Excipients and Formulation Assessments of Complex Generic Products: Best Practices and Lessons Learned

Staff Fellow (Pharmacologist), DPTR, OSCE, OGD, CDER, FDA

Dr. Stuti Agarwal holds a B.S. in Chemistry and Biology from Lucknow University, India and a M.S. in Biotechnology from Hamdard University, New Delhi, India. She completed her Ph.D. in Pharmacology and Toxicology with concentration in Molecular Biology and Genetics from Virginia Commonwealth University (VCU), USA. She joined the Office of Biological Products (OBP)/OPQ in 2016, where she conducted research on T-regulatory cells and its modulation for cancer treatment. She joined the Division of Regulatory Sciences (DARS)/The Office of Translational Sciences (OTS) and conducted cutting edge work on developing Immune-humanized mice by transplanting neonatal human tissue and cord blood cells, to be used as a tool to test immunogenicity of biological products/drugs. She joined DPTR/OGD in 2020, where she conducts safety assessment of impurities, residual solvents, excipients, and extractables/leachables in generic drug products. In addition to her review work, Stuti is actively involved in several intradisciplinary and interdisciplinary working groups for process improvement and reviewer training. She is also involved in doing external outreach to industry regarding generic drug products.

Global Head of Regulatory Science, Viatris, Inc.

Nitin Bhattad serves as Global Head of Regulatory Science of Injectables at Viatris. He joined the organization over 16 years ago and has well over 24 years of experience in research and development, regulatory affairs, and the pharmaceutical industry. His current focus area is regulatory science, strategy, and operations for complex and conventional injectable and ophthalmic products.

Nitin’s work involves Non-Biologic Complex Drugs (NBCDs–peptides, microspheres, liposomes, iron complexes, etc.), drug-device combinations, certain biosimilars, and conventional sterile products. In addition, he has experience previously working with solid oral dosage forms. Nitin holds a Master’s degree in Pharmaceutical Technology from Nagpur University in India and a Senior Management Program Certification from Indian Institute of Management in Calcutta.

Senior Pharmacologist, DB III, OB, OGD, CDER, FDA

Dr. Pamela Dorsey is a Senior Pharmacologist for the Office of Bioequivalence within the Division of Bioequivalence III. As a Senior Pharmacologist, Pamela performs primary and secondary bioequivalence assessment for generic drug products. Pamela has been with the Food and Drug Administration (FDA) for over 8 years. Prior to joining the FDA, she was a post-doctoral fellow at Boston University Medical Center in the Whitaker Cardiovascular Institute. Pamela received a B.S. and M.S. in Chemical Engineering from North Carolina Agricultural and Technical State University, and a Ph.D. in Pharmaceutical Science from The University of Georgia.

Division Director, DCR, OSCE, OGD, CDER, FDA

Dr. Lisa Faulcon is the Director of the Division of Clinical Review in the Office of Safety and Clinical Evaluation within the Office of Generic Drugs (CDER), at FDA. In this role, she leads a group of interdisciplinary scientists responsible for providing the clinical assessment of generic drug products and ensuring that allowable differences between a generic drug product and its reference listed drug do not alter the safety or efficacy profile. She began her FDA career in 2012 as a Medical Officer in the Center for Biologics Evaluation and Research’s Office of Blood Research and Review. In 2016, she joined the Office of Science in the Center for Tobacco Products (CTP), where she was actively engaged in the development of policies and procedures related to the clinical review of tobacco products and served as the Human Subjects Protection Liaison responsible for ensuring compliance with federal policies, procedures and regulations pertaining to human subjects’ research. Prior to joining FDA, she served as an Assistant Professor of Pediatrics in the Division of Pediatric Hematology at the Johns Hopkins University. Dr. Faulcon received a B.A. in Biology from the University of Virginia before obtaining her medical degree from the Temple University School of Medicine.

Lead Physician, OSCE, OGD, CDER, FDA

Dr. Amrita Ghosh is trained, and board certified in internal medicine and hospice/palliative medicine and holds a Ph.D. in Molecular Biology where she characterized the genetic profile of human bone-marrow derived stem cells. Prior to working at FDA, she has seen patients in the community and continues to do so. She has worked at the FDA for four years and served as Lead Physician for two years where she serves as secondary reviewer for clinical reviews and consults for the generic drug review process. She serves on working groups in relation to the safety of pediatric excipient evaluation and plans and provides education on this and other topics.

Senior Pharmacologist, ORS, OGD, CDER, FDA

Dr. Priyanka Ghosh is a Senior Pharmacologist within the Division of Therapeutic Performance. Her areas of expertise include products in the topical and transdermal drug delivery area. In her current role, Dr. Ghosh leads regulatory science research initiatives related to topical and transdermal drug products, including projects related to development of noninvasive imaging techniques for evaluation of cutaneous pharmacokinetics, under the GDUFA regulatory science program. Dr. Ghosh also leads the development of general and product-specific guidance, review strategies for pre-ANDA meeting requests and citizen petitions and is the co-chair of the Bioequivalence Standards for Topicals Committee within OGD. Prior to joining FDA, Dr. Ghosh completed her Bachelor’s degree in Biotechnology from West Bengal University of Technology (India) and a Ph.D. in Pharmaceutics and Drug Design from the University of Kentucky.

Staff Fellow, DTP I, ORS, OGD, CDER, FDA

Dr. Anubhav Kaviratna is a Pharmacologist in the inhalation and nasal drug products team in the Division of Therapeutic Performance I. Dr. Kaviratna is responsible for the development of product-specific guidances, controlled correspondences, and pre-ANDA meeting reviews. Dr. Kaviratna also serves as a project officer for regulatory science research initiatives through the GDUFA program. Prior to joining OGD, Dr. Kaviratna worked with the Office of Pharmaceutical Quality (OPQ) where he reviewed the drug product quality information for the development of USP monographs, lab-based investigations, and lifecycle management of brand and generic drug products. Dr. Kaviratna received a Ph.D. in Biomedical Engineering from the Indian Institute of Technology Bombay, India.

Pharmacologist, DTP I, ORS, OGD, CDER, FDA

Dr. Megan Kelchen is a pharmacologist in the Division of Therapeutic Performance I. Her area of expertise includes drug products for topical, transdermal, and mucosal drug delivery. Dr. Kelchen is responsible for the development of product-specific guidances for generic drug development, and reviewing and responding to controlled correspondences, citizens petitions, and pre-ANDA meeting requests. Dr. Kelchen is also engaged in regulatory science research initiatives related to the development of bioequivalence standards for related to topical, transdermal, and mucosal drug products through the GDUFA regulatory science research program. Prior to joining FDA, Dr. Kelchen received a Bachelor’s degree in Biology from Wartburg College and a Ph.D. in Clinical Pharmaceutical Sciences from the University of Iowa.

Acting Director, DOBPRA, OGDP, OGD, CDER, FDA

Dr. Timothy H. Kim currently serves as the Acting Director in the Division of Orange Book Publication and Regulatory Assessment (DOBPRA). He oversees the Orange Book publication and related IT projects supporting the publication’s content and has previously served as a reviewer for Orange Book drug product and patent listings, in addition to reviewing controlled correspondences related to reference listed drug (RLD) and reference standard (RS) inquiries. Prior to the FDA, Timothy served as a pharmacist for the National Institutes of Health (NIH) and George Washington University Hospital. Timothy received his Pharm.D. at the University of North Carolina, Chapel Hill.

Controlled Correspondence Coordinator, DFR, ORO, OGD, CDER, FDA

LCDR Elizabeth Kim is a Controlled Correspondence Coordinator for the Division of Filing Review (DFR) in OGD’s Office of Regulatory Operations (ORO). In this role, LCDR Kim reviews and responds to inquiries submitted by generic drug manufacturers or associated industry on a specific element of generic drug development. Prior to joining the FDA in 2015, LCDR Kim worked as a family nurse practitioner providing primary care in various clinical settings. LCDR Kim obtained a Master of Science in Nursing degree from the University of Maryland School of Nursing.

Deputy Director, DTP I, ORS, OGD, CDER, FDA

Dr. Darby Kozak is the Deputy Division Director for the Division of Therapeutic Performance in the FDA’s Office of Generic Drugs. Dr. Kozak leads a group of interdisciplinary scientists on the development of new analytical methods and equivalence evaluation methodologies for complex drug substances and parenteral, ophthalmic, otic, and inhalation formulations. Prior to joining the FDA, Dr. Kozak was Chief Scientist for Izon Science and Research Fellow at the Australian Institute for Bioengineering and Nanotechnology. Dr. Kozak has a B.Sc. in Chemical Engineering from the University of Washington (Seattle, WA) and Ph.D. in Chemistry from the University of Bristol (United Kingdom).

Acting Deputy Division Director, DLRS, OGDP, OGD, CDER, FDA

Colleen Lee is currently serving as the Acting Deputy Director of the Division of Legal and Regulatory Support (DLRS) in the Office of Generic Drug Policy (OGDP). As a member of DLRS, she advises OGD colleagues on generic drug application-specific legal, regulatory, and policy issues to enable generic drug approvals and provide the public with high quality, affordable medicines. With over ten years of experience at the FDA, Colleen has worked in a variety of roles including the drafting of regulations and guidance documents and the developing and implementing of compliance policies.

Deputy Division Director, DFR, ORO, OGD, CDER, FDA

Dr. Julia Lee is the Deputy Division Director in the Division of Filing Review, Office of Regulatory Operations within the FDA’s Office of Generic Drugs. She has over 10 years of experience in the filing review of abbreviated new drug applications submitted to the Agency. Prior to working at the Agency, she was a retail pharmacist at Walgreens. She has also worked in the Chesapeake-Atlantic node of the Pediatric Emergency Care Applied Research Network as a clinical research assistant. She received her Doctorate of Pharmacy at the University of Maryland, School of Pharmacy and her Bachelor of Science in Chemistry at The George Washington University.

Senior Physician, DCR, OSCE, OGD, CDER, FDA

Dr. Michelle Lin is a Senior Physician in the Division of Clinical Review. In this role, she routinely conducts safety assessment of excipients in generic products, comparative analyses reviews as well as other clinical consults and controlled correspondences. In addition to her review work, she is involved in several working groups for process improvement and reviewer training. Dr. Lin is trained, and board certified in pediatrics and pediatric endocrinology. She holds a medical degree from the University of Florida School of Medicine. She completed her pediatric residency at the University of Texas Houston followed by a fellowship in Pediatric Endocrinology at Emory University.

Team Lead IVIVC & Analytical, Sandoz

Dr. Babita Mallick is the Team Lead of the Analytical Development team at Sandoz Development Center (SDC) India. In addition, she is the analytical expert for complex injectable & BD&L projects; site lead for OpEx initiatives on SmartOps/Lab automation, and active member of Lean Six Sigma. She is equally enthusiastic about people and culture as Psychological Safety site lead.

Babita has been with Novartis-SDC for over three years and comes with diverse industrial experience. Prior to Sandoz, she was working with Dr. Reddy’s Laboratories as Spectroscopy Functional Lead & Characterization Expert. She is responsible for setting up Raman COE, spectroscopy capabilities, and establishing herself as the advanced solid-state characterization expert for complex generics; injectable/topical/inhalation and oral solid. She started her career as Raman Application scientist at Renishaw Inc. providing technical support to Marketing & Sales for semiconductor, petroleum, pharma industries, and academia. She holds a Ph.D. degree (2011) from Indian Institute of Science (IISc.), Bangalore on Femtosecond Nonlinear Raman spectroscopy. During her Ph.D., she developed and patented a novel Ultrafast Nonlinear Raman technique in the field of vibrational spectroscopy. Babita received her M.Sc. degree in Chemistry from Indian Institute of Technology Madras (IITM) and B.Sc. in Chemistry from Delhi University. She is a technologist by passion who loves to connect business goals to technical needs. She is energized by her compassion to share knowledge with others, enjoys reading-watching detective books, and is trained in the classical dance Bharatanatyam.

Regulatory Counsel, DPD, OGDP, OGD, CDER, FDA

Dr. Melissa Mannion is a Regulatory Counsel with the Division of Policy Development in the Office of Generic Drug Policy (OGDP). In her current role, Melissa works to develop and implement new and improved policies, guidances, regulations, and other policy documents to support the approval of high-quality generic drugs on the first lawful approvable date. She serves as a policy subject matter expert on a range of complex issues pertaining to generics, including bioequivalence requirements, pre- Hatch-Waxman ANDAs, inactive ingredient sameness, disclosure concerns, and importation. In her ten years with FDA, she has also served as a Pharmacist and Regulatory Counsel in CDER’s Office of Compliance. Melissa has more than 15 years of experience encompassing public health policy research, regulatory and legislative affairs, pharmaceutical purchasing and distribution, professional affairs, and retail pharmacy operations. Melissa earned her Bachelor’s degrees in Human Biology and Psychology from the University of California San Diego, and her Pharm.D. and J.D. degrees from the University of Maryland Baltimore.

Lead Pharmacologist, DTP I, ORS, OGD, CDER, FDA

Dr. Bryan Newman is a lead pharmacologist and team lead for inhalation and nasal drug products in the Division of Therapeutic Performance I (DTP I), Office of Research and Standards (ORS), under the Office of Generic Drugs (OGD). Dr. Newman’s work focuses on developing product-specific guidances, and addressing controlled correspondences, citizen petitions, consults, and pre- ANDA meeting requests. He also serves as a project officer and contracting officer’s representative for regulatory science research initiatives related to inhalation and nasal drug products. Dr. Newman received his B.S. degree from Louisiana State University in Biochemistry and his M.S. and Ph.D. degrees from the University of Michigan in Pharmaceutical Science.

Staff Fellow, DP II, OB, OGD, CDER, FDA

Dr. Hiren Patel is a bioequivalence assessor in the Division of Bioequivalence II within Office of Generic Drugs (OGD). Prior to joining FDA, he earned his M.S. and Ph.D. with specialization in Pharmacokinetics at Long Island University, Brooklyn, NY.  At FDA, he is responsible for assessing the bioequivalence of the various dosage forms of generic drugs. He is the lead for the topical and transdermal drug products and the advanced techniques for demonstrating bioequivalence of such complex drug products within the Office of Bioequivalence. He is the co-chair for Bio-Equivalence Standards for Topicals Committee within OGD. He has also actively served as a consultant in the research initiatives which are the collaborative efforts of FDA and global research institutions pertaining to the topical and transdermal drug products funded through FDA. Dr. Patel is also actively involved in the review panel for the Product Specific Guidance for the generic topical drug products.

Lieutenant Commander, USPHS, Supervisory Regulatory Officer, DFR, ORO, OGD, CDER, FDA

Lieutenant Commander (LCDR) Vinh Phung is currently a supervisor in the Division of Filing Review, Office of Regulatory Operations, Office of Generic Drugs. He received his Doctor of Pharmacy from Massachusetts College of Pharmacy and Health Sciences in 2010 and commissioned into the US Public Health Service Commissioned Corps in 2017. Collectively, he has over 10 years of experience in varying capacities. He started with the FDA as a filing reviewer and progressed to project manager and team leader positions. Prior to joining FDA, LCDR Phung served on active duty in the US Air Force where he held a spectrum of clinical, administrative, and leadership roles.

Co-Director of CRCG, Professor of Pharmaceutical Sciences and Ralph F. Shangraw/Noxell Endowed Professor in Industrial Pharmacy and Pharmaceutics, University of Maryland

Dr. James E. Polli is Professor of Pharmaceutical Sciences and Ralph F. Shangraw/Noxell Endowed Professor in Industrial Pharmacy and Pharmaceutics at University of Maryland. His research interest is oral drug absorption and formulation, involving laboratory and clinical research. He has served as advisor to 24 Ph.D. graduates. Dr. Polli is co-Director of the recently initiated Center for Research on Complex Generics, an FDA-funded collaborative agreement with the Agency. He is Director of the online M.S. in Regulatory Science program (www.pharmacy.umaryland.edu/regulatoryscience).

Co-Director of CRCG, William I Higuchi Collegiate Professor of Pharmacy Associate Professor of Pharmaceutical, Sciences Biointerfaces Institute, College of Pharmacy, University of Michigan

Pharmacologist, DB II, OB, OGD, CDER, FDA

Dr. Xinran Li is the primary assessor for the in vivo and in vitro bioequivalence studies of generic drug products in the Office of Bioequivalence in the FDA’s Center for Drug Evaluation and Research. She received a Ph.D. in Pharmaceutical Science from the University of Texas at Austin in 2013. Xinran has experience supporting complex drug reviews across different dosage forms as well as regulatory assessment for ANDA submissions.

Team Lead Complex Drug Products, DTP I, ORS, OGD, CDER, FDA

Dr. Yan Wang is the team lead for Complex Drug Substances & Formulation Team in the Division of Therapeutic Performance, Office of Research and Standards. In her current role, Dr. Wang works with a group of interdisciplinary scientists developing product-specific guidances, addressing controlled correspondences, pre-ANDA meeting requests, citizen petitions, and internal consults in the areas of complex drug substances and complex formulations for various routes of administration and dosage forms. She also manages research projects on developing new analytical methods, in vitro characterization, and drug release testing methodologies for complex drug products. She specializes in complex parenteral, ophthalmic, otic, intravaginal, and intrauterine formulations.

Lead Pharmacologist, DB III, OB, OGD, CDER, FDA

Dr. Yi Zhang holds a B.S. in Pharmaceutical Science from Peking University Health Science Center and a Ph.D. in Pharmacology from Chinese Academy of Medical Sciences. He joined Office of Bioequivalence (OB)/Office of Generic Drug (OGD)/FDA in 2014 as a primary assessor, where he conducts critical evaluation of bioequivalence studies in regulatory submissions for generic drug products. He has served as a Team Lead since 2019 to carry out the secondary assessment and works collaboratively to address complex issues identified during bioequivalence assessments. He is currently involved in several working groups and research projects at divisional and office levels to support scientific and regulatory-based decisions making for the review of generic products.

Branch Chief, OPPQ, OPQ, CDER, FDA

Susan holds a B.S. in Chemistry from Syracuse University and a M.S. in Biotechnology from Johns Hopkins University. During her 23 years with then FDA, she served in the Office of Generic Drugs as Chemistry Team Leader for many years, specializing in antibiotics. She joined the Office of Policy for Pharmaceutical Quality in 2015 and is currently a Branch Chief in the Division of Regulations, Guidance and Standards. She is the lead for the FDA’s Inactive Ingredient Database (IID). In this role, she is responsible for overseeing IID improvements. Susan has served on many FDA committees and working groups related to product safety and quality. She is currently a member of the FDA’s Center for Drug Evaluation and Research (CDER) Excipient Working Group.