In July 2011, the European Commission (the Commission) published draft guidance – under Directive 2011/62/EU – on good distribution practice (GDP), which, it claimed, would help combat the proliferation of counterfeit medicines into the pharma supply chain. At the public consultation, however, industry players and logistics providers responded critically to some of the proposals within this directive. They warned that the proposals could ultimately push up the cost of distribution across Europe and would require significant investment.
It is widely recognised that current GDP guidance – established almost two decades ago – fails to address the changes in pharma practices and procedures, as well as growing external threats, including the increasingly sophisticated methods used by those looking to proliferate the market with substandard, unregulated products.
Nevertheless, one of the major bones of contention is the requirement for pharmaceuticals companies and their suppliers to reclassify any site in which a consignment remains for a period of more than 24 hours, meaning countless sites would be subject to full oversight and regulatory inspection, and GDP authorisation. This, said Bristol-Myers Squib in a written response, could render fewer logistics providers willing to get involved with today’s pharma chain.
Whether this is a good thing, or even a realistic proposition, remains to be seen, but the chorus of criticism is set to grow louder still at news of another proposal contained within the draft. The document says that, if refrigerated products are to be kept on a site ‘for any period of time’, site operators will need to obtain a wholesaler’s authorisation, which, the industry claims, will result in the need for further investment into those facilities. As an example, the document says, storage areas should be ‘temperature mapped under representative conditions and should take into account seasonal variations’, adding that ‘an initial mapping should be carried out prior to the commencement of use’.
Vast and variable distribution
As the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) quality standards manager John Taylor points out, the need for a suitable supply and cold chain is critical. "The control of the storage and distribution environment of medicinal products is essential to ensure that the high level of product quality, achieved by observing good manufacturing practice, is maintained throughout the distribution network," he says.
The distributor requirements within the pharma sector are vast, making the distribution extremely complex. In a previously published MHRA document on the cold chain, Taylor writes: "The distribution chain is seldom simple and distribution systems may vary enormously. In its simplest form, the chain involves shipment directly from the manufacturer to the customer or end-user. In its more complex form, the distribution chain may involve a number of storage and transit locations, including airports and docks, and a variety of transport facilities, including aircraft."
It is because of these vast variations in the cold chain that such robust regulation is required. Declining to comment on the specifics of the draft legislation, Taylor says the MHRA "appreciates the concerns expressed by the industry in responding to the Commission’s consultation". He confirms that the UK will be launching its own consultation process with regard to the falsified medicines directive in coming months.
Continuous temperature monitoring
While the move by the Commission to update the guidelines is laudable, it has prompted these and other concerns among industry practitioners. But some of the issues raised might already have been addressed if the sector had comprehensively adopted measures supported and pressed for by the MHRA more than 18 months ago.
Firstly, says Taylor, storage and logistics providers should be aware of the conditions under which products must be stored and transported. "They [logistics providers] should have appropriate facilities in place to ensure that products are held and transported under controlled conditions – temperature and, where necessary, humidity – and that temperatures are monitored, preferably continuously," he claims. "Temperature mapping of storage facilities should be conducted to identify hot and cold spots, and sensitive products should not be held in these locations. Temperature monitoring devices should also be calibrated regularly."
Continuous temperature monitoring is something that the MHRA has voiced its support of since 2010. There are currently no specific requirements for distributors or storage providers to continuously monitor medicinal products – not even in the recent GDP guidelines – and, to clarify, nor is the MHRA specifically calling for them. "The [UK] Government’s policy is that the development of new UK legislation should not place undue burden on industry," Taylor says.
According to Taylor, continuous temperature monitoring is not the only way to maintain the stability of medicinal products, and it most certainly isn’t the most critical issue facing pharma players and their partners. "Although the MHRA is supportive of continuous temperature monitoring, it is one of a number of tools that can contribute to the assurance of product quality."
Good relationships along the supply chain
Speaking in a recent article on supply-chain security for pharmaceutical-technology.com, Napp Pharmaceuticals’ Cathy Brown expresses the importance of good relationships with supply-chain and logistics suppliers. "Good relationships and prior auditing of sites and facilities can also be beneficial, so that cooperation and understanding of the nature of the supplies… is made clear at the start," she says.
Her views are echoed by Taylor in a cold-chain context. "There should be technical agreements in place between manufacturers/distributors and their contract acceptors that lay down the conditions under which products should be stored and transported," he declares. "Where appropriate, the agreements should specify the means of transportation, transit times, routes and who to contact in the event of the conditions not being met."
He warns that the dangers of not working with partners and understanding their capabilities are just too catastrophic to contemplate; a compromise in the cold chain could potentially lead to substantially compromised product quality, a product recall or even a financial penalty.
"Manufacturers and distributors should be aware of the impact that exposure to adverse storage and distribution conditions may have on the quality and stability of the products they handle," he says. "They should take necessary steps to control and monitor storage and transportation temperatures within acceptable limits, determining whether these conditions are being met and taking appropriate measures if they have been exceeded."
And, according to Taylor, it is crucial to act quickly when problems do arise. "It is important to know the conditions under which products are stored and transported, so that appropriate corrective and preventive actions can be taken to assure their quality," he stresses. One of the steps he encourages both manufacturers and suppliers to take is to "walk the route". In doing so, he says, you can observe the conditions that are normally encountered and then take appropriate actions to protect the product against them.
In the face of the Far East’s increasing popularity as a manufacturing base, it is becoming ever more common for medicinal products to travel significant distances before they reach the end-user. As a result of this, consignments could potentially be exposed to myriad environments and climates, each posing their own challenges; from hot and dry to cool and damp conditions, issues of humidity and pressure are just some of the concerns.
Safeguarding the quality of pharma supply
Transporting pharmaceutical products is a complex but integral function that has evolved over the years. A multifaceted discipline, it requires the input of stakeholders from the minute a product leaves the manufacturing facility up until its arrival in the hands of clinicians or patients. In order for the chain to work at an optimum level, Taylor urges pharma companies to select partners that are familiar with the sector.
While it is important for manufacturers to know who they are working with, it is also critical for their partners to understand the nature of their clients’ work. "Observe the labelled storage and transportation conditions, and the requirements of your contract givers," Taylor urges. "Don’t assume that someone else in the supply chain will take responsibility for your failure to maintain product quality."
While recent proposals from the Commission have received what can at best be described as a lukewarm response, it is due to consultations like this and subsequent regulation that the pharma supply and cold chain is of such high quality. "Regulations have always sought to safeguard product quality throughout the distribution chain," concludes Taylor. "Recent guidance has built on these policies, and the experiences of regulators and the industry, in order to improve and enhance quality measures."
All stakeholders have a critical part to play in the establishment and maintenance of a stable and secure chain – and that role doesn’t begin at the point of collection and end when a consignment has been delivered. It is equally important to have your voice heard on matters for consultation, raise your concerns and share your ideas.
Collaboration is a word that has seeped into the mainstream business lexicon in recent years, but without it industry practices and understanding of the environments in which we operate would not have evolved. This is as true for regulation as it is for distribution.
