The changing landscape of clinical trial manufacturing

With regulation changes, the death of the blockbuster, focus on personalised medicines and less R&D spend than ever before, the clinical trial manufacturing landscape has undergone many changes. SCM Pharma’s Dianne Sharp reviews the sector and outlines what companies of the future could look like

Dianne Sharp: Less time and less money is what we are all dealing with in our sector

Clinical timelines are seriously under pressure and that is a fact. You just need to work with a handful of pharmaceutical and biotechnology companies of any size to know where the pressure point is. And contrary to what people may think, it is always time, and not always cost. Meeting deadlines, proving or killing projects quickly, moving the product through each phase and getting the product to market as quickly as possible to maximise patent time is what it’s all about in drug development. Speed and time are very much of the essence in drug development and clinical trials.

Nevertheless, cost is still a major driver of any clinical trial project and funds are harder to come by than ever before. For Big Pharma, there is simply less spend and resource in R&D than there was 10 years ago, and higher expectations of better returns on investment. We have all seen the high level executive exits and falling share prices of those deemed not to be performing. And for smaller virtual companies and biotech organisations access to finance from venture capitalists, private investors and banks is not as easily or widely available as in the pre-2009 days. Less time and less money is just the reality of what we are all dealing with in our sector.

When only around 1 in 1,000 compounds make it to human testing, it is understandable that proof of concept becomes a key benchmark to be achieved as quickly as possible with as low an investment as possible, to mitigate the financial risks – all while ensuring the highest possible safety, ethical and regulatory standards are met.

Having manufactured new drug products for clients across the world over the past decade, SCM Pharma has seen first hand the regulatory standards required to develop and make new drug products. It is no easy process. So with this backdrop of ‘get moving’, serious pressure is on.

Getting personal

Patient populations are getting smaller because drugs are more targeted, and this has added an extra dimension to clinical trial programmes over the last few years. Orphan drugs, for instance, are developed specifically to treat rare medical conditions; and this, coupled with the closer targeting of therapies to patient sub-groups, has increased the demand for smaller, more flexible batch sizes. However, this obviously increases pressures on pricing as the development investment needs to be recovered over a smaller number of doses.

To motivate the development of therapies in these areas, various licensing authorities have introduced ‘fast-track’ programmes to support and encourage innovation and research for these patients. Again this underlines the principle of the need for speed. In drug development time really does mean money.

In January 2013, the New York Times reported that the development of these orphan drugs is increasingly attractive to pharmaceutical companies, which are searching for new sources of revenue as sales of more traditional, mass-market drugs have been lost to generic competition. The competition to treat these rare disorders underlines how shifting commercial dynamics are driving the pharmaceutical industry in new directions.

By 1983, only 38 drugs in the US were approved to treat such diseases. By 2010, 352 orphan drugs were approved: one-third for cancer, as reported by the BBC. By 2011, the orphan drug market was worth more than US$50bn.

When it comes to manufacturing orphan drugs at a commercial level, their supply chain is actually more akin to clinical development scenarios. The pressure to provide access to therapies for patients who can benefit from them means that the orphan approval process is often accelerated. This has provided new opportunities for nimble and efficient CMOs.

As patient populations get smaller as drugs are more targeted, this had added an extra dimension to clinical trial programmes over the last few years

Another big area of change experienced over the past few years is in the types of clinical projects. Large molecule programmes outweigh small ones and we have also seen an increase in potent product projects. The latter has been primarily driven by the increase in oncology-related products, while the growth in large molecule programmes has driven an increase in parenteral presentations due to the often poor oral bioavailability of these formulations. With only a limited number of CMOs that can handle potent products and a global reduction in sterile capacity, finding the right CMO partner can be tricky, given the large number of players in the CMO market.

So although there are fewer drugs in development and increased pressures for those involved in clinical trial development, there have been some new opportunities due to the move away from big blockbuster drugs towards personalised medicines.

So what does this all mean for CMOs and CDMOs involved in clinical development and manufacturing?

It is important to understand where all these contract organisations are coming from before we hypothesise where they are all going. A significant level of growth in CMOs in the past 15 years has occurred as the result of large pharma companies divesting old sites and becoming less vertically integrated. Unfortunately, the changing landscape as outlined will squeeze returns.

Sharp: In reality, the clinical trial sector needs flexibility and agility

In reality, this has just moved the problem of over-capacity, under-investment, inflexibility and scale from one part of the industry to another. There are now a significant number of sites focused on large-scale manufacturing that are just not relevant for the clinical sector. In addition, more and more pharma companies are offering ‘contract services’ via empty sites and under-utilised resource.

Fortunately, for the core CMO businesses out there, these new entrants are on a steep learning curve when it comes to tech transfers, capacity planning with multiple clients/projects, marketing, customer service and many other service-led differentiators that just don’t come naturally to companies that were historically ‘in-house’ manufacturing operations.

In reality, the clinical trial sector needs flexibility and agility. With this in mind, CMOs and CDMOs need to change to be more adaptable. This is the dawn of agile manufacturing in our sector: agile sites, agile supply chains and agile businesses that can move with the times, adapt to pressure and change in products and volumes.

Learning lessons from the automotive and FMCG sectors, the pharma manufacturing sector also needs to adopt lean operations. This is not about cutting costs; the origins of lean and agile manufacturing approaches can be found in Total Quality Management (TQM), which focuses on continuously improving the quality of products and processes at every stage from initial design to finished product.

For these approaches to be truly successful they need to be embraced by the whole supply chain to bring about a paradigm shift in the sector; there is, therefore, a real opportunity for CMOs to lead the change and demonstrate the benefits to clients and ultimately patients of these approaches.

Clinical manufacturing is more competitive and more global then ever. Unfortunately, with fewer new projects on the horizon, not everyone will survive

As is the case at SCM Pharma, more contract manufacturers are offering sites that can provide end-to-end solutions so that precious time is not lost in tech transfers. Why use several different contract partners when one can grow with you and your product from pre-clinical to commercial scale? The success of a relay race is often determined not by the speed of the individual legs but in the smoothness of the baton handover. In addition, integrated CMO partners understand the realities of each stage of the process including commercial manufacture and will therefore design early phase processes with the commercial scale in mind.

There is no doubt that clinical manufacturing for both large scale, non-sterile products and more specialised sterile products is more competitive and more global then ever. Unfortunately, with fewer and fewer new projects on the horizon, not everyone will survive.

There will continue to be significant consolidation and M&A activity in the CMO/CRO sector over the next decade, leading the way for ‘the big boys’ alongside several smaller, niche, specialised suppliers.

Drug discovery has and should continue to have an undeniably momentous impact on society and patient outcomes. CMOs are fundamental enablers for this trend to continue, supporting the faster and cost-effective delivery of new therapies from lab benchtop to patient.

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