Unleashing the Power of Biologics: Exploring the Governance and Regulation of Membrane-Based Virus Purification (MVP) Technologies

Abstract

Background: Biologics is an exciting and growing area of medicine. Within the larger field of biologics, the use of viral vectors and virus-like particles (VLPs) is increasingly common, making it crucial to develop innovative and practical unit operations for the related purification process. Objective: Some scientists and engineers propose that membrane-based downstream virus purification (MVP) platforms would allow for more scalable and cost-effective production of these critical particles. However, the so-cial, political, and ethical implications of these advancements remain largely unex-plored. This paper aims to explore various pivotal facets of MVP technology govern-ance and regulations within the U.S. context, including (1) government policy ar-rangements related to the implementation of the technologies, (2) stakeholder atti-tudes, policy preferences, and behaviors, and (3) the fundamental factors that shape these attitudes, policy preferences, and behaviors. Methods: In doing so, we analyze publicly available federal and state government documents pertaining to biomanu-facturing, healthcare, and legislative attempts. Additionally, we will perform a stake-holder analysis on relevant industries, healthcare service providers, and recipients. Conclusions: Our goal is to outline the socio-political, ethical, and regulatory factors pertaining to the regulation and governance of these technologies.

1. Introduction

The field of biologics refers to a class of therapeutic products derived from biological sources such as living cells, tissues, or organisms. The market for these products is expanding rapidly, with sales projected to exceed USD 436 billion for 2024 [1]. Virus particle-based therapeutics are among the most promising categories of biologics, with newly developed treatments addressing common health concerns ranging from cancer to heart disease. The rapid expansion of this field has driven demand for particular constituents of these treatments—specifically, virus particles and virus-like particles (VLPs)—which serve as the delivery mechanism for medicines in the context of these treatments.

The membrane-based virus purification (MVP) system is currently under development and is idealized as a sophisticated and highly selective method designed to isolate and purify virus particles and VLPs from a mixture of biological substances. Hypothetical MVP systems utilize specialized membranes that can differentiate particles based on size, charge, and other properties. As a result, the MVP system has the potential to dramatically increase the efficiency and scale by which distinct VLPs can be separated out for use in treatments. VLPs are instrumental in vaccine development and therapeutic applications because they can mimic the structure of viruses without being infectious, enabling the immune system to recognize and respond to potential pathogens more effectively. We argue that the unique potential ability of MVP systems to produce highly refined VLPs in relatively large quantities could be a crucial next step for the development of cost-effective biologics treatments.

Even when compared to other medications, biologics remain notably expensive, thereby limiting their effectiveness, particularly for low- and middle-income patients [2]. As a result, driving down the cost of manufacturing processes (such as the isolation of VLPs) is critical in making existing biologics more efficient and affordable, while also incentivizing the exploration and development of new therapies. However, a critical lack of existing large-scale commercial production platforms for these crucial particles is slowing efforts to expand access to these treatments. Most of these costs (around 80%) are concentrated downstream of the bioreactor stage, a part of the production process that includes the production of virus particles and VLPs [3,4]. Thus, MVP systems provide a potential solution allowing for the production of safe, effective, and high-quality biologic treatments regarding a wide range of medical issues.

The many additional technical and financial challenges inherent in the creation of biologics speak to the need to not only expand and build on our current production methods but also to understand the regulatory controls regarding these processes. An accessible and rationalized regulatory process would allow innovators to optimize the effectiveness of MVP technological development and the potential for profit while minimizing the risk of adverse effects. As with the rest of the pharmaceutical industry, regulations are a key component of the manufacturing process, especially those centered around producing VLPs. Regulatory agencies at the federal and state level play a pivotal role in ensuring the safety, efficacy, and quality of manufacturing processes designed to produce various treatments. Furthermore, compliance with and understanding of these regulatory standards is critical for manufacturers, researchers, and other stakeholders involved in the various aspects of MVP technology development and subsequent VLP production efforts.

While the MVP technology holds some significant promise in enhancing the efficiency and scalability of virus purification processes, it also introduces a unique set of regulatory challenges. Given the emerging nature of MVP technologies, the existing regulatory frameworks, mainly established for conventional biopharmaceutical manufacturing processes, may not fully account for the specific requirements and risks associated with these platforms. The following table (

Table 1. Regulatory overview.

Regulation Title	Regulation Description	Year	Source
Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications	Qualification of biological starters to test for adventitious agents is advised; validation of processes for inactivating adventitious agents using different model viruses is advised; ID-ing all potential contaminants is advised; current good manufacturing processes for “cell substrates” and “viral seeds” are advised; diploid cell strains; continuous cell lines; biological raw materials; ancillary reagents; serums, trypsin, amino acids, or biological reagents.	2010	https://www.fda.gov/media/78428/download (Accessed on 15 March 2024)
Guidance for Industry: Q2(R1) Validation of Analytical Procedures: Text and Methodology	This regulatory subdocument contains nonbinding recommendations for validating analytical procedures, largely in the context of the existing regulatory document “Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications”. The scope of the regulations is contained within the topic of testing for the validity of various analytical procedures, categorized as testing for specificity, linearity, accuracy, range, precision, detection limit, quantitation limit, and robustness.	2021	https://www.fda.gov/media/152208/download (Accessed on 15 March 2024)
Q5A(R2) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin Guidance for Industry	This guide describes the evaluation of the viral safety of biotechnology products, including viral clearance and testing. Project-wise, it refers to AAV, viral vectors writ large, and related components and materials.	2024	https://www.fda.gov/media/163115/download (Accessed on 15 March 2024)
Q13 Continuous Manufacturing of Drug Substances and Drug Products Guidance for Industry	This guidance applies to CM of drug substances and drug products for chemical entities and therapeutic proteins. It is applicable to CM for new products (e.g., new drugs, generic drugs, and biosimilars) and the conversion of batch manufacturing to CM for existing products.	2023	https://www.fda.gov/media/165775/download (Accessed on 15 March 2024)
Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients	The ICH guidance Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients is intended to provide guidance regarding good manufacturing practice (GMP) for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the quality and purity characteristics that they purport, or are represented, to possess.	2018	https://www.fda.gov/media/112426/download (Accessed on 15 March 2024)
Guidance for Industry: Q9 (R1) Quality Risk Management	This guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality. These aspects include development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances, drug (medicinal) products, and biological and biotechnological products (including the use of raw materials, solvents, excipients, packaging and labeling materials in drug (medicinal) products, and biological and biotechnological products).	2023	https://www.fda.gov/media/167721/download (Accessed on 15 March 2024)
Guidance for Industry: Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process	This guidance is intended to assist manufacturers of biotechnological/biological products in the collection of relevant technical information that serves as evidence that the manufacturing process changes will not have an adverse impact on the quality, safety, and efficacy of the drug product. The document does not prescribe any particular analytical, nonclinical, or clinical strategy. The main emphasis of the document is on quality aspects.	2005	https://www.fda.gov/media/71489/download (Accessed on 15 March 2024)

) displays the existing regulations related to MVP technologies.

One of the primary regulatory challenges lies in ensuring consistency in the quality, safety, and efficacy of products derived from MVP systems. For example, current regulations, such as the Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications [5], provide a framework for ensuring biological raw materials and viral seed lines are free from contaminants and meet quality standards. However, MVP systems with advanced membrane-based purification techniques may require updates or extensions to these guidelines to address the unique risks of large-scale virus purification. Further regulatory considerations can be drawn from the Q5A(R2) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin [6], which discusses viral clearance and safety for biotechnology products. These safety concerns are directly relevant to MVP technology, particularly in its use for virus-like particles (VLPs) in vaccine development. As MVP platforms gain traction, refining such regulations will be critical to ensure that viral contaminants are adequately removed while maintaining the scalability and cost-effectiveness that MVP systems promise. Additionally, regulatory frameworks such as Q13 Continuous Manufacturing of Drug Substances and Drug Products [7] emphasize the importance of quality assurance in continuous manufacturing processes. While this regulation is tailored to drug substances and therapeutic proteins, it highlights the need for real-time monitoring and quality control—something that will be increasingly important as MVP systems become a core component of biologics manufacturing.

At the same time, these challenges present significant opportunities for regulatory innovation. Given the precision and scalability offered by MVP systems, regulatory entities could explore the development and implementation of more flexible and adaptive regulations. These regulations would be designed to encourage innovation while ensuring that stringent safety standards are sustained. This could involve the creation of pilot programs or new regulatory frameworks that facilitate faster approval processes for MVP-derived products. Such frameworks might be particularly beneficial in areas like gene therapies or pandemic response initiatives, where rapid scalability and swift deployment are critical to addressing urgent health challenges. By embracing these opportunities, regulators can strike a balance between fostering technological advancement and safeguarding public health and safety.

As such, the goal of this paper is to provide a comprehensive understanding of the associated regulatory landscape in the United States. Moreover, understanding the processes involved with regulatory policy change is vital for adapting to evolving guidelines, incorporating new scientific insights, and addressing emerging challenges, and thereby fostering continuous improvement in biologics development and delivery. In essence, an understanding of the regulatory environment not only facilitates market entry for MVP technology but also promotes public confidence in the safety and efficacy of these innovative medical interventions.

This paper is structured to outline the relevant regulatory scope, mechanisms, and content that pertain to the development of MVP technology for the manufacture of VLPs for biologic treatments. First, we consider the history, regulatory scope, and feedback mechanisms regarding the lead regulatory agency addressing this technology, the Center for Biologics Evaluation and Research (CBER). We then identify stakeholders and how their attitudes and preferences fit into the regulatory environment, with the overall goal of understanding the social, political, and ethical factors that shape the regulation, governance, acceptance of, and engagement with these technologies within the wider societal framework. Following the identification and discussion of individual stakeholders, we offer a model outlining the MVP technological development process and discuss dynamic interactions between the stakeholders throughout the phases of the model before discussing paths forward for the development and regulation of this nascent technology.

2. Regulatory Overview

Originating as an offshoot of the Laboratory of Hygiene in the late 1800s, the Center for Biologics Evaluation and Research (CBER) did not attain its current scope as a regulatory agency until the late 1980s, when it was split off from the Center for Drugs and Biologics in response to the growing and diverse nature of the then-newfound field of biologic treatments. Residing within the Food and Drug Administration (FDA), which is itself housed in the Department of Health and Human Services, CBER is granted its regulatory authority through the Public Health Service Act and specific sections of the Food, Drug, and Cosmetic Act [8].

CBER’s mission is to protect and enhance public health through the regulation of biological and related products. Specifically, CBER regulates a wide range of products, including allergenics, cellular therapies, gene therapies, blood, blood products, tissue, tissue-based products, vaccines, xenotransplantation products, selected in vitro diagnostics, devices that manufacture a biologic at the point of care, and some drug products related to cellular therapies and blood banking. CBER also reviews new biological products and new indications for already approved products and decides on approval based on a risk–benefit analysis for the intended population and intended use of a product. Furthermore, it also has regulatory purview over a wide range of manufacturing processes integral to the formulation of finished biologic treatments [8].

2.1. Regulatory Scope

The products regulated by CBER are often derived from cutting-edge biomedical research, offering the most effective means to treat a variety of illnesses with few other treatment options [8]. The regulations governing the manufacturing processes potentially incorporating MVP technologies are varied in scope; however, the relevant regulations can be seen as largely concentrated within three topic areas. The first topic area, testing, has to do largely with guidance for standardized testing involving a wide range of processes, such as the usage of particular cell lines and reagents. CBER strongly recommends comprehensive testing to ensure that adventitious agents and other potential contaminants are tested for, identified, and inactivated, minimized, or altogether removed from manufacturing processes and outputs [9].

The second topic area refers to the penumbra of risk management and quality control. While these regulations apply to different stages during the pharmaceutical product cycle, they are specifically relevant to the aspects of the technological development process that concern the manufacture of MVP technologies, such as the use of raw materials and solvents in development and manufacturing [10].

The last key area of regulatory scope we identify refers to ensuring that any changes to manufacturing processes concerning biologically based products are implemented in such a manner as to avoid any adverse impacts on end products. This is critical even in the developmental/manufacturing stage, as aspects of any work done in this stage can have significant effects much further along in the product life cycle [11,12]. (For the full list and summary of relevant regulations, please refer to Table 1).

Regulations, as eventually prescribed, created, and/or adopted by federal and state agencies, inherently impose different levels of burden. Many more established, end product-based regulations in different, more established regulatory subsystems under the purview of the FDA contain what are often referred to in regulatory documentation as “legally enforceable responsibilities”. However, as is typical for much of FDA guidance, the CBER-derived regulations relevant to MVP technological development generally describe “the agency’s current thinking on a topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited” [13]. In short, this type of guidance is not legally binding on other stakeholders or the FDA and is generally intended to provide insight on the current thinking of the regulatory agency and offer advice across a wide range of elements [14,15]. Alternative approaches are usually allowed for these non-binding guides, as long as they satisfy other statutes and regulations [16].

For MVP system development, only a handful of regulations listed previously were identified from CBER that directly pertained to the initial stages of product development, prior to direct involvement with pharmaceutical companies. These particular regulatory documents pertain to a range of key areas and largely center around the identification and removal of contaminants and adventitious agents, safety measures for drug substances, active pharmaceutical ingredients, cell substrates and viral seed lines, and good practices for quality control, analytical procedures, qualification, and methodologies. These front-end regulations are critical for analyzing how important stakeholders are for the future of MVP technology will interact with the process in significant ways and, in turn, display their own policy preferences, behaviors, and interests. Given that MVP technology innovation is tied to the broader field of biologics, we can expect (and must, given the lack of existing literature on the effects of MVP-related regulation) that as the broader field of biologics goes, so will MVP technology development to some significant degree.

Lastly, it is important to acknowledge the role that regulations not directly related to MVP technologies may still play in the technological development process. While the regulatory burden on MVP technological development may consist of a relatively small handful of non-binding guidance documents, the same cannot be said for the broader body of regulations relevant to biologics as an entire field, to which many hundreds of guidance documents exist. The burden of this broader regulatory environment must be carefully considered, as stakeholder perceptions, behaviors, and attitudes pertaining to MVP technology relate in large part not only to their perceptions of MVP technology itself (which may be relatively underdeveloped) but also to perceptions of biologics and their regulatory environment.

2.2. Feedback

An aspect that is critical to the regulatory process in this subsystem concerns public and industry feedback. Feedback occurs at multiple levels throughout the pharmaceutical product development process. It largely occurs through federal rulemaking, which is at the same time an instrument of bureaucratic agencies and a forum by which democratic governance occurs. The rules that inform and delimit the actions of federal agencies are established by congressional authorization, shaped by executive branch priorities, and influenced by participation from public interest groups, business concerns, and the general public [17].

At the federal level, multiple mechanisms allow for feedback between federal regulators and relevant stakeholders. Hwang and colleagues [17] posit four primary policy-making tools used by federal agencies, with rulemaking and administrative orders involving public comment on the promulgation of rules. Public comment periods allow for a broad spectrum of feedback across the subsystem (and sometimes beyond), although the primary commentators are often from industry [17,18]. The end result of these processes are legally enforceable rules.

The other two policy-making tools used by federal agencies involve either informal guidance or adjudication [17]. With the former, advisory boards of external stakeholders and experts review regulatory issues, including those pertaining to products resulting from, and thereby related to, MVP processes, and provide input and recommendations. Other examples, like workshops, avenues for requests for specific information, pilot programs, and other initiatives, supplement these feedback mechanisms in meaningful ways. Regarding the latter, adjudication, U.S. federal agencies may consider specifics of a case to establish new principles or policies in a formal administrative law context.

Due to the far-reaching impacts of technology development and related regulations, there has been a coordinated effort at the international level. Currently, for instance, there is an established procedure allowing for collaboration and feedback between regulatory authorities and the pharmaceutical industry at the international level [19]. Here, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an international organization that brings together regulatory authorities from a large selection of other countries alongside industry representatives to develop and promote international guidelines for the development, registration, and approval of pharmaceutical products throughout pharmaceutical product life cycles [19]. While the ICH itself does not impose regulations within specific countries, its guidelines are influential and often adopted by regulatory authorities worldwide, including in the United States. In conclusion, while the FDA is the regulatory authority responsible for ensuring the safety, efficacy, and quality of pharmaceuticals in the United States, it also actively participates in the work of the ICH and often adopts ICH guidelines in the development of its own regulatory framework. ICH-derived guidelines thus form much of the basis for relevant FDA regulations surrounding MVP processes in the American context.

3. Stakeholder Analysis

In this section, we consider the primary stakeholders in MVP technological development and their associated reactions to biologics development in general, especially related to MVP development. The first and most obvious stakeholder is the Food and Drug Administration (FDA); however, there are other established participants in the policy arena that decide which treatments are available and covered, such as the healthcare providers and health insurance companies, the pharmaceutical industry and biotechnology firms, and researchers and scientists. Finally, there are the more ephemeral, yet still highly important players: the patients that choose to use (or not) treatments and the general public.

3.1. The Food and Drug Administration (FDA)

As the primary source of regulatory policy for the medical field in the United States, the FDA (specifically CBER) is a key stakeholder in the biologics industry, and especially so for innovators of MVP products. As it does across a wide range of other regulatory issue areas, the FDA plays an important role in guiding the conversation around the development and implementation of regulations. FDA regulations typically fall into one of four primary categories: good manufacturing practices (GMPs), clinical trials, new drug applications, and post-marketing surveillance [12]. Given that MVP technology is neither a drug nor a component of a drug, but rather a tool to mass produce components for future treatments, many of the regulations in the clinical trials, new drug applications, and post-marketing surveillance categories do not necessarily apply. However, given that the FDA’s regulatory policy is concerned with such topics as risk management, adventitious agents, and possible contamination, MVP technologies would be expected to overlap significantly with GMP-related regulations. While the regulatory burden still overwhelmingly falls during the latter stages of the drug development process [12], the FDA is still significantly involved in earlier stages, even in tangential industrial development efforts, like prospective MVP initiatives.

The primary motives of the FDA are to ensure the safety, efficacy, and security of human drugs and drug products. Additionally, the agency seeks to advance public health by speeding innovations that make medical products both safer and more effective, but also more affordable to everyday Americans [20]. In short, the market plays a strong role in determining FDA behavior.

In addition to these stated motivations, other incentives affect FDA regulatory behavior. The FDA generally errs on the side of caution, with an emphasis on the perceived risks of approving a drug that fails over the perceived benefits of promoting an effective medical product [21,22]. Given the role that MVP technology can potentially play in the safety of newfound biologic treatments, it seems extremely likely that this pattern of risk perception will also extend to MVP technology development efforts. It is important to note the contrast here between drug safety reviews and industrial safety reviews. While congressionally mandated deadlines, such as the Prescription Drug User Fee Act, often motivate significant haste on the part of the FDA [23,24], forcing regulation into the aftermarket arena [18,21], these deadlines are absent in regard to industrial safety deadlines for biologics industry safety reviews, indicating the potential for more consistency from an implicit precautionary principle.

Last among the major factors likely impacting FDA attitudes, preferences, and behaviors is the agency’s relationship with other stakeholders in the MVP technology development process. Subsystem actors, including healthcare providers and insurance corporations, pharmaceutical industry stakeholders, scientists and researchers, as well as more ephemeral actors such as patients and the general public, are all provided explicit windows and mechanisms with which to provide feedback and interface with the regulatory process [21]. The FDA is further incentivized to interact with these stakeholders throughout the regulatory process, as feedback and involvement can often lower political risk, reduce workloads, and result in better policy outcomes overall [25]. Furthermore, the FDA collaborates with other stakeholders on the international stage through its involvement with the ICH, which in turn fosters international continuity and cooperation on regulatory policy.

3.2. Healthcare Providers and Health Insurance Companies

For healthcare insurance companies and medical providers, the adoption of medical innovations offers both opportunities and challenges. A range of complex factors can serve to incentivize or disincentivize insurance companies in regard to biologics and associated technologies such as MVP technology. By investigating financial incentives, including reimbursement structures and payment models, we can disambiguate the factors motivating these companies to support new technology for healthcare solutions. Additionally, by analyzing the collaborative efforts between these stakeholders and other entities, we can explore how these partnerships drive the investment and adoption of medical innovation.

Health insurance companies offer various types of financial incentives, such as reimbursement programs, to facilitate payment for healthcare services. Some common types of reimbursement programs include fee-for-service, where healthcare providers are paid a fee for each service they render to patients, and value-based payments, which are centered around the quality of service a patient receives [26]. To that point, the Affordable Health Care Act was responsible for the implementation of a change in incentives, fueling the adoption of value-based payments across insurance companies and providers [27].

Implementing high-cost innovations into healthcare systems with budgetary constraints has significantly transformed the reimbursement environment, offering a larger variety of options [28]. Supporting this perspective, Kocher [29] maintains that healthcare insurance companies require tangible economic benefits that likely provide quantifiable financial gains or advantages associated with adopting certain practices, policies, or innovations. Additional research has further indicated the influence of financial incentives in the adoption of various payment structures [30,31]. Furthermore, healthcare providers may substitute between patients who may be considered more or less profitable relative to their current insurance coverage. Notably, while fee-for-service programs do not create financial incentives, they do incentivize healthcare providers to increase services, which in turn increases reimbursement from insurance companies and/or patients [32], and engenders a range of different incentives that can serve to increase healthcare costs overall. In the broader context of healthcare policy dynamics, changes in reimbursement structures play a pivotal role in influencing healthcare insurance companies as well as healthcare providers’ practices.

This can specifically affect MVP technology in several ways. First, assessment of the efficacy and cost-efficiency of products derived using MVP technology will affect the demand for and use of any potential technological developments in this particular area. Furthermore, a tumultuous policy climate with large-scale policy changes, whether to the ACA or other key pieces of regulation and legislation, may have significant impacts on the incentive structure for these stakeholders, affecting their interest in promoting the adoption of biologic treatments. As a result, factors in the larger political and economic environment can have an overwhelming impact upon the likelihood of innovation and adoption of new technologies [33].

Healthcare innovation is greatly influenced by healthcare providers’ perceptions of the benefits and risks associated with new technologies [34]. The rate at which innovations diffuse depends on how providers assess these factors, thereby impacting a healthcare organization’s readiness to adopt and integrate new solutions [35]. It is essential for healthcare providers, in their role as key stakeholders in innovation adoption, to understand the contributing factors shaping innovation readiness, such as innovation strategy, financial resources, and organizational leadership. Effective management of innovation strategy is crucial in the healthcare system, facilitating rapid development and fostering innovation [36]. Strategic alignment, resource allocation, and leadership are vital components collectively determining a healthcare organization’s readiness [35]. An organization’s attitude and behavior toward innovation significantly influence its ability to adapt in the evolving healthcare landscape, impacting adoption and diffusion. Van den Hoed et al. [37] emphasize leadership as the main factor, which summarily consists of several critical sub-factors such as innovation strategies, programs, processes, and inter-organizational linkages.

Moreover, the lack of collaboration between engineers and managers in healthcare can impact an organization’s readiness for innovation [38]. Innovation strategy, or its absence, is critical in stakeholders’ capacity to navigate challenges and drive adoption. Healthcare providers’ readiness to adopt innovations additionally hinges on other related factors as well, including resource availability and cost-effectiveness [30,34,38]. For example, medical innovations require high levels of investment that may not be perceived as focused on the long term, increasing perceived financial risks [29,36] due to health insurance coverage typically spanning 18 to 24 months. This time window thus shapes services and payment models offered by providers [29,30]. As a result, the substantial investment needed in both time and organizational resources for innovation underscores the importance of proper planning, leadership, and risk management strategies in determining readiness. Additionally, insurance coverage duration indicates a timeframe within which providers may need to recoup investments, potentially affecting their willingness to adopt innovations, especially earlier in the technological development process.

In summary, establishing an effective innovation strategy entails aligning an organization’s leadership, organizational culture, and financial resources, all of which serve as pivotal drivers shaping the environment for medical innovation adoption. Moreover, recognizing and understanding the political and economic influences at play in the larger healthcare system is essential for developing strategies aimed at promoting innovation adoption and fostering continuous development in healthcare.

3.3. Pharmaceutical Industry Stakeholders

Industrial producers and pharmaceutical companies play a crucial role in the implementation of MVP technology through the associated development of treatments, optimization of supply chains, and dynamic interactions with other stakeholders. At the same time, they are not immune to many different challenges that can arise during these processes. Some of the key challenges include regulatory requirements, manufacturing complexities, cost considerations, and safety and quality assurance. Understanding industrial producers and pharmaceutical companies’ perspectives is critical for driving innovation and ensuring patient access to essential and life-saving therapies as well as advancing healthcare both within the United States and abroad.

In the realm of biotherapeutic manufacturing, enhancing both production capacity and efficiency is crucial for meeting the demand for biologics. Moleirinho et al. [39] emphasize the idea that the manufacturing of biotherapeutic particles, including viruses and VLPs, presents unique production and purification hurdles due to their intricate physicochemical properties. Downstream manufacturing processes are still evolving, with ongoing developments focusing on new resins, matrices, and operation modes to improve purification efficiency while achieving higher yields and reducing overall costs [40].

Therefore, from the industrial producers and pharmaceutical companies’ perspectives, the complex production and purification hurdles of complex biotherapeutic particles may be viewed as providing both opportunities and risky challenges [41]. For example, proactive industrial producers and pharmaceutical companies may see this as an opportunity to develop or adopt cutting-edge purification methods. However, more cautious companies focused on cost reduction may be hesitant to invest in new technologies unless they can demonstrate significant efficiency gains or cost savings [39].

3.4. Membrane Producers

Membrane producers play a dual role as both key suppliers and stakeholders in the biopharmaceutical industry [42]. Building on this role, producers are integral to ensuring that supply chain management remains robust and efficient as the demand for advanced therapies continuously expands [43]. In one instance, Cytiva [42], a biologics supplier producing a range of filtration and purification products, such as VLPs, AAV vectors, and other new biotechnologies, recently invested USD 600 million in a new resin manufacturing site in the United States. Other stakeholders likewise produce filtration technologies (including membranes) intended to improve product quality and lower operation costs. Because biologics require specialized raw materials such as cell lines, growth media, and purification agents, which are often sourced from limited suppliers [44], there is the need to pay close attention to the actions and success of actors in this sector.

Trade organizations likewise play an important role. As a stakeholder, Cytiva collaborates across the biopharmaceutical industry with other suppliers and compliance agencies all over the world, utilizing the Biophorum Operations Group forum where information is exchanged to enhance material supply and address variation, while establishing clear communication guidelines across the sector. Furthermore, managing a reliable supply chain for these critical components has become increasingly difficult and risk-prone due to recent global supply chain disruptions, such as those exacerbated by geopolitical tensions and the COVID-19 pandemic [45].

Recent government policies such as the Inflation Reduction Act (IRA) have influenced the manufacturing of VLPs, AAV vectors, and other new biotechnologies, particularly in areas of pricing and supply chain development [46,47]. These challenges are significant and complex due to an increase in regulatory requirements [42]. The Inflation Reduction Act (IRA) pursues the aim of controlling inflation on prescription drugs [47]. For example, BioSpace [46] reported that Pfizer aims to increase their biologics portfolio while reducing small molecules in response to the IRA’s provision that allows biologics to be exempt from price negotiations for up to thirteen years, while small molecules carry a nine-year exemption. However, the IRA has potential ramifications that may lead to an increase in overall healthcare costs due to costly biologic procedures that may soon outweigh the benefits of small molecules in the near future. Additionally, companies merge and split more frequently, resulting in additional auditing in supply networks [42]. As a result, when disruptive technologies and new regulations emerge, membrane producers must continuously adapt to meet the evolving needs of biopharmaceutical manufacturers, making them indispensable partners in a rapidly changing regulatory environment buffeted by ethical, safety, efficiency, and competitiveness concerns.

Ethical concerns about therapies among various stakeholders, including government regulators, patients, and the general public, can be another important element of technological development that pharmaceutical industry stakeholders respond to. For example, membrane filtration technology might be highly beneficial for the advancement of gene therapy, which showed promising results in treating certain genetic conditions [48]. However, there are ethical concerns about manipulating human embryos that need to be addressed in order to ensure responsible and ethical use of these technologies while safeguarding individuals’ rights [49]. As a result, industrial producers and pharmaceutical companies may be increasingly motivated to support innovative therapies if it is possible that these ethical concerns can be addressed [50].

With regards to safety and efficacy, product characterization plays a pivotal role in the process of development and production, particularly in compliance with FDA regulations [51]. For example, in the realm of adeno-associated virus (AAV) (In gene therapy, AAV vectors are engineered to carry a therapeutic gene instead of the virus’s natural genetic material. Once introduced into the body, these vectors can infect cells and deliver the therapeutic gene, which can then be expressed by the cell’s machinery. This process allows for the correction of genetic disorders by compensating for defective genes, producing therapeutic proteins within the body, or manipulating gene expression for therapeutic benefit.) vectors for clinical research and stringent characterization protocols are imperative, encompassing aspects like vector identity, safety, purity, potency, and stability [51,52]. To achieve this, various tests are conducted at different stages of development, tailored to each phase of clinical studies. These tests verify the identity of the vectors, check for any harmful contaminants like bacteria or viruses, and assess purity and potency [53]. Even though compliance with these regulations may require considerable effort and resources, industrial producers of components for pharmaceutical treatments involving AAVs and VLPs, as well as pharmaceutical companies, generally exhibit a cautious yet cooperative attitude towards government regulations, particularly those set forth by agencies like the FDA. These regulations are seen as necessary safeguards to ensure the safety, efficacy, and quality of pharmaceutical products, including AAV vectors and VLP-based treatments [54].

Finally, the pharmaceutical sector has a significant interest in end product prices with concerns about the proper balance of profitability, competitiveness, and resource allocation. As can be expected, these issues can raise concerns among shareholders as well [55]. According to Heled [56], the issue of high prices for biologics persists despite the enactment of the Biologics Price Competition and Innovation Act (BPCIA) in 2010. The act was set to establish a more streamlined regulatory pathway for the approval of biologics and biosimilars, therefore enhancing affordability and competition while ensuring patient safety. From the perspective of industrial producers and pharmaceutical companies, increased transparency and access to manufacturing information could potentially foster greater competition in the biologics market, driving down prices and increasing market access for patients. This, in turn, could benefit the pharmaceutical sector by spurring innovation and potentially expanding their market share. At the same time, the proposed disclosure of manufacturing information may raise concerns among industrial producers and pharmaceutical companies about protecting proprietary information and maintaining a competitive advantage [57].

Despite attempts to overcome various hurdles to biologics access and affordability, the persistent difficulty of manufacturing these complex treatments continues to supersede advances in easing regulatory burdens and streamlining production processes. Overall, biologic products undergo stringent regulation throughout their entire life cycle, encompassing safety, effectiveness, and manufacturing standards, to gain market approval, as well as oversight in areas such as promotion and pricing [58]. This regulatory oversight is crucial for the industrial and pharmaceutical sector as it ensures that pharmaceutical and biologic products meet rigorous safety and efficacy standards, thereby safeguarding public health and maintaining consumer confidence. However, in the realm of industrial producers and pharmaceutical companies, various factors come into play, influencing their strategies and decisions. The complexity of biotherapeutic manufacturing, including unique production hurdles, poses both opportunities and risks for these entities [59].

In summary, membrane producers must provide careful consideration to ethical concerns, particularly regarding innovative therapies like gene therapy. Additionally, ensuring safety and efficacy through rigorous product characterization is crucial, necessitating compliance with FDA regulations. Moreover, concerns about end product prices persist despite regulatory efforts, such as the BPCIA, prompting proposals for increased transparency in manufacturing information disclosure to foster price competition [60]. Thus, understanding these factors and potential interplays is essential for industrial producers and pharmaceutical companies to navigate the evolving landscape of pharmaceutical development and regulation effectively. This necessitates a thorough understanding of not only the technical aspects of manufacturing and compliance but also the broader system-wide socio-political dynamics that in turn shape regulatory frameworks and market conditions.

3.5. Scientists and Researchers

Scientists and researchers involved in membrane filtration technology development exhibit a particular set of attitudes, preferences, and behaviors when it comes to FDA regulations. There is a general consensus among scientists that adhering to FDA guidelines is imperative for ensuring the safety and efficacy of MVP technologies. This commitment to regulatory compliance stems from a collective understanding of the importance of rigorous testing and validation to meet FDA standards [61].

In terms of preferences, researchers often appreciate clear communication from the FDA regarding regulatory expectations. Regular updates, workshops, and guidance documents from the FDA are valued, as they assist scientists in staying abreast of evolving regulatory requirements. Collaborative interactions between scientists and regulatory agencies through pre-submission meetings or consultations contribute to a more streamlined and efficient regulatory process, aligning the preferences of researchers with the FDA’s commitment to fostering innovation while ensuring safety [6].

Behaviors of scientists and researchers in this field are marked by a meticulous approach to documentation and testing protocols. Rigorous preclinical studies are conducted to generate robust data supporting the safety and performance of new technologies, such as MVP processes. Researchers also actively engage in preparing thorough regulatory submissions, such as investigational device exemptions (IDEs) or premarket approval (PMA) applications, demonstrating a proactive commitment to fulfilling FDA requirements.

In summary, scientists and researchers in the realm of membrane filtration technology largely demonstrate a conscientious and collaborative approach to FDA regulations. To not comply with FDA regulations is to risk not just productivity in the short term but also their academic reputations and careers, so compliance is standard. Their attitudes reflect a commitment to upholding high standards of safety and efficacy, while preferences center around clear communication and collaborative engagement with regulatory bodies [62]. This behavior is characterized by adherence to testing and documentation protocols throughout the developmental and regulatory processes, showcasing a focus on advancing technology within the framework of FDA guidelines.

3.6. Patients

Understanding patients’ perspectives is crucial for creating treatments that meet their specific needs and preferences. Research has demonstrated that involving patients in healthcare decision-making improves health outcomes [63,64]. Incorporating patient views into healthcare procedures and regulatory decisions is essential to prioritize patient-centered care and improve treatment effectiveness and safety [64]. Furthermore, recognizing patients’ unique experiences and needs concerning the benefits, risks, and quality of new treatments and associated technologies is paramount. While including patient preference information in regulatory submissions for medical devices is optional, the FDA outlines considerations for and encourages the completion of such benefit–risk evaluations [64].

Incorporating patient preferences into biologics development lifecycles and regulatory proceedings is crucial for several reasons. Treatments that align with patient expectations can lead to improved clinical outcomes and increased adherence to treatment regimens [65]. As a result, regulatory agencies, such as the FDA, are increasingly recognizing the importance of patient-focused drug development [63,66]. As a result, products that align with patient expectations are more likely to gain regulatory approval and achieve market success. This prioritization of patient preferences supports the shift toward patient-centric healthcare, where treatments are tailored to individual needs and values [63]. Considering patient preferences can also have significant economic benefits, such as improved resource utilization and potentially lower healthcare costs [63,65].

Patients’ understanding of biologic treatments can also influence their attitudes towards different treatments [66]. Doubts about clinical effects and, critically, regulatory pathways can negatively impact patient attitudes [67], potentially limiting their interest in and engagement with new medical treatments and associated technologies. Emotional responses to their condition, information-seeking behavior, and previous experiences with treatments have also been found to shape patient perceptions towards biologics in particular [68]. However, the ability of patients to make informed decisions regarding their healthcare journey may be hindered by a lack of proper information. As a result, there should be an emphasis on the importance of incorporating patient perspectives into communicating about new medical technologies and associated treatments. These communications should be modulated by factors such as the nature and severity of the illness being treated, treatment availability, and the pros and cons of those treatments [63,69].

In summary, patients’ risk perceptions play a critical role in the acceptance of biologics and medical technologies [70]. Understanding patient preferences, behaviors, and attitudes towards regulation can inform regulatory decisions, especially for patients with elevated medical needs. Furthermore, communication between innovators and industry stakeholders and patients must be recognized as an essential component of treatment efficacy and utilization and should be treated as such throughout the technology development process.

3.7. The General Public

As one of the key stakeholders in any medical field, public attitudes, preferences, and behaviors concerning regulatory policy are shaped by a multitude of interconnected factors. Public opinion, as highlighted by work by Burstein [71], Erikson [72], and others, is a significant determinant of regulatory processes and outcomes. The perception of risk, a crucial aspect in regulatory decision-making at the collective level, is, importantly, linked to public preferences regarding regulatory policies [73]. This critical factor is not uniform across demographics, with a range of variables exerting significant influence.

Education levels, as explored by Li and Li [74], play a pivotal role. Higher education levels often correlate with an understanding of new technologies (like biologics). Gender differences, highlighted by Li and Li [74] and Hu et al. [75], indicate that men and women perceive risks differently, influencing their regulatory preferences. Political affiliation also shapes attitudes toward regulation, with conservatives typically favoring limited government intervention and liberals typically supporting stronger regulatory measures [76]. Age, as noted by Kim et al. [77], affects perceptions of new technologies and associated risks, with older Americans traditionally perceiving higher risks from new technologies.

Media coverage is an influential force in affecting public perceptions of emerging technologies [78] and can shape public sentiment in regard to biologics in positive or negative ways. In the same vein, the pharmaceutical industry’s image, perceived transparency, ethics, and influence on regulatory bodies, as outlined by Farino et al. [79], impacts public attitudes toward regulation. Economic factors, specifically the cost of biologics and its relationship with regulatory decisions [80], are also critical in influencing public opinion, particularly in terms of access to treatments. Perceptions of regulatory agencies, such as the FDA, also contribute significantly to public attitudes. Trust in these entities plays a crucial role in shaping perceptions of the necessity and effectiveness of regulation [81]. Cultural and ethical beliefs regarding technological advancements, genetic engineering, and the use of biological products, explored by Santoro et al. [82] and Silverman [83], introduce an ethical dimension that can sway public attitudes toward regulatory policies as well. In essence, the confluence of these many factors creates a complex web that significantly affects the public’s stance on regulatory policies in the dynamic field of biologics, which in turn will directly affect MVP technology development.

4. MVP Technology Development Process Model

The stakeholder attitudes, preferences, and behaviors within MVP processes constitute critical knowledge for groups seeking to innovate in this key area. Similarly, the factors that affect these variables and the subsequent interactions with and viewpoints towards regulation are also essential information points. However, of equal or surpassing importance to the individual static qualities of particular stakeholders are the dynamic aspects of these individual stakeholders, taken in the context of the technological development process, and in their interactions throughout the development timeline.

To better organize understanding of how stakeholders interact with the regulatory process, we offer a dynamic analysis that incorporates the previously identified stakeholders into a functional elongated technological development model, based on the existing work of Caetano et al.’s Technology Development Process Model [84] and Cooper and Edgett’s Technology Stage Gate Model [85]. By taking key elements of these popular and commonly employed frameworks and extending the endpoint past the completed technology stage into additional production and market launch stages, we gain a more holistic understanding of the breadth of development and implementation for an MVP-based biologic product and allow for a more comprehensive understanding of the interactions between stakeholders, regulations, and related preferences, attitudes, and behaviors. The model in question can be seen in Figure 1. We discuss the progression through our proposed model and how individual stakeholders interact with each other within the confines of the model in the following section. To better understand the dynamic stakeholder interactions, we establish a series of phases, each composed of multiple stages. This additional organizational element reflects several important facets of the technology development subsystem and the stakeholders involved within it. While the stage-based analysis of the MVP technology development process explained by the TDP model is appropriate based on existing research, the actual policy subsystem (like other policy subsystems) is much messier, and involvement by individual stakeholders at different points in the process is relatively inconsistent. Unavoidable human constraints such as insufficient time, delays in communication, and imperfect information lead to the logical conclusion of imperfectly delineated relationships between stakeholders in the developing technology subsystem. As a result, by demarcating the time series into phases containing multiple stages, we can more accurately project stakeholder interactions based on the inherent qualities of human nature and subsystem relationships. As such, we have established the following four phases: a conceptual phase, an experimental phase, a pre-production phase, and a launch phase.

The TDP model is appropriate based on existing research; the actual policy subsystem (like other policy subsystems) is much messier, and involvement by individual stakeholders at different points in the process is relatively inconsistent. Unavoidable human constraints such as insufficient time, delays in communication, and imperfect information lead to the logical conclusion of imperfectly delineated relationships between stakeholders in the developing technology subsystem. As a result, by demarcating the time series into phases containing multiple stages we can more accurately project stakeholder interactions based on the inherent qualities of human nature and subsystem relationships. As such, we have established the following four phases: a conceptual phase, an experimental phase, a pre-production phase, and a launch phase.

4.1. The Conceptual Phase

Due to their largely conceptual nature, the stages in this phase see a lack of involvement and interaction between many of the major stakeholders. For example, the general public is largely uninvolved at this stage, as individual (non-patient) members often lack awareness of emerging technologies in the medical field. Patients, on the other hand, serve as a relatively activated stakeholder at this stage, and indeed, many in the medical industry not only consider perceptions and opinions of patients’ experiences in this phase when conceptualizing different approaches, technologies, and treatment goals, but also seek to expand these influences in the name of ethical concerns, arguing to re-label patients as “public research partners” [86] and framing patient involvement in terms of amplifying previously marginalized voices in medical research and development [87].

Both the insight and perceived needs of patients often inform the activity of the most active stakeholder group in this phase—scientists and researchers, who consider a whole host of passive and external influences on their decision-making processes in these early stages. Compliance with FDA regulations is a significant consideration even at this early stage, with the importance of regulatory adherence to scientists and researchers (and other stakeholders with which they want/need to collaborate further on in the TPD model) influencing the consideration of these factors in this phase. However, it is important to note that compared to later phases with more active dynamic interaction, FDA involvement at this stage is still relatively minimal [88]. The healthcare industry, in addition, may recommend, either passively or actively, specific focus on particular areas of innovation for these scientists and researchers as well, summarily guiding this group and driving progression through the model into the second phase.

4.2. The Experimental Phase

The experimental phase is characterized, more so than any of the other phases, by a concentration of efforts within a singular stakeholder group, to the exclusion of dynamic interactions. At this point in the TPD model, scientists and researchers are working to translate their ideas into reality through experimentation, prototype development, and design and engineering efforts, largely independent of passive or active influences from other stakeholders. Responses to the preferences, attitudes, and behaviors of other stakeholders are concentrated more so in the conceptual phase and later phases. The primary interaction noted in the literature at this stage is “optional” adherence to good manufacturing practice (GMP)-categorized regulations concerning testing, risk management, and GMPs. Again, while adherence to the small body of MVP-specific regulation is officially characterized as recommendations, and not technically legally enforceable [14,15], other stakeholders, including scientists and researchers, often adhere closely to these recommendations so as to streamline adherence to more established, binding FDA regulations further on down the road.

4.3. The Pre-Production Phase

Unlike the previous two phases, the pre-production phase sees a marked increase in both the quantity and scope of dynamic stakeholder interactions. Whereas previous phases were largely centered around the innovation efforts of scientists and researchers, this stage sees significant interactions for almost all of our previously identified stakeholder groups. This begins with FDA-based regulatory policy, and it is in this phase that we see a diversification of regulatory burden away from primarily scientists and researchers to a broader range of regulatory burden for pharmaceutical and healthcare industry stakeholders as well. At the same time, not only will stakeholders consider the regulatory burden specific to MVP technology, but they will also consider the much broader burden of general medical device and clinical trial regulations as well, as these factors will be tangentially related to the outputs from MVP technology; while not directly related to technological development, their importance to the overall process must be acknowledged. Again, the burden of these additional, broader medical industry regulations will fall largely on the more established healthcare and pharmaceutical industry stakeholders.

Beyond the regulatory interactions of the FDA with other stakeholders, there exist multiple significant dynamic interaction patterns occurring in regard to the other stakeholders in the subsystem. While there exists an investment in regulation from the FDA to industry stakeholders, we expect a similar effort from industry stakeholders in regard to adhering to these regulations. Due to the various penalties involved, be they financial, regulatory, or opinion-based, industry stakeholders are highly incentivized to comply with MVP-related regulation, especially in these later stages of the TDP model. Among specific industry stakeholders, we can comfortably expect healthcare industry stakeholders to be particularly concerned with regulations pertaining to clinical trials and medicinal efficacy, while pharmaceutical industry stakeholders are more concerned with manufacturing and purification standards.

The second pattern we expect to see from industry stakeholders pertains to their active interaction with scientists and researchers. While we might consider scientists and researchers as having a single perspective while working towards a common goal, the reality is that there are likely many competing teams working on developing similar prototypes. Although MVP technology is still fairly early in development, we can comfortably project increasing interest in developing this technology moving forward. As such, industry stakeholders will likely have a strong interest in interacting with scientists and researchers in this stage to promote the most promising prototypes. The decisions that result will likely be based in large part on assessments of efficacy, potential profitability, potential regulatory hurdles, and other standard considerations for the selection of medical technology prototypes.

The final instance of dynamic interaction that we project within this phase centers on patients. Although obtaining information about new medical technologies and treatments can be challenging, this advanced stage makes such information more accessible and available within more reasonable timeframes. As such, patient involvement in trial programs and other processes tangential to the development of MVP technology becomes more pronounced, in turn affecting the preferences, attitudes, and behaviors of actors more directly involved in the development of MVP technology overall.

4.4. The Launch Phase

As MVP technology ushers medical innovation towards the actual administration of related medical products to patients, we must consider the dynamic interactions within the launch phase. At this phase, the initial work by scientists and researchers has largely passed on to industry-side stakeholders—whether healthcare insurance and provider stakeholders or production-centered stakeholders. Pharmaceutical industry stakeholders are particularly active in their interactions with the FDA at this phase, as they continue to strictly adhere not only to CBER’s MVP-related regulations, but also the broader body of general regulation pertaining to various aspects of medical treatments and devices, such as clinical trials or post-launch evaluation, which while tangential for the purposes of this focused analysis, are still relevant in the overall context.

Relatedly, health insurance companies and providers are also heavily involved in post-launch evaluation and regulatory oversight alongside pharmaceutical industry stakeholders, as they seek to identify successful products while adhering to the operational necessities imposed by the various aspects of MVP-related regulations. At the same time, they liaise extensively with patient stakeholders, who communicate interest and investment in the various treatments, evaluations, and developments occurring in this phase. Patients, and to a lesser degree the general public, additionally weigh the values of availability, quality, price, and safety heavily during this phase. In turn, these influential opinions cycle back to the FDA and CBER, summarily affecting regulation and other stakeholders throughout the model.

In essence, our analysis of stakeholder preferences, attitudes, and behaviors within the MVP technology subsystem reveals a complex and profoundly impactful network of interactions. While some stakeholders, such as scientists and researchers, are more active in the early phases, many others ramp up their involvement and collaboration as we progress through the steps outlined in the TDP model. Collectively, these stakeholders stand to gain or lose significantly from their engagements with regulation within the MVP technology development subsystem. Recognizing and understanding these dynamic relationships serves as a vital catalyst not only for advancing their individual interests within the subsystem but also for propelling the broader frontiers of medical science and treatment forward.

5. Discussion

As membrane filtration technology continues to develop, we can anticipate significant developments in membrane filtration regulation by the FDA as associated advancements in biotechnology and pharmaceutical manufacturing continue to evolve. Alongside an increasing focus on precision and efficiency in drug production, membrane filtration technologies are likely to play a pivotal role in ensuring the safety and quality of a wide range of biologic treatments.

One foreseeable trend, which is mirrored in industry development in similar technological arenas, regards the implementation of more stringent guidelines for membrane filtration processes [89]. As the pharmaceutical industry adopts increasingly complex biologics and personalized medicines, regulators will need to address the unique challenges related to the filtration of diverse molecules and particles. This may involve refining existing standards and introducing novel regulatory frameworks tailored to specific product categories.

Moreover, as membrane filtration techniques become more integral to manufacturing processes, the FDA could place greater emphasis on real-time monitoring and control systems. Continuous monitoring of filtration parameters, such as pore size, flux rates, and integrity, could become standard practice to ensure consistent product quality and minimize the risk of contamination. Additionally, advancements in sensor technology and data analytics may enable the implementation of predictive maintenance strategies, enhancing the reliability and efficiency of filtration systems while adhering to regulatory requirements. Overall, we expect the FDA to adapt its regulations in response to the evolving landscape of membrane filtration technology, prioritizing safety, efficacy, and innovation in pharmaceutical manufacturing.

5.1. Future Research

Looking forward, there are a number of areas that offer enticing research opportunities, in terms of both expanding and deepening our investigation of the effects of membrane filtration regulation on technological innovation. More research into the role of federal-level regulatory burdens that fall outside of the FDA penumbra, through agencies such as the CDC, is needed to increase our understanding of this complex regulatory environment of stakeholders, regulation, and emerging technology.

In the same vein, state-level and institutional regulations, through both state governments and agencies and university-level IRB-based regulations, are both underexplored and potentially important sources of relevant regulatory policy, especially as awareness of and investment in biologics writ large continues to grow at a rapid pace. It is likely that as membrane filtration technology becomes a more developed part of this broader, developing field, that additional beliefs, attitudes, and behaviors will manifest themselves in different ways across the range of stakeholders we have identified, necessitating updates and even potentially the repositioning of our findings in future contexts.

5.2. Conclusions

In closing, we want to first reiterate the importance of the development of VLP-manufacturing technology to the affordability and availability of biologic treatments moving forward. Without a scalable and cost-efficient means of providing essential material for producing treatments, costs will remain high and access for middle and low-income patients will continue to be an area of medical and moral concern. Membrane filtration technology offers a potential solution to these issues, yet as an emerging technology, faces potential regulatory barriers that could slow or entirely disincentivize its development.

Our analysis of the potential regulatory burden for this technology within the American context specifically, and relating exclusively to the primary regulator, the Center for Biologics Evaluation and Research (CBER), indicates a complex web of attitudes, behaviors, and preferences from a wide range of stakeholders. Not only is the Food and Drug Administration (FDA) involved, but other stakeholders including healthcare insurance companies, healthcare providers, the pharmaceutical industry, scientists and researchers, patients, and the general public have the potential to influence the regulation of this new technology. In advancing a sequential stage-based model, derived and specialized based on the existing Technology State-Gate and Technological Development Process models, we identify what we believe to be key motivations, opinions, and patterns of behavior, based on the existing regulatory policy environment, and informed by stakeholders’ potential attitudes, preferences, and behaviors in this emerging technological area.

Our findings indicate both room for growth for innovation in membrane science for the filtration of VLPs, but also the need for cautious, careful consideration of the regulatory burden on both the development of suitable membrane technology, but also the broader application of the technology to the biologics industry at large. As the biologics industry continues to grow, regulatory burdens will expand in scope and sophistication, leading to an easy projection for significant change in the regulatory policy environment in the immediate future. It is our hope that this analysis of the MVP regulatory subsystem can assist in engendering a more effective, ethical, and affordable biologics industry moving forward. This adaptation will require not only the revision of existing policies but also the proactive development of new regulatory approaches that are responsive to technological advancements and societal needs. Policymakers must remain vigilant in identifying potential risks associated with MVP technology while fostering an environment that encourages innovation and equitable access. Additionally, interdisciplinary collaboration among scientists, regulatory bodies, industry stakeholders, and public health advocates will be essential in creating balanced regulations that protect public health without stifling technological progress. We hope that this analysis of the MVP regulatory subsystem contributes to the development of a more effective, ethical, and accessible biologics industry by offering a comprehensive understanding of the regulatory landscape and its intersection with stakeholder interests. Ultimately, our goal is to support the creation of regulatory frameworks that not only enhance the efficiency and safety of biologic treatments but also ensure that these innovations are accessible to all populations, thereby benefiting public health on a broad scale and driving forward the frontiers of medical innovation.