How do you simplify labels to increase efficiency, while remaining regulation-compliant? We discuss strategies for dealing with the challenge of multilingual packaging while staying on the right side of the law.
There have been trade-offs in business processes since the first time a hungry, but cold, cave man swapped half his mammoth meat for a seat by the fire. In the pharmaceutical industry, the increasing sophistication of drugs and the testing processes that guarantee their efficacy and safety demands labels that are simultaneously as comprehensive as possible and easy to understand.
Investigational Medicinal Products (IMPs) undergoing multiple trials require labelling that maximises efficiency, while conforming to stringent regulatory requirements concerning handling. IMPs must be manufactured, stored and distributed in strict accordance with good manufacturing practices, and be packaged and labelled in accordance with the relevant trial protocol.
The language and translation systems used on these can be rather costly, so packaging manufacturers must carefully consider what is required of them.
Make it streamlined
With the high costs and strict handling requirements for many biopharmaceutical products entering development, it is essential that pharma companies and trial operators avoid overproduction, oversupply and inventory expiration, and streamlined labelling can help with this.
Patients must be able to understand and use the drugs that are being offered to them. Off-putting, or overly cumbersome designs may affect a patient’s willingness to participate in a trial, thereby potentially reducing its overall effectiveness.
While this is widely known, top-down legislative and design implementations are only starting to filter through. A report by Drs Jeetu Gangil and Girish Thunga from the Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, India, entitled ‘Prescription Drug Labeling Medication Errors: A Big Deal for Pharmacists’, highlighted that the issue of label simplification was a widespread problem across all areas of medical research and practice.
Their report found that “errors due to look-alike or sound-alike medication names are common and are responsible for thousands of deaths and millions of dollars in cost every year”. It also stated that studies had shown that up to a quarter of all medication errors were attributed to name confusion, and a third to packaging and labelling confusion. “Thousands of medication name pairs have been confused based on similar appearances or sounds when written or spoken, or have been identified as having the potential for confusion,” it noted.
The problem seems to be widespread and entrenched. For several years, plans by FDA to oblige companies to simplify drug packaging, naming and labelling to reduce medication errors have been pursued, but only marginal gains have been made.
Stephen Barlas, an analyst and writer who covers American government policy, said in 2010 that the topic was urgent, as simplifying product labelling could see fewer accidents and medical errors, leading to reduced healthcare costs. He says that drugs with similar names were a major cause of medication errors.
Complex issues
In a 2013 talk, Kenneth Getz, director of sponsored research programmes and research associate professor at the Tufts Center for the Study of Drug Development, described clinical trials becoming increasing complex almost to the point of unmanageability, a significant reason for this being “a shift in focus from acute to chronic illness, collection of increasingly intricate data elements, and concern about potential requests from regulatory agencies,” according to the forum on Value and Science-Driven Health Care (designed by Board on Health Sciences Policy at the American National Institute of Medicine). He went on to assert that trial complexity not only increased direct study costs, but also negatively affected broad-level trial performance, and that “closer attention to each element in the trial design could help to alleviate the complexity associated with unnecessary procedures, protocol amendments, and irrelevant data collection”.
Other conclusions from the talk were critical of the current state of clinical trials operations, particularly labelling and packaging. “Opportunities exist to reduce the costs of clinical trials without compromising quality through the use of a variety of simplification approaches, either incremental or transformative,” it was proposed.
Christopher Granger, director of the Duke University cardiac care unit and professor of medicine at the Duke University Medical Center, added: “The reasons that many of these cost-saving strategies have not been more widely implemented may have to do with investigator and sponsor risk aversion, interest in maintaining the status quo, and a lack of international harmonisation.”
IMP assembly (assembly in this context refers to the act of labelling a product, rather than manufacturing it) is heavily regulated. The comparatively recent changes to Annex 13 in the EU Good Manufacturing Process have led to some changes as packaging and labelling of investigational medicinal products is likely to be more complex and more liable to errors, according to the official publication by the EU bodies. The errors are also harder to detect and more frequent than for marketed products, particularly when ‘blinded’ products with similar appearance are used. Professionals recommend that precautions against mis-labelling, such as label reconciliation, line clearance, and in-process control checks by appropriately trained staff should be intensified. Many see a clear-cut, preplanned system as the best solution. This would include a set text used by all trials, and would reuse language from previous trials to reduce the time and resources spent on labelling.
How can these cost-saving simplifications be achieved – and include packaging and labelling initiatives – while remaining within FDA and EMA regulations?
Human factors
One regulatory-compliant way that labels can (and indeed must, thanks to legislation) remain simple is by studying human factors, or ergonomics. The idea has taken hold in pharmaceutical and medical manufacturing over recent years, and is now seen as key to maintaining a happy clientele.
While many think of human factors as being mostly concerned with making things easy to use for those with mobility issues (such as the elderly), the discipline covers everything to do with design and function, and therefore encompasses labelling and packaging.
One way in which labelling could be severely simplified and be able to curtail costs and complexity is the idea of readability. This is the way in which instructions and names are shown on the packaging. FDA has researched and stipulated many guidelines on a range of ergonomic issues. Advice includes ensuring that, when giving instructions, “each procedure should consist of short, concise sentences written in simple, familiar words”, and that writing should “split procedures into several short paragraphs, instead of using a smaller number of longer paragraphs” in order to improve patients’ comprehension and reading speed.
The guidelines go on to give more complex instructions – for, ironically, how to give less complex packaging advice – urging designers to use the active, rather than the passive, voice when writing the labelling for clinical trials drugs, and warning against lengthy justifications and rationales, which “draw the reader’s attention from the procedural steps”.
Labelling should also be written in a way that minimises “technical terminology, polysyllabic words and complicated expressions”. Regulatory advice is to keep it simple and concise, and to not provide excess information in a written form that may overload or confuse patients, causing them to take the medication incorrectly, leading to illness. Clean, readily understandable information that is comprehensible to anyone of any education level, age or language proficiency is the goal.
“Readability, often neglected by authors of medical device labelling, assesses how hard instructions are to read” the guidelines continue. “Readability depends on writing style (word use, sentence characteristics), rather than on content. Write labelling so that its readability lies below the user group’s reading grade level.”
FDA then specifies to write at a sixth-grade level (usually age 11–12) in order to reach most device users.
Pictograms may also help to improve labelling while staying within regulations. Ergonomics experts regard them as a great leveller, as well as a way of presenting instructions without potentially confusing words. They also make the drugs more global in their reach and reduce the number of languages labels must be reprinted in.
Keep it simple
A 2014 Middle Eastern study, led by a team from the College of Pharmacy at Qatar University, on the ‘Development and evaluation of pictograms on medication labels for patients with limited literacy skills in a culturally diverse multi-ethnic population’ came to similar conclusions.
The study set out to discover if pictograms might be an effective means of issuing medicine-label instructions, and to “evaluate comprehension of the pictograms or conventional text supported with verbal instructions in foreign workers with low literacy skills”.
The team concluded that pictograms were a vital part of this, and that “Medication labels consisting of simple pictorials supported by verbal instructions were better comprehended by individuals with low literacy skills than labels with written plus verbal instructions in a language that the individual did not understand.” Simple packaging was shown to work best for all, not just for those with limited proficiency in the language in which the clinical trials were undertaken, while pictogram-only labels were the “least comprehended” among participants.
What this all means is that sensible, professional-level decisions must be made by clinical trial operators and drug manufacturers in order to foster inclusivity over simplicity.
The regulatory burden is not so great for labelling that it can’t be mitigated when designing labelling and packaging information. Clear, concise wording, and easy-to-understand pictograms that sidestep any confusion over translation and literacy differences, are the way forward.