Small Molecule Drug Development and Manufacturing Expert

Expertise

Summary

• Drug development from proof-of-concept to commercialization in early to mid stage biotech and large pharmaceutical companies.
• Extensive background in biotechnology and small molecule development, manufacturing, quality, analytical, regulatory, outsourcing, project management and business development.

Services

• Marketed products: Biotech Products: Remicade (infliximab), Simponi (golimumab), Retavase (reteplase), Eprex (epoetin), ReoPro. Small Molecule: Patanol, Azopt and Volfenol%uFFFF.
• Development drugs: Large molecules: AntiIL5, AntiTNF, AntiIL12/23, DC-MAb (ADCC), DAB, Stem cell. Small molecules: Anticancer, Anti-infective, Anti-inflammatory, Antisense, AntiGlaucoma.
• 3rd party outsourcing: Lonza Biologics U.S./U.K., Kyowa Hakko Kirin, Baxter, Schering Plough, Ben Venue, Patheon, Hospira, Abbott, Cardinal Health, BioAnaLab, Millipore, BioReliance, AAI, and CRL.
• 2nd party outsourcing: Johnson & Johnson companies in U.S., Ireland, Switzerland, the Netherlands, Puerto Rico.
• Business development: Teva, Cephalon, Abbott, Pfizer U.S./U.K., Schering-Plough, ViroPharma, Kingston, BioVector.
• Project management: Project Leader, CMC Leader, Portfolio team. Steering committee. Long range planning.

Technical Skills

• Mammalian and microbial-derived protein drug substance process development.
• Biotech Drug Substance (DS) and Drug Product (DP) technology transfer, manufacturing, process validation, cleaning validation, testing, and comparability.
• Small molecule DP tech transfer, aseptic manufacturing, process validation, cleaning validation and testing.
• Sterile liquid and lyophilized drug product (proteins, peptides, small molecules) development.
• Biotechnology and small molecule analytical method development/validation, Quality Control (QC) and Quality Assurance (QA).
• Chemistry, Manufacturing and Controls (CMC) regulatory for proteins and small molecules.
• Regulatory agency interactions for BLA, MAA, NDA, PAS, Type I-II, CBE, PAI, IND, IMPD, CTA, meetings.
• Batch record investigations, release investigations, stability investigations, compliance investigations, OOS, NCRs, quality audits, and quality systems.
• Quality and contract services agreements.
• Contract Manufacturing Organization (CMO) selection and CMO contract negotiations. Vendor oversight
• Financial understanding of business. Business development and due-diligence for licensing.

Experience

Independent Consultant, Present

Undisclosed Company, Vice President, Biotechnology Operations, 2010 - Present

• Development of all biotechnology candidates in U.S. and Australia pipelines: Cinquil (Reslizumab, AntiIL-5 for IV/SC); Anti-IL12/23; AntiRANKL; DAb; Drug-Antibody Conjugate-ADCC/Anti-cancer. IgG1, IgG4, stem cell. Cell line: NS0, CHO
• Directed groups in U.S, and Australia, 4 to 6 FTEs (PhD, MS, BS), 3 consultants and managed budgets.
• Oversaw biotechnology drug substance (mammalian) and drug product process development, scale-up, tech transfer, manufacture, process validation, BLA studies and technical support from clinical to commercial.
• Primary point of contact with CMOs. Negotiated cost reduction with CMOs and achieved $5 million in savings.
• Designed strategies for tech transfers, analytical testing and GMP manufacturing campaign for DS and DP.
• DS upstream: Guided selection and activities for cell construct, cell culture and fermentation optimization, fed batch vs. perfusion, cell banking, manual vs. automatic cell counting, Chemically Defined Media (CDM), animal-component free media, air-lift vs. stirred tank, stainless steel vs. disposable (Wave) bioreactor, on-line monitoring.
• DP downstream: Evaluated new technologies for purification, bulk packaging, yield and process improvements.
• Technology transfer and manufacturing: Managed DS development, tech transfer and scale up and manufacture from 10L lab to 400L/500L pilot to 800L/1000L clinical scale (Wave, disposable, CHO process) for Anti-IL12/23 MAb, Anti-RANKL, DAb, DAC. CMOs: Lonza, Kyowa Hakko Kirin.
• Manufactured post-validation DS at 5000L intended commercial scale (stainless steel BRx, NS0 process) for late stage Phase III studies for reslizumab.
• Directed Process Limit Effect (PLE) studies using PE, DOE tools and BLA studies for reslizumab.
• DP: Executed site transfer, process validation for reslizumab DP. Developed strategy for pre-launch manufacture of reslizumab DP. Supported all clinical DP manufacturing.
• Executed reslizumab DP pre-filled syringe (PFS) development for subcutaneous administration.
• Comparability: Implemented product comparability studies for DS and DP significant manufacturing changes.
• Analytical: Supported methods validation, quality control testing, stability protocols, release and stability specs for DS/DP. Guided bioassay, residual Host Cell Protein (HCP), DS characterization, reference standard assays and extractable/leachable studies.
• Quality: Successfully resolved disputes with CMOs for batch release. Supported quality investigations, NCR, OOS, LIR, audits. Approved services and supply agreements. Reviewed quality agreements.
• Regulatory: Collaborated on IND, EOP2, pre-BLA, CTA, IMPD, PIP, SA, FDA meeting related CMC regulatory submissions. Designed studies and responses for CMC regulatory questions.
• Approved CMC submissions.
• Key contributor for CMC regulatory strategies for Phase I-III biotech candidates in development.
• Biotech Drug (BD): Reviewed business development opportunities for CMC assessment.
• Internal Partners: Project management, technical operations, supply chain, research, development, marketing, business development, legal, finance. External partners: alliance partners, regulators, CMOs, and suppliers.
• Project Management: CMC Leader, corporate, CMC, long range planning, regulatory, quality team and steering committee member. Provided leadership, updates. Offered support, resources, solutions to resolve team challenges.

Undisclosed Company, 2007 - 2010

• Serving positions as Vice President and Senior Director of Chemistry, manufacturing, controls and quality.
• Development of Cinquil (Reslizumab, Anti-IL5 humanized MAb) for IV and SC administration. Cell line: NS0.
• Directed a group of 5 FTEs (PhD, MS, BS, Admin. Assist) and 8 - 12 consultants and managed budget.
• Executed process development, tech transfer, manufacturing, validation, analytical, QC, QA for production of reslizumab DS and DP by CMOs. Negotiated manufacturing and quality agreements with CMOs.
• Implemented strategic decision-making and "do it right the first time" philosophy leading to $15 million in cost savings.
• Primary point of contact with CMOs. Selected DS and DP CMOs and executed activities for:
• DS: Reslizumab drug substance cell banking, cell culture and fermentation optimization, process development, manufacturing, process validation, cleaning validation, QC and characterization testing and Biologics License Application (BLA) studies (viral clearance, cell bank testing, cell line stability, resin and membrane reuse, resin/membrane cleaning, column cleaning, process intermediate stability, DNA and Genetic characterization, process limit effect/PLE, impurity clearance, reprocessing, filter validation, mixing, process characterization).
• Scale up and site transfer: Manufactured Reslizumab DS from 10L lab to 200L pilot to 2000L clinical scale at U.K. site to 5000L intended commercial scale at U.S. site (stainless steel BRx, air-lift, fed-batch, mammalian NS0 process).
• DP: Reslizumab drug product development, manufacturing, scale-up, technology transfer, process validation, cleaning validation, QC and in-process testing, BLA studies (formulation robustness, compatibility, mixing, CCOQ, F/T, filter validation, process characterization, reprocessing).
• Reslizumab subcutaneous DP development for pre-filled syringe (PFS).
• Product comparability studies for DS and DP significant manufacturing changes.
• Analytical method development, transfer, validation. DS/DP characterization. Bioassay, BIACore, ELISA.
• Forced degradation: DS/DP product and process impurity characterization, extractable/leachable studies.
• Quality control testing of DS and DP. Stability protocols. DS and DP release and stability specifications.
• Clinical supplies: Managed clinical supplies inventory and distribution for reslizumab DP.
• Quality: Created Quality Systems and SOPs for COAs, specs, deviations, change control, and clinical supplies. Performed quality audits of CMOs. Supported BR, OOS, NCR, LIR, manufacturing investigations, excursions.
• Regulatory: Designed CMC regulatory strategies in collaboration with company and CMO regulatory for filings.
• Prepared CMC sections in e-CTD for PreIND, IND, CTA, EOP2, BLA/MAA and regulatory responses.
• BD: Successfully created Chemistry, Manufacturing, Controls and Quality (CMCQ) functions and managed business due diligence for CMCQ from 15 Biotech and Pharma companies ultimately leading to company's acquisition.
• Resolved CMC regulatory and technical challenges for funding.

Centocor, Inc. , (Johnson & Johnson Company) Malvern, PA, 2003 - 2006

• As Principal Scientist of Process Sciences, Global Technical Services, executed technology transfer and manufacturing support for Remicade, ReoPro, Eprex, Retavase DS/DP at J&J sister-companies in U.S., the Netherlands, Puerto Rico, Ireland, Switzerland and CMOs in U.S. and Italy.
• Directed 4 to 6 (PhD, MS, BS) professionals.
• Received Innovation Award for Excellence in Lyophilization for Remicade.
• Commercial DS: Supported mammalian or microbial process related tech transfers and studies for viral inactivation step, raw material source, cell culture and purification changes for Remicade, Retavase, Eprex, ReoPro drug substance.
• Commercial DP: Managed tech and site transfers, process validation, cleaning validation and supplier and source changes for Remicade, Retavase, Eprex and ReoPro drug product manufacture. Supported BD Hypak Bulk to SCF PFS change.
• Performed process validation, filter validation, cleaning validation.
• Supported stopper, vial, raw material and supplier changes and manufacturing scale/site changes.
• Scaled up to 150L-600L. Resolved freeze-thaw, lyophilization, hold-time and shipping excursions. Implemented West RU stopper change. Managed Remicade life cycle management.
• Facility: Supported qualification of a new commercial manufacturing facility: building, utility, equipment (RFP, FAT, SAT, P&ID, tanks, mixers, isolators, filling lines, auto-loaders, commercial lyophilizers), machinability trials, IOQ.
• Process excellence: Implemented process improvement (40% cost reduction) by reducing lyophilization time at all Remicade commercial manufacturing sites.
• Identified primary package change, and new label claims for manufacturing yield improvement (60%).
• Executed capacity increase at CMO sites in Europe.
• Development: Contributed to new product development studies including for Stelara and Simponi.
• Regulatory: Successful PAS, CBE30, Canada, Type I, II CMC submissions in e-CTD.
• Quality: Supported PAI and GMP inspections, change controls and manufacturing deviations and investigations.
• Customers: Regulatory, Operation, Logistics, Marketing, Clinical, Finance, Development, QA, QC, CMOs.
• Project Management: Project Leader for two bulk and two fill-finish projects. Member of PAI, CMC, Corporate, Regulatory, Change Control, DS Tech Transfer, DP Tech Transfer, Business Planning and new facility teams.

AAI International/AAI Pharma, Wilmington, NC, 2001 - 2003

Associate Director of Formulations and Pharmaceutical Development

• Directed 15 to 25 professionals, 5 direct reports. Groups in Wilmington, NC and Charleston, SC. Recruited PhD, MS, BS scientists and managed budgets.
• Managed development, technology transfer, manufacturing and technical support for bulk protein drug substance, sterile liquid and lyophilized biopharmaceuticals and tablet and capsule pharmaceuticals.
• Development: Resolved bulk protein issues.
• Executed development of sterile liquid and lyophilized biotech and small molecule DP. Immediate and modified-release tablets (wet granulation, dry blending, coating) and capsules.
• Manufacture: Scaled up tablets to 10 to 100-300 Kg and capsules to 10-30 Kg for clinical manufacture.
• Supported batch record deviations and manufacturing failure investigations, and recommended CAPA.
• Set development and commercial stability protocols.
• Defined product in-process, stability and release specifications.
• BD: Provided technical representation on sales and marketing team for securing development projects from pharma and biotech companies. Secured $15 million projects from clients.

Battelle Pulmonary Therapeutics, Inc. , Columbus, OH, 2001

• As Director of Pharmaceutical Development, collaborated with management for electrohydynamic device-based aerosol drug development for oral inhalation.

Aronex Pharmaceuticals, Inc., The Woodlands, TX, 1996 - 2000

• Positions filled: Director of Development and Operations and Assistant Director/Manager, in Formulation Development and Pharmaceutics Departments.
• Development of Nyotran (nyostatin), Atragen (tretinoin), Annamycin, Aroplatin (platar) and Zintevir (an oligonucelotide).
• Guided 30 professionals. 6 direct reports. Hired PhD, MS, BS scientists. Managed $3.5 million budget.
• Oversaw preformulation, formulation, technology transfer, process validation, manufacturing, QC, stability, method development and validation for drug product and drug substance (API).
• DP development and manufacturing: Conducted formulation ruggedness, compatibility, E&L, freeze-thaw, shipping validation and ICH and photo stability studies. Scaled up lyophilization and liquid DP processes including solvent-based lyophilization for one DP.
• Supported DP tech transfers and analytical method transfers to CMOs. Executed Phase I-III sterile fill and lyophilized drug product manufacturing, process validation, registration batches at CMO.
• Process excellence: Redesigned packaging and developed new manufacturing process to increase DP yield.
• API manufacturing: Managed contractor in Asia for an anti-cancer API. Scaled up an API to 3 Kg in-house.
• Analytical: Assisted in method development, validation, stability, and quality control for DS and DP.
• Regulatory: Primary CMC technical contact with FDA.
• Made CMC presentations to FDA, and French Health Ministry during pre-NDA, and NDA meetings.
• Prepared and approved CMC sections for Nyotran NDA and MAA and Atragen NDA. Prepared CMC responses to FDA questions during NDA review.
• PAI: Main CMC technical person for successful PAIs of Nyotran and Atragen at contract sites and in-house.
• Customers in: Finance, business development, regulatory, operations, clinical, preclinical, QA, and QC.
• BD: Contributed to option agreement from Abbott, Chicago, IL for licensing of Nyotran NDA post-approval.

Alcon Laboratories, Inc., Fort Worth, TX, Senior Scientist II/I, 1992 - 1996

• For the Formulation and Drug Delivery Development Departments, developed of antiglaucoma, antiallergenic, antinflammatory and macular degeneration prevention drugs.
• Managed group of 3 direct-reports (1 Ph.D., 1 MS, 1 BS) and 6 temps.
• Executed formulation, scale-up and technology transfer and for sterile solutions, semi-solids, suspensions and drug delivery systems for ocular drugs and proteins.
• Development and Commercial products: Contributed to formulation and product development of Patanol (Olapatidine ophthalmic solution), Azopt (Brinzolamide ophthalmic suspension), Volfenol (Diclofenac ophthalmic solution) and Timolol gel solution.
• Manufacturing: Supported tech transfers. Scaled up solutions (1 to 100 to 500 Kg), suspensions (1 to 100 Kg), and delivery systems (from 1 to 100 Kg) for Phase II-III clinical and registration batch manufacture.
• Patents: Author on issued U.S. and European patents on ophthalmic drugs.
• Regulatory: Supported IND and NDA submissions.

Honors & Publications

Credentials

• Dissertation: Formulation of Controlled Release Ocular Delivery Systems of Pilocarpine.

Academic and Professional Affiliations

• American Association of Pharmaceutical Scientists. Rho Chi Honors Society. ASQ.

Publications and Patents

• Author of numerous publications, invited presentations and posters.
• Numerous patents filed, national and international.

Education

• Ph.D. Pharmaceutical Sciences, University of Arizona, Tucson, AZ
• M.S. Pharmacology/Natural Products, University of Bombay, Bombay, India
• B.S. Pharmacy, University of Bombay, Bombay, India