Pharmaceutical Development, Formulations, Scale-up, Project Management

CHIEN-HSUAN (SARA) HAN, Ph.D.

Tel: 408-***-**** *************@*****.***

SUMMARY

Seventeen (17) years of industrial experience in Formulation/product development/scale up including pre-formulation, formulation/drug delivery, process development, clinical supply preparation, scale-up, process qualification/validation, and technology transfer from pre-IND to NDA/ANDA for oral dosage forms (solid oral and pediatric liquid).

• Developed CMC scope, Gantt and budget for project team

• Developed various types of oral formulation including immediate and modified release solid formulations (matrix and/or membrane-controlled, gastro-retentive, layer-coated beads, multi-layer tablets, abuse-deterrent formulation) and immediate release solubility-enhanced pediatric liquid formulation for NDA/ANDA, which led to 5 generic (2 IR, 3 ER) and 2 brand commercial products.

• Experienced in out-licensing development including due diligent evaluation and development plan/timeline establishment, and plan execution and management for milestone/royalties payment, which led to 1 commercial, 1 NDA, 3 late-stage products.

• Experienced in establishing RFP/contract and managing CRO/CMO for formulation/process development and CTM preparation for drug product including CRO/CMO selection, quote negotiation, on-site visit, progress monitoring for various phase clinical trials.

• Experienced in evaluating and establishing manufacturing process specifications of drug product by Quality-by-Design (QbD) studies.

• Experienced in scale-up, technology transfer, CMC regulatory filling/response and process validation, for 5 commercial products.

• Experienced in authoring and reviewing regulatory documents including Module 3/quality overall summary in INDs and NDAs

• Fifteen (15) years of leadership in managing and coaching highly educated team to efficient and effectively meet the deliverables

Eight (8) years of managing R&D laboratories to meet regulatory safety/DEA requirement

• Eight (8) years of planning and managing department budgets

PROFESSIONAL EXPERIENCE

2015 May- 2017 July Adamas Pharmaceuticals, Emeryville, CA

Senior Manager, Formulations

Responsible for formulation/process development and scale-up of pipeline products; preparation of CTMs for Phase I-III trials for IND/NDA, led to one (1) IND, with anticipated Phase I results for patent application.

• Developed formulation strategy with research/PK, clinical, marketing and legal teams

• Established development plans and contracts with CMO/CRO, and manage contract development activities within approved budget and timeline

• Established CMC development timeline and budget with project management, analytical, process/manufacturing, QA, and RA to fulfill business strategy

• Author and review pharmaceutical development sections for regulatory submissions (Module 3/quality overall summary)

2007- 2015 March Depomed, Newark, CA

Associate Director, Formulations

Led the team to develop various gastric retentive oral formulations/process for internal and licensing-out development, which led to multiple INDs, CTMs, one (1) NDA, and one (1) commercial product, with milestone and high single digit royalty payment, and four (4) granted US and worldwide patents and one (1) European patent. Selected and worked with CRO/CMO for developing liquid pediatric formulation and CTM preparation for Phase IV studies.

• Led a group of professionals (BS, MS, PhD) to develop formulation/process/early stage analytical development for oral gastric retentive sustained release dosage forms for NDA. Expanded proprietary technology platform to improve in-vivo deliver capability as well as drug loading including gastric retentive IR/ER bi-layer formulation, delayed pulsative press-coated formulation, and abuse-deterrent formulation. Authored development plan/deliverables/FTE and timeline. Interfaced with cross-functional teams including project management, pre-clinical, analytical, operation, PK, QA, RA, clinical, legal, and marketing. Authored and reviewed pharmaceutical development sections for regulatory submissions.

• Led development of out-licensed gastric retentive technology (IR/ER bilayer gastric retentive sustained release formulation) including technical evaluation and authored strategic planning, timeline, and deliverables for BD due diligent/contract negotiation. Developed and managed formulation/process/analytical activities to meet milestones. Updated senior management on progress. Authored development report for tech transfer.

• Mallinkcrodt Pharmaceuticals – controlled substances

• Boehringer Ingelheim – fixed dose combination

• Janssen (J&J)

• Ironwood Pharmaceuticals – resin polymer delivery

• Selected and worked with CRO/CMO for pediatric liquid formulation development with taste-masking and solubilization enhancement, and CTM preparation for Phase IV study, including RFP, quote negotiation, on-site visit, and monitoring the progress.

• Implemented process QbD at development stage for identifying critical process parameters including granulation, drying, milling, blending, and compression and guiding specification establishment.

• Served as technical expertise in establishing IP strategy for protecting developing and commercial products

• Served as technical expertise in identifying new product and new technology opportunities to provide strategies for technical challenges.

• Responsible for annual department budgeting including estimates of FTE, and capital equipment planning and acquisition.

• Managed formulation/process laboratory to fulfill OSHA/DEA requirement. Familiar with controlled substances handling requirement.

IMPAX Laboratories, Hayward, CA

2004-2007 Associate Director, Brand Product Development

2000-2003 Manager, Product Development (Generic)

1998-2000 Group Leader, Product Development (Generic)

1998 Formulation Scientist, Product Development (Generic)

Various positions with responsibilities on (1) development and regulatory submission (ANDA/IND/NDA) of solid oral immediate and extended release products (tablets, capsules, delayed released capsules, bilayer tablets, press-coated tablets, oral disintegrating tablets), (2) product development from R&D pre-formulation/formulation to process development, scale-up, process validation, and technology transfer to production, and (3) formulation IP strategy development for product protection. It led to three (3) controlled- release and two (2) immediate release commercial generic products, one brand sustained release product, 3 granted US and worldwide patents.

• Led a group of professionals (BS, MS, PhD) to develop stable formulation and robust manufacturing process for generic and brand products

• Developed formulation/manufacturing process and bioequivalence (BE) trials that led to the successful development of three sustained-release and two immediate-release marketed generic products

• Developed formulation/manufacturing process and bioavailability/bioequivalence (BA/BE) studies to support Phase I-III clinical studies for brand products

• Initiated and implemented in-vitro/in-vivo correlation (IVIVC) for generic and brand oral controlled release products to minimize the number of BA/BE studies (IVIVC and pharmacokinetic modeling)

• Established CMC development timeline for generic and brand products to fulfill business strategy

• Managed CMC activity for multiple projects through cross-functional departments including product development, analytical (R&D/QC), quality assurance, regulatory affairs, and contract manufacturing/packaging sites to support clinical and stability batch manufacturing and testing

• Authored technical reports and prepared CMC section of IND/NDA/ANDA including pharmaceutical development and responses to inquiries from regulatory agencies

• Established formulation strategy with legal department for product protection/intellectual property

• Managed contract manufacturing activities to meet timeline

• Searched and evaluated new technology for licensing-in opportunities

Inhale Therapeutic Systems (former Nektar Therapeutics), San Carlos, CA

1997-1998 Internship, Pre-formulation Group

• Characterized solid state (crystallinity and polymorphism) protein formulations to support the optimization of spray-dry manufacturing process (DSC, hot-stage microscopy, and X-ray powder diffraction)

• Characterized glass transition temperature of protein to support physical stability of protein formulations (modulated DSC)

• Established the effect of humidity and temperature on aerosol powder for optimization of spray-dry manufacturing process (VTI)

• Developed methods on drug-specific particle size distribution and deliver dose efficiency assay of protein formulation in aerosol delivery to evaluate powder uniformity (HPLC)

• Studied chemical stability of protein formulations to support BA study (HPCL, UV)

University of Minnesota, College of Pharmacy

1994-1997 Research Assistant, Department of Pharmaceutics

• Studied solubilization of poorly water-soluble compound retinoids by bile salt micelles to improve its oral bioavailability (DSC, HPLC, UV, Fluorescence Spectroscopy)

• Studied the phase transition of skin liquids to develop better transdermal carrier with improving percutaneous absorption (DSC, birefringence, hot-stage microscopy, FI-IR, Small-angle X-ray diffraction)

University of Minnesota, College of Pharmacy

1993 Teaching Assistant, Dispensing Pharmacy Laboratory

• Supervised undergraduate during the compounding of solid and liquid dosage forms

National Taiwan University, School of Pharmacy

1991-1992 Research Assistant, Medicinal Chemistry

• Synthesized and purified selective, reversible, and irreversible ligands for the ĸ opioid receptor (TLC, NMR, LC, FI-IR, UV)

EDUCATION

1992-1997 Ph.D. in Pharmaceutics

University of Minnesota, College of Pharmacy

Department of Pharmaceutics, Minneapolis, MN

1987-1991 B.S. in Pharmacy, College of Pharmacy, National Taiwan University, Taiwan

PATENTS/PATENT APPLICATIONS

US Patent

1) US8,688,929 (2014)

CH Han, SYE Hou, and ML Reid. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic.

2) US 8,394,408 (2013)

CH Han, SYE Hou, and ML Reid. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic.

3) US 8,377,453 (2013) (WO2009114648, EP2262484, CA2720108, CN102105136)

CH Han, SYE Hou, and ML Reid. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic.

4) US 8,372,432 (2013)

CH Han, SYE Hou, and ML Reid. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic.

5) US 8,007,827 (2011) (WO2007040997, PCT/US2006/036694, EP1940361, CA2125481, CN101312716)

CH Han, L Hsu, and AF Hsu. Pharmaceutical dosage forms having immediate release and/or controlled release properties.

6) US 7,094,427 (2006)

CH Han, L Hsu, and AF Hsu. Combination immediate release controlled release levodopa/carbidopa dosage forms.

7) US 6,333,332 (2001)

CH Han and G Liaw. Stabilized pharmaceutical compositions containing bupropion hydrochloride.

US Patent Application

1) US 201********

CH Han, SYE Hou, and ML Reid. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic.

2) US 200******** (WO2009017716, CA2694602, CN101888828, EP2192892)

VE Cowles, SYE Hou, B Berner, CH Han, RD Fell, and C Gu. Pulsatile gastric retentive dosage forms.

3) US 200******** (WO2006073729)

AF Hsu, CH Han, and L Hsu. Oral disintegrating dosage forms.

4) US 200********

CH Han, L Hsu, and AF Hsu. Pharmaceutical dosage forms having immediate and controlled release properties that contain an aromatic amino acid decarboxylase inhibitor and levodopa.

PUBLICATIONS

1) C Chen, CH (Sara) Han, M Sweeney, and VE Cowles. Pharmacokinetics, efficacy, and tolerability of a once-daily gastroretentive dosage form of gabapentin for the treatment of postherpetic neuralgia. J. Pharm. Sci. 102(4), 1155-1164 (2013).

2) CH (Sara) Han. Minireview: Gastroretentive Drug Delivery System: AcuForm® Technology. Sustained Delivery, Newsletter of AAPS Modified Release Focus Group (2010).

3) CH Han and TS Wiedmann. Spectral properties and ion dissolution behavior of retinoids I. Aqueous solutions. Int. J. Pharm. 172, 241-253 (1998).

4) CH Han, CL Zimmerman, and TS Wiedmann. Spectral properties and ionization behavior of retinoids II. Bile salt solutions. Int. J. Pharm. 172, 229-240 (1998).

5) TS Wiedmann, K Kvanbeck, CH Han, and V Roongta. Ionization and solubilization of 4-alkyl-benzoic acids and 4-alkyl-anilines in sodium taurodeoxycholate solutions. Pharm. Res. 14(11), 1574-82 (1997).

6) CH Han, R Sanftleben, and TS Wiedmann. Phase properties of mixtures of ceramides. Lipids 30(2), 121-128 (1995).

PRESENTATIONS

1) S Han. (2011) HPMC and Polyethylene Oxide for Controlled Release Gastroretentive System. Colorcon Modified Release Forum (invited speaker), West Point, PA.

2) S Han. (2010) Gastroretentive Drug Delivery. AAPS Bay Area Discussion Group Dinner Event (invited speaker), Dec 16th, 2010, San Mateo, CA.

3) TS Wiedmann, K Kvanbeck, CH Han, and V. Roongta. (1997) Ionization and Solubilization of 4-Alkyl-benzoic acids and 4-Alkyl-anilines in Sodium Taurodeoxycholate Solutions. Eleventh Annual Meeting of the American Association of Pharmaceutical Sciences, Boston, MT.

4) CH Han, CL Zimmerman, and TS Wiedmann. (1996) Dependence of Ionization of Retinoids on the interaction of Bile Salt Micelles. Tenth Annual Meeting of the American Association of Pharmaceutical Sciences, Seattle, WA.

5) CH Han, CL Zimmerman, and TS Wiedmann. (1996) Ionization and Aggregation Behavior of Retinoic acid in Aqueous and Bile Salt Micellar Solutions. 28th Annual Pharmaceutical Graduate Student Research Meeting, Minneapolis, MN.

6) CH Han, CL Zimmerman, and TS Wiedmann. (1995) The Effect of pH on the Dissolution of Retinoids in Aqueous and Bile Salt Micellar Solutions. Ninth Annual Meeting of the American Association of Pharmaceutical Sciences, Miami Beach, FL.

7) TS Wiedmann, XH Cai, DJW Grant, CH Han, CY Li, and CL Zimmerman. (1995) Solubilization of Drugs by Bile Salt/Phospholipid Aggregates. 22nd International Symposium on Controlled Release of Bioactive Materials, Seattle, Washington.

8) TS Wiedmann, XH Cai, DJW Grant, CH Han, CY Li, and CL Zimmerman. (1995) Bile Salt Solubilization Effect for Drugs. 69th Colloid and Surface Science Symposium, Salt Lake City, Utah.

9) CH Han, R Sanftleben, and TS Wiedmann. (1994) Thermal Properties of Ceramides as Model Skin Lipids, eighth Annual Meeting of the American Association of Pharmaceutical Sciences, San Diego, CA.

10) CY Cheng, HY Lu, LW Hsin, and CH Han. (1991) Synthesis of Substituted Lactam via Nucleophilic Ring Cleavage of Cyanoalkylaziridines. International Chemical Conference, Taipei, Taiwan.

AFFILIATIONS/ORGANIZATION MEMBERSHIPS

American Association of Pharmaceutical Scientists (AAPS), Controlled Release Society (CRS)

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