Please introduce yourself to the readers of Lawyer Monthly & what is your professional background and education?
Hello there, I am Stuart Levy, a chemistry and chemistry, manufacturing, and controls consultant to the biotech and Pharma industry, based in Arlington, MA, a “collar suburb” very close to Cambridge and Boston. I am a sole-proprietor, independent consultant, with 29 years of industrial experience as a chemist at medium-sized and small, entrepreneurial biotech pharmaceutical companies and vendors (contract R&D and manufacturing organizations, CDMOs). I have been an independent consultant, serving startups and established small biotechs in chemistry and CMC for 14 years.
Education, Undergraduate and Graduate
I pursued a bachelor’s degree in molecular, cellular and developmental biology at the University of Colorado, Boulder (CU). I completed my bachelor’s degree in 1987, in Biochemistry, at University of Illinois, Chicago. I had two independent study lab rotations as an undergraduate, one with Professor Merrill Gassman, a plant biologist, extracting and purifying one of the enzymes of interest in the Gassman group, and one with Professor Jacques Kagan, performing acetylcholinesterase functional assays in mosquito larva homogenates and extracts, in order to assess the efficacy of phototoxic, biodegradable synthetic pesticides as a means of control of mosquito populations which are known carriers of tropical and other debilitating microbe-based diseases.
I’ve also worked as a Process Chemist, SUGEN, South San Francisco, CA – 1998-2000 a Contract Medicinal Chemist, Eli Lilly and Co, Corporate Center, Indianapolis, IN, 1998 and a Research Scientist SERES Laboratories Santa Rosa, CA, 1995-1998
What are your technical areas of expertise?
Organic synthesis, organic chemistry, stereochemistry, chemical process development and manufacturing, process troubleshooting, solid state chemistry, catalytic chemical transformations (asymmetric, stereoselective, redox, chemocatalytic and biocatalytic), development and technology transfer of syntheses/scalable/scaled up processes for production and manufacturing of raw materials, custom reagents including catalysts, raw materials, key and regulatory starting materials GMP process intermediates and final APIs.
Full spectroscopic characterization and identification of APIs, intermediates, starting materials, raw materials and impurities, impurity control strategy and implementation, development of sufficiently sensitive and specific analytical methods (HPLC, XRPD, LC-MS, KF, IR, NMR (dynamic, and structural), analytical method troubleshooting and distinction between true attributes and artefactual data in key raw materials, regulatory starting materials, APIs, drug product intermediates and drug products, as well as specialized reagents that have limited stability.
Drug product preformulation and development (for solid oral, parenteral/injectable, suppositories topical and other types of administration to patients), controlled release and other specialized means of drug delivery, drug product intermediates (spray dried dispersions, extrudates from hot melt and related processes, blends, granulations, semi-solids, process development, and manufacturing, packaging, Global import/export of starting materials, intermediates, APIs and drug products.
Radiosynthesis of radiolabelled APIs for whole-body autoradiography, metabolic distribution and human clinical PK-ADME studies.
Regulatory CMC – drafting, reviewing and editing of written submissions (pre-IND, IND, pre-EOP2, EOP2, pre-NDA, NDA, SUPAC biowaivers, supporting memos and R&D reports and summaries), high-level regulatory CMC advisors to regulatory CMC and quality assurance leadership and groups, writing/reviewing of SOPs, facility quality/technical audits, mock-PAIs, responses to feedback and questions from regulatory agencies, particularly FDA and EMA, but any others as well.
Oversight and leadership – regularly hired to be de facto Senior/Executive VP of CMC and to devise and implement entire CMC program strategies, brought in at C-Level/Board/VC/Investor level, range of oversight can include vendors, internal R&D and production, regulatory CMC, quality, import/export specialists, reg CMC, CMC, drug product, analytical, API, and quality consultants, tech ops, procurement and supply chain.
Significant interactions with adjacent functions – clinical, pharmacology, toxicology, quality, regulatory, program leadership and management, C-level executives, CEOs, boards, and investors/VCs/PE firms.
How did you become an experienced expert witness?
I became a CMC/pharmaceuticals/chemistry expert witness by realizing that the quality of my testimony at a disposition as a former employee at PPD Dermatology, as determined by a review of the deposition transcript, disposes me well for expert witness work. In addition, I was strongly encouraged by my elders in the industry, who were, in fact, very successful expert witnesses, to position myself to accept this type of work based on what they knew about me and saw in me. I was also very interested in breaking into expert witnessing, having worked for a year at a patent law firm as a jack of all trades and messenger, and having translated an Argentinian patent into English (I am professionally proficient and fluent in written and conversational Spanish).
What are the expert witness services you provide?
Expertise in Chemical and Pharmaceutical Development
- Evaluation and optimization of synthetic routes to drug candidates
- Adaptation of discovery chemistry routes for scale-up
- Chemical process development and optimization
- Creation and execution of fit-for-purpose R&D, production and cGMP manufacturing strategies and plans
- Design of syntheses of stable isotope and radiolabeled molecules for in vivo studies
- Physicochemical characterization
- Solid state chemistry – polymorphism, salt screening and selection
- Sourcing of raw materials, excipients and standards
Vendor Selection, Engagement and Management
- API, drug product, analytical, custom synthesis, QA and regulatory support
- Creation of requests for proposal
- Definition of scope of work, deliverables and timelines
- Facilitation of performance and completion of work
- Technology transfer – assembly of tech transfer packages, performance of tech transfer to and between vendors and organizations
- Excellent vendor network
Problem Solving
- Troubleshooting of chemical process development and API manufacture, drug product process development and manufacture, analytical method development
- Leadership of expert teams in the solution of complex technical problems
- Broad, multidisciplinary consultant network
Assistance with Strategy and Management of Drug Development Programs
- Coordination of CMC activities
- Liaison between technical functions, regulatory, QA; Effective, clear communication across disciplines
Technical and Regulatory Documentation
- Drafting, review and editing of development reports
- Authorship, review and editing of CMC regulatory documents, including INDs, NDAs, amendments, biowaivers
Regulatory/QA
- Interpretation and application of FDA and ICH guidance pertaining to CMC development activities
- Practical experience in quality audits and mock PAIs in US, India and Japan
I’ve worked with a range of Organizations:
- Entrepreneurial start-up biotechs
- Medium-sized established biotechs
- Small and large CMC vendors – API, solid state, drug product, preformulation, formulation development, solids manipulation (production and manufacture of DP intermediates, particle engineering and particle size reduction), analytical
- Big Pharma
- Venture Capitalists
- Private Equity Firms
- Other interested parties
- Expert witness recruiters (indirect engagement), law firms and their clients (direct engagement)
Duties
- Technical expertise and support
- Strategic and tactical expertise and support, judgement calls for which I have responsibility
- Logistical expertise and support – shipping, import/export, US, EU and Asian Customs, problem-solving in this realm
- Interpretation of legally binding contracts for attorneys, from a technical/practical POV
- Soft skills – negotiation, persuasion, liaison, motivation, driver, leader, emissary between groups in conflict, facilitation of performance and legal fulfilment of contractually obligatory work
What are the most difficult aspects of being an expert witness?
The most difficult aspects come during the due diligence/initial deep dive into the case file – this is the period during which I have to use my side’s theory of the case and their version of the points of contention in order to determine whether or how I can get behind their position, in a way that does not compromise my expertise or integrity as a scientist.
I have become very skilled at this in the last 9 years, but it is still far and away the hardest thing I have to do – listening closely to attorney and client, asking the right questions to nail down the theory of the case according to me, and then to devise and present a means of how this will be implemented in the form of an expert report, or other deliverable.
What are the most interesting cases you’ve worked on?
I present two, because they are interesting for very different reasons:
Case 1 (my first case ever, in 2016) – Damages Phase for a Huge Blockbuster Drug
I was on the side of the generics company looking to begin selling their drug 4-5 years in advance of patent expiration, Hatch-Waxman; opposing expert had a “platinum” CV, and I was very intimidated by that at first. Lead counsel told me to forget about that completely, they knew I was their guy, the best man for the job. Once I read the opposing expert’s report, I saw the enormous flaws and holes in his reasoning – he had been too far away from “hands-on” for too long, and his opinions and assertions reflected that. I read 150 manufacturing batch records and wrote my report within one month. My report settled the case.
What made this report so interesting and compelling to me is that I had my first expert witness “Eureka” moment, in which the vision of how I would argue the validity of the client’s position, based purely on logic and facts.
What made it so enjoyable was a requirement to theorize, based on my expertise and my understanding of the process in question, with regard to how long it would take the client to bring the process online, and in what timeframe. As a pharmaceutical development strategic and technical expert, it was a pleasure to sketch this out in sufficient detail and rationalize the results – I was then at the point in my consulting career where I was beginning the shift in consulting to long-range planning and fleshing out manufacturing strategy and implementation for client leadership, boards, and investors. It was a very rich, rewarding time, and the pleasure I take in doing my job in the industrial legal realm has only grown and aged exceptionally well.
Case 2 – Wrongful Death of a Chemical Expert – Liability of the Insurance Company for Lost Earnings Dueue to Premature Death
I was on the side of the widow. I was hired directly by the attorney representing her. I could not for the life of me understand why he wanted to engage my services until we spoke. The chemist was about to make the transition from executive at a vendor (API CDMO) to consultant. He was in his early 60’s, and 10-15 years of earnings as a consultant was a reasonable expectation. The trial was in a suburb of Toronto, Ontario, Canada. My report was very strong. However, when my turn came to testify, the opposing attorney challenged me, claiming I had no standing to testify in Canada about a Canadian consultant. The judge, who was biased against my attorney and for the defendant insurance company’s attorney, invalidated 2/3 of my report, base on the defense lawyer’s claim, so the testimony immediately became much more challenging. At a lunch break, the attorneys and I bought crackers and soda from the court vending machine, and holed up in a conference room, to formulate a plan.
We came back into the courtroom, and I resumed my testimony, pushing the envelope as much as possible, right up to the limits of what the judge would allow, and I certainly traversed into slightly forbidden territory, as agreed between me and the lawyers. I also learned that, unlike in the US, in Canada, it is allowed for the witness to speak back to the opposing attorney and correct deliberately inaccurate statements and assertions. The judge was Scots-Irish, and she had quite a temper. She started to get angry with me about the nature of my post-lunch testimony (described above) very quickly. On the stand, I could see her face getting redder and redder, and the tension between us was palpable. Instead of addressing me, she addressed my attorney with extreme hostility and barely contained rage, and then softly turned to me and very sweetly and quietly asked me to exit the courtroom! I left both confused, intimidated, and more than a little worried that I was going to be disqualified; after a short recess, we were called back.
My lawyer and his associate raced toward me, and he told me “you were perfect – you’ve done nothing wrong, and you’re not being disqualified. Now, go back in there and finish strong!” My testimony resumed, with me talking directly to the jury, as (before). The last question my attorney had for me was a touchy one – “how much would the decedent have made in a year of consulting, on average?”
The defense attorney had just gotten to his feet (but hadn’t verbally objected), and I was able to give my answer just before the judge tried to cut me off – the figure made it into the trial transcript, and the plaintiff won the case! Very dramatic and exciting!!!!! Here I was before that, in the anteroom of the courtroom, thinking that things had totally tanked, and they did not.
What are the most exciting areas in chemical and pharmaceutical development?
The Confluence of Increase in Flow Chemistry’s Capability, Process Analytical Technology (PAT), Big Data, and AI, to Expand Flow Chemistry’s Utility in the Pharmaceutical Industry
This has already been occurring, and has resulted in highly controlled, real-time monitored chemical and pharmaceutical processes that can be adjusted as they occur and Proven Acceptable Range (PAR) and Normal Operating Ranges (NOR) boundary limits are approached. Ultimately, this ongoing R&D and manufacturing will expand the thinking of regulatory agencies about the meaning of quality by design (QBD), design of experiments (DOE), and control of unit operations and entire processes.
The confluence of physical chemistry of materials, advances in and further refinement in the development of existing and emerging modalities in enabling technologies for drug product intermediate and finished drug product R&D, production and manufacturing
Chemical Space, a region in which new, unique molecules emerge, had, for a long time, been relegated mostly to” theoretically interesting” molecular classes, e.g., highly strained, energetic molecules or molecules that violated well-established scientific rules, e.g., aromaticity and anti-aromaticity, etc. The pharmaceutical industry has recently (2005-2024) made significant inroads in chemical space, and now probably dominates that realm, due to enhanced (see third most exciting area below) capabilities to accomplish chemical transformations that were previously impossible, extremely difficult or impractical due limits in equipment and energy sources required. As a result, conventional approaches to preformulation, formulation development, and drug product production and manufacturing was confronted with the need to render these new drug candidates into tractable, efficacious dosage forms that could navigate, intact, the often circuitous, challenging route to the appropriated tissues and sites of action. The issues being addressed currently involve increasingly lower aqueous solubilities of drug candidates, to the point that an increasing proportion of new drug candidates require enabling technologies, and an increasing proportion of those are DCS 2b drugs (solubility-limited drugs that are highly insoluble but permeable), on the border with BCS 4 drugs (neither soluble nor permeable nor soluble). This issue is being addressed to a very small extent via structural modifications to the drug candidate via synthetic chemistry, but the success rate of this strategy is often very low (>10%).
The Development of New Chemical Reactions That Allow Access to Previously Impossible to Make or Impractical to Make Chemical Structural Motifs
The advent of rediscovery and improvement of the performance of previously impractical chemical reactions has resulted in the aforementioned foray into chemical space, populating this realm with an increasing proportion of molecules that are truly structurally and physicochemically unique. This has been a double-edged sword, in that, while these new structures address previously undruggable targets in pharmaceutical medicinal chemistry, discovery, development and clinical realms, this has been accompanied by physicochemical challenges – extremely poor solubility, more complex syntheses, processes, characterization, rendering into a dosage form with acceptable performance (in vivo dissolution, distribution, delivery to the target, pharmacokinetics, metabolism, etc.
All of the above are on balance very positive phenomena, but anything novel also presents technical and regulatory challenges that must be overcome. CDMOs with more conventional capabilities will need to continue to develop and shift their capabilities and technologies, in order to keep up with novel technologies discovered and invented in the academic and emerging industrial realms, as well as “boutique vendors” whose sole purpose is to innovate.
What are the essential elements for an expert report?
- Introduction – Context – clear, accurate descriptions and assessments of the theories of the case for both plaintiff and defendant
- Tying the above to the parties’ contentions, arguments and conclusions, as they relate to their respective theories and contentions (also often part of the introduction)
- Clear presentation of client’s position that is fact and data-based
- Challenging/refutation of the opposing parties’ questionable contentions, again based on facts and data
- If requested by counsel or a ruling by a judge, construct theoretical projections, based on facts and data as expected of one skilled in the art
- Statement as to whether arguments made are more likely than not, citing arguments made and conclusions reached earlier in the report
- Provision of a final opinion, entailing all aspects of the case that are at issue
What makes a great expert witness?
- An individual who is skilled in the art that is/are the areas of interest; ability, with the attorneys to present expert’s competence during Daubert Challenges or Voir Dire
- High verbal ability – written and spoken, as it relates to the case subject matter and in general; ability to be concise and humble while teaching or explaining to a judge, jury, opposing counsel or one’s attorneys
- Tenacity – usually the most important quality of both a scientist and expert witness
- The ability to work diligently and carefully under time pressure and the watchful eyes of the client and attorneys
- Soft skills – persuasion, diplomacy, judgement (knowing what to say and not to say, and how to say it), ability to navigate real-time conflict and uncomfortable situations arising from such events
- Understanding of the fundamentals of the law, as it relates to the matter (this is, without exception, by the attorneys, but one must always read between the lines and ask clarifying questions)
- Coachability and ability to be guided through the process by attorneys
- 360⁰ thinking – all sides of an issue, including anticipation of challenges from the opposing counsel and client, so that both stipulations and challenges/refutations can be made as accurately/rationally and diplomatically as possible
Stuart G. Levy, Ph.D., Principal
SGL Chemistry Consulting, LLC
92 Fairmont St. Arlington, MA 02474
Tel: (781)316-2594
Email: [email protected]
www.sglchemistryconsulting.com
Published by: www.lawyer-monthly.com – June 4th, 2024