Despite the plethora of new molecule entities, the industry is as reliant as ever on small molecules — with its resurgent clinical pipeline and the highest number of FDA approvals for decades.
However, the shifting focus of drugs that are launched for the benefit of hundreds of millions of patients to smaller patient subgroups has led to a need for manufacturing assets to cater for smaller volumes (and not to produce hundreds of metric tons of API annually).
With this change, the nature of the sponsoring company has changed too; from around 50 years ago until very recently, most small molecules in the clinical pipeline were being developed by the top 30 pharmaceutical companies. Now, most molecules are in the hands of small and virtual pharma companies, many of which are backed by venture capital or private equity funding.
For CDMOs looking to support the development of new small molecule drugs, it is important to recognise the changing profile of the customer base and the services they require. Historically, smaller biotech companies lacked the expertise and investment to support late-stage clinical trials and their focus would be to outlicence or divest a product soon after successfully completing Phase II trials.
The product would then be inlicenced by a larger pharmaceutical company with the resources and clinical know-how to conduct the expensive and time intensive Phase III trials, as well as co-ordinating production to ensure a successful product launch.
Recently, the rise in orphan drugs aimed at targeted patient populations has resulted in more of the development now being taken on by these smaller companies. The reduced clinical burden and expense of testing their therapies on a reduced subset of patients — rather than conducting several trials in multiple indications as well as co-ordinating hundreds if not thousands of patients — has made the possibility of advancing the product to commercial launch a viable prospect.
Unlike large pharmaceutical companies, smaller companies typically have little or no manufacturing capabilities and are therefore wholly reliant on their CDMO partners; they typically outsource most of their drug substance and drug product needs. With limited internal resources to manage suppliers, this usually means working with fully integrated CDMOs that can offer a broad range of services and expertise throughout early stage development as well as manufacturing.
CDMOs, therefore, need to offer a broad range of manufacturing volumes, but also need to be prepared for the more niche volume requirements of API and drug product that are typical for these applications. Additionally, they should be flexible and able to respond to sudden changes in volumes owing to additional clinical trials or changes in market demand.
The focus on certain therapeutic areas such as oncology has fuelled the rise in the development of highly potent molecules. These too require lower overall volumes in terms of API demand … but also require manufacturing within dedicated, contained assets with experienced staff to undertake the safe handling and production.
This changing landscape offers opportunities for contract manufacturers. The broadening of the customer base means that those CDMOs in a position to offer integrated solutions during the lifecycle of a drug can benefit from strong partnerships with the growing number of new companies who are taking their products through the clinical pipeline and to market.
