Rewind the clock by a couple of decades and it would be hard to imagine the pharmaceutical supply chain looking like it does today. Back then, it was as simple as sending a few pills in a bottle around the world with no real regard to the external environment. Today, logistics experts face the daunting task of supply chains with precisely controlled temperatures that are extremely sensitive to outside conditions. How did it come to this?
One of the main factors behind this change has been the drugs themselves. Until relatively recently, simple, small-molecule drugs were the norm, but as many of those products fell off the patent cliff, pharmaceutical companies began turning to biologics, many of which are temperature-sensitive.
“Within the pharmaceutical industry, the emergence of bioscience has significantly increased the demand for cold chain infrastructure,” said Deloitte in a recent market report. “Biologics, blood products, and vaccines all require a stringent set of guidelines that must be followed in order to ensure product safety and viability. Variations in temperature can partially or wholly void a shipment and lead to millions of dollars in lost sales for the company.”
Practice makes perfect
Another factor behind increased supply chain complexity is the amount of regulation with which companies are now forced to comply. Most notable was the Good Distribution Practice (GDP) introduced by the EU in 2013, which required medicines to be obtained from the licensed supply chain and then stored, transported and handled under the correct conditions.
“Cold-chain handling has drawn increased regulatory interest over the past five years,” said Mark Lipowicz and Nicholas Basta from Pharmaceutical Commerce. “Government and industry have put forward practical guidelines for qualifying cold-chain transportation processes, sensors and packaging in much the same way as manufacturing processes are qualified as part of good manufacturing practices (GMPs).
“Specifically, there is now a growing body of approved GDPs. Industry has responded energetically and expertly, such that logistics managers using qualified packages, pack-outs and channels today consider those to be reliable strong links in their supply chain and capable of “absorbing risk” from other aspects of logistics.”
This new regulatory burden is made even more challenging by the global scope of today’s supply chains. Understanding the EU’s GDP requirements is crucial, but with other countries around the world introducing their own regulations, it is often not enough.
It’s not uncommon for a company to have an API made in India or China, turned into vials or pills at a CMO in the US or Canada, packaged and labelled in Europe and then distributed around the world.
Picking the right vendor to produce and transport these products isn’t easy. In the past, the number of equipment manufacturers and transportation companies involved in supply chain logistics was limited.
Today, there are hundreds of API companies and dozens of businesses offering everything from data loggers to special boxes, and active containers and passive containers. What are the key things pharmaceutical companies should do before choosing a vendor?
“For these organisations, the decision of where to purchase raw materials, components, manufacturing and testing equipment, and even consulting services, needs to be well informed (and documented),” according to Jonathan M Lewis and Nancy Cafmeyer, experts at Advanced Biomedical Consulting, in an article on PharmTech.com.
“The results of making poor purchasing decisions can lead to situations that impact product quality, regulatory compliance, company profits and even the reputation of the company.”
At the heart of having a compliant supply chain is vendor qualification, the process through which pharmaceutical companies manage their outsourced activities and purchased materials. According to FDA, vendor qualification should involve four different steps: prior assessments through audits and material evaluation; a written agreement that defines responsibilities and communication processes; a monitoring and review process that assesses the performance of the contract acceptor; and finally a monitoring system for incoming ingredients and materials that ensures they come from approved sources.
One way to do all of this, according to Lewis and Cafmeyer is following the QUEST method, which they call a “simple, effective, and compliant approach to vendor qualification”. This begins with a ‘question phase’, in which a pharmaceutical company documents what it requires from a vendor. Does, for example, the firm being contracted have a track record of selling products to the pharmaceutical sector? Is it large enough to transport or package the quantities required?
After defining what’s needed comes the ‘understanding phase’, in which shortlisted vendors are contacted to further gauge their suitability. “At least three vendors should provide the information requested in its entirety,” write Lewis and Cafmeyer. “At this point, it is imperative that each vendor package be thoroughly assessed for adequacy and completeness, and be understood with regard to the vendor’s ability to meet the company requirements specified.”
Evaluation is the third stage. The best potential vendor is identified from the shortlist, before a site audit at the potential vendors’ facilities and then, finally, the track phase, in which the performance of the chosen party is continuously monitored and improved by addressing any mistakes made.
When it comes to choosing the right mode of transport, there are various issues to consider from a compliance standpoint. Though some in the industry believe that a ‘modal shift’ is under way from aircraft to ships, Bell argues that all three forms of transport – air, road and sea – require consideration and proper risk management.
“In our company, there is no one-size-fits-all solution,” Jeroen Janssens, senior manager at the Centre of Excellence for Packaging and Cold Chains at GSK Vaccines told World Pharmacetical Frontiers. “It’s about looking at the most optimised model, whether it is air, sea or land, that offers the best quality and sustainability. What’s important is preserving the integrity of the product, in our case shipping vaccines in a cold chain at 2–8°. We will do whatever is required to move our product from A to B in the right conditions. And if we can do it in a way that is sustainable for our planet, then that would be a very good thing indeed.”
A la mode
So what are the risks that each one carries? When it comes to transporting pharmaceutical products by sea the problem is often finding the right partner.
“They may not be eager to transport high-value goods in refrigerated conditions,” said Janssens. “Because the weight of our goods is relatively low, the container is very sensitive to variations in external temperatures. The liabilities involved in transporting high-value goods means it isn’t easy to find a partner who wants to actually work with you.
Then, when you do find someone, you have to agree on how the product is going to be shipped. From a pharmaceutical point of view, good distribution guidance documents require us to qualify the equipment we use. When it comes to the qualification of containers, quite a lot of things need to be explained to sea-line companies in terms of what those expectations are.”
The problem with air, says Janssens, is security. “At a high level you can argue that ocean freight offers more security for your products than air because you have a container that you can secure until it’s opened at the destination,” he said. “There are fewer handling points than there are with air freight and therefore fewer ways it can go wrong.”
Janssens’ view is certainly borne out in the industry. Speaking at the Life Science and Pharmaceuticals conference in London last December Julian Wann, global category leader for freight and logistics at Astrazeneca was trenchant in his criticism of the air cargo sector, accusing it of failing to cater for pharmaceutical industry’s needs.
“It’s not all about price, it’s about getting there,” he said. “The value is in having the right product at the right place at the right time and the highest percentage of our problems comes from air freight. There are gaps on the tarmac at the airport. And security is a problem. Products get stolen at airports, and if they get into the wrong hands, people can die – and they are our products.”
According to Dan Bell, vice-president, regulatory compliance and technical affairs at Marken, whatever the mode of transport a company chooses, the compliance and qualification process is fundamentally the same: quality agreements need to be in place and each point of the supply chain – however large – needs to be mapped out with the key risks mitigated.
“You need to pull together all of these elements so that you map it out, look at the handle points, look at the ambient temperatures and use that information to make choices about how you are going to mitigate risk,” he says. “Each mode of transport has its own challenges but there are best practices and you have to look at it as a whole.”
New understanding
Those still getting their heads around these challenges could certainly be forgiven, but over the coming months and years, things will only get tougher. Whether it’s new regulations, or advances in technology like cell, gene and immontheraphy products, the supply chain is likely to get even more complex. The fundamental issue, however, of vetting and qualifying suppliers will remain the same.
“Just as an individual consumer has the responsibility for verifying the quality of goods and services he or she plans to purchase,” say Lewis and Cafmeyer, “pharmaceutical and biopharmaceutical companies are responsible by regulation as well as through moral obligation to ensure that their vendors will consistently provide raw materials and components… that yield safe and effective drugs, and other therapeutic products.”
