Please introduce your self to the readers of Lawyer Month-to-month & what’s your skilled background and schooling?
Whats up there, I’m Stuart Levy, a chemistry and chemistry, manufacturing, and controls guide to the biotech and Pharma business, based mostly in Arlington, MA, a “collar suburb” very near Cambridge and Boston. I’m a sole-proprietor, impartial guide, with 29 years of commercial expertise as a chemist at medium-sized and small, entrepreneurial biotech pharmaceutical corporations and distributors (contract R&D and manufacturing organizations, CDMOs). I’ve been an impartial guide, serving startups and established small biotechs in chemistry and CMC for 14 years.
Training, Undergraduate and Graduate
I pursued a bachelor’s diploma in molecular, mobile and developmental biology on the College of Colorado, Boulder (CU). I accomplished my bachelor’s diploma in 1987, in Biochemistry, at College of Illinois, Chicago. I had two impartial research lab rotations as an undergraduate, one with Professor Merrill Gassman, a plant biologist, extracting and purifying one of many enzymes of curiosity within the Gassman group, and one with Professor Jacques Kagan, performing acetylcholinesterase useful assays in mosquito larva homogenates and extracts, so as to assess the efficacy of phototoxic, biodegradable artificial pesticides as a method of management of mosquito populations that are recognized carriers of tropical and different debilitating microbe-based illnesses.
I’ve additionally labored as a Course of Chemist, SUGEN, South San Francisco, CA – 1998-2000 a Contract Medicinal Chemist, Eli Lilly and Co, Company Middle, Indianapolis, IN, 1998 and a Analysis Scientist SERES Laboratories Santa Rosa, CA, 1995-1998
What are your technical areas of experience?
Natural synthesis, natural chemistry, stereochemistry, chemical course of growth and manufacturing, course of troubleshooting, strong state chemistry, catalytic chemical transformations (uneven, stereoselective, redox, chemocatalytic and biocatalytic), growth and know-how switch of syntheses/scalable/scaled up processes for manufacturing and manufacturing of uncooked supplies, customized reagents together with catalysts, uncooked supplies, key and regulatory beginning supplies GMP course of intermediates and closing APIs.
Full spectroscopic characterization and identification of APIs, intermediates, beginning supplies, uncooked supplies and impurities, impurity management technique and implementation, growth of sufficiently delicate and particular analytical strategies (HPLC, XRPD, LC-MS, KF, IR, NMR (dynamic, and structural), analytical methodology troubleshooting and distinction between true attributes and artefactual knowledge in key uncooked supplies, regulatory beginning supplies, APIs, drug product intermediates and drug merchandise, in addition to specialised reagents which have restricted stability.
Drug product preformulation and growth (for strong oral, parenteral/injectable, suppositories topical and different sorts of administration to sufferers), managed launch and different specialised technique of drug supply, drug product intermediates (spray dried dispersions, extrudates from scorching soften and associated processes, blends, granulations, semi-solids, course of growth, and manufacturing, packaging, World import/export of beginning supplies, intermediates, APIs and drug merchandise.
Radiosynthesis of radiolabelled APIs for whole-body autoradiography, metabolic distribution and human scientific PK-ADME research.
Regulatory CMC – drafting, reviewing and modifying of written submissions (pre-IND, IND, pre-EOP2, EOP2, pre-NDA, NDA, SUPAC biowaivers, supporting memos and R&D experiences and summaries), high-level regulatory CMC advisors to regulatory CMC and high quality assurance management and teams, writing/reviewing of SOPs, facility high quality/technical audits, mock-PAIs, responses to suggestions and questions from regulatory businesses, significantly FDA and EMA, however any others as effectively.
Oversight and management – repeatedly employed to be de facto Senior/Government VP of CMC and to plan and implement complete CMC program methods, introduced in at C-Degree/Board/VC/Investor degree, vary of oversight can embrace distributors, inside R&D and manufacturing, regulatory CMC, high quality, import/export specialists, reg CMC, CMC, drug product, analytical, API, and high quality consultants, tech ops, procurement and provide chain.
Vital interactions with adjoining features – scientific, pharmacology, toxicology, high quality, regulatory, program management and administration, C-level executives, CEOs, boards, and buyers/VCs/PE companies.
How did you turn out to be an skilled skilled witness?
I grew to become a CMC/prescribed drugs/chemistry skilled witness by realizing that the standard of my testimony at a disposition as a former worker at PPD Dermatology, as decided by a evaluation of the deposition transcript, disposes me effectively for skilled witness work. As well as, I used to be strongly inspired by my elders within the business, who have been, in reality, very profitable skilled witnesses, to place myself to just accept this kind of work based mostly on what they knew about me and noticed in me. I used to be additionally very involved in breaking into skilled witnessing, having labored for a yr at a patent legislation agency as a jack of all trades and messenger, and having translated an Argentinian patent into English (I’m professionally proficient and fluent in written and conversational Spanish).
What are the skilled witness companies you present?
Experience in Chemical and Pharmaceutical Improvement
- Analysis and optimization of artificial routes to drug candidates
- Adaptation of discovery chemistry routes for scale-up
- Chemical course of growth and optimization
- Creation and execution of fit-for-purpose R&D, manufacturing and cGMP manufacturing methods and plans
- Design of syntheses of steady isotope and radiolabeled molecules for in vivo research
- Physicochemical characterization
- Stable state chemistry – polymorphism, salt screening and choice
- Sourcing of uncooked supplies, excipients and requirements
Vendor Choice, Engagement and Administration
- API, drug product, analytical, customized synthesis, QA and regulatory help
- Creation of requests for proposal
- Definition of scope of labor, deliverables and timelines
- Facilitation of efficiency and completion of labor
- Expertise switch – meeting of tech switch packages, efficiency of tech switch to and between distributors and organizations
- Glorious vendor community
Downside Fixing
- Troubleshooting of chemical course of growth and API manufacture, drug product course of growth and manufacture, analytical methodology growth
- Management of skilled groups within the answer of complicated technical issues
- Broad, multidisciplinary guide community
Help with Technique and Administration of Drug Improvement Packages
- Coordination of CMC actions
- Liaison between technical features, regulatory, QA; Efficient, clear communication throughout disciplines
Technical and Regulatory Documentation
- Drafting, evaluation and modifying of growth experiences
- Authorship, evaluation and modifying of CMC regulatory paperwork, together with INDs, NDAs, amendments, biowaivers
Regulatory/QA
- Interpretation and utility of FDA and ICH steerage pertaining to CMC growth actions
- Sensible expertise in high quality audits and mock PAIs in US, India and Japan
I’ve labored with a variety of Organizations:
- Entrepreneurial start-up biotechs
- Medium-sized established biotechs
- Small and enormous CMC distributors – API, strong state, drug product, preformulation, formulation growth, solids manipulation (manufacturing and manufacture of DP intermediates, particle engineering and particle dimension discount), analytical
- Huge Pharma
- Enterprise Capitalists
- Personal Fairness Companies
- Different events
- Skilled witness recruiters (oblique engagement), legislation companies and their purchasers (direct engagement)
Duties
- Technical experience and help
- Strategic and tactical experience and help, judgement requires which I’ve duty
- Logistical experience and help – transport, import/export, US, EU and Asian Customs, problem-solving on this realm
- Interpretation of legally binding contracts for attorneys, from a technical/sensible POV
- Comfortable expertise – negotiation, persuasion, liaison, motivation, driver, chief, emissary between teams in battle, facilitation of efficiency and authorized fulfilment of contractually compulsory work
What are probably the most troublesome elements of being an skilled witness?
The most troublesome elements come through the due diligence/preliminary deep dive into the case file – that is the interval throughout which I’ve to make use of my facet’s concept of the case and their model of the factors of competition so as to decide whether or not or how I can get behind their place, in a means that doesn’t compromise my experience or integrity as a scientist.
I’ve turn out to be very expert at this within the final 9 years, nevertheless it remains to be far and away the toughest factor I’ve to do – listening intently to lawyer and consumer, asking the best inquiries to nail down the idea of the case in response to me, after which to plan and current a method of how this may be applied within the type of an skilled report, or different deliverable.
What are probably the most fascinating circumstances you’ve labored on?
I current two, as a result of they’re fascinating for very completely different causes:
Case 1 (my first case ever, in 2016) – Damages Part for a Large Blockbuster Drug
I used to be on the facet of the generics firm trying to start promoting their drug 4-5 years upfront of patent expiration, Hatch-Waxman; opposing skilled had a “platinum” CV, and I used to be very intimidated by that initially. Lead counsel instructed me to neglect about that utterly, they knew I used to be their man, one of the best man for the job. As soon as I learn the opposing skilled’s report, I noticed the big flaws and holes in his reasoning – he had been too distant from “hands-on” for too lengthy, and his opinions and assertions mirrored that. I learn 150 manufacturing batch data and wrote my report inside one month. My report settled the case.
What made this report so fascinating and compelling to me is that I had my first skilled witness “Eureka” second, wherein the imaginative and prescient of how I might argue the validity of the consumer’s place, based mostly purely on logic and details.
What made it so gratifying was a requirement to theorize, based mostly on my experience and my understanding of the method in query, with regard to how lengthy it might take the consumer to convey the method on-line, and in what timeframe. As a pharmaceutical growth strategic and technical skilled, it was a pleasure to sketch this out in adequate element and rationalize the outcomes – I used to be then on the level in my consulting profession the place I used to be starting the shift in consulting to long-range planning and fleshing out manufacturing technique and implementation for consumer management, boards, and buyers. It was a really wealthy, rewarding time, and the pleasure I take in doing my job within the industrial authorized realm has solely grown and aged exceptionally effectively.
Case 2 – Wrongful Demise of a Chemical Skilled – Legal responsibility of the Insurance coverage Firm for Misplaced Earnings Dueue to Untimely Demise
I used to be on the facet of the widow. I used to be employed straight by the lawyer representing her. I couldn’t for the lifetime of me perceive why he wished to have interaction my companies till we spoke. The chemist was about to make the transition from government at a vendor (API CDMO) to guide. He was in his early 60’s, and 10-15 years of earnings as a guide was an inexpensive expectation. The trial was in a suburb of Toronto, Ontario, Canada. My report was very sturdy. Nonetheless, when my flip got here to testify, the opposing lawyer challenged me, claiming I had no standing to testify in Canada a few Canadian guide. The choose, who was biased towards my lawyer and for the defendant insurance coverage firm’s lawyer, invalidated 2/3 of my report, base on the protection lawyer’s declare, so the testimony instantly grew to become way more difficult. At a lunch break, the attorneys and I purchased crackers and soda from the court docket merchandising machine, and holed up in a convention room, to formulate a plan.
We got here again into the courtroom, and I resumed my testimony, pushing the envelope as a lot as attainable, proper as much as the bounds of what the choose would permit, and I definitely traversed into barely forbidden territory, as agreed between me and the attorneys. I additionally discovered that, not like within the US, in Canada, it’s allowed for the witness to talk again to the opposing lawyer and proper intentionally inaccurate statements and assertions. The choose was Scots-Irish, and she or he had fairly a mood. She began to get indignant with me in regards to the nature of my post-lunch testimony (described above) in a short time. On the stand, I might see her face getting redder and redder, and the strain between us was palpable. As a substitute of addressing me, she addressed my lawyer with excessive hostility and barely contained rage, after which softly turned to me and really sweetly and quietly requested me to exit the courtroom! I left each confused, intimidated, and greater than a bit nervous that I was going to be disqualified; after a brief recess, we have been known as again.
My lawyer and his affiliate raced towards me, and he instructed me “you have been excellent – you’ve completed nothing mistaken, and also you’re not being disqualified. Now, return in there and end sturdy!” My testimony resumed, with me speaking on to the jury, as (earlier than). The final query my lawyer had for me was a sensitive one – “how a lot would the decedent have made in a yr of consulting, on common?”
The protection lawyer had simply gotten to his ft (however hadn’t verbally objected), and I was capable of give my reply simply earlier than the choose tried to chop me off – the determine made it into the trial transcript, and the plaintiff received the case! Very dramatic and thrilling!!!!! Right here I used to be earlier than that, within the anteroom of the courtroom, considering that issues had completely tanked, and they didn’t.
What are probably the most thrilling areas in chemical and pharmaceutical growth?
The Confluence of Improve in Movement Chemistry’s Functionality, Course of Analytical Expertise (PAT), Huge Information, and AI, to Broaden Movement Chemistry’s Utility within the Pharmaceutical Trade
This has already been occurring, and has resulted in extremely managed, real-time monitored chemical and pharmaceutical processes that will be adjusted as they happen and Confirmed Acceptable Vary (PAR) and Regular Working Ranges (NOR) boundary limits are approached. In the end, this ongoing R&D and manufacturing will increase the considering of regulatory businesses in regards to the which means of high quality by design (QBD), design of experiments (DOE), and management of unit operations and whole processes.
The confluence of bodily chemistry of supplies, advances in and additional refinement within the growth of present and rising modalities in enabling applied sciences for drug product intermediate and completed drug product R&D, manufacturing and manufacturing
Chemical Area, a area wherein new, distinctive molecules emerge, had, for a very long time, been relegated largely to” theoretically fascinating” molecular lessons, e.g., extremely strained, energetic molecules or molecules that violated well-established scientific guidelines, e.g., aromaticity and anti-aromaticity, and so on. The pharmaceutical business has lately (2005-2024) made important inroads in chemical house, and now in all probability dominates that realm, resulting from enhanced (see third most fun space beneath) capabilities to perform chemical transformations that have been beforehand inconceivable, extraordinarily troublesome or impractical due limits in gear and vitality sources required. Because of this, typical approaches to preformulation, formulation growth, and drug product manufacturing and manufacturing was confronted with the necessity to render these new drug candidates into tractable, efficacious dosage types that would navigate, intact, the usually circuitous, difficult path to the appropriated tissues and websites of motion. The problems being addressed at the moment contain more and more decrease aqueous solubilities of drug candidates, to the purpose that an growing proportion of recent drug candidates require enabling applied sciences, and an growing proportion of these are DCS 2b medication (solubility-limited medication which are extremely insoluble however permeable), on the border with BCS 4 medication (neither soluble nor permeable nor soluble). This problem is being addressed to a really small extent by way of structural modifications to the drug candidate by way of artificial chemistry, however the success price of this technique is typically very low (>10%).
The Improvement of New Chemical Reactions That Permit Entry to Beforehand Unattainable to Make or Impractical to Make Chemical Structural Motifs
The appearance of rediscovery and enchancment of the efficiency of beforehand impractical chemical reactions has resulted within the aforementioned foray into chemical house, populating this realm with an growing proportion of molecules which are really structurally and physicochemically distinctive. This has been a double-edged sword, in that, whereas these new buildings handle beforehand undruggable targets in pharmaceutical medicinal chemistry, discovery, growth and scientific realms, this has been accompanied by physicochemical challenges – extraordinarily poor solubility, extra complicated syntheses, processes, characterization, rendering right into a dosage kind with acceptable efficiency (in vivo dissolution, distribution, supply to the goal, pharmacokinetics, metabolism, and so on.
The entire above are on stability very optimistic phenomena, however something novel additionally presents technical and regulatory challenges that have to be overcome. CDMOs with extra typical capabilities might want to proceed to develop and shift their capabilities and applied sciences, so as to sustain with novel applied sciences found and invented within the educational and rising industrial realms, in addition to “boutique distributors” whose sole function is to innovate.
What are the important components for an skilled report?
- Introduction – Context – clear, correct descriptions and assessments of the theories of the case for each plaintiff and defendant
- Tying the above to the events’ contentions, arguments and conclusions, as they relate to their respective theories and contentions (additionally typically a part of the introduction)
- Clear presentation of consumer’s place that’s truth and data-based
- Difficult/refutation of the opposing events’ questionable contentions, once more based mostly on details and knowledge
- If requested by counsel or a ruling by a choose, assemble theoretical projections, based mostly on details and knowledge as anticipated of 1 expert within the artwork
- Assertion as as to if arguments made are extra possible than not, citing arguments made and conclusions reached earlier within the report
- Provision of a closing opinion, entailing all elements of the case which are at problem
What makes an excellent skilled witness?
- A person who’s expert within the artwork that’s/are the areas of curiosity; skill, with the attorneys to current skilled’s competence throughout Daubert Challenges or Voir Dire
- Excessive verbal skill – written and spoken, because it pertains to the case subject material and basically; skill to be concise and humble whereas educating or explaining to a choose, jury, opposing counsel or one’s attorneys
- Tenacity – often probably the most essential high quality of each a scientist and skilled witness
- The flexibility to work diligently and punctiliously beneath time strain and the watchful eyes of the consumer and attorneys
- Comfortable expertise – persuasion, diplomacy, judgement (realizing what to say and to not say, and methods to say it), skill to navigate real-time battle and uncomfortable conditions arising from such occasions
- Understanding of the basics of the legislation, because it pertains to the matter (that is, with out exception, by the attorneys, however one should at all times learn between the strains and ask clarifying questions)
- Coachability and skill to be guided by means of the method by attorneys
- 360⁰ considering – all sides of a difficulty, together with anticipation of challenges from the opposing counsel and consumer, in order that each stipulations and challenges/refutations can be made as precisely/rationally and diplomatically as attainable
Stuart G. Levy, Ph.D., Principal
SGL Chemistry Consulting, LLC
92 Fairmont St. Arlington, MA 02474
Tel: (781)316-2594
E-mail: sglevy@sglchemistryconsulting.com
www.sglchemistryconsulting.com
Printed by: www.lawyer-monthly.com – June 4th, 2024