Expert Details

Expert in Chemistry R&D and cGMP Manufacturing, Pharmaceutical Development

Expert ID: 728603 Massachusetts, USA

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Expert has worked on research, development and manufacturing problems involving stereochemistry throughout his academic training and industrial career. Relevant examples include: development of scalable chiral and asymmetric syntheses; improvement of reaction stereoselectivity; tracking of chiral integrity in chemical processes; chiral analysis of starting materials, intermediates and product APIs; sourcing of optically active raw materials; understanding and exploitation of epimerization and racemization; resolution using chiral chromatography and fractional crystallization of diastereomeric salts.

Although Expert's industrial career has been concerned mostly with chemical and pharmaceutical development, he has also made significant contributions to discovery efforts at a number of organizations at which he was employed. Based on his postdoctoral studies, Expert has maintained an active interest in the area of prodrugs. One product that Expert worked on in his career that has been approved by the FDA is Fospropofol, a phosphate prodrug of the sedative propofol. He has also been an active participant on discovery projects while at Elixir Pharmaceuticals, assisting in the management of the outsourced work on the synthesis of compounds for testing and development of SAR, and as the leader of the new target sourcing effort while at PPD Dermatology. Expert has demonstrated the ability to identify new therapeutic targets in a given area, and to assess the chemical tractability of a given target. He was involved in a business development capacity while at PPD Dermatology, to identify and contact organizations and institutions deemed to be doing early discovery work in areas that were relevant to the establishment of a drug pipeline. Expert also had responsibility for the performance of due diligence on chemical matter and evaluation of the viability and merit of in-licensing, investment and partnering opportunities while employed at Elixir Pharmaceuticals, and Magen Biosciences/PPD Dermatology over the past five years.

During the last thirteen years, Expert's responsibilities have expanded to include all aspects of CMC development, including analytical method development and pharmaceutical development. He is proficient in leading efforts in preformulation, including salt screening and selection, polymorph screening, development of stability-indicating methods, forced degradation studies and physicochemical characterization of lead drug compounds. Expert's experience has extended to formulation development, including excipient compatibility studies, prototype generation and evaluation, and scale up to production scale. He has overseen the production of GLP suitable tox lots and GMP manufacture of Phase I supply for two NCEs, and has been involved in Phase III and registration lot manufacture for the commercialization of a type II diabetes drug that is already on the commercial market in Japan. This work involved significant strategic planning and management of a partnering relationship with the business and CMC functions of a major Japanese pharmaceutical company. It included auditing of API manufacturing facilities in Japan and preparation for a pre-approval inspection (PAI) by the FDA. Evaluation and interpretation of drug product stability data was also integral to this project. He has also worked on the development of a fixed dose combination for a tablet. Expert has direct experience in leading development efforts for drug products administered orally (tablets and capsules) and topically (creams and ointments). The above work resulted in the filing of two INDs, which were accepted by the FDA with no CMC questions. Expert was a key author on the CMC sections of both submissions. He was also a key author on the pre-NDA briefing book for the commercialization effort described. The FDA had no questions on the CMC section of this submission, even though it was a legacy product.

Expert has also worked on solid oral dosage formulation development efforts for drugs that are poorly water soluble.

Expert had responsibility for the evaluation, selection and management of drug product vendors for the projects summarized above.

Expert's industrial career has been extensively involved in the solution of challenging problems in the area of chemical process development. He has worked in the laboratory on multistep syntheses of multiple classes of chemical compounds, including amino acids, carbohydrates, nucleosides and nucleotides, polyazamacrocycle chelating agents for MRI, peptidomimetics, heterocycles, alkaloids, ionophores, dyes, cannabinoids, organophosphorus compounds. His accomplishments have included development of novel practical synthetic routes to target compounds, development of scalable, robust processes for production and manufacture, process optimization, improvement of yield, stereochemical purity, API quality and operational simplicity and transfer of technology from R&D into kilo labs and then into pilot and multipurpose manufacturing plants. Expert has participated in and led multidisciplinary scientists charged with solving complex chemistry problems and delivering scientifically sound results in a timely and efficient manner.

In the course of his academic training and industrial career, Expert has enhanced and deepened his capabilities in his core technical area of synthetic organic chemistry. His primary expertise is in the area of chemical route selection for the multistep organic synthesis of small molecule drug candidates. He draws from his knowledge of synthesis and reaction mechanism to troubleshoot and solve problems in the synthesis of discovery scaffolds, development of chemical processes, introduction of stable and radioisotopes into molecules for bioanalytical applications. Expert is currently a regular reviewer for the ACS journal Organic Process Research and Development.

For 19 of his 23 years in industry, Expert has worked at organizations for which chemical process R+D, production and manufacturing were at least partly, if not completely, virtual. As a consequence, he has acquired expertise in the selection, engagement and management of contract organizations devoted to custom synthesis, production and manufacturing of API for preclinical and clinical bulk drug supply. Expert has experience leading and managing work at every phase from late discovery through Phase III registration and validation lots. His hands-on experience in the laboratory at biotech pharmaceutical companies and as an employee at API vendors (Ricerca and SERES Laboratories) informs his ability to have the full perspective from both sides of the fence, and has made him an extremely effective leader and manager of outsourced chemistry efforts. Expert performed numerous manufacturing runs under cGMP at SERES laboratories, and was a project leader for the process development and manufacture of the initial clinical supply of a drug that is now FDA-approved while at Ricerca. He has a thorough understanding of the practical application of GMP to the manufacture of APIs and drug product. Expert is also an expert in the preparation and assembly of technology transfer packages for outsourced work, and has demonstrated repeated success in the timely and efficient implementation and execution of chemical technology transferred to API manufacturing vendors.

During the last 5-6 years, Expert has worked on a number of late-stage manufacturing processes. He took a legacy process and oversaw and led the update of the R&D and manufacturing to meet current regulatory agency expectations. This work included the development of state of the art analytical methods, screening experiments to determine ranges investigated in DoE/PAR studies for all process operations, identification and the development of limit tests for all process intermediates and impurities that were designated potential genotoxic impurities, sourcing of key raw and regulatory starting materials, and re-validation of the manufacturing process. Expert also wrote all of the S sections of the New Drug Application (NDA) for this drug. Due to Expert's efforts, the manufacturer passed the FDA's pre-approval inspection (PAI), and the drug was approved.

Another project Expert was involved in was to write a development history report for a drug as part of its conditional marketing authorization (CMA) in the EU. This report covered all chemistry R&D and manufacturing, from the synthesis patented by the client through the registration manufacturing campaign batches, and formed the basis for CMA section 3.2.S.2.6, Manufacturing Process Development of the regulatory submission.

Devised and executed CMC strategy for the development of a drug candidate for topical treatment of inflammatory skin disease, including: API scale up, production and GMP mfr, topical formulation development, ointment drug product production for GLP tox studies and GMP ointment drug product for Phase I clinical trials, synthesis of 14C-radiolabeled API for in vivo PK/ADME studies, development of analytical methods for drug substance and drug product, and drafting, editing and finalization of relevant sections of the CMC section of the IND for this candidate. IND was accepted by FDA with no CMC questions.Functional project leader for an in-licensed small molecule candidate for the treatment of metabolic disease. Created and refined a detailed plan for the development of this candidate. Staffed and led a virtual development team composed of experts in areas other than API - formulation, toxicology, PK/ADME, quality, regulatory, analytical. Had responsibility for coordination and execution of all preclinical development activities, including direct responsibility for all CMC activities. Led production of >10kg API suitable for GLP tox studies, manufacture of 800g GMP API and 10,000 Expert-filled capsules for Phase I clinical supply. Wrote API process CMC section of IND and made significant contributions to drug product, analytical and characterization sections of IND. IND was accepted by FDA with no CMC questions. Led CMC activities related to an effort to commercialize an in-licensed type II diabetes drug that was approved for use in Japan. Key author and reviewer of pre-NDA briefing book CMC section. Key author of successful request for biowaiver based on SUPAC guidance for in vitro dissolution testing. Led and managed the manufacture of Phase III clinical supply, registration lots and analytical method validation. Established and strengthened the relationship between CMC functions at the client company and the Japanese licensor. Led and managed the development of a fixed dosage combination tablet for this drug with another well known type II diabetes drug.Led and managed the CMC development effort for a discovery candidate for the treatment of metabolic disease. Provided scientific direction, leadership and management to the synthesis and scale up of the API, resulting in the production of >1kg of API suitable for GLP studies within < 5 months of candidate nomination. Managed and led two salt screening studies to give a water soluble API. Identified issues relevant to the formulation development of this candidate, including physicochemical properties and stability.Leader, new target sourcing team. Established a process for researching and evaluating new approaches to topical small molecule therapies for dermatologic diseases in order to build a dermatology pipeline. Identified biological mechanisms of action relevant to dermatologic diseases and determined tractability based on natural product and medicinal chemistry hits in the literature. Sought scientific collaborators and partners in industry and at academic and research institutions. Expert witness assignment - prepared a draft expert report for the damages phase of a Hatch-Waxman case that was instrumental in settling the case for the client. The subject matter of the case and the drug cannot be disclosed, since the report was never filed with the court and is thus not part of the public record. The drug in question was a "blockbuster" drug, and the stakes were very high.Transitioned an API manufacturing process from Phase I to pivotal Phase II, including process evaluation and gap analysis, vendor selection, engagement and management, in-depth solid state chemistry evaluation that resulted in an improved isolation of the final API, design and oversight of the development and implementation of a radiosynthesis for human AME studies, and transition of project away from previous vendor. Drug was approved 18 months ago.Oversaw the re-validation of a legacy process within 15 months. Activities included R&D screening experiments to better understand the process, DoE studies on each operation of process, update of analytical methods to meet current technical and regulatory expectations, registration manufacturing campaign, process validation campaign, writing of NDA S sections.Led investigation of viability of alternate chemistry for a manufacturing process that had reached its limit of scalability. Worked closely with specialized vendor to study and improve process steps to increase process yields and efficiency. Conducted sourcing of key starting materials and regulatory starting materials that needed to be custom-produced.Performed vendor selection for a second commercial manufacturer for a new drug headed toward NDA submissionLed and oversaw R&D and production during preclinical development of numerous small molecules, and transitioned the programs into early clinical development from the point of view of CMC development and API manufacturing

Expert may consult nationally and internationally, and is also local to the following cities: Boston, Massachusetts - Worcester, Massachusetts - Springfield, Massachusetts - Lowell, Massachusetts - Cambridge, Massachusetts - Brockton, Massachusetts - New Bedford, Massachusetts - Hartford, Connecticut - Manchester, New Hampshire - Providence, Rhode Island

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Education

Year Degree Subject Institution
Year: 1992 Degree: PhD Subject: Chemistry Institution: University of Illinois, Chicago
Year: 1987 Degree: BS Subject: Biochemistry Institution: University of Illinois, Chicago

Work History

Years Employer Title Department Responsibilities
Years: 2008 to 2010 Employer: (Undisclosed) Title: Director, Chemistry Department: (Undisclosed) Responsibilities: He was responsible for all aspects of chemistry in this organization, including R&D, CMC, management of outsourcing, support of biological research, new target sourcing and evaluation. Supervised two experienced PhD organic chemists.
Years: 2005 to 2008 Employer: (Undisclosed) Title: Director, Pharmaceutics and Manufacturing Department: (Undisclosed) Responsibilities: He was responsible for all CMC work (done virtually, using outsourcing) for internal discovery and in-licensed and partnered development projects. Included API, formulation development (oral), analytical method development and validation.
Years: 2001 to 2005 Employer: (Undisclosed) Title: Senior Staff Scientist, Chemical R&D Department: (Undisclosed) Responsibilities: He was the senior bench chemist in the process chemistry group. Performed discovery and process research. Managed all technology transfer and outsourcing activities for chemical process R+D and GMP manufacturing. Led a development team in process R+D for APIs.
Years: 2000 to 2001 Employer: (Undisclosed) Title: Senior Research Chemist / Project Leader Department: (Undisclosed) Responsibilities: Project leader and lead bench chemist for a development effort to develop a process for a discovery compound, product a GLP tox lot and multi-kg manufacture of Phase I supply for parenteral administration. Transferred process to pilot plant for 20kg scale mfg run. Led R&D to devise commercial route to this API.
Years: 1998 to 2000 Employer: (Undisclosed) Title: Process Chemist Department: (Undisclosed) Responsibilities: He set up the first chemical process development laboratory at SUGEN. Responsible for the management of multiple outsourced manufacturing projects. Performed process R&D to optimize later-stage (Phase II and III) development candidates.
Years: 1995 to 1998 Employer: (Undisclosed) Title: Scientist Department: (Undisclosed) Responsibilities: Conception and development of new chemical processes for drug candidates, from mg to kg scale. Custom synthesis of discovery compounds. cGMP manufacture of APIs up to multi-kg scale. Writing of proposals based on client inquiries. Management of client relationships.
Years: 1992 to 1995 Employer: (Undisclosed) Title: Postdoctoral Fellow, Medicinal Chemistry Department: (Undisclosed) Responsibilities: Synthesis of prodrugs of cytotoxic nucleotides. Synthesis of an isopolar, isosteric analog of 2-chlorodeoxyadenosine monophosphate to bypass the requirement for kinase activation of the nucleoside. Synthesis of a series of ionizable cannabinoid analogs for localization of their activity to peripheral tissues as antiinflammatory agents.
Years: 2010 to 2018 Employer: (Undisclosed) Title: Principal Consultant Department: (Undisclosed) Responsibilities: Presently self employed in a sole proprietor chemistry practice. Provides expertise in chemical synthesis, chemical development, salt selection and solid state characterization, CMC development strategy, API manufacturing, preformulation and formulation development to start up and biotech pharmaceutical companies.

International Experience

Years Country / Region Summary
Years: 1999 to 1999 Country / Region: Dresden, Germany Summary: Was sent to an API vendor in Germany while employed at SUGEN to conduct process R&D to optimize the process for a Phase III registration manufacturing campaign. He found a means of isolating a late intermediate in the process in very pure form, resulting in API product with improved quality. The results obtained in the laboratory by Expert were converted to operating instructions, and the technology developed was transferred into the multipurpose manufacturing plant to manufacture feasibility and then registration lots of this API.
Years: 2005 to 2008 Country / Region: Nagoya, Fukui, Tokyo, Nagano, Japan Summary: While employed at Elixir Pharmaceuticals, Expert traveled three times to Japan, to establish a working relationship with the CMC group at Kissei Pharmaceuticals, from whom Elixir had in-licensed a type II diabetes drug approved in Japan for commercialization in the US and the EU. Work included obtaining essential technical information pertaining to drug development, performing due diligence quality audits of contract API mfg organizations and providing progress reports on development of a dosage form of the drug suitable for Western hemisphere patient populations. Negotiation of supply schedules and agreements for the API with Kissei was also performed.
Years: 2007 to 2007 Country / Region: Chiplun, India Summary: Expert traveled to India to perform a quality audit of a generic manufacturing plant run by USV that produced a generic active ingredient that was intended to be used in a fixed dosage combination tablet that Elixir was developing with the Kissei drug. The objective was to qualify USV as a reliable, low cost supplier of this generic API for development and commercialization of this combination drug.
Years: 2005 to 2007 Country / Region: Hyderabad, India Summary: Visits to chemistry vendors to manage work
Years: 2007 to 2007 Country / Region: India Summary: Visited chemistry vendors, participated in a quality audit of a generic API manufacturer
Years: 2013 to 2013 Country / Region: Netherlands Summary: Visited solid state vendor that had done work for my client to discuss next owrk to be done
Years: 2014 to 2014 Country / Region: Yokohama, Japan Summary: Visited a big pharma to provide a training course in the development of molecules for the treatment of inflammatory dermatological disease
Years: 2014 to 2014 Country / Region: Brussels, Belgium Summary: Visited sterile product manufacturer to perform quality audit and to discuss issue of particulates in dosage form manufactured for my client
Years: 2014 to 2014 Country / Region: Biasca, Switzerland Summary: Visited API manufacturer to discuss process validation work on behalf of my client
Years: 2015 to 2015 Country / Region: Clonmel, Ireland Summary: Participated in quality audit of solid dosage drug product manufacturer for my client
Years: 2015 to 2015 Country / Region: Biasca,. Switzerland Summary: Visited API vendor for technical discussions and quality audit of facility
Years: 2015 to 2015 Country / Region: Madrid, Spain Summary: Technical visit to evaluate sterile dosage form manufacturer for client
Years: 2016 to 2017 Country / Region: Basel, Switzerland Summary: Oversight of a technology transfer and adaptation of a legacy API manufacturing process to prepare for process validation as part of the re-introduction of the drug to the US market

Career Accomplishments

Associations / Societies
American Chemical Society, Organic Division;
Northeast Section of the ACS;
Publications and Patents Summary
Expert has seven publications and two patents in synthetic organic chemistry.

Additional Experience

Expert Witness Experience
Successfully completed first expert assignment in March, 2016. Wrote draft report that was used to successfully negotiate a settlement that was favorable to the client. Case cannot be disclosed because the report was not finalized and I did not testify, so I am still confidentially retained, and my work is not a matter of public record.
Vendor Selection
Expert in the identification, evaluation, selection, engagement and management of vendors for organic synthesis, API process development and manufacture, radiosynthesis, analytical development, formulation development and manufacture, solid-state chemistry, quality assurance, regulatory.
Other Relevant Experience
Chemical and Pharmaceutical development professional with unique understanding of how technical and logistical functions work together in drug discovery and development. Efffective liaison within CMC subdisciplines and between CMC and adjacent functions, e.g., discovery, PK/ADME, toxicology, clinical, finance. Add value beyond significant contributions in core area of expertise due to strong relationships with representatives of all other disciplines. Very effective at moving entire project forward, due to hands on experience and understanding of how all CMC functions are integrated in a successful drug development effort.

Language Skills

Language Proficiency
Spanish Expert is proficient in conversational Spanish. He pursued a double major in Spanish literature and biochemistry while an undergraduate at the University of Illinois, Chicago. He did not complete the degree in Spanish literature, but he did complete coursework at an advanced level that required the reading of works of literature in Spanish, the writing of multiple term papers, exams and final exams in Spanish, and classroom participation that was completely in Spanish. Expert has also translated patents and manufacturing batch records from Spanish to English.

Fields of Expertise

stereoselective reaction, stereochemistry, asymmetric synthesis, asymmetric induction, chiral synthesis, enantioselective catalysis, epimerization, molecular chirality, racemic mixture resolution, racemization, prodrug, chemotherapeutic drug, drug therapy, asymmetric induction, chiral synthesis, enantioselective catalysis, epimerization, molecular chirality, racemic mixture resolution, racemization, drug degradation, drug dosage form development, drug formulation, pharmaceutical analysis, pharmaceutical design, drug identification, drug development, drug screening, drug processing, pharmaceutical research and development, pharmaceutical manufacturing, pharmaceutical product shelf life testing, preclinical research, chemical process troubleshooting, new chemical process research and development, chemical process development, new chemical process development, organic compound process development, chemical processing, chemical synthesis, heterocyclic compound synthesis, organic chemical purification, organic chemical separation, organic synthesis, synthetic organic chemistry, organic reaction, process chemistry, addition reaction, chemical intermediate, chemical reaction, chemical transformation, preclinical research, process optimization, active pharmaceutical ingredient, bulk pharmaceutical chemical manufacturing, Chemistry, Manufacturing and Controls, chemical process control, Current Good Manufacturing Practice, multi-step organic compound manufacturing, chemical production quality management, Good Manufacturing Practice, organic compound manufacturing troubleshooting, investigational drug, process validation, manufacturing process optimization, organic chemical purification, organic chemical separation, organic synthesis, synthetic organic chemistry, organic reaction, process chemistry, addition reaction, chemical intermediate, chemical reaction, chemical transformation, pharmaceutical scale-up, drug targeting, investigational drug procedures, drug discovery, deprotection, pharmaceutical technology, bulk drug, contract manufacturing, product traceability, pharmaceutical manufacturer, crystallinity, yield enhancement, derivatization, organic compound manufacturing, industrial research, racemic mixture, pharmaceutical intermediate, new chemical process, diastereoisomer, stereoisomer, chirality, enantiomer, pharmaceutical research, chemical research and development, drug stability, pharmaceutical industry, drug analysis, chemical production, heterocyclic chemistry, production process, isomerism, epimer, new drug, organic functional group, chemical reaction mechanism, pharmaceutical drug, chemical process, organic reaction mechanism, chemical compound, organic compound, pharmaceutical reactor, pharmaceutical chemistry, organic chemistry, organic chemical structure, dosage form, chemotherapeutic agent, chemistry, applied organic chemistry

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