Industry Consultant (Former FDA)

Professional Experience

Assisting clients in introducing new medical products both in the U.S. and EU.  Providing regulatory, quality, and market analysis for devices, drugs, drug/device combinations and IVDs for clients world-wide.  Accomplishments include:

• Development of theranostics for candidate screening and selection in clinical trials

• Architect for discussions resolving a 6-year feud between the FDA and industry partner

• Formulation of regulatory & quality framework for commercializing lab-developed PCR diagnostics

• Developed agency-accepted documentation for moderate & major LOC software containing devices

• Designed a QA and regulatory framework for a distributed software system including security

• Developed a PMA pathway for a commercialized device sold under enforcement discretion

• Addressing regulatory concerns in the context of recalls and consent decrees

• Inspection, Pre-inspection and 3^rd party audits of device, drug, and sterilization facilities globally

• Implementation of ISO 13485, CFR §211 & CFR §820 compliant quality systems worldwide

• Regulatory oversight and management of NMEs for use in new combination products

• Oversight and interpretation of global trial data from diverse sites including Thailand, Brazil, and South Africa

Directed regulatory efforts for market entry of a first-in-kind electromechanical imaging and treatment device in oncology.  Focused regulatory and clinical efforts to expedite approval.  Developed design strategies to minimize regulatory overhead and engineering costs.  Accomplishments include:

• Developed the regulatory, testing and quality framework for software in a Class III device

• Drove implementation of a comprehensive 21 CFR §820 and ISO 13485 compliant quality system

• Oversaw the company’s first full CE-mark  – successful

• Regulatory and quality audits for Due Diligence of potential acquisitions and mergers

• Implemented company’s first suite of supplier audits and incoming inspections

• Initiated strategies for addressing post-market surveillance and CAPA

• Simplified clinical trial designs to expedite enrollment and approval

• Consolidated product versions to minimize regulatory and engineering overhead

Development of regulatory strategies for high risk, combination medical devices: drug/device and tissue/device.  Development of regulatory strategies for introducing innovative Class III medical technologies.  Oversight of preparations for submissions world-wide.  Accomplishments include:

• Added 20M to corporate profits by formulating  quality and regulatory strategy for parametric release – a company first

• Pre-emptive strategy for addressing post-market regulatory inquiries and CAPA

• Consolidation of quality system implementation across manufacturing sites worldwide

• Drove submissions and strategy for an in-trial DES

• Regulatory strategy, pre-IDE’s, and filings for U.S. & Canadian clinical trials involving stem cells

• Doubled revenue for a pre-amendment product by expanding indication – accomplished with legacy data

• Formulation of worldwide regulatory strategy for venous stenting,  a new corporate focus 

• Oversight and submission of product portfolios -  PMA, 510k, EU design dossiers, device licenses

Analysis and approval of high-risk (PMA) medical devices.  Review of regulatory strategies for introducing innovative medical technologies.  Working within OIVD, development of clinical and regulatory standards.  Exploiting opportunities at both the NIH and FDA to develop new contrast agents for cardiovascular imaging. Accomplishments include:

• Premarket approval (PMA) of high risk medical devices including presentations to panel 

• Pre-approval inspections for high risk devices and drugs

• Oversaw 1 of only 3 directed, international inspections for that year.  From the FDA perspective, one of the most productive company audits in CDRH history

• Risk and fault analysis for devices containing software

• Briefing outside agents on avenues to market for innovative technologies

• Initiated a collaborative partnership to develop x-ray and MRI contrast agents for atherosclerosis

• Development of software for quality control of clinical laboratory data

• Review and clearance of abbreviated, special, traditional 510k  and CLIA applications from industry 

A joint position with the Food & Drug Administration, Stanford, and the Medtronic Foundation.  Worked with the FDA to approve and streamline the approval of medical devices and combination medical products.  Focus on IVDs with emphasis on microarrays. Accomplishments include:

• Developed of new quality paradigm for reviewing software-containing devices 

• Premarket approval (PMA) of high risk medical devices and combination medical devices

• Review and clearance of abbreviated, special, traditional 510k and CLIA applications from industry 

• Pre-IDE planning with FDA and corporate partners

Exploited small angle x-ray scattering to study protein folding, changes in protein conformations, ligand docking, and RNA folding.  Accomplishments include:

• Increased collaborative and research work by 100%, growth involving collaborations with 10 teams of researchers on 3 continents and 5 countries

• Reduced turnaround time for results by more than 1000%, achieved by developing a new software system to eliminate bottlenecks in data interpretation

• Initiated new research projects in protein folding, RNA folding, and protein chaperones

• Drove new funding initiatives

• Trained new graduate and post-doctoral students in small angle x-ray scattering and biochemistry

Developed new experimental techniques for analyzing and constraining complex dynamical systems.   Accomplishments include:

• Discovered new chemical phenomena in the Briggs-Rauscher reaction  

• Developed kinetic and computational models to analyze this behavior  

• Trained a post-doctoral fellow in applying these techniques

Developed new testing methodologies, focusing on challenges in cross-product integration and inter-departmental coordination.  Note: this position was concurrent with my Ph.D. work.   Accomplishments include:

• Identified structural impediments limiting cross-product coordination and hampering productivity

• Devised and promoted new practices to increase cooperation between departments

• Initiated the analysis and selection of software to facilitate coordination

• Determined the vendor and product best able to meet MDL’s organizational requirements

Design and testing of real-time decision systems including an object-oriented rule engine. Note: this position was concurrent with my Ph.D. work.  Accomplishments include:

• Improved quality by initiating the first automated testing system in the company  

• Increased product quality, implementing a 300% increase in code coverage in 5 programs on 4 platforms

• Reduced lag time by implementing an overnight testing regime

• Development of rule-based engine for real-time data processing

Developed and tested chemical drawing and database systems.  Design of user interface.  Creation of large chemical databases.   Accomplishments include:

• Oversaw releases of company’s first Windows software

• Designed and created the first databases for the flagship product –still packaged with the system

• Employee of the Month, July 1991 

• Sought and controlled a 200% budget increase

• Reorganized a 14-person group to improve effectiveness  

• Improved quality by instituting an automated testing system

Presentations and Invited Lectures

“Value Based Laboratory Tests — What Went Wrong on the Way to the Fair?”

February, 2010 

Molecular Methods Tri-Conference, San Francisco

“Translational Bioengineering: Overcoming the Ultimate Barrier to Entry: Commercialization, Regulation, and the FDA” October, 2009

BMES 2009 Annual Fall Scientific Meeting

“Mapping Out Preclinical and Human Studies to Support Safety: Getting to First-in-Man Clinical Trials” March, 2008

 RAPS Horizons, San Francisco

“Barriers to Entry: Regulatory Implications for Vaccines and Biologics” October, 2006

National Institute of Allergy and Infectious Diseases

“Elucidations of Protein Folding by Small Angle X-ray Scattering” October, 2005

Dept. of Laboratory Medicine, NIH

“The Security Implications of Education, Innovation and Globalization” April, 2004

Homeland Security Institute, ANSER

Awards and Honors

Adjunct Professor, Dept. of Chemistry, Ivy Tech Community College - 2010

CLSI Standards Committee: User Verification of Performance for Precision and Trueness (EP-15) - 2009

Regulatory Affairs Professionals Certification, United States - 2007

Regulatory Affairs Professionals Certification, European Union - 2007

Center for Device and Radiological Health Medical Device Fellow - 2006 

Medtronic Medical Device Fellow – 2005

Professional Organizations

American Association for the Advancement of Science

American Association for Clinical Chemistry

American Chemical Society

Regulatory Affairs Professionals Society

Education

Publication List

1. Jan Lipfert, Ian S. Millett, Soenke Seifert, Sebastian Doniach (2006) “A Sample Holder for Small-Angle X-ray Scattering Static and Flow Cell Measurements” Rev. Sci. Inst., 77(4): 6108-6111 

1. Linda Columbus, Jan Lipfert, Heath Klock, Ian Millett, Sebastian Doniach, Scott A. Lesley (2006), “Expression, purification, and characterization of Thermotoga maritima membrane proteins for structure determination” Prot. Sci., 15: 961-975

1. Bojan Zagrovic, Jan Lipfert, Eric J. Sorin, Ian S. Millett, Wilfred F. van Gunsteren, Sebastian Doniach, Vijay S. Pande (2005),“Unusual compactness of a polyproline type II structure” Proc. Nat. Acad. Sci., 102: 11698-11703

1. Bojan Zagrovic, Guha Jayachandran, Ian S. Millett, Sebastian Doniach, Vijay S. Pande (2005), “How large is an α-helix?  Studies of the radii of gyration of helical peptides by SAXS and MD” J. Mol. Bio., 353: 232–241

• Vladimir N. Uversky, Ghiam Yamina, Larissa A. Munishkina, Mikhail A. Karymov, Ian S. Millett, Sebastian Doniach, Yuri L. Lyubchenko, Anthony L. Fink (2005), “Effects of nitration on the structure and aggregation of  α-synuclein” Mol. Brain Res., 134: 84-102

1. Yu Bai, Rhiju Das, Ian S. Millett, Daniel Herschlag, Sebastian Doniach (2004), “Probing Counterion Modulated Repulsion and Attraction Between Nucleic Acid Duplexes in Solution” Proc. Nat. Acad. Sci., 102(4): 1035 - 1040

1. Jonathan E. Kohn, Ian S. Millett, Jaby Jacob, Thomas M. Dillon, Nikolina Cingel,Soenke Seifert,P. Thiyagarajan,Tobin R. Sosnick, M. Zahid Hasan, Ingo Ruczinski, Sebastian Doniach, Kevin W. Plaxco (2004), “The dimensional scaling of the large majority of chemically unfolded proteins is indistinguishable from random coil behavior” Proc. Nat. Acad. Sci., 101( 34): 12491-12496

1. Ahmad, A., Millett, I.S., Doniach, S., Uversky, V, .N., Fink, A. L. (2004), “Stimulation of insulin fibrillation by urea-induced intermediates” J. Biol. Chem. 279(15): 14999-5013

1. Ahmad, A., Millett, I.S., Doniach, S., Uversky, V, .N., Fink, A. L. (2003), “Partially folded intermediates in insulin fibrillation” Biochem.,  42(39): 11404-11416.  

1. R. Das, L.W. Kwok, I.S. Millett, Y. Bai, T. T. Mills, J. Jacob, G.S. Maskel, S. Seifert, S.G. Mochrie, P. Thiyagarajan, S. Doniach, L. Pollack, D. Herschlag (2003) “The fastest global events in RNA folding: electrostatic relaxation and tertiary collapse of the Tetrahymena ribozyme” J. Mol. Bio., 332(2): 311-319

1. Permyakov S.E., Millett I.S., Doniach S., Permyakov E.A., Uversky V.N. (2003) “Natively unfolded C-terminal domain of caldesmon remains substantially unstructured after the effective binding to calmodulin” Proteins, 53(4): 855-862

1. J. Goers, A.B. Manning-Bog, A.L. McCormack, I.S. Millett, S. Doniach, D.A. Di Monte, V.N. Uversky, A.L. Fink (2003) “Nuclear localization of alpha-synuclein and its interaction with histones” Biochem., 42(28): 8465-8471  

1. R. Das, T. Mills, L.W. Kwok, G.S. Maskel, I.S. Millett, S. Doniach, K.D. Finkelstein, D. Herschlag, L. Pollack (2003) “Counterion distribution around DNA probed by solution X-ray scattering” Phys. Rev. Lett., 90(18):1881-1883.

1. A.S. Meyer, J.R. Gillespie, D. Walther, I.S. Millett, S. Doniach, J. Frydman (2003) “Closing the folding chamber of the eukaryotic chaperonin requires the transition state of ATP hydrolysis” Cell, 113(3): 369-381

1. Vladimir N. Uversky, Liza Nielsen Garriques, Ian S. Millett, Sven Frokjaer, Jens Brange, Sebastian Doniach, Anthony Fink (2003), “Prediction of the Association State of Insulin Using Spectral Parameters” J. Pharm. Sci.,  92: 847–858 

1. Ian S. Millett, Sebastian Doniach, Kevin W. Plaxco (2002) “Toward a Taxonomy of the Denatured State: Small Angle Scattering Studies of Unfolded Proteins” Adv. Protein Chem., 62: 241-262

1. Vyacheslav M. Abramov,  Anatoly M. Vasiliev,  Valentin S. Khlebnikov,  Raisa N. Vasilenko, Nataly L. Kulikova, Igor V. Kosarev,  Alexander T. Ishchenko,  Joel R. Gillespie,  Ian S. Millett, Anthony L. Fink, Vladimir N. Uversky (2002), “Structural and Functional Properties of Yersinia pestis Caf1 Capsular Antigen and Their Possible Role in Fulminant Development of Primary Pneumonic Plague” J. Proteome Res., 1: 307-315

1. Pierre O. Souillac, Vladimir N. Uversky, Ian S. Millett, Ritu Khurana, Sebastian Doniach, Anthony L. Fink  (2002), “Effect of association state and conformational stability on the kinetics of immunoglobulin light chain amyloid fibril formation at physiological pH” J. Biol. Chem., 277: 12657-12665

1. Pierre O. Souillac, Vladimir N. Uversky, Ian S. Millett, Ritu Khurana, Sebastian Doniach, Anthony L. Fink (2002), “Elucidation of the molecular mechanism during the early events in immunoglobulin light chain amyloid fibrillation: Evidence for an off-pathway oligomer at acidic pH” J. Biol. Chem., 277: 12666-12679

1. Vladimir N. Uversky, Jie Li, Pierre TSouillacT, Ian S. Millett, Sebastian Doniach, Ross Jakes, Michel Goedert, Anthony L. Fink (2002), “TBiophysical Properties of the Synucleins and Their Propensities to Fibrillate. Inhibition of TT-synuclein assembly by - and -synucleins”T J. Biol. Chem., 277: 11970-11978

1. Wing-Yiu Choy, Frans A. A. Mulder, Karin A. Crowhurst, D. R. Muhandiram, Ian S. Millett, Sebastian Doniach, Julie D. Forman-Kay, Lewis E. KayP ^P(2002). “Distribution of molecular size within an unfolded state ensemble using small-angle X-ray scattering and pulse field gradient NMR techniques.” J. Mol. Bio., 316(1): 101-112

1. Ian S. Millet, Lara E.Townsley, Fabrizio Chiti, Sebastian Doniach, Kevin W. Plaxco (2002). “Equilibrium collapse and the kinetic ‘foldability’ of proteins” Biochem. 41(1): 321-325

1. Rick Russell, Ian S. Millett, Mark W. Tate, Lisa W. Kwok, Bradley Nakatani, Sol M. Gruner, Simon G.J. Mochrie, Vijay Pande, Sebastian Doniach, Daniel Herschlag, and Lois Pollack (2002). “Rapid Compaction During RNA Folding.”  Proc. Nat. Acad. Sci., 99(7): 4266-4271

1. Rick Russell, Xiaowei Zhuang, Hazen P. Babcock, Ian S. Millett, Sebastian Doniach, Steven Chu, Daniel Herschlag (2002). “Exploring the Folding Landscape of a Structured RNA.” Proc. Nat. Acad. Sci., 99(2): 155-160

1. Ritu Khurana, Joel R. Gillespie, Anupam Talapatra, Lauren J. Minert, Cristian Ionescu-Zanetti, Ian Millett, Anthony L. Fink (2001). “Partially Folded Intermediates as Critical Precursors of Light Chain Amyloid Fibrils and Amorphous Aggregates.”  Biochem., 40(12): 3525-3535

1. Rick Russell, Ian. S. Millett, Sebastian Doniach, Daniel Hershlag (2000). “Small Angle X-ray Scattering Reveals a Compact Intermediate in Folding of the Tetrahemena Group I RNA Enzyme.” Nat. Struct. Bio., 7(5): 367-370.

1. Vladimir N. Uversky, Joel R. Gillespie, Ian S. Millett, Anna V. Khodyakova, Raisa N. Vasilenko, Anatoly M. Vasiliev, Igor L. Rodionov, Galina D. Kozlovskaya, Dmitry A. Dolgikh, Anthony L. Fink, Sebastian Doniach, Eugene A. Permyakov, Vyacheslav M. Abramov (2000). “Zn²⁺-Mediated Structure Formation and Compaction of the "Natively Unfolded" Human Prothymosin.” Biochem. Biophys. Res. Comm., 267(2): 663-668.

1. Uversky, V. N., Gillespie, J. R., Millett, I. S., Khodyakova, A. V., Vasiliev, A. M., Chernovskaya, T. V., Vasilenko, R. N., Kozlovskaya, G. D., Dolgikh, D. A., Fink, A. L., Doniach, S., Abramov, V. M. (1999). “Unfolded Human Prothymosin Adopts Partially Folded Collapsed Conformation at Acidic pH.” Biochem., 38(45): 15009-15016.

1. Kevin W. Plaxco, Ian. S. Millett, Daniel J. Segel, Sebastian Doniach, David Baker (1999). “Chain Collapse can occur Concomitantly with the Rate-limiting Step in Protein Folding.” Nat.  Struct. Biol., 6(6): 554 - 556.

1. Ian Millett, William Vance, John Ross (1999). “Measurements of Phase Response in an Oscillatory Reaction and Deduction of Components of the Adjoint Eigenvector.” J. Phys. Chem. A, 103(41): 8252-8256.

1. G. Bernstein, S. Labov, D. Landis, N. Madden, I. Millett, E. Silver, P. Richards (1991). “Automated temperature regulation system for adiabatic demagnetization refrigerators.” Cryogenic, 31: 99-102.

1. E. Silver, S. Labov, F. Goulding, N. Madden, D. Landis, J. Beeman, T. Pfafman, L. Melkonian, I. Millett, Y. Wai (1989). “High Resolution X-ray Spectroscopy Using Germanium Microcalorimeters.” Proc. SPIE, 1159: 423-432.