Pack mentality – clinical trial packaging29 August 2014
The packaging of drugs for clinical trial purposes has taken on greater significance in recent years as pharma companies look to develop greater adherence among patients. We talk to Charlotte Ullits Houlbjerg, head of clinical supply packaging at Lundbeck, about the various factors that need to be taken into account in the design process, budget considerations and the potential overlap with commercial drug packaging.
Freighted with tight timelines and numerous budget issues, clinical trial packaging can be a tricky undertaking for pharmaceutical companies.
In fact, it is only in the last few years that Big Pharma has begun to slacken the purse strings and make serious investments in clinical trial labelling and design, having previously been dissuaded by the notion that few drugs ever resulted in full-scale commercialisation.
However, attitudes have changed in tune with the globalisation of the clinical trials sector, which continues apace. As a result, the erstwhile mindset of cost-cutting has been superseded by a genuine effort to make packaging and labelling as innovative and patient-friendly as possible.
This reversal in attitudes is largely based on the idea of patient adherence. Put simply, if a patient is able to take a trial drug in the manner intended by the manufacturer - thanks to clear and instructive packaging - the greater the chance of eventual commercialisation.
Simply does it
According to Charlotte Ullits Houlbjerg, head of clinical supply packaging at Lundbeck, there is a wealth of factors that need to be taken into consideration when designing packaging for today's clinical trials, as a result of its newfound currency. The first, she says, concerns adhering to bespoke product requirements.
"The first thing to think about is the investigational medicinal product (IMP) requirements," she says. "So, you need to ask yourself - is there any specific packaging issue that I should be aware of? That could be a stability requirement, cold conditions or special foils, for example. Depending on the market, there could also be specific requirements around the packaging material, for example child-resistant packaging. These are all things that need to be considered in the design process."
The next stage, says Ullits Houlbjerg, is to contemplate the nature of the respective trial. As trials are often contingent on absolute objectivity and impartiality, foolproof blinding and concealment of drugs is paramount.
"A lot of trials are blinded," she says. "We can't make any notes on the medication saying what is inside. It has to be totally concealed. I also try to think about how it can be achieved in the simplest way - for instance, using as few colours as possible."
Yet, despite the seemingly complex nature of packaging and labelling, the watchword is simplicity - clearer, less complicated instructions are seen to prompt greater adherence and understanding among patients.
"The patient has to be the primary consideration, always," explains Ullits Houlbjerg. "Therefore, the packaging needs to be simple and intuitive, with as few parameters in place as possible. It should also be small and discreet, so it is easy for the patient to carry around, if need be."
As mentioned above, the theme of patient adherence is being increasingly promoted across the clinical trials sector. Consequently, the incorporation of the likes of a dosing calendar - to offset forgetfulness - and other visual reminders has become more commonplace in recent years.
Simple-to-understand language on treatment protocol is also used to ramp up comprehensibility, while many contemporary adherence packages include more graphics and icons to facilitate better patient-uptake figures.
"Graphics are really useful if they are simple and self-explanatory," says Ullits Houlbjerg. "For example, using a sun symbol to denote daytime or a moon for night. Numbers can also be used to replace days, too. At Lundbeck, we try to avoid language when we can, because these products need to go to many countries. So we will only have language in the booklet, and the main packaging material will only have symbols and numbers, with no written words. This keeps the simplicity."
The right tools
Since 2011, Lundbeck has significantly increased the number of trials that are packed internally - before then almost all trials were farmed out to third-party contractors. In 2013, Lundbeck packed nearly ten times as many production orders for clinical trials as in 2012. Today, its packaging department is able to provide an array of services, including advice on packaging designs and manual and automated packaging of various presentations.
"As soon as we receive a demand for a clinical trial, we ensure that we have everything in order to be able to do the packaging - that includes the right equipment, the right tools, the packaging materials and the physical capabilities to do the packaging," says Ullits Houlbjerg. "We also work alongside our sister R&D department over how we can do this in the best possible way for the patient."
It is an investment that appears to have served Lundbeck well. In light of this, how do budget considerations affect the group's current clinical trial packaging activities?
"Due to it being so expensive, we do try to use as little IMP as possible," says Ullits Houlbjerg. "We also work continuously to improve the way we work using LEAN. One of the key drivers for clinical packaging is to be reliable and have a high-quality product, to have short lead times, and to be more flexible and competitive than contract manufacturers.
"A key to success in clinical packaging is to provide high-quality products". With our packaging material, we have special suppliers - clinical as opposed to commercial - so as to be able to get the right quality levels."
Clinical vs commercial
As alluded to by Ullits Houlbjerg, there is a clear need to differentiate between packaging used for commercial products, and designing for clinical trials.
For commercial packaging, it is more or less the same well-known process that is repeated routinely for many years. For clinical trials, almost every packaging order consists of a new process in terms of a new drug or a new design including new packaging materials.
The lack of routine in clinical packaging demands a lot of the staff and their procedures in order to succeed. Throw into the mix the themes of dosage titrations and cross-border supply chain logistics, and it is hardly surprising that clinical supply packaging makes for such a demanding undertaking.
"I would say that the added complexity is the main difference between clinical trial and commercial drug packaging," says Ullits Houlbjerg. "For clinical trials, there is the blinding issue, for instance, which means we have to mix up different products in a controlled way, and we have to keep them concealed. That adds a layer of difficulty.
"I would also argue that there is a greater demand for accountability when it comes to clinical trials. The use of the unique randomisation numbers used in clinical trials needs tight control to ensure accountability of every individual package at all times."
So, is there a strong case for deploying the same packaging for clinical trials that will eventually be used for the commercial drug?
It's hard to say. On the whole, packaging demands the use of a primary container for stability purposes; any changes in the primary container between clinical trials and commercial use could present various problems.
However, others would counter that a trial should be seen as a data-gathering exercise rather than an experiment in brand management.
Yet, the following is indisputable: the earlier a pharmaceutical company contemplates pack design, the more holistic the viewpoint will be on the IMP life cycle as it looks towards commercialisation.
It's a philosophy that's starting to gain traction, too. Players that can better integrate adherence-enhancing tactics into their clinical trial packaging are more likely to yield a better success rate in a commercial environment and will ultimately attain the most impressive profit margins.