Download PDF Summer Bridge on Advanced Biomanufacturing for Medicines June 16, 2025 Volume 55 Issue 2 This issue of The Bridge features cutting-edge perspectives on the rapid progress and innovation in advanced biomanufacturing for medicines. Biopharmaceutical Manufacturing Platforms: Breaking Away from Our Past Monday, June 16, 2025 Author: Paul C. Collins The new era of creativity and diversity of treatment modality in the biopharmaceutical industry has accelerated the need to adopt new platforms. “Platform” is a term that is often used in the biopharmaceutical manufacturing industry, but with different connotations and intentions depending on whether the originator is from a regulatory authority or a biopharmaceutical company. The United States Food and Drug Administration (FDA) has had a long-stated goal of modernizing biopharmaceutical manufacturing and raising the level of technology to be more in line with that of other manufacturing sectors (Arden et al. 2021; Rantanen and Khinast 2015). The notable starting point for this modernization effort was the Quality by Design (QbD) initiative in the early 2000s (Woodcock 2004). QbD sought to achieve a different approach to pharmaceutical process development and manufacturing with a mutual goal for industry, society, and regulators being “a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drugs without extensive regulatory oversight” (Yu and Woodcock 2015). QbD, as initially proposed, offered an aspirational opportunity whereby the traditional procedural approach to assuring compliance might be improved by demonstrating greater scientific understanding and incorporating more advanced approaches. However, achieving the QbD goal was left open to the interpretation of individual companies. As such, the biopharmaceutical industry never came to a common understanding of an end goal, and the opportunities associated with QbD were incompletely realized. Since that time, the FDA has continued to issue new guidances associated with approaches to biopharmaceutical manufacturing modernization (Collins 2018). Guidances dealing with the term “platform” were very recently issued, with a guidance on advanced manufacturing technologies (AMTs) (FDA 2024a) and the platform technology designation program (FDA 2024b). In the latter guidance, the FDA describes a platform technology within the specific manufacturing context as a “well understood and reproducible technology” that “facilitates the manufacture or development of more than one drug through a standardized production or manufacturing process or processes.” The term “designated platform technology” is used by the FDA when a newer AMT (or other existing technology not in the AMT program) has been deemed to meet the “well understood and reproducible” requirements associated with their designated platform program. Platforms, therefore, from a regulatory perspective, are typically associated with efforts to improve pharmaceutical manufacturing efficiency and robustness, and they should reduce the need for regulatory oversight—in keeping with the goals for QbD. From an industry perspective, platforms may often be conceived as unit operations defined by pieces of equipment along with the instrumentation and computer automation necessary to control them. An excellent example of a well understood existing platform is the one by which most monoclonal antibodies (MAbs) are made. Figure 1 is a simplified representation of a standard MAb manufacturing platform. While some companies may use slight derivations of the operations shown here, the major purposes of this platform are ubiquitous in the biopharmaceutical industry: Thawing of frozen mammalian cells and inoculum development Production bioreactor and MAb expression Primary recovery and cell removal Capture chromatography for initial impurity removal Polishing chromatography for final purification Viral filtration Buffer exchange and concentration to render the active ingredient Over 100 MAbs now have been approved and matriculated into the marketplace (Mullard 2021), with the overwhelming majority utilizing the above-described platform or a reasonably close facsimile (Pluschkell et al. 2025). Platforms are also useful to businesses for ensuring quality: Familiarity with equipment and similarity of process across products increases experience in manufacturing operations. Looking back at figure 1, a MAb process making an oncology product looks a lot like a MAb process making a diabetes product—the difference is the DNA inside the cell, with a few process condition changes to account for the specific generated molecule. The equipment associated with the cell culture platform through to the final active ingredient remains largely the same. Training across products is largely the same, allowing for excellent reproducibility in manufacturing execution. Having a clear and common vision of future success for biopharmaceutical manufacturing platforms is key. Platforms are therefore best viewed as business constructs for biopharmaceutical manufacturers—an approach to maximizing capital investment by utilizing the same equipment over and over to minimize cost while maintaining flexibility with suppliers and partners similarly invested in the platform. However, the investment made in these industrial platforms over years of use de-incentivizes new platforms, as new platforms require large capital investments. New processing platforms likely require a greater degree of technical explanation in regulatory filings to ensure authorities are comfortable that product control strategies will be reliable (Algorri et al. 2022; NASEM 2022). Increased effort, complexity, and risk in regulatory filings and manufacturing site inspections tend to be viewed negatively. Displacing existing platforms for ones that are newer and more technologically advanced is thus bad for business. And if existing platforms can be massaged to produce new products, why should they be changed? Inflection Point: The Challenge of New Treatment Modalities The aspirational QbD initiative was conceived in a time when MAbs and small molecules dominated the pharmaceutical landscape, and, as such, established manufacturing platforms were available to service these two broad classes of modalities. While displacing these platforms with improved technology may have been an FDA goal, timing was poor in that the incumbent platforms had demonstrated their utility. In the 20+ years since, the promises associated with decoding the human genome are being seen in biopharmaceutical R&D portfolios. Peptides, oligonucleotides, and other genetic medicines have proliferated (Davies 2013; Matsuyama et al. 2023). Carrier molecules such as lipid nanoparticles have been designed for the purpose of delivering these new molecules to their intended target if the molecule alone cannot (Hammond et al. 2021). Concurrent with the proliferation of these new treatment modalities and delivery vehicles is a new creativity in how these might be combined for patient benefit. These combination molecules pose interesting platform challenges and choices as they combine features seen in both chemical synthesis and biotechnology, such as the carrier-linker-drug options shown in figure 2. One example of these conjugates is the antibody-drug conjugate (ADC) in the figure 2 inset, which is the combination of an antibody, a synthetic linker, and a cytotoxic payload—a molecule that targets a cancer cell with the antibody portion and releases the cytotoxic payload into that cell. In considering how to make an ADC, it can be broken down into its parts—MAb, linker, and synthetic payload—and the individual components made through existing platform approaches. Combining the three elements of the ADC creates some platform challenges, such as ensuring that appropriate chemical conjugation conditions can be maintained in a biologics facility. With some minor modifications to existing equipment and added processing inefficiency, it is likely that a molecule such as an ADC can be made in existing platforms. However, when the multitude of potential combinations illustrated in figure 2 are considered, it should be expected that future conjugate structures could include a MAb, peptide, or alternative targeting structure with any number of linked payloads such as oligonucleotides, radionucleotides, or carriers containing payloads (Grairi and Le Borgne 2024; Lindberg et al. 2021; Wathoni et al. 2022). Can the entire array of creative new potential molecular entities be accommodated by existing platforms? What is the value of new versus retrofit? Peptide synthesis provides an interesting angle from which to view the importance of the platform decision. Peptides are an important molecular approach to treating disease, with insulin perhaps being the best-known example. But outside of insulin and the tremendous effort to synthesize and purify it over 100 years ago, the synthesis of peptides has only become a major biopharmaceutical manufacturing need in the last 10 years (Thayer 2011). The breakthrough approach for peptide synthesis was discovered in the 1960s (Stawikowski and Fields 2002). Solid-phase peptide synthesis (SPPS) was the term given to the synthetic approach, and this approach provided the ability to generate any peptide given knowledge of its amino acid sequence. SPPS is effective and powerful as a technique but unfortunately not efficient from an environmental/sustainability perspective (Andrews et al. 2021). For many years, producing even one kilogram would have been incredibly unusual for SPPS, and it was likely never an approach intended for multi-metric tonnage needs (Thayer 2011). Nevertheless, the SPPS platform has become established and increasingly available in the contract manufacturing marketplace (Brooks 2024; CDMO News 2024; Vecchione 2023). Scaling SPPS to fulfill the high-volume needs associated with the incretin peptides now utilized for diabetes and related metabolic disorders has led to the inadvertent establishment of a technically inefficient manufacturing platform that lacks agility and environmental sustainability. This occurred because the industry was caught without a better large-scale alternative at a time when world peptide needs exploded. Other approaches to generating peptides do indeed exist. Biological methods can be utilized to manufacture peptides, and they offer opportunities with regard to reduction of solvent usage and beneficial economics, particularly at larger scales (Du et al. 2022; Enninful et al. 2024). As such, biological systems could, and should, represent an excellent manufacturing platform. Yet, cell expression systems require engineering to facilitate the production of peptides containing unnatural amino acids, and subsequent engineering would be needed for new unnatural amino acids. This is theoretically possible to accomplish but would require an industry-level focus on this potential platform to enable it to compete with the incumbent SPPS platform. Replacing SPPS with potentially more desirable platforms will be difficult to achieve, regardless of the benefits associated with doing so. The reality is that the perception of risk must be lowered to encourage the creation and implementation of new platforms. The speed with which non-optimal, yet existing, approaches such as SPPS have been scaled and adopted, combined with the industry aversion to implementing newer platforms, speaks to the lack of patience in the industry for manufacturing groups to adapt to the changes in molecular structure or to invest in more technically efficient approaches to generating material. The pressure placed upon biopharmaceutical companies’ CM&C units to keep pace with molecular creativity will result in the propagation of existing platforms that are not technically, environmentally, or economically efficient. Having a clear and common vision of future success for biopharmaceutical manufacturing platforms is key. If we do not achieve this common vision, it is likely that, just as in the case of QbD, success will be defined in multiple, individual ways—none of which truly advance the goals of efficiency, agility, or flexibility, and most of which will not enable reduced regulatory oversight. Recommended Path Forward “Perception is reality” is an aphorism that holds particularly true in the regulated pharmaceutical manufacturing industry. Despite regulatory agency encouragements over 25 years to innovate new manufacturing platforms, the perception remains that great risk is associated with doing so (Collins 2016; Pluschkell et al. 2025). The reality, therefore, in the pharmaceutical manufacturing industry, is that the perception of risk must be lowered to encourage the creation and implementation of new platforms. Public-private partnerships and consortia, such as the National Science Foundation Engineering Research Centers (NSF 2025) and the National Institute of Standards and Technology Manufacturing Institutes (NIST 2025), have long been utilized in the United States as an attempt to strengthen competitiveness in the global marketplace. Yet, it is difficult to point to broad implementation of biopharmaceutical manufacturing platforms identified from such efforts. The reason for this is likely rooted in the typical consortia structure itself. Most consortia models tend to receive their inputs from member entities. As such, they receive a large number of different inputs based on the interests/ideas/preferences of individual partners. Consolidating sets of differing member tactics into a mutually agreeable strategy is always difficult, and output from these efforts tends toward very incremental improvement. A different approach is needed to make step-change advances, and the question becomes how best to foster this. Companies may well discover that in the realm of new modalities, they are independently creating similar new technologies and taking similar approaches. As their commonalities are discovered, these similar approaches could be generalized into a consensus platform for the industry. This approach would be effective, but it does require a desire to collaborate and share without a formal interaction structure. It is also an approach that is likely to have a similar trajectory to that of the QbD initiative, yielding more incremental progress due to its more serendipitous nature. Proactively bringing together stakeholders to embrace a desired future is more likely to transform the industry in a shorter period. The role of public-private partnerships currently utilized to generate excellent ideas for the industry simply needs to be modified to reach a more tangible endpoint. Manufacturing USA and the national institutes underneath that banner are comprised of member companies from industry and academic research groups, and they have intimate connections to government agencies. Such a collaboration is structurally well-suited for a heavily regulated manufacturing industry needing improved technology and provides a way to defray the perceived regulatory filing risk associated with change. The National Institute for Innovation in Manufacturing of Biopharmaceuticals (NIIMBL) has developed a good understanding of current trends, future needs, and challenges associated with biopharmaceutical manufacturing (Pluschkell et al. 2025). The next logical step is to play a proactive role in helping industrial partners implement platform change. The US FDA has offered an intriguing opportunity in the establishment of their guidelines around manufacturing platforms. More important, however, would be the purposeful connection of these guidance documents. How might we not only rapidly generate AMTs but intentionally progress them to designated platform status? The role of institutes such as NIIMBL could be key to the success of such an endeavor. Establishing the future vision of biopharmaceutical manufacturing platforms and associated AMTs, and prioritizing which become designated platforms should optimally be done through these institutes for the benefit of the entire sector. A critical part of the vision needed to benefit all manufacturers is the concept of open-source technology. While open-source is an understood concept in the software industry, it is not in pharmaceuticals. Particularly within the branded-manufacturer space, intellectual property and patenting are incredibly important. Of the multiple types of patents available, the composition patent, which describes the components of the medication, is the primary patent in terms of value to the innovator biopharmaceutical company (Gurgula 2020). Patents associated with how medications are manufactured are secondary patents and are often referred to as “methods” patents. Methods patents have lesser value than primary composition patents and are also much more difficult to establish (Price and Rai 2019; Rai and Price 2021). If the biopharmaceutical industry can agree that such method patents are not worth pursuing, then perhaps the time has arrived where we can agree that our primary area of competition is on the molecule alone. If this sort of understanding could be gained, a new type of pre-competitive collaboration might be achieved, one that would enable the acceleration of new technology platform integration. Ideas for this type of collaboration might be found in examining these two quoted sections from the platform designation guidance: “A different sponsor may also be able to leverage platform technology data if they receive a full right of reference to the leveraged data under a business arrangement with the originator of the platform technology.” “Leveraging data from a prior product that used the designated platform technology, such as leveraging batch and stability data from a related product as prior knowledge that can supplement product development studies.” Could NIIMBL or an equivalent institute perform the role of receiving the full right of reference on behalf of all their member companies? Could NIIMBL or an equivalent institute own member company data in a way that allows prior knowledge to be shared across member companies? This type of collaboration is possible, given some appropriate guardrails are in place, if manufacturers can agree that they really don’t derive financial benefit through owning new manufacturing platform technologies. Having a central entity steer the usage of platform-derived data across companies and gaining the buy-in of regulatory agencies would defray the real and perceived risk of doing something new. Some biopharmaceutical companies, particularly those filing newer modality molecules, will struggle with the perception that they might be giving up valuable IP and therefore not participate in the effort. However, there will be those that do participate, and the “coalition of the willing” will generate change for others to ultimately follow. Without an approach such as this, incumbent manufacturing platforms in the biopharmaceutical industry will be difficult to displace, and the level of technical and economic efficiency associated with them will continue to degrade as the complexity of new molecules increases. A new era of treatment modality creativity and diversity is upon our industry, and the need to adopt new platforms has been accelerated. Conclusion Incorporating new and superior technologies into biopharmaceutical manufacturing platforms has been a goal of the US FDA for nearly 25 years. While this goal is not new, a new era of treatment modality creativity and diversity is upon our industry, and the need to adopt new platforms has been accelerated. Advanced manufacturing technologies and the platforms that will derive from them are the right approach to modernizing this sector. Achieving a state where advanced manufacturing technologies can be developed, matured to designated platform status, and implemented broadly within the biopharma sector will require a shift in how the process of change is implemented. A clear vision of success is needed in the very near future, and collaborative, centralized groups that represent industry, academia, and government must cement that vision and then outline a clear roadmap to implementation. References Algorri M, Abernathy MJ, Cauchon NS, Christian TR, Lamm CF, and Moore CMV. 2022. Re-envisioning pharmaceutical manufacturing: Increasing agility for global patient access. Journal of Pharmaceutical Sciences 111(3):593–607. Andrews BI, Antia FD, Brueggemeier LJ, Diorazio LJ, Koenig SG, Kopach ME, Lee H, Olbrich M, Watson AL. 2021. Sustainability challenges and opportunities in oligonucleotide manufacturing. The Journal of Organic Chemistry 86:49–61. Arden SN, Fisher AC, Tyner K, Yu LX, Lee SL, Kopcha M. 2021. 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Contract Pharma, Sept 6. Wathoni N, Puluhulawa LE, Joni IM, Muchtaridi M, Mohammed AFA, Elamin KM. 2022. Monoclonal antibody as a targeting mediator for nanoparticle targeted delivery system for lung cancer. Drug Delivery 29(1):2959–70. Woodcock J. 2004. The Concept of Pharmaceutical Quality. American Pharmaceutical Review 7(6): 10-15. Yu LX, Woodcock J. 2015. FDA pharmaceutical quality oversight. International Journal of Pharmaceutics 491:2–7. About the Author:Paul C. Collins is director of research, James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University.