Spring 2017 - Current Topic
FINDING THE GOOD IN GOOD SCIENCE
Note: This document expresses Dr. Jenke’s personal views and opinions and is not a position established and supported by Triad Scientific Solutions, LLC. This document is not professional advice and does not constitute a professional service provided by either Dr. Jenke or Triad Scientific Solutions.
When members of the E&L community gather to develop standards, guidelines and best demonstrated practice recommendations, there are three principles they should obey:
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The standards must be based on “good science”,
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The standards must be effective and efficient, and
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The standards must fit every conceivable circumstance well.
It is the inability to achieve these principles that makes the generation of standards, guidelines and recommendations so frustratingly challenging.
Consider the last principle, for example. It is intuitively obvious in a diverse field such as pharmaceuticals that this principle is impossible to achieve as it is clear that a rigorous standard (which is specified set of tests coupled to a specified set of acceptable test results) cannot fit all the diverse circumstances equally well. It is the same problem as trying to design a glove that fits every human being. If the underlying purpose of the glove is “to keep one’s hands warm”, then a standardized glove can be designed that will address this requirement, to some degree, for most people. However, because the glove must keep everybody’s hands warm, it is logical that there will be design tradeoffs which will mean that while it keeps everyone’s hands warm, it does not keep everyone’s hands as warm as they would personally like it. Furthermore, there may be other trade-offs, such as “these gloves are not very sexy”, or “these gloves do not match my coat” or “these gloves make my hands itch”.
While the challenges in making standards that are generally applicable in the greatest number of circumstances are considerable, this is not the point that I want to address in this discussion. Rather, I want to address the challenges associated with good science.
Good science suffers from with the same problem as designing a standardized glove. As good scientists, we learned and we understand that there are very few universal scientific truths; rather, a scientific truth is a truth only under the rigorously defined set of circumstances upon which it is based. When we perform an experiment and draw a conclusion from that experiment, we understand the conclusion is only perfectly valid for the set of defined experimental circumstances we started out with. Extension of that same conclusion to other circumstances involves a certain measure of risk, specifically the risk that in changing the circumstances we have invalidated (knowingly or unknowingly) some fundamental principle that defines the applicability of our conclusions. Thus, we understand that there is an inherent trade-off when we make scientific generalizations and put them into standards, guidances and recommendations. That is, we sacrifice some of the good in good science for the sake of providing a direction that is generally right in the greatest number of circumstances.
The challenge we face as practitioners of good science is not in recognizing good science per say but recognizing the boundaries that differentiate between good science properly applied and good science improperly applied. When we are tempted to use a standard, or leverage a “rule of thumb” or “do this because everybody else is doing it”, as good scientists we must ask ourselves “am I taking a good idea in certain circumstances and applying it to the wrong circumstances?”. If the answer is yes, then surely this is as bad as using “bad” science in the first place.
Let me illustrate this with an example. I use this as an example not because it a particularly bad practice but because it effectively illustrates my point. The following, taken from the PQRI OINDP Best Practice recommendations, is well known and commonly applied in the E&L community.
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The Working Group recommends that analytical uncertainty be evaluated in order to establish a Final AET for any technique/method used for detecting and identifying unknown extractables/leachables.
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The Working Group proposes and recommends that analytical uncertainty in the estimated AET be defined as one (1) standard deviation in an appropriately constituted and acquired Response Factor database OR a factor of 50% of the estimated AET, whichever is greater.
The question I would ask you to consider is “where is the good science and the not so good science in these recommendations?”
Here is my answer. It is well known that response factors will vary among the universe of compounds that could be extractables and leachables. Thus, it is good science that a general concept such as the AET, which presumably is applicable to all possible extractables/leachables, take this variation into account. Furthermore, we all understand that basing actions on relevant and sufficient data is the cornerstone of good science, and thus that the requirement to consider “an appropriately constituted and acquired Response Factor database” is a requirement to do good science. However, it must be obvious that the direction to universally “use a factor of 50%” is not necessarily good science. While the derivation of the 50% is itself good science, as it was based on a response factor database (which is somewhat small in the context of the databases available today), it is obvious that the 50% is only relevant for the compounds in that database and the analytical method with which the data was generated. Universal and unquestioned application of the factor of 2 rule to compounds that were not in the original database and to analytical methods other than the method used to generate the data is not the best science; rather, it is poor science, not because the science itself is bad but because the good science aspects are being applied out of context.
To a good scientist, arguments such as “it is better than nothing” or “everybody else is doing it” are inexcusable. Certainly, the idea that “it is better than nothing” has to be examined objectively and harshly. The improper application of science is not guaranteed to be better than doing nothing because it is not the case that the improper application of science will always make things better. In fact, the history of improper application of good science is littered with examples of bad outcomes derived from applying good sciences incorrectly.
Listen, nobody said doing good science was easy. We understand that part of the driving force for recommending that the factor of 2 be universally applied is that back then few people could access a database. Thus, it was nearly impossible to practice the good science required in the recommendation and people, rather than do nothing, gravitated to the other part of the recommendation. However, today, it is virtually impossible to run into a reputable E&L laboratory that is not eager to talk about their database. Thus, in this case, our ability to do good science has finally caught up with our responsibility to do good science. It is proper that we accept that responsibility and be held accountable for meeting that responsibility.
This is true not only to adjusting the AET for analytical uncertainty but in numerous other places where our current capabilities enable our ability and address our responsibility to practice and preach a higher degree of good science than has ever been possible. Currently applied recommendations, standards, guidelines and practices must be adjusted, as appropriate, to leverage this new and higher degree of good science and new recommendations, standards and guidelines must be drafted to reflect this new and higher degree of science. We aspire to better science because we are capable of better science. More importantly, if we are going to talk the talk, we best start walking the walk.
In-Depth Interview with Dr. Dennis Jenke, continuing Principal Consultant for Nelson Labs Europe, on the Past, Present and Future…
* No part of this interview may be copied or used in any context without the written permission from Dr. Dennis Jenke.
I understand that after almost 33 years with Baxter, playing a leadership role in its Extractables & Leachables Programs, your career has taken a new direction.
Yes, that is true. For the past decade or so the names “Dennis Jenke” and “Baxter” have been synonymous in the E&L world. However, if there is anything that is constant in the world it is change and an opportunity to move in a new direction presented itself.
While that opportunity allowed me to retire from Baxter, I realized that I was not ready to retire from the bigger mission, which has always been the practical application of good science to sustain, enhance and save lives. The question was how best to continue the mission, how best to use my skills, knowledge and talents to advance science and improve the human condition.
The answer came easy enough as I have had the great fortune over my career to collaborate with many equally driven, skilled and knowledgeable individuals and organizations. It became clear to me that my mission is best served by my greater freedom to operate in the sense of forging and developing newer and deeper collaborations.
Thus, I started Triad Scientific Solutions and why I focused Triad’s efforts and energies into identifying and developing collaborations with individuals and organizations that share my conviction that good science, practically applied, provides the foundation for sustaining, enhancing and saving lives.
I hear that you are very enthusiastic about new opportunities that the future may hold for you. Can you elaborate further on this?
-Baxter’s mission to sustain and save lives resonated with me from the moment that I joined the company so many years ago and became the focal point of all that I accomplished while at Baxter. As I matured and developed in my role at Baxter I recognized and understood the foundational role that good science, practically applied for the benefit of the patient, plays in achieving this mission.
One of the major reasons I continue to pursue new opportunities is the realization that the mission to sustain, enhance and save lives is as much a personal mission as it was a corporate mission and thus pursuing the mission is not just the focus of a career, it is the focus of a lifetime.
In addition to being elevating, inspiring and motivating, this mission of sustaining, enhancing and saving lives is embraced by many people. I look forward to an even greater opportunity to forge new and more extensive collaborations.
With an elevating and inspiring mission, an innate desire to contribute and virtually limitless opportunities to collaborate, who wouldn’t be enthusiastic?
You are continuing your collaboration with Nelson Lab Europe, one of the leading CRO’s in the discipline of Extractables & Leachables and Material Characterization. Could you explain a bit more why you chose Nelson Labs Europe to partner up with in building your new future?
In what now seems almost a previous lifetime, I enjoyed a long, productive and necessarily informal “relationship” with the Nelson Labs Europe team for quite some time. What is new about this relationship moving forward is my freedom to interact with Nelson Labs Europe and its clients in a more formal, rigorous and extensive manner. This relationship was, and will continue to be, based on the strongest of foundations, a shared commitment to good and practical science, practiced for the ultimate good of patients.
I view my ongoing collaboration with Nelson Labs Europe as a case of a shared commitment. The ultimate question to me is commitment to what and commitment to whom. As business, both Triad Scientific Solutions and Nelson labs Europe have financial responsibilities to its stakeholders, no different than organizations that participate in the food, cosmetic and healthcare industries. However, as science-based institutions, both Triad and Nelson Labs Europe have understood and embraced their responsibilities to the scientific community. Thus, both organizations and their associated members have actively advanced what is collectively and figuratively termed “good science” by dedicating the necessary resources in the pursuit of “good science” and sharing the results of that effort with the scientific community so that advances made by one can be shared with and used by many.
Moreover, both Triad and Nelson Labs Europe understand that “good science” for science sake is not enough and that it is the practical application of good science that supports the development and commercialization of products that sustain, enhance and save lives. Thus, Triad and Nelson Labs Europe have focused their investigations into good science so that they produce practical outcomes that enable efficient and cost-effective product development, commercialization and support.
As I see it, Triad and Nelson Labs are two sides to the same coin. While we have a shared passion and mission, we have complementary skills and knowledge. Where Triad has no laboratory capabilities, one of the strengths of Nelson Labs Europe is its modern, state of the art laboratory facility, staffed by talented, experienced and dedicated multi-disciplinary scientists. Where Nelson Labs Europe has a profound capability to implement and execute studies, Triad has the experience and understanding to design, interpret, report, justify and defend studies. Nelson Labs Europe’s excellence in tactics is complemented by Triad’s long history of developing and establishing strategic standards and best practice recommendations.
Having said all this, the case for continuing our collaboration was pretty obvious and compelling.
The role of “Principal Consultant” with Nelson Labs Europe sounds like a lot of science, chemistry, analytics and data management will still be involved. What exactly will the role as a “Principle Consultant” entail?
Let’s first address what I call the “community service” side of this role. Both Nelson Labs Europe and I have science-based interests that we are actively exploring, pursuing and investigating. Serving as a Principal Consultant to Nelson Labs Europe gives me greater access to their programs and thus affords me a greater opportunity to contribute to all aspects of those programs, including their design, implementation, interpretation and reporting. Additionally, this collaboration with Nelson Labs Europe allows me to vet my own scientific interests and pursuits with highly trained, knowledgeable, experienced and talented individuals and gives me access to resources that are beyond the abilities and capabilities of my own Triad organization.
Moreover, both Nelson Labs Europe and I have a long and somewhat different experience in this industry and this collaboration provides us with the ability to share, discuss and examine those experiences with a depth and a level of detail that was not previously possible. It is hard to imagine our organizations sitting in a room together with nothing to discuss and with nothing coming out of those discussions. I am convinced that our collaboration will allow both organizations to dream big and accomplish bigger, benefiting the scientific community and industry in general and our clients in particular.
Ok, let’s switch to the “business” side of this role. As a Principal Consultant to Nelson Labs Europe I will have appropriate access to their policies, processes and procedures. It is reasonable to expect that I will be able to provide Nelson Labs Europe with insights into and perspectives on such policies, processes and procedures which will lead to enhanced capabilities, improved efficiency and effectiveness, greater scientific rigor and superior robustness.
My role as a Principal Consultant to Nelson Labs Europe allows me to engage with its current and future clients both tactically, with regard to individual studies, and strategically, with regard to programs, processes and policies. Such engagement includes, but is not necessarily limited to, development, design, interpretation, reporting and justifying appropriate tactics and strategies.
Having said this, it is important to understand that this role as Principal Consultant provides a means for Triad and Nelson Labs Europe to work together to advance science and serve clients. Nevertheless, both organizations maintain the independence necessary to support their own objectives and to serve their own clientele.
You mentioned that you appreciate the approach that Nelson Labs Europe is taking in the way they perform Extractactable & Leachable Studies. However, with your profound knowledge in Extractables & Leachables, gathered through your 33-year long career in this field, I could imagine that there are some areas where you could make a substantial contribution to the science and protocols of Nelson Labs Europe.
In general, Nelson Labs Europe’s strength is in the analytical laboratory, where an E&L study is implemented. Thus, once an extract has been generated, Nelson Labs Europe is virtually unmatched in its ability to effectively and efficiently establish the identity and approximate concentration of all relevant entities in the extract.
On the other hand, Triad’s strength lies in the planning of the E&L study, the selection and justification of extraction conditions, and the reporting and interpretation of the analytical results. Thus, there is a significant opportunity for Triad to step in and elevate the level of science applied to both the front end of an E&L study (e.g., experimental design) and the back end of the same study (data reporting and interpretation).
Let’s consider the back-end of the E&L study specifically. Nelson Labs Europe’s strength lies in the generation of data that provide a complete and accurate picture of a test articles extractable’s or leachables profile. While this data is important, many clients lack the ability to convert the available data into information. This is where Triad steps in, specifically answering the clients’ critical questions, such as “so what does this data mean to me?”.
Furthermore, the universe of extractables and leachables is actually quite large, driven by the great diversity in food, cosmetic, and pharmaceutical products and applications. It is safe to say, in a general sense, that given their different experiences and roles in the E&L world, Nelson Labs Europe and Triad have developed a critical mass of information and understanding in certain parts of the food, cosmetics and pharmaceutical world and that these parts have both adjacencies and discontinuities. In areas of adjacencies, it is easy to imagine that our experiences will complement one another. In areas of discontinuities, it is easy to see how we both will able to learn from one another. In the end, building on adjacencies and learning from discontinuities will move both the Triad and Nelson Labs Europe organizations forward in terms of both the science and its practical application.
This situation is very much like the parable of the blind men and the elephant. In this story, several blind men are allowed to touch one part of an elephant and are then asked to describe the elephant based on the part they have touched. Of course, each man’s description of the elephant is quite different as they each touched very different parts of the elephant’s anatomy. The difference in their descriptions causes the blind men to quarrel among themselves as they are individually confident in terms of what they have experienced. It is only when they are reminded of the limited nature of their experiences that they are able to meld their individual experiences together to produce a more realistic picture of the elephant.
What I am suggesting by noting this parable is that by pooling their individual E&L experiences, Nelson Labs Europe and Triad are uniquely positioned to combine their individual develop and implement effective and efficient practices, policies and procedures that are science-driven and client-focused.
I also could hear that you are very enthusiastic about your future involvement in Nelson Labs’s Research & Development Programs which are currently running. Could you explain your involvement in those R&D programs?
It is always exciting to work with Nelson Labs Europe on their ongoing R&D programs because they address the two aspects of R&D that I am most interested in, establishing “good science” and making “good science” practical and applicable. Maybe even more importantly, they are not afraid to push the envelope and ask not just what is the next logical step but what is that critical leap that needs to be taken to really rocket the field forward. There is a real synergy going on here between Nelson Labs Europe and myself and I cannot count the times I have walked out of a meeting with them thinking either “I wish I had thought of that” or “man, I can really do something with that idea!” I am pretty sure the feeling is mutual.
While I have enjoyed working with Nelson Labs Europe staff members on some of their previous R&D programs, my participation was limited and largely superficial, as dictated by the organizational dynamics that existed at that time. However, as a Principal Consultant, I can jump into to these programs with both feet and work side by side with the Nelson Labs Europe researchers, designing, reviewing, adjusting, interpreting and reporting these programs. Instead of seeing filtered data through someone else’s eyes, I will have appropriate access to the original data, which will allow me a “bird’s eye view” of all the details. This is really important because I have found that one discovers the most unusual things when one is working in the grass.
The name “Dennis Jenke” is almost synonymous for high quality scientific articles in the Extractables & Leachables domain. Whether it was about the science, the concepts, the materials, the nature of the compounds or the way a risk assessment could be performed, your scientific articles were always much appreciated and had a large impact on the Industry. Are you planning to continue these efforts and bring continued value to the E/L-community?
Absolutely and this is one of the major reasons why a close collaboration between Triad and Nelson Labs Europe is so important to me. You see, contributions to the scientific literature come in three flavors: reviews, opinions and technical contributions.
As reviews and opinions are generally based on information that is either available in the public domain or which has obtained previously as “experiences”, they can be generated once one has established a topic and once one has secured the necessary relevant public information. However, technical contributions are a different beast entirely as they generally discuss innovative and relevant research that has been recently conducted.
When I left Baxter, I lost both the ability to generate the new data which is the foundation of technical contributions and access to data generated by like-minded colleagues. I know that losing such access was a great concern for me and I think it was unfortunate for both industry and the E&L scientific community. However, the collaboration between Nelson Labs Europe and Triad gets me back into the game, so to speak, as it provides me access to Nelson Labs’ existing data (fully respecting the confidential nature of client data) as well as giving me access to resources for performing the new studies which produce the data that is the foundation of good science and technical contributions.
In some ways, it is like a child finding itself in a new play room, with all sorts of new toys to play with. The question is not whether to play or not, it is what toy do I play with first?
I understand that the same will be true for your participation as a presenter on many Extractables & Leachables Conferences?
Let’s be honest, I do not go to E&L Conferences to speak, I go to E&L Conferences to listen. Speaking is the means of getting invited to these conferences; listening is the means of surfacing and understanding the technical and practical issues associated with the profession we have termed E&L.
People ask me all the time where do you get the ideas for your publications? Well the answer is I listen. If I hear the same question over and over again, then the best way to provide an answer is to either present or publish the answer (assuming I either have or can find the answer). If a question or topic is interesting or timely or “consequential”, then it’s a race for me to get back to the lab or back to the literature to get my facts straight and my thoughts organized and “put them into print”. When I hear someway say something that I think is particularly profound (or particularly naïve), it is an opportunity to reflect and ask “why is that right (or, why is that wrong”? If I think I have figured it out (and I think that others have not), then this is another opportunity to use the power of the pen.
OK, so what I said is not 100% true. Beyond its technical definition, good science includes the concept of communication. Science is not good science, no matter how evolved it is technically, until it is known to, understood by, and practiced in the entire scientific community. Thus, a scientist has the dual responsibility of performing good science and then communicating that good science.
Because I believe in the communication piece so strongly, I will continue to be active in E&L Conferences as long as I have something relevant and meaningful to talk about and as long the Conference organizers will have me.
Another point that I want to bring up is your representation in Standard Setting Organizations and Industry Consortia. For the last 15 years, you were very heavily involved in ELSIE, PQRI (Parenteral DP/Ophthalmic DP), USP, ISO 10993, and I may forget some others. Your involvement and impact in the technical guidances which have been – or – are being developed, is tremendous. Do you plan on continuing those efforts?
I believe the profession of scientist carries with it certain responsibilities. One of those responsibilities is to move science forward. Another is to ensure that when science moves forward, the advances in knowledge and technology are harnessed so as to improve the human condition. This is what serving with standard setting or thought-leading organizations is all about; harnessing good science to produce standards that are efficient, effective and which appropriately accomplish their objective, which in the food, cosmetic and pharmaceutical industries boils down to producing the greatest possible user benefit with the smallest possible user risk.
Over the past decade, tremendous progress has been made with respect to growing the science and capturing it in effective and efficient standards. While some activities have either crossed or are straddling the finish line, much work remains to get these industries to the point where all the necessary standards reflect the practical application of what we term good science.
As long as the organizations are willing to have me, and as long as my science is good and relevant, I intend to be actively involved in the process of establishing best demonstrated practices and capturing those practices in meaningful standards.
Furthermore, although individuals and organizations have created so much data and information, the data is largely pigeon-holed. Thus, the really big ideas and the really big advances are stymied because no one individual or one team has access to all the data and all the information that allows them to put all the pieces together. One of the purposes for organizations such as ELSIE is to provide the means, and to a certain extent the resources, to bring it all together and make the next giant step forward. It is probably pretty clear that I support such activities 110% and will do anything I can to help them move their initiatives forward.
I would assume that, apart from the role as “Principal Consultant” with Nelson Labs, there may be some other activities you may engage in?
It is important to understand that while my role as Principal Consultant provides a means for Triad and Nelson Labs Europe to work together to advance science and serve clients, both organizations will maintain the independence necessary to support their own objectives and to serve their own clientele.
As it is clear that Nelson Labs Europe will perform projects and support clients independent of my involvement, so too it should be clear that working through Triad I will be involved with projects and clients independent from Nelson Labs Europe.
For example, we talked just a bit ago about involvement with standard setting organizations and the like. This volunteer involvement requires that participants act in the best interest of “society” as a whole, moving beyond the needs and interests of the organizations that they may represent. Necessarily, then, such activities clearly fall outside my role as a Principal Consultant for Nelson Labs Europe and as the Chief Executive Scientist of Triad.
We also previously talked about publications and presentations. While I fully anticipate that there will be publications and presentations that result from my collaboration with Nelson Labs Europe, I also fully anticipate that there will be publications and presentations that are fully independent from this collaboration.
You know, we started this conversation noting that I have retired from Baxter. When I reflect on all the things we have talked about, I begin to ask myself “What retirement?”