Taking the long view in clinical trials
Outsourcing services is an established principle in the pharmaceutical sector and one that is now widely accepted in many other industries as companies large, small and virtual recognise that one of the keys to business success is focussing on core competencies – particularly in straitened times.
There remain two fundamental approaches to outsourcing, however, the one being that it is a strategic decision, the other that it’s a short term solution to supplement in-house capabilities where sudden demand is experienced.
Given the complex and highly-regulated nature of the pharmaceutical sector, both for licensed products and those in development, it’s not surprising that the generally-expressed preference is for the strategic approach. This is evident in the substantial global partnerships between the major pharma multinationals and some of the larger players in clinical trials supply, but these are the exception rather than the rule. In reality there is still a huge proportion of the business that is reactive, the main driver for which is lack of in-house capacity, expertise or technology.
In the clinical trials field in particular, a natural conclusion might be that the increasingly hi-tech nature of medicines means that study sponsors simply don’t have the technological capabilities to handle them in-house. Again the reality is somewhat different: here at Brecon we’ve seen a significant shift towards parenterals in recent years, which from a packaging perspective involves a relatively low-tech hand- or automatic labelling process.
The capacity question pertains particularly to the virtual sector of the pharmaceutical industry, whose business philosophy is based on outsourcing every business function other than intellectual property. This knowledge gives the supply community a degree of visibility – but yet again, there’s a flipside in that many virtuals are based on a single product that, once sold on or commercialised, effectively signals the end of the business.
For a supplies and logistics specialist like Brecon, there are also distinct differences between contracts agreed direct with the sponsor and those emanating from CROs. There are pro’s and con’s to each: direct relationships are potentially more transparent, while CRO involvement can be beneficial from a project management perspective.
For the trial sponsor, there is a significant benefit in working with a company like Brecon in that they are able to draw on the experience the company has gained across projects delivered for a wide range of clients – essentially a supplies specialist is well-positioned to develop and maintain best practice. An example comes from a very large UK-only study we’ve been working on for a number of years. The concept of the study was to eliminate direct patient interaction, with enrolment and monitoring all managed via the internet and study medications being posted to the patient’s home. The objectives were to reduce costs and facilitate patient enrolment and retention by minimising the demands on their time.
Based on this experience, we were recently able to recommend a similar approach to the sponsor of a new trial and our advice included the best way to design and make up patient packs to maximise compliance and security – even taking into consideration obscure facts such as the size of a standard UK letterbox.
What’s clear is that there is no such thing as a typical client relationship in our business. Some issue us with a complete packaging specification and use us as a straightforward fulfilment service; in other cases, clients send us a study protocol and rely on us to scope out every aspect of supplies packaging, storage and distribution. Capacity is essentially what’s at the root of every decision to outsource. Requirements vary and the key is being able to fulfil demand in a timely and professional manner. In choosing to work with a contractor, clients pass the responsibility for managing capacity to us. We therefore need to be in a position to react quickly: for something as complex as clinical trials packaging, this means having highly-trained staff across a range of disciplines – project management, regulatory, packaging and distribution management to name just a few – available for deployment at short notice.
Globalisation has had an enormous impact on clinical trials in recent years as the pharma sector seeks to reduce costs and speed time to market. As a result, the geography of the clinical trials map has changed beyond all recognition as traditional centres for studies are replaced by new hotspots in emerging markets such as China, India, South Africa, Latin America and Eastern Europe, where the recruitment of naïve subjects is easier than in established markets. What is also true, however, is that management of studies has become much more complex as a result.
Clinical trial protocol development may begin in one country, with review performed by members in corporate locations in another two countries, study execution managed by three corporate locations and two outsourced partners … and so the trail continues.
But while the drivers may be the same the world over, there remain substantial differences between local and regional legislation. The impact of the EU Clinical Trials Directive has been much discussed but it’s still surprising how limited the knowledge of a non-EU sponsor can be with regard to the requirements for setting up a trial and releasing product for use within European countries. Clients increasingly rely on their service suppliers to provide guidance and to supplement their in-house knowledge – and in the case of virtual companies, to provide all the knowledge.
Staying abreast of evolving legislation is an undertaking in itself. A good example is the recent Annex 13 update to the Clinical Trials Directive, which took effect on July 31, 2010 and which has significant consequences for both sponsor and supplier. The Annex builds on the original Directive’s provision for the retention of samples from each packaging run, requiring enough product to be retained now to enable two full analytical tests to be completed in accordance with the IMPD (Investigational Medicinal Product Dossier). The material to be retained includes the starting materials, packaging materials, the product in the primary packaging and the finished product.
As previously, samples are also kept for identification purposes and these should include samples of the final packaging. These samples must be kept for two years after the end of the last trial in which the specific batch was used.
This raises issues about who should keep the product and where it should be stored and also about cost – with a small-scale trial involving an expensive product, the Annex requirement can mean that the volume of product to be retained could be higher than what is required for the trial per se.
As trials become more global, there’s a preference from sponsors to work with suppliers who can demonstrate commensurate global reach, in our case so that trial supplies can be handled by a single partner from phase I onwards. It’s also clear that clients are thinking more about the entire life cycle of their product and are looking for partners who can take formulations from phase I right through to full commercialisation.
Since Brecon became part of AmerisourceBergen Corporation in 2006, we’ve sought to respond to this requirement by building a harmonised and proven global service for both clinical supplies and commercial packaging. In the clinical supplies arena, we have established AndersonBrecon Clinical Services to offer identical services on either side of the Atlantic. This is proving particularly popular with sponsors of large global studies, who are often based in Europe or the USA. Procedures and paperwork are replicated across the two sites to create a seamless interface, regardless of whether the project is led from Europe or the USA and whether product is packed in either location or both.
The ‘one-stop shop’ requirement encompasses packaging and complementary services: increasingly analytical services form part of the project scope (more so because of Annex 13 requirements), as do global logistics capabilities.
We referred earlier to the growing proportion of new drugs to be formulated as parenterals, which, insofar as early stage trials are concerned, involves a relatively low-tech packaging and labelling process. It’s a very different story where storage and distribution of these products is concerned, however, with many formulations requiring cold chain or controlled ambient handling to maintain efficacy. Many trial sponsors simply don’t have the physical storage capacity, or the capability to manage every stage of distribution with guaranteed temperature control.
The solution to handling and distribution challenges such as these is a network of depots, either owned by the supplies contractor or sub-contracted and managed as an integral part of the operation. Clients need to be confident that their products are being handled appropriately and securely at every stage of distribution, so every depot needs to be highly qualified by the supplies management company.
Increasingly, we are putting temperature sensors onto ambient shipments and using validated, temperature-controlled shipping systems. Controlled ambient shipments are a service that clients are using more and more frequently as part of their commitment to total quality and in response to this approach becoming increasingly seen as industry best practice.
Technology has made a huge difference to the way in which projects are managed. In a global business, the need for 24/7 communication and information remains paramount. Where clinical studies across multiple territories are involved, a project manager may wish to check on inventory, shipping schedules, location of supplies in transit or other aspects of his study at any given moment. With this comes the expectation that electronic records are compatible, for example between the IVRS company and the supplies specialist and between the supplier and sponsor for inventory management purposes. The key is a robust IT infrastructure, with a platform able to deliver the flexibility to accommodate varying client requirements, while delivering the high levels of control required for clinical trials in particular. A significant investment at Brecon will see us take a major step towards these goals within the coming weeks, when we combine and migrate various information sources onto a single ERP system. Rolling out across our Group globally, the system offers a dedicated web portal for each client, which can be customised to provide real time status information according to a range of client-specified criteria.
It’s a fair assumption that, when asked about the challenges facing the pharmaceutical sector, most laymen would put cost pressures at the top of the list. In our experience it’s less straightforward than that. There’s a sense of collective responsibility to manage cost and deliver value, but this doesn’t normally translate into aggressive cost negotiation at project start-up. What we are seeing is a more ‘joined up’ approach, with clients focusing beyond the task at hand. A good example is how logistics considerations have become integral to project management, with packaging design increasingly influenced by how the product will be shipped. Absolutely paramount is our ability to handle projects quickly and efficiently, getting the right drug to the right place at the right time. A well-managed project will ultimately deliver more value than one based purely on price.
This article was first published in Manufacturing Chemist, February 2011
