Feb. 22, 2018
Smithers: Your opening presentation looks at how the USP is reinventing monographs – can you tell us about the drivers for this and what impact you hope to have?
Dennis Jenke: The USP’s mission is to ensure the quality and safety of pharmaceutical products. Since the systems used to (a) manufacture the pharmaceutical product, (b) store the pharmaceutical product from manufacturing to use and (c) administer the pharmaceutical product at time of use can impact quality and safety, it is necessary and appropriate for the USP to provide monographs that speak to these items in such a way that the monographs leverage the best available science and respect practical realities. Providing such monographs requires both the revision of existing monographs (for example for packaging) and the creation of new monographs (for example, manufacturing systems).
A cornerstone of the USP approach is the concept that the most effective way to ensure that a system is suited for its intended use is to construct that system from materials and components that are intentionally selected as being suitable based on scientific data collected in a standardized manner. Thus, the USP monographs are designed to produce data relevant to material and component selection. While such information may also be relevant to regulatory qualification, securing regulatory approval for the system or its associated drug product is outside the scope of the USP monographs.
Given the great diversity in pharmaceutical products, the USP monographs are designed to be minimum standards that address the most commonly encountered pharmaceutical situations and which may need to be augmented in certain circumstances.
It is my hope that clearly communicating the foundational essence of the USP approach will support, clarify and justify the details contained in individual USP monographs.
Smithers: The field of E&L analytical chemistry has evolved considerably over the last decade – what do you think the next 5 years have in store for our industry?
Dennis Jenke: Although there is no dismissing the point that analytical chemistry applied to E&L has evolved over the past decade and that this evolution has helped define and establish what we recognize today as “good science” and “best demonstrated practice”, I believe it is a mistake to conclude that the great advances in E&L over the last decade have been strictly advances in analytical chemistry, specifically related to advanced analytical methodologies that allow us to see more at lower levels and then to better identify those things that we see. Moreover, I think that it is a mistake to believe that we are at the point of limited return, where future developments in analytical chemistry will produce diminishing returns in terms of scientific and practical aspects of E&L.
However, if the focus in future analytical development is” let’s go lower still and let’s focus on identification”, then any development is not addressing the major challenges moving forward. These major challenges are reducing redundancy and driving standardization via information sharing, producing better extractables and leachables quantitation in screening, and taming the beast of the drug product matrix so that leachables screening of drug products can become more prevent and extractables screening of systems can become less prevalent.
Furthermore, we tend to think of analytical as a chemistry activity. It can, and is, also a biological activity. For example, when we identify and quantify an extractable or leachable and turn that information over for toxicological safety assessment, the toxicologist infers the safety effect that the extractable or leachable could have. However, one can envision a future where the effect of the extractable or leachable on a living system can be directly established by relevant and biological appropriate testing.
Smithers: You are chairing a discussion on BPOG vs USP – can you characterize the key issues?
Dennis Jenke: The fact is that there never has been and there currently is not an issue of BPOG versus USP. Rather, the entire industry has to leverage the needs and experiences of the various stakeholders concerned with establishing the suitability of pharmaceutical manufacturing systems for use (including suppliers, users, regulators, interested parties, and, ultimately, patients) and to somehow reconcile those needs and experiences with the oftentimes competing demands of good science practically applied to diverse circumstances. Furthermore, an additional issue is one of scope, specifically recognizing the fundamental and clear difference between characterization and qualification.
Yes, there has been some teeth-gnashing, hair-renting, eyes-to-the-skies moments along the way. Because the issue is complex, the needs are competing, and sometimes the science is either lacking or poorly understood, there have been legitimate differences of opinion that could only be resolved as the science gets better, the view point are tested (and contested) and a workable compromise is established.
You asked what the key issues were? To me the key issues were haste, lack of essential good science and an unwillingness to compromise, somehow expecting that a single generalized outcome could fit every stakeholder as if it were customized for their own unique needs and circumstances.
It would be foolish to declare victory today and say that these key issues have been fully resolved. However, I believe that the “big issues” are largely behind us and that what remains to be reconciled is not the cake itself but rather the frosting on that cake.
Smithers: What are the key issues you and your panelists hope to address during the panel
Dennis Jenke: I can only speak from the USP perspective. The USP, in developing its <665> monograph, claimed to have “aimed for the middle”. It is my hope that the panel will help us understand how well we hit the target. Furthermore, the <665> monograph is, by intent and desire, “science-based”. The panel provides interested parties the opportunity to share and debate some of their own good science. Lastly, the USP struggled (yes, that is the right word) to balance the requirements of a standard (that, in fact it be standardized), with the sincere desire of stakeholders to “do their own thing” if so-doing could be justified. Again, it is my hope that the panel will help us understand whether the current approach in the revised <665> strikes an acceptable balance.