For many pharmaceutical producers, it’s quite probable that the publication of Delegated Acts associated with the EU Falsified Medicines Directive signalled the start of a race against time to meet new legislative obligations
One of these — that of assigning and verifying a unique product identity at item level — is potentially the most significant technical and logistical challenge that manufacturers have faced in decades. Yet, the evidence would suggest that the majority of industry players are still not ready. Domino’s Bart Vansteenkiste provides a blueprint for those yet to complete their serialisation journey.
Adopted in 2011 (FMD 2011/62/EU) and aimed at stemming the flow of falsified medicines infiltrating the legal pharmaceutical supply chain within the European Economic area, the EU Falsified Medicines Directive (FMD 2016/161/EU), due to come into force on 9 February 2019, will completely change the landscape of the European pharmaceutical supply chain. Italy, Belgium and Greece have until 2025 as they already have a unique numbering system in place that aims to prevent falsified medicines reaching the market.
The scope of the Directive places new obligations on all branches of the industry — manufacturers, generics producers, contract packers, repackers, importers, wholesalers and distributors — and on any producer intending to supply pharmaceutical products into any of the 28 EU countries. Broadly, the requirements fall into five categories:
From 2019 onwards, once all parts of the Directive come into force, manufacturers failing to comply with any aspect of the above will no longer be allowed to market their products in Europe.
As ever, the details should not be overlooked and although some requirements are relatively straightforward — such as the provision of tamper evidence — others have caused much debate. Foremost amongst these is the unique identification of packs at item level. Although every pharmaceutical pack has been required for many years to carry variable data in some form, the Directive is a significant shift in that data will be unique to each pack rather than to each batch.
Furthermore, there is the concern that much of the currently deployed coding equipment is simply not capable of serialisation, meaning that many manufacturers will need to implement a wholesale upgrade of their coding kit. Yet, to categorise serialisation as a purely engineering challenge, which seems to be an obvious point to make, is to seriously underestimate its impact across the business.
To categorise serialisation as a purely engineering challenge is to seriously underestimate its impact across the business
Project engineering new equipment into existing lines is the essential first step; but, beyond that, the critical success factor is senior stakeholder engagement to establish a robust serialisation infrastructure, which recognises that each physical pack has an associated data asset, and that association must remain intact throughout the supply chain.
With no legislative imperative and no global standard, wide-scale serialisation projects have been relatively few and far between to date. And, prior to the introduction of the European Medicines Verification System (EMVS), none had gone to the full extent of the Directive, which will require product data to be uploaded to a pan-European infrastructure against which product IDs will be verified at the point of sale or dispensing.
Those projects that have been undertaken, either for piloting purposes or to put in place tactical solutions to serve markets such as Turkey and China, where item level identification is already in play, have provided some useful lessons for companies now planning their own serialisation strategies. However, many companies have chosen to use third-party local providers to achieve compliance in these cases, missing out — in effect — on a valuable opportunity to make a start on tackling the challenge head-on.
From an engineering perspective, updating lines and the installation of serialisation-capable coding equipment is a project much like any other, with predictable timelines and considerations such as where the coding and inspection equipment will be located and how it will be mounted.
The ability to handle the coding requirements of different regions is desirable and there are options in terms of coding technology, with thermal inkjet and laser being the principal choices. Variables such as substrates, speeds and pack design need to be factored in as usual and there may be a company specific preference based on legacy technology and experience.
And, because codes need to be verified as well as applied, printed code quality is a critical factor. Data matrix codes are designed with inherent redundancy but, subject to the scrutiny of vision systems, text is less forgiving, needing to achieve high levels of consistency to avoid rejection.
The scenario thus far varies little from a typical installation: however, the engineering challenge, according to early adopters, lies in returning to ‘business as usual’ in terms of operating efficiency. Anecdotal evidence suggests that the reject/rework level in the early stages can be as much as 10%, far in excess of what is acceptable. This decreases with time, with rates well below 1% being achievable — but it takes commitment, effort and engineering know-how.
Line speed is a key consideration with one company reporting 300 units per minute as comfortable, 400–450 per minute being achievable but not fully robust, and 500 per minute and beyond still a technical challenge. The combination of low running speeds and high reject rates — at least in the early stages of implementation — is a ‘perfect storm’ in terms of operating efficiency: where there is no legal requirement to serialise, the temptation to switch the equipment off to get product out will be strong.
The level of illicit pharmaceuticals reaching the consumer has reached alarming levels, with millions of pills being confiscated and thousands of websites being shut down
A thorough understanding of the normal (and abnormal) operating practices of manufacturing lines is essential to ensure that these ‘use cases’ can be accommodated in the serialisation system design. For example, early projects did not take into consideration that lines may be stopped and isolated overnight in the middle of a production order. This had the effect of prematurely closing the serialisation lot; so, needless to say, ‘pause’ and ‘resume’ functions were quickly introduced.
Planned or unplanned, stoppages are an issue when serialisation is concerned, increasing the levels of spurious rejects by several degrees. Well-maintained lines staffed by highly trained operators have been shown to produce the best results, so it’s worth reviewing maintenance schedules and taking advice from the equipment supplier on how to optimise performance.
With the engineering and operating factors addressed, there then remains the question of how to manage the huge volumes of data that will be generated. On top of item-level serialised data, there are additional layers associated with aggregation through the supply chain.
There is no model for this: it is unclear at this stage how data will need to be supplied to regulators and what the obligations are on the manufacturer to replicate and retain that information and for how long. The strategy will vary from one company to the next, but the planning process needs to start before the deluge begins.
The concept of ‘no pain, no gain’ might have been invented to describe the process of implementing serialisation. We’ve focused so far on the pain and there’s no doubt that the next couple of years will be challenging. But there are benefits too: the principal driver for the Falsified Medicines Directive, and similar legislation around the globe, is patient safety.
The level of illicit pharmaceuticals reaching the consumer has reached alarming levels, with millions of pills being confiscated and thousands of websites being shut down. Ultimately, we see serialisation raising the bar for overall equipment effectiveness (OEE), with the data offering a valuable resource to help identify factors adversely impacting production.
There’s a steep learning curve involved in getting there, but help is at hand in the form of counsel from your equipment suppliers and from industry peers who have led the way. Furthermore, serialisation may provide opportunities for improved patient engagement, and has the potential to provide a powerful tool to facilitate improved adherence and patient experience — a huge benefit for the entire pharmaceutical industry.