Protein forms of an antibody or other therapeutic drug targets are becoming more complex, targeting smaller populations of patients, demanding highly skilled workers, significant expertise, and expense.
Additionally, regulatory expertise is a key component for Pharma and Biopharma companies focused on getting products to market faster. As a result, aligning early and late stage development services, along with regulatory consulting through commercial product, is a growing trend among CDMOs.
R. Barry Holtz, Ph.D., President of iBio, a provider of contract development and manufacturing services from early stages through regulatory approval and commercial product launch, discusses the trends driving outsourcing, as well as where R&D is going and what some of the biggest opportunities are. –KB
Contract Pharma: What are the most significant pharma trends impacting CDMOs and services?
R. Barry Holtz: Pharmaceutical companies are absolutely outsourcing more, using CDMOs to reduce “time to clinic.” Pharmaceutical companies are focused on getting products to market, and manufacturing for large pharma and small companies alike is increasingly being outsourced.
The regulatory compliance component is becoming an important CDMO offering. CDMOs are offering these services because discovery-based companies often do not maintain their own regulatory affairs departments. It is challenging to get into early stage manufacturing without enormous commitments in personnel, training and recruitment. Consequently, regulatory affairs is an expense that these firms do not necessarily fund in-house any longer.
Reducing time to clinic is one of the key concerns of pharmaceutical companies both large cap and small cap. CDMOs now have to be prepared and responsible for getting customers to their next financial milestone – whether that’s getting products to the clinic or having an Investigational New Drug (IND) application filed with the FDA.
CP: What are some of the latest motivators for sponsors with respect to outsourcing?
RH: Once a drug is discovered, even when the drug is outsourced for manufacture, pharmaceutical companies have to deal with paying for their internal resources or “burn rate”, which is always a financial challenge. Outsourcing relieves some of the capital spend challenge, however, the more rapidly the CDMO can get the product to clinic reduces the operating capital for the parent company.
CDMOs can help the customer focus on these financial drivers and put resources in place to rapidly move the new product forward. Many times getting to their next financing event boils down to getting products to the clinic, showing some clinical progress or in filing a successful IND.
As I mentioned earlier, when you look at the typical divisions in a small pharma company, process development, manufacturing, quality assurance and quality control may all be well represented. The missing component is generally regulatory affairs.
CDMOs are becoming more vertically integrated than ever before, increasingly focused not only on process development and early stage work, but the regulatory component as well.
To address the regulatory requirement, CDMOs are aligning themselves with regulatory experts and consulting firms to create “start here, stay here” or “lab to launch” vertical outsourcing businesses at a rapid rate.
IBio has developed a partnership with CBR International Corporation (CBR) in Boulder, CO. The arrangement allows us to provide strategic regulatory and clinical services in addition to drug development. CBR has years of experience and can provide risk analysis, regulatory affairs and e-publishing to support to large and small customers.
CP: What service areas are you seeing an increased demand for, and from what sectors?
RH: The industry is now moving into “designer” proteins, targeting smaller populations of patients with diseases that lack generic treatments. These proteins have structural nuances that are not always compatible with traditional expression systems. Some are toxic to mammalian cell production or are not produced at levels that provide necessary financial targets. There is increasing interest in having a “portfolio” of expression systems to rapidly screen molecules and down select into systems that will move the therapy forward rapidly and economically.
The analytical services component of the business has changed. When talking about making new designer proteins, it’s critical to thoroughly understand their structural and post-translational elements in great detail and be able to rapidly analyze these components in different expression systems.
The capability to do a deep structural dive into the protein forms of an antibody or other therapeutic, demands a highly skilled workforce and significant expense. Consequently, we are seeing considerable increased demand high end mass spectrometry services. We also have noticed an increase volume of business in the small-scale finish and fill services. It is almost easier to get 200,000 vials filled than it is to get 1000 vials filled criteria.
CP: What is your perspective on where research and development is going? Where do you think some of the biggest opportunities are?
The biggest opportunity for CDMOs is being able to offer services all the way through to the launch of product.
CDMOs in the past have specialized in early stage trials, because that has been the highest profitability for them. But in reality, we are finding that customers would like to start, and stay, in the same manufacturing facility the entire time, and they want to be assured that they have a secure launch pad for their product.
Therefore, CDMOs are going to become more vertically integrated, and there will be many more mergers and acquisitions in the industry.
The ancillary benefit to CDMOs from these changes in the industry is that companies like ours are no longer constrained by geography. iBio is based in Texas, and we have clients from all over the world. Discovery companies are still largely centered on both coasts, but manufacturing has migrated to locations offering economies of people and logistics.
Geography, not being limiting factor any longer, is prompting even more innovative ways to do business. Companies like ours are beginning to offer a tech transfer approach with our clients as a new business model across the board. We have several tech transfer programs to empower clients and partners to use our technology. We supply training, facility design and early stage product development to partners in other geographies such as China and South Africa.
This is good business and can bring new biologic therapies to underserved markets.
Dr. Holtz has 30 years of experience in the development of bioproducts and biopharmaceuticals and design of biopharmaceutical manufacturing facilities. Dr. Holtz led the design/build team for construction and commissioning of the current iBio facility. Serving 15 years as Senior Vice President for Large Scale Biology Corporation, Dr. Holtz was responsible for the product development, clinical development and manufacturing compliance of the company's proprietary therapeutics portfolio. Dr. Holtz led a team that developed and produced a recombinant, plant-made, patient-specific vaccine for the treatment of indolent Non-Hodgkin's Lymphoma from the bench to human clinical trials. Dr. Holtz has led the development of three other Greenfield facilities and several smaller biotherapeutics production facilities.