Vol.5 No.1 2012
Research paper : Research and development of a monopivot centrifugal blood pump for clinical use (T. Yamane et al.)−24−Synthesiology - English edition Vol.5 No.1 (2012) of development based on clinical needs.” We restored chapter 4 to cover the development results as it did originally. 2 Relevancy between design verification of the pump and experimentsComment (Motoyuki Akamatsu)At the beginning of subchapter 4.1, it is written that design verification was efficiently conducted to solve problems. Please explain why the flow visualization test and the in vitro thrombogenicity test were necessary so that the readers outside of the field may understand. Please explain the degree of advantage by comparing with the research and development of other pumps.Question (Jun Hama: Energy Technology Research Institute, AIST)In the chapter concerning design verification of the pump, the flow visualization test, the in vitro thrombogenicity test and the durability test are explained. What is the whole picture of design verification of pumps? Please write your response to each category of verification of the three tests in more detail.Answer (Takashi Yamane)I added the following to subchapter 4.1.“Before the application to Pharmaceuticals and Medical Devices Agency (PMDA), the efficacy, safety, and quality designated in pharmaceutical law should be evaluated. The company was in charge of the evaluation of safety and quality. AIST was in charge of the evaluation of efficacy and conducted a flow visualization test, an in vitro thrombogenicity test, and a durability test for design evaluation.”These evaluation techniques were requested by the clinical side and I added what kind of effect there was in subchapter 4.2.“As mentioned above, the medical team advised us of the concept of evidence-based medicine, namely we do not go directly to multiple animal experiments but utilize in vitro testing to obtain scientific evidences. We conducted sufficient flow visualization experiments and in vitro thrombogenic tests and minimized the number of animal experiments. The important advice led to an efficient development and this can be regarded as the fruit of the M/E collaboration.”Moreover, I added its effect in chapter 5.“The necessary time for development was 9 years. We kept the number of animal experiments low and accumulated sufficient engineering data which could become bases of design and could be used as descriptive material for users.” 3 Standard for approval of assist pumpQuestion (Jun Hama)How is the standard of approval for assist pumps for cardiovascular surgical procedure stipulated? Answer (Takashi Yamane)Basically, there are standards for safety in pharmaceutical law; however there is no standard for efficacy. Efficacy is determined not by numerical evidence but by the duration of evidence (data taken during 6 hours in this case).4 Development of evaluation techniqueQuestion (Jun Hama)How should we understand that the evaluating endpoints and verification experiment would be approved in Japan and overseas as a method of evaluation? For example, what kinds of measures are you taking in order that these methods of evaluation would be recognized more widely as a conventional evaluation technique rather than a specific evaluation method of artificial heart design? Answer (Takashi Yamane)We included visualization tests in the evaluation method of the artificial heart of ISO. Evaluation methods vary depending on how far the companies want to file. Examples are explained in chapter 6. In December 2010, we conducted flow visualization for EVAHEART by Sun Medical Technology Research and the data was submitted to premarket approval of PMDA and to the investigational device exemption (IDE) of FDA. 5 Decision for productization and resetting of targetQuestion (Motoyuki Akamatsu)One of the points of this paper is the decision made when Senko Medical Instrument Mfg. Co. Ltd. joined the research aiming for productization and the resetting of the target later. Although there must have been many other researches for artificial hearts, please write the reason why this company chose to commercialize this monopivot centrifugal pump, or why it saw the possibility of productization. Question (Jun Hama)It can be presumed that the difficulty of productization related to medical fields is the reason why the target to develop an artificial heart in collaboration with a university was changed to extracorporeal circulatory pump in the productization efforts with a company. Would you explain to us the reason for that change in detail? Answer (Takashi Yamane)The reason for the decision the company made for the productization of monopivot centrifugal pump was based on an introduction by a university professor who was a research partner of the monopivot centrifugal pump development. There were only five groups which had reached animal experiments among the institutes researching rotatary type artificial hearts in 2002. It seems to me that among these groups, only AIST was in a position where the company could easily participate in. We mentioned the process of resetting the development target in chapter 3. Doing business with inexpensive, low-risk products or disposable products is the basic stance of the collaborating company. This company can easily procure polymer material and is good at processing it. With our design, it assembles the pump with little adhesive, using a cheap manufacturing method that does not use O ring or screws often used for ordinary products. There was a prospect that, if the monopivot mechanism of AIST was used, an inexpensive product without ball bearings and shaft seals could be made. That was the reason for aiming at productization of a circulatory assist pump based on the AIST’s method.6 Medicine-engineering collaborationComment (Motoyuki Akamatsu)Concerning medicine-engineering collaboration, as of medicine, there is the basic research point of view of medical doctors of research and the clinical view from treatment and diagnosis of patients at hospitals. As for engineering, there are university professors and researchers of public research institutions in the field of engineering, and engineers involved in productization at companies. I think if you can organize the parties involved, it would be of use to the readers.Answer (Takashi Yamane)There are usually two types for the medicine-engineering collaboration. One is where a company and a hospital collaborate as a manufacturer and a user, to realize a product because the law prohibits medical device manufactures from being users themselves, which is different from general industry. The other is where universities, hospitals or research institutions offer seeds and companies join them to realize productization according to the needs. The case presented in this paper is the latter case. I added the examples of successful productization of artificial assist hearts (VAD) in subchapter 4.2.