Safety in numbers
The task of meeting the “Safety Features” requirements of the EU Falsified Medicines Directive (EU-FMD) is daunting. Serialisation expert, Christoph Krähenbühl, 3C Integrity, deconstructs the final draft Delegated Act to summarise the key actions required by pharma manufacturers in implementing serialisation programmes
By early 2019, every pharma manufacturer that supplies Europe – whether originators, generics manufacturers, virtual pharma companies, parallel traders, re-packagers or CMOs – must have adapted their packs, implemented tamper evidence capability and established systems, processes and master data to be in full compliance with the EU-FMD. If they do not, they are no longer in a position to sell their products in the European market.
As practitioners, we have worked with pharma companies to implement these capabilities. The deadline for implementation is approaching, the challenges are many and the capacity to provide equipment and solutions for the hundreds of pharma manufacturers and the thousands of manufacturing lines producing for the European market are being booked as we speak.
The 10 major considerations for pharma manufacturers:
1. Timelines for EU states: The European Falsified Medicines Directive (EU-FMD) will impact every participant in the healthcare supply chain in 32 states in Europe from late 2018 or early 2019. This includes the 28 EU member states and three non-EU European Economic Area (EEA) members Norway, Iceland and Liechtenstein, as well as Switzerland. The exceptions are Belgium, Italy and Greece, which are deemed to have pre-existing features in place that will see their compliance timeline extended by a further six years.
2. Scope of products: All prescription-only medicines supplied to the public are in the scope of this legislation and the first items on the OTC blacklist have been announced. The list of prescription medicines that are excluded contains radionuclides, medicinal gases, IV solutions in ATC therapeutic subgroup B05B ‘blood substitutes and perfusion solutions’, contrast media as well as homeopathic medicinal products. The proposed black-list of OTC products that will be subject to the safety features requirements is even shorter and consists of two strengths of omeprazole capsules. The inclusion of this product gives a good indication of how the risk-based approach will be administered: This is a product that is OTC in some and prescription only in other markets and omeprazole was also subject to falsification alerts in April 2013.
3. Unique identifier and data carrier: Every manufacturer now needs to establish the capability to generate, print, capture, verify and store and manage the four- or possibly five-element Unique Identifier carried in a 2D Data Matrix printed on each and every pack. Getting the right code on the right pack sounds trivial but there are a number of practical challenges associated with this. It requires a sound understanding of product codes – in particular the GTIN/NTIN situation – a robust master data management system and process, high data quality and above all the mature understanding in the organisation that what is required is a step change from managing the product code carried on the sales pack as part of the artwork to ensure the correct code is printed alongside the other data elements.
4. Pack, artwork, tamper-evidence: The key concept that has been at the core of the EU-FMD from the outset is the systematic mandatory verification of all packs at the point-of-dispense. This verification includes both the Unique Identifier and the Tamper-Evidence device. Chapters 3 to 6 (Articles 10 to 30) describe what this means in practice for many of the alternative dispensing practices found in the rich and complex healthcare supply chain in Europe e.g. for pharmacists and people operating within healthcare institutions.
5. Item-level but also ‘aggregation ready’: While the European approach focuses on the pack/item-level for the major use case envisioned (point-of-dispense verification), there are a number of situations where operating at a higher level of aggregation will make a lot of sense - and has been deemed acceptable by the law-maker. It makes sense that even if manufacturers limit their implementation initially to item-level, their requirements should specify the aspiration to provide at least ‘aggregation ready’ equipment.
6. Europe-wide ‘repositories’ infrastructure: The responsibility to upload the data to the repositories has now been clearly assigned to the Marketing Authorisation Holders supplying pharmaceutical products into the European Market. This obliges every MAH to establish a secure and capable company repository to fulfil their data reporting, data management and record-keeping obligations.
7. Obligations on parallel distributors/repackagers: Article 40 sets out the obligation on all brand owners and repackagers, to ensure the decommissioning of the unique identifier of a medicinal product in every national or supranational repository for products that have been recalled, (temporarily) withdrawn or – and that is new in this version of the DA – have been stolen or will be provided as free samples (Article 41). This means that brand owners and parallel distributors will require the system capability to upload additional ‘status changes’ of the serial numbers and – as an additional obligation on repackagers – to capture and upload the serial numbers of the packs that have been ‘consumed’ when creating the new packs that will be parallel distributed.
8. Challenges for contract manufacturers: Contract manufacturers (CMOs) may not fall under the direct data upload obligation but it is difficult to see how they would be in a position to control the supply of the appropriate information to their customers without establishing a CMO company repository. Given the typical CMO’s position of supplying multiple customers and possibly managing a complex mix of prescription and OTC products for a range of markets, the size of the challenge facing them may dwarf the challenges faced by other pharma manufacturers.
9. Cost implications: Pharma manufacturers are required to fund the establishment and on-going operation of the Europe-wide repositories system infrastructure. This will add to the cost though the good news is that through the organisations representing their interests at the European level, work has already been done to establish a capable but cost-effective approach via the European Stakeholder Model.
10. Technology and support: Serialisation technology stack is only part of the work that needs to be undertaken. Against the background of tight timelines, companies setting off now on their implementation journey cannot afford to risk getting things wrong at this late stage. The budget for every EU-FMD readiness programme therefore needs to make provision for the technology and expert help and support that will more than pay for itself in the long run.