Keeping Up With Demands

Just as the change in profile of the average customer seeking out a manufacturing partner has led to a restructuring of the CMO / CDMO landscape, evolution in the types of projects pharma and biopharma companies decide to take on impacts the services their contract counterparts invest in.

The smaller the patient populations, the bigger the push for CDMOs

To accommodate the rise of programs using targeted medicines to treat rare disorders, many CDMOs have restructured their supply chains accordingly.

The Orphan Drug Act of 1983 has played an immense role in the attention orphan products now receive. Before its enactment, only 38 orphan drugs existed; between 1983 and July 2020, the FDA approved 599 drugs for the treatment of rare diseases. In fact, throughout the past five years, roughly half of all drugs approved by the FDA have been for orphan or rare disease indications.

Shuang Liu, CEO and founder of ConSynance Therapeutics, a clinical-stage virtual biopharmaceutical company focusing on rare diseases in the central nervous system, sees clear benefits to operating within the US beyond its regulatory appeal: “The US is the leading country for rare disease research thanks to its patient-centric ecosystem fostered by the government, patient advocacy groups, industry, research institutions, and the general regulatory environment. The US has the most favorable environment for rare disease research given the ability to take on high-risk endeavors that have the potential to transform the treatment of rare disease patients and significantly improve their quality of life.”

The capital inflow into the space has enabled companies with ambitious programs to fund research into diseases that can be so rare they are not even registered within the FDA, much less have a preexisting approved treatment. The market for these drugs is inherently smaller, sometimes in the mere thousands, which has flipped the traditional development and manufacturing model on its head, a far cry from blockbuster drugs that are designed to reach millions of patients.

One of the most fundamental ways service providers have accommodated to working on smaller batches is in the way they approach supply chains. According to Mark Egerton of Quotient Sciences, pharmaceutical companies developing drugs to treat rare disorders have two options in terms of distribution. They can either invest substantially into producing large quantities of product with an extended shelf life or hold off until patients have already been recruited and then deliver the drug to this population in a near just-in-time fashion. The latter is often attractive when dealing with patient populations so small that the recruitment process for trials can be a long and unpredictable journey.

Thomas Loewald, CEO of Cambrex, drew two conclusions from the fact that the number of orphan drug approvals currently exceeds non-orphan drug approvals: First, his company needed to establish more flexible manufacturing assets to accommodate a greater variety in batch sizes and the technologies to assist with the development of the molecules in question. Second, projects for more targeted medicines require greater analytical capabilities. “Smaller batch sizes lead to a higher level of demand for analytical resources relative to manufacturing, as each batch must be tested the same way, whether it is enough material to treat 10 patients or 10,000 patients,” Loewald explained. “We have seen an industry-wide shortage in analytical resources, creating a very strong demand in our analytical service portfolio.”

In addition to generating a stronger focus on supply chain flexibility, the heightened interest in treating rare disorders has itself driven more demand for outsourcing to service providers. As Patricio Massera, CEO of AGC Biologics commented, smaller production volumes make it more difficult for small and mid-sized developers to find value in establishing their own manufacturing capacity. “CDMOs offer a great opportunity for orphan drug developers to outsource manufacturing capabilities so they can focus on the science and strategic planning to get their products to the market,” he explained.

Going green

Over the past handful of years, rising ESG concerns have made their mark within nearly all major industries. Life sciences is no different.

Customers of service providers are demanding more environmentally conscious manufacturing methods and sustainably sourced products, and the requirement is not unfounded. According to the European Environmental Bureau, more than 100,000 tons of pharmaceutical products are consumed annually around the world. Throughout their manufacture, consumption, and ultimately disposal, chemical ingredients are released into the surrounding environment. It is estimated that between 30-90% of the APIs in an oral dose are excreted as urine. As these products are designed with the express purpose of causing pharmacological effects in living organisms, their release into the broader ecosystem can lead to unintended consequences.

Industry agnostic concerns such as carbon footprint are also ever-present; it has been widely reported that the pharma sector historically generates more greenhouse gases than the automotive industry. Broadly adopted initiatives to shorten and strategically reshuffle supply chains will likely mitigate the problem, but some CDMOs believe that is not enough. Green chemistry aims to reduce pollution at the source by minimizing or eliminating altogether the environmental risks posed by chemical feedstocks and products.