Navigating international serialisation requirements and regulations
Alyn McNaughton, technical director for Lonza Edinburgh, Lonza Pharma & Biotech discusses the requirements and regulations surrounding serialisation legislation.
Whilst there has been general agreement amongst countries around the world regarding the need to guard against drug counterfeiting and ensure drug security, consensus is not yet formed on how best to address the issue. It is broadly accepted that serialisation plays a vital role, but how best to generate, manage and record data across the supply chain remains a hot topic of debate. The one thing I can say with absolute certainty about serialisation is that by the time this article is published it will already be out of date.
Run an internet search and you’ll find numerous articles, all with dates and deadlines that no longer exist. With over 40 sets of local legislation enacted globally, or being enacted, it is a challenge to stay current with the varying and changing requirements for each country. This is compounded by the suspension of regulations, or suspension on enforcement, in some territories.
However, serialisation legislation does finally seem to be arriving at the point of no return: It appears unlikely that a further delay to introduction dates or an extension to the suspension of enforcement will occur. Companies will benefit from reviewing how their serialisation systems stack up against global regulation – and keep in mind that there always may be new changes around the corner.
According to the World Health Organisation (WHO), an estimated one in 10 medical products in low- and middle-income countries is substandard or falsified and “no countries remain untouched.”(1) Serialisation is required to combat counterfeit products and grey markets to allow better control over supply chains, including an enhanced recall capability.
For those immersed in serialisation, you will already know it has a language all its own and new to most of us with pharmaceutical/scientific backgrounds. For those of you who have not yet been exposed, what is seemingly a simple concept may appear a bewildering sea of terminology. It is therefore first important to understand what serialisation, aggregation and track & trace mean at a high level. I’ve tried to simplify and standardise these definitions from the myriad of regulations and guidance available:
Serialisation is the act of adding a unique identifier to each pack, usually starting at the level of the smallest sellable unit.
Aggregation is providing serialised unique identifiers to the cartons, bundles, shippers and pallets that the smaller units are supplied in and grouping the smaller unit identifiers under the larger ones.
Track & trace is the ability to identify each unit, wherever it is in the supply chain, and feed this information back to a central repository. This is slightly different from pedigree requirement, where information only travels in one direction with the product, reporting where the serial number is reported back at key supply chain milestones and verification at point of dispense where the serialisation is only checked during the final dispense to patient by the healthcare provider.
So, where are we with current legislation?
In the European Union, the Falsified Medicines Directive (FMD)(2) deadline of 9 February 2019 is fast approaching. This requires saleable unit serialisation, aggregation and reporting (track & trace), along with adding a tamper evidence requirement, previously absent in the EU. However, some countries within the EU – Italy, Belgium and Greece, with their own pre-existing systems – have until 2025 to comply.
The United States (US) Drug Supply Chain Security Act (DSCSA)(3) already mandates serialisation from November 2017, although penalties for non-compliance will not be actively enforced until late November 2018. Aggregation introduction is planned out to 2019, with track & trace introduction from 2020-2023.
The China Food and Drug Administration (CFDA) was running a mandatory serialisation (electronic supervision) program in which, by Dec 2015, all pharmaceutical products were to be included in a national standard for drug serialisation and traceability, but the CFDA announced the suspension of this provision on 20 Feb 2016(4). Regulations are challenging to follow; though progress on a modified system does seem to be occurring, the final requirements do not yet appear to be clear.
Turkey, Brazil, Argentina, Saudi Arabia, South Korea and Egypt all have serialisation systems in place, with traceability development at differing stages – from no traceability at all to Turkey’s track & trace, which has been in place since 2011(5). By the time this article is published I suspect this list may be slightly longer.
India, Russia and Australia, along with many other countries, have all made a commitment towards at least some unique identification of medicines, to the extent that, should these commitments be met, over 80 percent of the world’s medicines will be at least serialised by 2020 (6).
All sounds good so far, but there are still some key challenges to be met both locally and internationally. The first of these is that there is no international standard for what information is actually included in the identifier, be it a printed barcode or RFID. Regulations surrounding this that currently exist have common themes, but no accepted single approach. This means that local legislation will still need to be taken into account when a unit is to be serialised with its identifier. This may get even more complicated if a single packed product is to be split across two regions with differing requirements, as the batch would need to be separated and both parts serialised independently. This includes the EU where, whilst there is a single regulation, member states still have the flexibility to apply their own national requirements. This already exists to some extent as a prescription drug in one country may be an over-the-counter (OTC) product in another.
The second challenge is the lack of a single accepted standard for the type of barcode or identifier used, though significant correlation has started to appear in the utilisation of the GS1 standard, which is already a globally recognised standard in other sectors. Even countries that initiated earlier programs, such as China, appear to be considering adopting this GS1 standard. However, the CFDA has also published non-GS1 standards as recently as 2017. This move toward an international standard is critical for a globally unified serialisation system. It is also important that automatic readers are able to enter data to minimise errors. It is estimated that in manual data entry, one keystroke in approximately every 300 will be in error, whilst for an automatic reader this is estimated at the equivalent of one keystroke in 350,000. Automated data becomes the other part of the challenge – first in understanding the requirements at each level of serialisation, and secondly in securely sharing this data into a central database.
Finally, it is crucial to understand the infrastructure involved in serialisation, which is commonly characterised into five levels:
Level 1 is the barcode and label printers, labellers, cameras and scanners.
Level 2 contains the aggregation devices and software that takes care of packaging.
Level 3 allocates the serial numbers, verifies them to the central database and ensures the aggregated numbers are grouped. (Levels 1-3 are associated with the site-level infrastructure.)
Level 4, which may or may not be on-site, is the system that manages and verifies the data in communication with the central databases and the serialisation solution vendor.
Level 5 is the network that includes the regulatory database along with all other partners in the supply chain network.
Understanding what this infrastructure requires at each packing line and each site is essential to ensure all the elements are in place for a functional serialisation system that communicates across all levels and involved partners – from the national medicines verification organisations to on-boarding partners and market authorisation holders to Contract Development and Manufacturing Organisations and back up the chain to distributers and healthcare providers and finally the patient. For example, at Lonza Edinburgh, where we develop, manufacture and pack liquid-filled hard capsules for a global customer base, we have invested in serialisation capability to match our current blister pack and carton lines, making sure the selection was of modular equipment. Our goal is to reflect the evolving nature of regulation and our own business needs by expanding the system and adapting to changes in requirements as they arise, thereby better ensuring safe and effective medicines for patient populations around the world.
Some of you will be challenged to have everything in place before the deadlines that will impact your products, or your place in the supply chain. For you I would advise to move forward with all haste rather than hoping for new leniency. For those who have your company systems established and verified, I would say don’t take your finger off the pulse now. I suspect that as we move forward the systems we have put in place will need some refinement to meet unrecognised challenges and meet new market demands, in amongst those challenges we already know exist.
References
Falsified Medicines Directive (Directive 2011/62/EU)
Drug Supply Chain Security Act (DSCSA)
http://www.chinadaily.com.cn/china/2016twosession/2016-03/08/content_23788067.htm