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Outsourcing


everyone has a different definition. Evans noted that there has been an emphasis on one-stop-shops over the past 10 years but added that, in Big Pharma, ‘one has to recognise that one organisation can’t do everything well all the time’. He suggested that one needs to decide on a project strategy that focuses on what a CRO does best otherwise the search for a one-stop- shop can become ‘an endless pursuit’. Saunders added that many contract


organisations appear to want to go down the route of becoming full service providers in order to conduct any part of the drug discovery process. ‘But everyone has a different view….although companies might have all the functions they may not be “integrated”,’ he said, adding ‘integration is a rare thing in the CRO world’. For a CRO, Sowin said that integration means everything from synthesis, through in vitro biology, GMP and toxicology. He pointed out that at Abbott a project manager would be appointed with responsibility for the whole process. If the CRO doesn’t have a specific capability, then Abbott will take that part of the process in-house in many cases to avoid time delays in a project. One particular area offering opportunities


for integration is process development, according to Maciocio, who noted that the real potential is in transferring the API to commercial product manufacturing. Another opportunity for differentiation is in particle engineering – reducing the particle size to increase activity – added Thomas Eckrich, an advisor on chemical product R&D at Eli Lilly.


Risk sharing or fee-based The financials of outsourcing can range from fee-based for a specific service through to full-service contracts. One business model that is gaining ground is the sharing of risk between the client and the service provider. But Evans recognised that the risk models are very different, for example, between medicinal chemistry and synthesis, a view echoed by Hunt who isn’t sure that everyone is talking about the same thing: ‘It is a spectrum,’ she emphasised. In Evan’s view, however, the risk is already built into the project. This is a risk business, added Hunt, saying that Big Pharma needs to share risk with its suppliers –‘both in success and in failures’. But she also said that Big Pharma doesn’t want to kill off its suppliers – ‘the bottom line is only part of the deal’. Hunt pointed out that Merck has looked at every type of business model in dealing with service providers but has seen a move


‘Getting the right CRO isn’t always the challenge, it is getting the right person’


David Perry Pfizer


towards risk-sharing. However, she hesitated to actually call it risk-sharing, seeing it more as a milestone bonus based approach. Abbott has also used risk-sharing models, but Sowin emphasised that it is important to ensure that the supplier isn’t losing money at any point as they will then want to see the project die. It is essential to agree a fair deal, he added.


One option suggested by Roger Bakale,


senior director, worldwide chemical process R&D for Teva Pharmaceuticals, might be to offer market space rather than royalties as an approach to ‘reward’ suppliers.


Risks in the supply chain With the globalisation of outsourcing, there are increasing risks in this extended supply chain, ranging from counterfeiting through adulteration to theft. As Eli Lilly’s consultant for development and commercial API sourcing, Tony Wiederhold pointed out: ‘Ten years ago we were buying more basic chemicals; now much more complex molecules are being purchased.’ Wiederhold, who is responsible for consultant development and commercial API sourcing, said that there is a need to check into supplier’s suppliers to ensure that adulteration is not a potential problem. As Mechelle Schumacher, sourcing


director at Amgen, emphasised, adulteration is a ‘very big deal…. there is no “magic bullet” why Amgen hasn’t had a problem but Amgen partners very carefully with its suppliers and goes on its suppliers’ supplier audits’.


Regarding counterfeiting, Thomas Christl,


acting director for the US Food & Drug Administration’s Office of Drug Security, Integrity and Recalls, stated: ‘It is important for industry to know who it is buying from and selling to – it needs to identify if a single supplier is the actual producer. Industry needs to play an active role.’


Schumacher pointed out that the industry


is already taking an active role through its Rx360 initiative, which is increasingly embracing suppliers of raw materials and intermediates (C&I, 2012, 8, 26); something that was welcomed by Christl.


Neil Eisberg is editor of Chemistry & Industry


Batch vs continuous processing


The pharmaceutical industry has traditionally used batch-based processes to manufacture its active ingredients (APIs), however, interest has grown in the use of continuous or flow processing. Discussion over the relative merits of the two approaches has been encouraged by new FDA guidelines that have focused attention on so-called Quality by Design (QbD) and how flow processes might offer a better solution for some types of synthesis, including, for example, reactions that require low temperature conditions for safety reasons. Nicholas Petousis, associate director, CMS, at SK Life Science, believes that the industry will see more continuous flow processes, as he believes that the increasing production of low volume drugs will benefit from flow processes for a number of reasons. He points out that the purity profile is better, and flow processes offer better mixing and require less solvent. However, he also recognises that continuous processing cannot necessarily be used for all steps in the synthesis of an API. It may be necessary to combine batch and continuous process steps although he believes that some downstream processes, such as crystallisation and drying, could also benefit from continuous process development. The view highlighted by Petousis


regarding downstream processing was shared by André Vries, business manager, Innosyn route scouting services, at DSM Innovative Synthesis, who pointed out that continuous crystallisations and extractions are increasingly being used, but he also emphasised that it wouldn’t be necessary to change all batch processes into continuous approaches. He noted that while in many cases the change to continuous processing is being made for safety reasons, there is also the desire to achieve higher yields that can be achieved.


One Big Pharma company that has invested significantly in flow processes is Eli Lilly, according to Lilly’s Thomas Eckrich, who noted that Lilly is also looking for outsourcing companies that have the same capabilities. As Petousis concluded, a lot of the barriers to continuous processing are coming down – the tools are getting better – but the mindset is the biggest barrier; ‘for sure, it is a brave new area but for others it is just part of the toolbox’.


Chemistry&Industry • November 2012 41


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