2022 Volume 4 Issue 2 Pages 40-44
The development of pharmaceutical drugs, medical devices, and bio-centric products has recently progressed by utilizing start-up-style mechanisms and venture investments. As this requires the involvement of various specialists, it is important to have human resource visionaries that can monitor such development and connect everyone involved. Regulatory science knowledge and expertise offer novel development perspectives and are valuable for clinicians who wish to convert translational research into real clinical work. We believe that such knowledge and expertise in regulatory science is indispensable for advancing core translational research, which is the development of pharmaceutical drugs and medical devices. In this way, translation refers to research data and the thinking and planning processes. Working in an academic research organization is undoubtedly far from a physician’s duties. This is challenging but rewarding work, and having different perspectives and knowledge of domains other than clinical expertise can be beneficial.
The development of pharmaceutical drugs and medical devices has recently progressed through start-up and venture investments. Human resources that can manage development and connect each specialist are indispensable, and the importance of regulatory science in translational research is growing. Human resources monitoring the development process and bridging various specialists involved based on knowledge and experience in the regulatory science might be necessary. Being a member of an academic research organization is challenging but rewarding for a physician. We believe having different perspectives and knowledge of domains other than clinical expertise is very helpful.
The Japan Pharmaceutical Manufacturers Association annually surveys and reports the total number of candidate product compounds from synthesis to approval. A 2021 report showed that 545,967 compounds were synthesized between 2015 and 2019. Of these, 146 were non-clinical, and 53 were in clinical development. Twenty-four drugs were ultimately approved from these compounds of interest, equating to an approximately 1/23,000 probability of success [1].
In recent years, there have been an increasing number of cases in which research and development (R&D) of pharmaceutical drugs, medical device developments, and bio-derived or -centric products are accelerated by new research “exit strategies” (Fig. 1) [2]. Essentially, these developments can progress more efficiently by utilizing an established start-up and venture investment pipeline in the United States and, more recently, Japan [3]. The National Translational Research Promotion Program in Japan promotes the development of translational research [4]. The recruitment and retention of diverse specialists are crucial for R&D progress. Therefore, human resource management that can connect involved specialists at each stage of the pipeline is required to establish bench-to-bedside commercialization.
Recent or conventional exit strategy in pharmaceutical drug and medical device development. Recent development tends to progress more efficiently by utilizing start-up-style mechanisms. Accelerator: entrepreneurial support organization or program; Basic research: discovery of new substances as drug candidates; Exploratory research: c.f., research for searching and creating new high utility compounds; IP (intellectual property): c.f., patent rights; Development research: c.f., non-clinical good laboratory practice study; Partnering: c.f., joint research agreements; Technology Transfer: the process of transferring (diffusing) technology from one individual or organization that owns or possesses the technology (technology) to another individual or organization.
The constant change in regulatory science (RS) attempts to harness the energy of the pharmaceutical development process [5]. Work experience in a Pharmaceuticals and Medical Devices Agency (PMDA) or academic research organization (ARO) helps familiarize oneself with these innovative regulatory. One of the present study’s authors belonged to several PMDA offices. During that time, they learned about regulatory affairs and regulatory reviewers’ roles and thought processes throughout various activities such as approval examination, clinical trial consultation, and clinical trial protocol surveys. Additionally, time in an ARO was academically valuable for clinical trial consultation. Having a seasoned perspective as a reviewer is valuable for physicians to promote translational research in the actual clinical work environment. We propose that knowledge and experience in RS might be indispensable for this process.
In translating research results to the commercialization phase, various processes rely on numerous knowledge domains. These include researching clinical needs and selecting target diseases, formulating target product profiles (TPPs), investigating medical device applicability, determining medical device classification, determining the required suite of non-clinical studies, determining the necessity of clinical study data, and formulating business models.
In each process, RS plays an important role (Fig. 2):
Various processes to be determined using manifold knowledge types. In translating research results to the commercialization phase, various processes must be determined using diverse knowledge types. In this case, knowledge of regulatory science might be particularly useful. From the point of view of technology management, three barriers exist: “Devil River”, “Valley of Death”, and “Darwinian Sea”. Devil River: The devil river is the barrier between a research and development project starting from basic research and proceeding to the development stage, with the goal of commercialization. In reality, many projects simply end here; Valley of Death: Valley of death is the barrier to whether a project that has advanced to the development stage will proceed to the clinical research stage. Many projects end without overcoming this barrier; Darwinian Sea: The Darwinian sea is a barrier where commercialized products and services are exposed to the rough seas of competition with other companies and acceptance by actual customers.
• In formulating TPPs, RS knowledge would enable the formulation of realistic TPPs and development roadmaps.
• In investigating medical device applicability, RS knowledge enables immediate judgment.
• In determining medical device classification, it is possible to accurately and quickly assess classification based on the understanding of international rules.
• RS knowledge empowers appropriate decisions in determining the required package of non-clinical studies and the necessity of clinical study data.
• In adapting to early-approval regulations, RS knowledge permits expert judgment on applicability.
• In applying insurance reimbursements, knowledge of the price calculation method would contribute to formulating appropriate strategies.
Both authors are physicians and belong to an ARO called the Tsukuba Clinical Research & Development Organization. One author had previously engaged in specific project acceleration activities using RS experience in the translational research department. The other author was involved in the consultation department. We constantly endeavor to apply these experiences in the clinical field however possible.
One author supported two developmental processes through translational research work as a tutor. In the RS-centered process, tutors serve as instructors, bring awareness, and promote team problem-solving. They also build mutual understanding between experts with specialized knowledge and translate technical terms for the team.
This author initially supported a team working on technology for making neuroprotective drugs. These drugs can scavenge reactive oxygen species and have been shown to reduce mortality, inhibit cerebral infarction, and improve neurological symptoms in a mouse stroke model [6]. The team had intended to present their research results, but they were composed of only academic researchers. The author was thus assigned as a tutor, bringing knowledge of pharmaceutical regulations and opening communication channels with regulating authorities. They revised their regulatory strategy and large animal study data package through focused discussion based on good laboratory practice. As a result, the PMDA consultation was successful, and the development was approved.
The author supported basic academic research and studied brain-machine interface technologies for electroencephalogram event-related potentials. This involved an electroencephalogram on the scalp that measures immediate attention increases. The researchers had already conducted various evaluation tests using the prototype on healthy people and patients with motor function disabilities [7, 8]. This brain-machine interface technology could potentially be applied to estimate mental activity without relying on motor function. The original team was composed primarily of researchers who were inexperienced in medical device development. The tutor was able to focus on medical device commercialization, and product development was ultimately successful. As a team member who developed the first seed idea, the tutor endeavored to accelerate this development. Clinical trials using second-generation derived technologies in a hospital now benefit from previous experience dealing with the commercialization of research valuable to society.
Another author who works as a neurosurgeon commits substantial time and effort to clinical work and belongs to the consultation department in the ARO. The primary purpose of this department is to support the planning and implementation of clinical research. The author handles a workload comprised of paperwork, meetings, and surgery. They check clinical trial protocols and consent forms for all clinical research conducted at the hospital for ethical issues and advise on study design improvements. They also revised our research application system, application forms, and guidance documents accordingly. Conducting these discussions with physicians and staff on proposed designs and clinical research content assists in creating new research opportunities to drive innovation.
Regulatory affairs are generally a considerable barrier for researchers and start-up teams due to a lack of mutual understanding between researchers and the industry. Academics often expect regulatory compliance to be an almost insurmountable obstacle. Despite this internal resistance, consultation helped to drive development smoothly with the additional internal support of members experienced in RS. Furthermore, it is difficult for researchers to formulate TPPs and development strategies for medical devices controlled by baroque regulations; RS bridges this gap.
With the help of RS, the development of new drug modalities and medical devices becomes proactive instead of reactive, and the evaluation criteria and contents of non-clinical and clinical data packages can be determined individually and strategically. Those with experience reviewing many products are familiar with the basic concepts of the development process, allowing them to facilitate the process of RS consultation smoothly.
We have listed what we consider to be the merits/demerits of working as an ARO member.
Pros• Intimate knowledge of clinical research and developmental flow.
• Stimulation from being involved in novel work that is different from clinical work.
• Opportunities to learn how other departments, hospital management, and regulatory authorities think.
• Opportunity to learn about studies by various researchers and, in some cases, become involved in developing the projects themselves.
• Increased opportunities to interact with various professionals such as administration, pharmacists, clinical research coordinators, etc.
• Acquisition of medical knowledge outside of areas of expertise and a wide range of knowledge related to commercialization not limited to the medical domain.
• Remote work opportunities.
• Improvements in organizational and logical thinking ability.
Cons• Considerable amounts of administrative work.
• Knowledge requirements of relevant legislation as a newcomer in the field.
• Multiple, possibly long, meetings.
• Limited time available for clinical work, such as surgery, could limit growth as a physician.
• Fortitude is required to tutor amateurs in research and development.
To overcome the cons listed above, we believe there is a need to increase the number of physicians with experience in regulatory science. It is necessary to prepare an adjusted and clear career plan for physicians with the necessary experience. In addition, to increase the number of clinicians interested in development, there might be a need to incorporate different performance evaluation metrics in academia and not rely solely on the number of papers published.
It might be necessary to have human resources specialists who can monitor the development process and connect specialists based on their RS knowledge and experience. We believe that translational research transcends just the research data and involves the actual thought and planning processes of various specialists. ARO duties are far removed from the duties of a physician and make for challenging but rewarding work. We believe having different perspectives from domains other than just clinical expertise can be highly beneficial.
We have no conflicts of interest to declare.
We thank Tomoyoshi Koyanagi, Takeshi Machino, Hiroshi Noguchi, Takeshi Yamada, Koichi Hashimoto, and Yoshihiro Arakawa for their role as members of the ARO in this article. We also thank Aiki Marushima, Ryohei P. Hasegawa, and Yuji Matsumaru for their activities in research work on this article. Furthermore, we wish to thank Drs. Alexander Zaboronok of the University of Tsukuba Faculty of Medicine Department of Neurosurgery and Bryan J. Mathis of the University of Tsukuba Hospital International Medical Center for further professional and language revision.
