualification of raw material ingredients used in MEVOPUR and REMAFIN-EP, and every incoming batch is checked versus a ‘fingerprint.’ That way we evaluate if there are extractables with a pigment, and if there are, we will try to select another pigment or route to achieve the end goal.
Q: What drug delivery devices are being targeted for MEVOPUR? Which device manufacturers are onboard?
Clariant: Our products are utilized widely across most applications with the exception of ‘permanent/long-term implants’ (in body for >30 days), and most of the well-known device manufacturers are likely to have a Clariant product. Some of these relationships stretch back well before MEVOPUR was introduced, but the MEVOPUR concepts prepare them for what is coming down the line from the regulators. In drug delivery devices such as inhalers and pen devices color plays an important role in safe identification of the drug type, and increasingly to improve aesthetics and patient interaction.
Q: How can the MEVOPUR additives enhance product marketability and increase patient adherence to treatment? Are there specific studies that you conducted regarding improvements in patient adherence?
Clariant: While not specifically in healthcare, the Clariant ColorWorks team participates strongly within the design community for major consumer brands, and that looks at the use of color, material trends and influences. Each year, we also produce our own ColorForward trending forecast. There are not yet specific studies, but we can parallel with what we know from other sectors, the anecdotal evidence gained, and by observing what design companies are working on. The conclusion is that visual appeal plays an important role in patient treatment compliance and, just like in consumer-oriented markets, color has a role to play. We now challenge the sector with color possibilities beyond the traditional ones and with the regulatory pre-testing already done … Controlled Consistent Compliant.
Q: How do you deal with certain challenges, such as shrinkage, that may be faced when using pigments on certain polymers?
Clariant: Not only does pigment influence the visual aspects, but can have an effect of the processing and/or mechanical properties of the polymer. This is particularly the case in so-called semi-crystalline polymers, such as polyolefins, because of what is known as a nucleating effect. The pigment can change the way the polymer crystallizes by acting as nucleant, and therefore its dimensions and properties. This is why we emphasize, too, that a change in a pigment or additive somewhere in the supply chain could present a risk of a change in reliable functioning of the device. This typically shows up when a device designed in one color is later made in other colors. If this is understood at the design phase, Clariant can help minimize this, but also we have MEVOPUR additives that can help to solve a problem if discovered later.
Q: Does the cleaning process differ for these products, given that there is color in them?
Clariant: Yes, it has to because a risk of a ‘change’ can also come from cross-contamination. We learned a lot over the last five years through the ISO13485 external annual audit process. We anticipated the need by putting in specific procedures for cleaning manufacturing lines between batches. This level is a step above what would be observed in the normal industrial production of a concentrate or compound. However, the auditor challenged us by asking, ‘How do you know the steps to clean actually work?’ The answer: Because we designed and conducted in each site a ‘Validation of Cleaning.’
Q: Could these color additives potentially be used with other mediums (besides polymer), such as glass?
Clariant: No, this is not our focus or experience.
Q: Could you describe the manufacturing process of MEVOPUR? How are the colors integrated into the product?
Clariant: The process of making a compound or concentrate is made up of three steps: Weighing and pre-blending of several pigments, additives and polymer powders in a mixer; dispersing this mixture under heat and pressure in an extrusion machine to form a molten polymer phase; then cooling and cutting to form the small pellets or granules that the customer buys. The difference for MEVOPUR is in the controls at each step.
Q: Have there been compliance hurdles you have had to face with MEVOPUR or concerns regulatory bodies have expressed?
Clariant: Not so far, but we are constantly monitoring regulations. We participate widely in industry sector groups, such as MedPharmPlast Europe, to understand what is coming and what the concerns are. We also start to have direct interaction with the regulatory bodies to seek their input. The regulators are primarily concerned with the device manufacturer/pharmaceutical company and this is where the responsibility lies for evaluating and controlling materials used. There are downstream processes, such as molding of parts and sterilization, which have significant influence on performance of the materials. We always state that what we do helps to manage or reduce the risk, but we cannot eliminate it on our own.
Q: Is there a special department that works with the drug-delivery device maker to solve such issues? If so, is such work done on site at the manufacturer? What if multiple locations are involved? Are there any specific examples in pharmaceutical circles?
Clariant: In 2010, once we had completed the set-up of the manufacturing sites, we set up a 100-percent dedicated and global team to the sector. This consists of the people with day-to-day contact with the customers, a back-room technical staff and a quality and regulatory team. We are working constantly with the pharmaceutical company, the device manufacturer, design firm, and sub-contractors. Many projects are managed on an international level, and we have many that start off in one continent and end up being produced in two or three locations globally. I cannot talk about specific examples because we respect the many NDAs that we have.
Q: Is Clariant still seeking certain approvals in the U.S. or elsewhere to expand the use of MEVOPUR in pharmaceutical/medical categories?
Clariant: Yes. We constantly expand this. We already included biological evaluations USP <87>, <88>, and recently for a new range of products targeted at pharmaceutical packaging we included USP <661> physiochemical tests. We cover many products with Drug Master Files.
Q: Where is Clariant conducting its research into medical color and performance masterbatches and compounds? One location? Several?
Clariant: The new product development is divided across the designated medical and ISO1485 certified sites in Lewiston, ME; Malmö, Sweden; and Singapore, based on their expertise and, in many cases, specific customer demands. The technical managers review projects and share information on a routine basis and projects are tracked globally. Efforts also are backed by resources at other company locations, including in Holden, MA.
Q: Are you partnering with any other companies or organizations in the research efforts?
Clariant: Yes. This is a frequently used model. It covers our suppliers, our customers, but also outside institutes. Some of these partnerships are new, others are more advanced, but unfortunately we cannot talk about them at this stage. There will be announcements in due course.
Q: MEVOPUR was featured at this year’s MD&M West 2016 and Pharmapack Europe 2016 shows. Can you summarize any key developments that resulted from the introduction of the product at those shows?
Clariant: One of the key questions, at least in Europe, is the impact of potential new medical device legislation. We are working in a cross-industry group—MedPharmPlast—to make sure we understand the implications of this, and can work with the regulator to achieve something workable.
Q: It seems the MEVOPUR move into pharmaceutical/medical applications was rather recent. If so, what’s next on the drawing board for the product?
Clariant: Not really recent. We have been involved in the sector for a long time, and with the specific approach with the MEVOPUR range since its inception in 2009. The portfolio is constantly expanding. There is a new product range in development that will allow us to enter a new application area, and we expect to announce it in October. Other than that, we are increasing our geographic footprint in India. Our sister business line, Business Line Healthcare Packaging, which manufactures systems for protection of drugs against moisture and oxygen, recently announced investment in a new factory in southeast India.
Q: Is Clariant considering licensing MEVOPUR to other specialty chemical companies within or outside traditional company territories?
Clariant: No. We have significant opportunities and healthcare is a strategic focus, so I don’t really see licensing as a model at this time.