BPI Theater at BIO preview: Bioprocess bottlenecks and BIOSECURE

The biopharma world is set to flock to trade organization BIO’s annual event next week. As usual, BioProcess International and BioProcess Insider will be hosting the BPI Theater on the showfloor on Tuesday 4 and Wednesday 5 June. 

Ahead of the event, and with one eye on BioProduction at CPHI Milan later this year, we take a look at the returning confidence and trends ahead for biologic production. We spoke with CPHI Annual Report expert Bikash Chatterjee (BC) of President of Pharmatech Associates – a USP Company. 

BPI: How do industry events/conferences like BIO and Bioproduction help drive evolution in the bioprocess space?  

BC: These large conferences are essential for a number of reasons. Firstly, they afford a vital window into leading edge, innovative approaches to drug development and commercial manufacturing. Second, panel discussions allow us to debate and understand the implications of critical industry issues that shape the business of biotech. 

And this year we of course have some really far reaching debates raging from the Inflation Reduction Act (IRA), onshoring considerations, to the BIOSECURE Act. Hearing the rationale and defense of evolving regulations helps understand regulatory thinking and expectations. 

Last but not least, these conferences serve as a catalyst for business, stimulating collaboration to drive innovation, opportunities for in/out licensing, or bringing together key suppliers, consultants, and contract service providers. Conferences such as BIO and CPHI Bioproduction are essential to keep the industry moving forward, and are an important part of our calendar every year. 

BPI: What bottlenecks still exist in the production of antibodies? 

BC: Advancements in upstream process intensification are leading to higher cell densities and antibody concentrations exceeding 10 g/L. This efficiency, however, creates new challenges in downstream processing because of increased product and contaminant levels. Typically, downstream antibody processing involves Protein A affinity chromatography, additional chromatography for polishing and viral clearance, and final formulation and filling.  

There is growing industry interest in alternative chromatographic methods that offer higher capacity, throughput, and lower costs. Affinity resins are being designed to bind non-Fc-containing fragments and offer better dynamic binding capacity, milder elution conditions, and are more compatible with clean-in-place operations. Alternative purification technologies like Protein G and L chromatography and non-affinity methods like, cation exchange, hydrophobic interaction, mixed-mode chromatography, precipitation, and crystallization are gradually gaining traction. While the predominant approach will remain Protein A resins, the diversification of antibody products and cost pressures could begin to drive change this. 

BPI: What are your thoughts on what the Biosecure Act means for biotechs looking for CRO/CDMO services? 

BC: The BIOSECURE Act bars firms that receive federal funds from using select Chinese service companies specifically citing the genomics companies BGI, MGI, and Complete Genomics; and WuXi AppTec. The bill’s latest iteration adds CDMO WuXi Biologics and gives the industry until 2032 to break its ties with the named Chinese entities. When the bill was originally introduced in January 2024 some feared it could impact industry and could potentially lead to drug shortages or delays in launching innovative drugs in the US.  

The new language in this draft offers an eight-year ‘grandfathering clause’ for contracts that entities enter into with biotechnology companies of concern prior to the effectiveness of the Act. The House bill also offers a “safe harbor” provision to clarify that biotechnology equipment or services will not include any that were produced or provided by the biotechnology companies of concern.  

Perhaps most importantly, the new language in the House bill provides a definition for “contract” — a previously vague term in the House and Senate bills— clarifying that the bill only applies to contracts regulated under the Federal Acquisition Regulation (FAR). FAR is the primary regulation used by executive agencies (DOD, DLA) when they are acquiring supplies and services with government funds.  

The grandfathering clause, safe harbor provision, and the new definition of what constitutes a contract all seem to be intended to give companies time to transition away from dependencies on the services and equipment of the biotechnology companies of concern. Nonetheless, the House bill aims to incentivize companies to transition their business to alternative equipment and service providers, and, given the scale of the biotechnology companies of concern, one would expect that to have sizable bearing, both on the individual biotechnology companies of concern and on the biotechnology ecosystem generally. So far, the bill’s impact has been minimal in the U.S., with the cost of debt financing and venture capital investment dominating many organizations’ strategy to bring their programs to market. It is too early to gage the impact the bill will have until the industry sees how the federal government will interpret and implement it.