Biologics drug development and manufacturing
PharmTech: What emerging technologies or practices do drug sponsors expect your organization to provide?
Andrew Strong: Industry expectations of CMOs for technologies include disposable technologies and single use systems. Cross–contamination and clinical development where single use technologies upstream and downstream are applicable. A broad, in-house analytical capability is also an expectation. In all cases, however, the bioprocessing technology needs to be scalable to commercial scale.
PharmTech: Are you seeing shifts in demand for particular types of services? Please describe.
Andrew Strong:The demand for cell line development coupled with platform approaches to process development and manufacturing has been increasing in demand. Big biotech has used this approach for a while, as well as some of the larger CMO’s, particularly where the drug of interest in an antibody. We’re also seeing an up-tick in the process development and manufacture for viral-based products, including personalized medicines, requiring BSL2+ facility containment. Kalon is particularly well suited for these needs, because of the ‘mobile clean room’ (MCR) approach that is unique to Kalon.
PharmTech: What pressing technical challenges have you seen in this market segment? What actions has your company taken to resolve the challenge? What actions does your company suggest?
Andrew Strong:The most pressing technical challenges are mostly on a case-by-case basis, and more often than not, related to the specific biological product in question. Having technologies that allow for solutions that will scale with the process to commercial scale, as part of the CMO tool box, remains an important capability. Analytical resources and reliable analytical methods are key to any challenge and it’s solution.
PharmTech: What advances do you see in science or technology in this market segment in the next five years?
Andrew Strong:Bioprocessing is becoming less of a unit operation and more continuous. Technologies that provide for continuous processing upstream and downstream are at the forefront for the next 5 years. Being able to process highly concentrated proteins without having to go through a lot of buffer exchange unit operations will impact time on plant, buffer-prep and QC resources and ultimately affect COGS.
PharmTech: What regulatory changes have positively or negatively impacted drug development/manufacturing processes in this market segment?
Andrew Strong:Allowances to do Phase appropriate cGMP for biologics has significantly helped support the emerging small biotech companies in getting to the clinic for early proof-of-concept. Although this change has been in place for some time now, it still provided positive benefit to the small biotech market segment.
PharmTech: What business trends have positively or negatively impacted drug development/ manufacturing processes in this market segment?
Andrew Strong:Large Biotech and big pharma have made a shift in strategy to outsource. This is a significant change to the mind-set from just a few years ago. As a result, the work process and communication flow with between biopharma and CMOs has improved. It’s more collaborative, more conducive to long term relationships and successful outcomes. The Not-invented-here mentality has softened, the interaction more collaborative than protective and allowing for a more successful outcome.
PharmTech: What changes are you observing in the organization and operations of drug sponsors in this market segment?
Andrew Strong:Drug sponsors have become more informed consumers of outsourcing services. We see a more savvy client, with better internal infrastructure to support outsourcing. Even the smaller, more virtual companies, understand what expertise they need from analytical, regulatory and process development. The use of consultants to support their interactions with CMOs has increased the virtual company’s understanding of what it takes to get to the clinic. We’re also seeing more commitment to outsource early, and to rely on external expertise at CMOs for the long haul. Commercial manufacturing capabilities have become an early request, rather than a late one.
PharmTech: How has quality by design influenced a drug sponsor’s expectations of suppliers?
Andrew Strong: Developing a process using well documented, science-risk based approach makes sense for CMO’s. The process of evaluating the approach to process development and critical process attributes, provides more comprehensive understanding of the process, and mitigates the risk of failure on scale-up. The FDA is requiring more thoughtful, methodology to process development through a QbD process. When operating on a fee-for-services basis, risk mitigation is critical to profitability. The technologies to allow for DOE based approaches to process development have allowed form more experimental approaches without increasing timelines or cost.
PharmTech: Describe the role that quality agreements play in contract services relationships.
Andrew Strong:Quality Agreements are a critical requirement for CMO relationships. In addition to providing ground-rules of roles and responsibilities, they (QAA) provide clarity.
PharmTech: How will FDA’s draft guidance on quality agreements affect the relationships between contract service providers and drug sponsors?
Andrew Strong:Quality Agreements, even before FDA draft guidance, have been a standard practice for CMOs. Having clearly defined approach to cGMPs, roles and responsibilities of the sponsor and the CMO is just a good practice to establish. The Quality Agreement improve the alignment and therefor the relationship between the CMO and the sponsor company by establishing the expectations around cGMP compliance, interpretation of cGMPs and align the parties before problems arise.