Increased vigilance at all points of the complex pharmaceutical supply chain is essential to protect the integrity of the product and the end-user. Val Petursson of Actavis outlines the risks, and reveals how technological advances and industry best practice are combining to protect the global cold chain.
Last time you took a simple pain reliever, you probably didn’t think about the supply chain complexity involved, and the timeline from the sourcing of the active pharmaceutical ingredient (API) up until you swallowed the drug with a drink of water.
Nor did you probably realise that, before you purchased the product, it very likely changed owners three to six times, and that all parties had the legal obligation to manufacture and transport it according to strict protocols and conditions – which, unknowingly, you then potentially violated several times as the end-user.
You may, for example, have bought the drug on a cold day in Europe and kept it in the car in case you needed it en route or at work. The temperature is sure to drop below the ambient level, and in some cases significantly below freezing point.
In other words, you have exposed the product to a temperature excursion, an exposure that all stakeholders – including the marketing authorisation (MA) licence holder, the distributor, the wholesaler and most likely the pharmacist – had until that point diligently managed to prevent by spending millions on their compliant manufacturing and cold chains, while still managing to sell you the package for as little as €2.
You may also have exposed your insulin to higher temperatures than all of the previous stakeholders in the supply chain, from the API manufacturer in China, the bulk manufacturer in India and the MA holder in Europe through to the distributor, wholesaler, pharmacy chain and outlet where you finally bought it.
Pharma companies have spent a considerable amount of time, money and effort over the last few years to secure end-to-end product integrity in order to achieve vertical supply chain integrity status.
To do this, they have likely addressed the following supply chain issues and innovations:
- manufacturing techniques and expensive temperature-compliant facilities with high-tech surveillance and alert systems frequent
- audits on the above
- high-cost reefers and trucks
- GPS satellites to protect from theft and allow real-time temperature excursion alerts
- two datalogger monitoring devices per shipment, and sometimes even per batch, in order to mitigate the very remote risk of a data logger defect
- bulky, passive or active temperature packaging to ensure en route air integrity, while at the same time trebling the freight cost.
Some stakeholders are already prepared for the most extreme changes to the good practice (GxP) guidelines thanks to strategic investment in recent years, whereas others have been more reluctant to meet the new demands and are now entering a period where they rapidly need to shape up.
Improving the sustainable cold chain
Despite all the expensive countermeasures, it is a fact that excursions happen every day and many, if not the majority of them, probably go unnoticed.
The reason is simple: the end-to-end supply chain is extremely long and unnoticed excursions are most likely to happen during a change of ownership of the product. With every change of title within the supply chain – for example, between the manufacturer and the MA holder, or the MA holder and the distributor – a new entity becomes the owner of the temperature tracking. This means a new tracking system, a new enterprise resource planning (ERP) system and new internal policies.
For the pharmacist, it is virtually impossible to prove to a customer that the product is in an acceptable condition as there is no end-to-end measurement.
They may be able to obtain partial tracking measurements from stakeholders, but with a big window of uncertainty, especially when the title of ownership changes. Each stakeholder is busy looking inwards to ensure that their leg of the supply chain has been carried out correctly. It is precisely this vertical approach that presents the biggest barrier to complete end-to-end sustainability.
Are GxP guidelines effective?
Awareness of the importance of the GxP and the storage requirements sometimes tends to diminish as one moves higher up the supply chain, with the end-user often clueless as to how to store the product. On top of this comes different GxP awareness and adherence between regions and local legislations.
Western Europe is the most demanding environment; the Americas, Eastern Europe, the Commonwealth of Independent States, Russia, Ukraine, the Middle East, the Far East and Africa are perhaps more tolerant. In real terms, this means that a product that originated with a very GxP-compliant manufacturer and MA holder can travel fully protected around the globe, only to be exposed to risks during the last mile due to low local GxP awareness at the upper end of the supply chain.
In addition to the costs, somewhere at the very end of the supply chain is a consumer, or a state or medical insurance company, who has unknowingly paid for quality they didn’t receive. GxP guidelines need to be realistic to all stakeholders. That means not focusing solely on what the manufacturer and MA holder at the start of the supply chain can or should comply with, but instead on what is realistic for the wholesalers, pharmacies and the customer. The higher up in the supply chain, the more challenging it becomes to maintain integrity as the big, bulky shipments get separated into smaller ones, with more picks and packs, more handling, and the number of shipments growing exponentially. Many of them go to markets or customers with a notably low GxP awareness and engagement from local authorities.
Remedies
As pointed out earlier, there is notable difference on how far pharma companies have moved towards GxP compliance and, in particular, good documentation practice (GDP). The obvious first steps for companies that have fallen behind is to achieve visibility on all moving goods, internally and, preferably, at external manufacturing sites. Without visibility there is no sustainability, only guesswork where opinions that are not based on facts tend to prevail.
For companies, this means streamlining their approach to logistics in a single global way, and amassing relevant data into a single internal or external system. With all logistic datasets in one system, a gradual visibility emerges into risky routes and meaningful route profiling can be undertaken. This process can take between one and three years depending on size, ERP landscape and the complexity of the company, but ultimately means that the organisation can reach a horizontal supply chain integrity status, as described before.
The next step towards a better and more enhanced sustainability would be starting to liaise with business partners on linking the logistic datasets together in order to extend the visibility beyond your own systems and ownership span. Cloud-based alternatives offer platforms for collaboration on this scale and a handful of leading pharma companies are pioneering this approach. Linking external partners, upstream or downstream, into their own ERP is definitely an option for most MA holders and manufacturers, and in many cases is simpler than opting for a cloud-based alternative.
Full horizontal supply chain integrity status would be reached when a customer receives a product for which they can check (online or via printout) its entire lifespan, from at least the bulk manufacturer all the way through to the pharmacy and up to the day they purchase the product. This would not only contribute to GxP compliance, but also deal with counterfeiting as well.
With the increased demand for product serialisation, it’s more than likely this will become reality within a few years. This could mean that when you buy your painkillers from 2016 onwards, you will get a pack with a label (RFI or barcode) that you need to scan at the pharmacy counter for an integrity check. This step will most likely tell you that you are, from this point on, responsible for the storage conditions of the product and will encourage you to store it in an ambient place or – in the case of a 2-8° product – a fridge.