• Twenty-eight years of industrial experience in all aspects of chemical development
• Twenty-four years of experience in oversight of external vendors performing chemical development, custom starting material production and API manufacturing, preformulation, formulation development, drug product manufacturing, and all associated CMC activities
• Eighteen years of experience in devising and executing integrated CMC development programs
• Hands-on, results-oriented leadership of CMC development and multidisciplinary teams
• Innovation in the conception of practical synthetic routes to pharmaceuticals, development and implementation of chemical processes for the manufacture of APIs and chemical process troubleshooting.
• Expertise in technology transfer and oversight of chemistry from the research laboratory to kilo labs, pilot plants and multipurpose plants at contract development and manufacturing organizations
• Experience in the development and manufacture of solid, semi-solid (topical administration) and sterile dosage forms
• Significant accomplishments in many areas of organic synthesis and drug candidate development: small molecules, chelating agents, bioconjugate chemistry, nucleosides and nucleotides, amino acids and peptidomimetics, heterocycles, alkaloids, cannabinoids, dyes, asymmetric synthesis and catalysis, self-assembly mediated by nanoparticles, organophosphorus chemistry.

Education: 

• PhD, Chemistry, University of Illinois Chicago
• BS, Biochemistry, University of Illinois Chicago

Services Offered: 

• Expertise in Chemical 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

Additonal Information: 

Acting Head, CMC, Nimbus Therapeutics, January, 2019 – December, 2020

Led a virtual team of CMC experts in development of a candidate to treat inflammatory diseases, from vendor selection through filing of IND, and then facilitated the transition of both the API and DP manufacturing to Phase II clinical supply

• Extended implementation of the development strategy to support a Phase Ib clinical trial using a second, optimized clinical dosage form
• Led activities to supply CTM for pivotal Phase IIb clinical trials

Led a second team in the development of a practical API production route to a cancer drug

Expert Technical and Strategic Consulting Responsibilities for past clients include:

Acting Head, CMC, Nimbus Therapeutics,, Boston, MA, January, 2019 – December, 2020

Led a virtual team of CMC experts in development of a candidate to treat inflammatory diseases, from vendor selection through filing of IND, and then facilitated the transition of both the API and DP manufacturing to Phase II clinical supply.

• Extended implementation of the development strategy to support a Phase Ib clinical trial using a second, optimized clinical dosage form
• Led activities to supply CTM for pivotal Phase IIb clinical trials
• Leading route-scouting effort undertaken by two expert vendors to develop an alternate asymmetric synthesis of a very expensive, complex, low molecular weight chiral starting material in order to drastically reduce COGs
• Solution entailed use of a chemocatalyst to set two chiral centers with high enantio- and diastereoselectivity
• A much more efficient synthesis has been demonstrated at the lab and pilot scales Led a virtual CMC team for development of a second candidate at Nimbus, an oncology drug.
• Led and oversaw the med chem scaleup/early production effort, and transitioned this work to a CDMO for further process development and production, culminating in delivery of a tox batch that was a key funding milestone for Nimbus.
• Synthesis was developed into a process, with the initial requirement for large scale preparative chiral separation for a key intermediate Led multiple route scouting efforts to replace a cumbersome production process for a high value regulatory starting material
• Selected vendors for three approaches – chiral pool synthesis, flow and asymmetric hydrogenation
• Results for flow and asymmetric hydrogenation approaches indicated tractability for simplification of the existing process and reducing both COGs and cycle times.

Epizyme, Cambridge, MA

Performed vendor evaluation and selection for a second commercial API supplier for a client poised to submit an NDA for their lead drug

Wrote a comprehensive development history report, from patented medicinal chemistry synthesis to enabling synthesis to commercial process. This report was used as a guide for the client’s CMA regulatory submission for section 3.2.S.2.6, Manufacturing Process Development

Assistance with resources, strategy and implementation for improvement of a chemical process that had reached its practical limit of scalability

• Assisted client with selection of appropriate vendor to perform PR&D and process optimization
• Evaluated and identified alternate potential key steps in the process that could most strongly impact scalability

Assisted with sourcing of regulatory starting materials (non-GMP) for an API in a development program transitioning from Phase IIa to Phase III clinical trials

US World Meds, Louisville, KY

Led technology transfer and optimization of a manufacturing process for an API for a previously approved legacy drug in preparation for its re-introduction to the US market

Performed API manufacturing process gap analysis, evaluation and remediation for a legacy product that became a new chemical entity (NCE) drug in the US market, including selection of regulatory starting material (RSM), challenge of process parameters, performance of DoE, analytical method development and validation, control of PGIs and process validation at a third party API vendor

• Managed vendor for entire scope of revalidation of manufacturing process
• Key participant at mock-PAI at vendor
• Drafted relevant sections within Module 3 for NDA submission
• The drug, lofexidine, was approved by the FDA in 2017
• Was lead advising scientist on a root cause investigation for the presence of particulates in prefilled syringes for an injectable drug, Apomorphine
• Led technical oversight for technology transfer, R&D, analytical development, scale-up, and manufacturing for an asset in-licensed from Novartis, Tegaserod

ARIAD Pharmaceuticals, Cambridge, MA

Process evaluation, RFP preparation, vendor selection, engagement and management for an API manufacturing process in transition from Phase I to Phase II clinical development; In addition to management and leadership of the PRD and API manufacturing work, the following activities were undertaken:

• Overall technical and gap analysis and risk assessment for forward progress of API process optimization and manufacturing in the transition to mid and late-stage development
• Management of in-depth solid state characterization and polymorph screening, which led to improved isolation of API
• Vendor selection, engagement and management for all aspects of the GMP radiosynthesis of a 14 C-labeled API for human metabolism and distribution studies
• This is now an approved drug, brigatinib

Medivation (now part of Pfizer), San Francisco, CAEvaluated, selected, engaged and managed API vendors for chemical process development, production and manufacturing for early development of drug candidates

• Led and managed simultaneous chemical development of two competing preclinical candidate analogs; Oversaw production of GLP toxicology study supply and GMP manufacture of Phase I clinical API supply of the preclinical candidate selected for clinical development; Included multi-kg scale chiral preparative HPLC separation of intermediate API free bases
• Management of API salt screening, selection, physicochemical characterization and polymorph screening for clinical development candidates
• Led and and oversaw API prodrug design, synthesis and evaluation of stability and viability
• Oversaw asymmetric synthetic route scouting
• Participated in and managed the development of a novel synthesis of a single diastereomer of an API possessing two chiral centers, using both a classical resolution and an asymmetric transformation on multigram (~500g) scale
• Assisted with discovery scaffold design and synthesis, and synthesis of challenging analogs to fill SAR holes in structural series
• Authored and reviewed of relevant IND CMC sections

Performed due diligence evaluation of CMC technical packages for assets under consideration for partnering and in-licensing

Takeda Pharmaceuticals, Yokohama, Japan

Engaged and led a team of subject matter expert consultants (formulation, toxicology, pharmacology) to provide expertise on development of small molecules for topical dermatological therapy to a big pharma company

Private Pharmaceutical Company

Performed gap analysis, preparation and execution of a plan to prepare for an FDA End of Phase 2 (EOP2) meeting for a client including development and definition of a viable drug product manufacturing process at the client’s internal facility, and a plan for transition to pilot, registration, PPQ, and commercial manufacturing of the product

Expert Witness in Hatch-Waxman drug litigation cases include

PPD v. TVM Lifesciences, et al, December 16, 2011, Full transcript of my deposition available – deposed by three attorneys for 6.5 hours, recorded by videotape

The current owner of the last company I worked at, PPD Dermatology, sued my former employers, including all company officers and the Scientific and Corporate Advisory Boards, accusing the original company of misrepresentation of the product that was Magen’s main asset during the entire time of my employment. The case was settled.

December 27, 2015 – March 1 2016 – employed by the Toronto law firm Goodmans LLP, in a matter that cannot be disclosed due to my report, which as a draft, settled the damages phase of a Hatch-Waxman case, and there is therefore no official report in the public domain. I will provide the name and contact information for the attorneys I worked with at Goodmans, LLP, on request.

April 18, 2016 – November 8, 2016 – Hatch-Waxman Expert for the drug roflumilast (I forget who the opposed parties were). I did 7 months of case preparation and background work on behalf of the client.

March 13, 2017 – January 11, 2019 – Hatch Waxman expert research and opinions provided to attorneys at Schiff Hardin over this time period, regarding infringement, etc for Bendamustine, to help define the most tractable aspects among the points of contention presented by both plaintiff and defendant

Report preparation and testimony before judge and eight jurors, wrongful death of a chemical expert. Testimony occurred on full, consecutive days, May 22 and 23, 2019. Despite the judge’s disqualification of 2/3 of my report, I was still able to testify effectively, and plaintiff (chemist’s widow) was able to win damages against Allstate Insurance

Hatch-Waxman Expert in a matter between Eisai and Sun Pharma, with Carlson Caspers representing Sun Pharma, 4/18/16 – 11/8/16. Engagement ended because parties that employed me tried to get me to stand behind an opinion that could not be supported.

Arent Fox Schiff, September, 2023 – very short engagement