How Colour Improves Device and Packaging Design Without Compromising Patient Safety or Regulatory Compliance
Increasingly, treatments become more self-administered where compliance to a regular regime is important, and over the counter (OTC) medicines are selected based on a “branding” principle. So perhaps there are design lessons from the personal care packaging (PCP) and consumer goods sectors?
A well-designed and attractively coloured device can have a dramatic impact on the success of a drug. One such device, used to treat chronic obstructive pulmonary disease (COPD), won its manufacturer a Queen’s Award for Industry. By the end of 2010 over one billion units of the device had been sold and the revenue stream had been extended well beyond what might have been expected from patent protection.
There are signs that the industry may change. New marketing executives at pharmaceutical companies are bringing their experiences from a mass consumer oriented business model. An example is a joint venture formed between Proctor and Gamble—with its strength in branding—and Teva, bringing its expertise in generic drug manufacture.
Whilst colour is increasingly used for the safe identification of medical devices, designers have followed more traditional approaches when it comes to colour selection for aesthetics, staying with colours they consider to be “safe”. They have felt protected by a “food contact” statement, unaware of the risk they faced from a routine change in supplier of a pigment or additive, even if the “chemical type” appeared the same. Even when they addressed the problem with a
so-called “no-change” document, their supplier was probably unaware of changes that were likely to happen further up the supply chain.
Unfortunately for device and pharmaceutical packaging producers, the situation has not improved. The regulatory authorities are more aware then ever of the potential impact of these changes on mechanical functions, on biocompatibility and on leachables into the drug. This heightened awareness can be seen manifesting as more scrutiny of materials during the FDA 510(k) process and more investigations by industry groups—for example on sources of leachables profile changes in metered dose inhalers (MDI) or parenteral drug packaging. As previously reported in Medical Plastics News, in 2011 an FDA guidance document stated: “Changes in material formulation of patient-contacting devices or device components may affect the biocompatibility of the device. These changes may also affect material properties and the safe and effective performance of a device. Therefore, a new 510(k) should be submitted for changes in material formulation for patient-contacting devices or device components.”
So do these restrictions force designers into an even more conservative approach? No, they don’t. However, understanding where risk comes from and dealing with this in the early stages of design are necessary if the industry is to move forward. If the risk of changes in materials can be managed, this can open new possibilities to use the experience from PCP. Fortunately at Clariant, we have understood what needs to be done to help manage risk of changes. Note I said manage, not eliminate.
One thing to appreciate is the context of scale. While the healthcare segment is very specialised and technically advanced, it is very small in terms of demand for polymers, pigments and chemicals. Indeed, estimated demand from the healthcare industry for polymers is just 5% of global output while for pigments and additive chemicals it is less that 0.05%. So suppliers of these products are generally not interested in discussing “change control”, and regard the sector as too complex and not worth the investment. For a pigment, the usual specification and certificate of conformity (CoC) offered is a colour index and, in addition, a relatively simple regulatory statement, for example FDA food contact. Changes in process or specification therefore can take place with no consideration on the impact on applications further downstream.
Going one step along the chain to compounding, raw materials represent 50-65% of a manufacturer’s costs, which means that there is often a need to change between suppliers or optimise formulations. Incoming quality control may only include confirmation of the document from the supplier, and not testing. This is not good news if you are concerned about maintaining mechanical properties or an extractable and leachable profile.
After a decision in 2009 to change its approach to the healthcare sector, Clariant decided to invest and took steps to manage the risk of changes, finally resulting in the launch of its Mevopur healthcare brand in October 2010. In 2012 we formed a dedicated team focused entirely on the sector.
There were four important elements to this reorganisation.
Global Approach: Specialisation of three plants (out of over 50 in Clariant Masterbatches) located in the USA, Europe, and Asia under the ISO13485 quality system with change control protocols. This is important because, firstly, production of a medical device may be required in different regions or be transferred and, secondly, back-up supply is normally a requirement.
Standardisation of raw materials—in terms of chemistry and supplier. This process involved the technical, product stewardship and supply chain functions of Clariant to assess each raw material not only on performance characteristics, but on regulatory criteria such as RoHS, Reach, BSE/TSE and so on, and whether the supply was available in each of the three sites. Without this the following element would make no sense.
Establishing a “fingerprint” based on physical attributes such as the Fourier transform infra-red (FTIR) spectrum, extraction (ISO10993 part 18) and biological evaluation (ISO10993 and USP parts 87, 88).
Batch testing: Rather than accepting the CoC from the supplier, we decided that it is necessary to test each incoming batch because we believed (and this has been proven) that changes in the raw material can occur even though the CoC indicates the colour index is in specification.
Fourier transform infra-red (FTIR) and Raman spectral analyses are used to give a rapid comparison to a chemical product’s fingerprint. As an example, FTIR analysis of samples of a typically used phthalocyanine blue pigment (pigment blue 15:3) from two suppliers shows a number of differences. Although the pigments from a colour perspective might appear to be the same, and have the same CAS registry number (a unique numerical identifier assigned by the Chemical Abstracts Service), the FTIR clearly shows they are not the same.
If such a change is detected between incoming raw material and our fingerprint, then the batch is quarantined, and if necessary we then carry out further risk assessment based on following the test protocol for extraction and biological evaluation.
As stated earlier, we at Clariant Masterbatches help to manage risk, because it is not practical to expect pigment or chemical suppliers to introduce the controls that a healthcare customer might expect. By using the above approach we can help to minimise the risk being passed down the
supply chain.
Unfortunately, the industry has not yet fully understood where these risks can occur. There is a common belief that protection comes from an “FDA Food Contact” statement as well as testing which has been carried out on a masterbatch or compound two years ago, or in some cases even longer. Worse still, there are often attempts to correct the problem by imposing a new quality standard with change control on a product originally formulated ten years ago.
In addition to these specific initiatives which manage risk, Clariant also helps designers via a range of offerings, including its ColorWorks colour centres, which have created tools that help designers select colours that are practical to process in plastics, and its ColorForward trends outlook.
Conclusion: In answer to the question “colour—untapped potential?”, we say categorically: “Yes—why restrict yourself to white when you may be able to have Hora da Caiprinha Green or In Vino Veritas Red.”