Dr. Andrei A. Zlota
Dr. Andrei Zlota is an expert in Quality by Design (QbD) implementation, and has more than 25 years process R&D and manufacturing experience at various corporations including Biopharm, Monsanto, Gillette and Sepracor.
Since 2006 when he started his private practice, Andrei has consulted with more than 36 companies worldwide, in the USA, Canada, Belgium, Croatia, France, Germany, Ireland, Switzerland and the UK, providing support with QbD internal guideline documents, CRO selection, risk analysis, statistical design of experiments (DoE), chemical engineering calculations for process scale-up, and process analytical technology (PAT). Both drug substance and drug product projects were successfully supported, tackling a wide variety of chemical processes and unit operations, including complex synthetic processes, API crystallizations, micronization and nanomilling, and complex formulations.
Recently Andrei published a paper about successes and challenges with QbD implementation: “Recommendations for Effective and Defendable Quality by Design (QbD) Implementation". Org. Process Res. Dev., 2022, 26, 3, 899-914. A manuscript is in preparation together with colleagues: “Needle-shaped Active Pharmaceutical Ingredient with Improved Flowabilty Produced by a Crystallization Process Developed using Quality by Design Methodology”. Org. Process Res. Dev., in preparation.
Since 2006, Andrei trained more than 3,000 scientists from 200 companies in the art and science of QbD (drug substance and drug product process R&D and manufacturing).
Andrei obtained a Ph.D. in Organometallic Chemistry from the Weizmann Institute of Science (1991), an M.S. in Organic Chemistry from the Technion, and an M.S. in Chemical Engineering from the Bucharest Polytechnic Institute.
Andrei A. Zlota, Presentations,
Publications and Book Chapters
- Zlota, A. A., et al. “Needle-shaped Active Pharmaceutical Ingredient with Improved Flowabilty Produced by a Crystallization Process Developed using Quality by Design Methodology”. Org. Process Res. Dev., in preparation.
- Zlota, A. A. “Recommendations for Effective and Defendable Quality by Design (QbD) Implementation" Organic Process Res. Dev. 2022, 26, 3, 899-914.
- “Fit-for-Purpose Quality by Design (QbD) Implementation, part 1: Risk Analysis and Statistical Design of Experiments (DoE)”, Chimica Oggi/Chemistry Today, 2020, 38(6), 36-38.
- “Quality by Design (QbD): A Progress Report from the Field”, Organic Process Research and Development Conference, Scientific Update, March 2018, Invited Speaker.
- Zlota, A. A., “Navigating Obstacles in the Successful Use of Statistical Design of Experiments (DoE) for Process Development”, Gordon Research Conference, July 2016.
- Zlota, A. A., “Crystallization Process Scale-Up, A Quality by Design (QbD) Perspective”, in “Polymorphs in the Modern Pharmaceutical Industry”, Second edition, Hilfiker, R., von Raumer, M. (Eds.), Wiley-VCH,, 2019.
- Zlota, A. A., “Who is afraid of QbD?”, PharmaChem Europe, 2013, January/February.
- Zlota, A. A., “Quality by Design (QbD) roadmaps; Mid-size and small pharmaceutical companies challenges to implement QbD effectively”, Chimica Oggi/Chemistry Today, 2012, 30(1), 74-76.
- Zlota, A. A. “Avoiding pitfalls in QbD implementation for API crystallization processes”, Scientific Update Scale-Up Conference (2010), invited paper.
- Zlota, A. A., Bakale, R. P., Saranteas, K. E.” Development of a robust scaleable process for the pilot plant manufacture of (S)-amlodipine-L-malate”, Organic Process Research and Development, in preparation.
- Zlota, A. A. “Chemical reactor mapping for safe and rapid scale-up”, Chemical Engineering Progress, in preparation.
- Zlota, A. A., “Chemical Process Scale-Up Tools: Mixing calculations, statistical design of experiments, and automated laboratory reactors”, in “Drug Discovery and Development”, Chorghade, M. S. (Ed.), Wiley, New York, 2007, 251-263.
- Zlota, A. A., “Still Crossing the Chasm: Chemical Engineering Modeling in Drug Discovery and Development”, 17th Symposium on Computer Aided Process Engineering, (Bucharest, Romania), Plesu, V. (Ed.), Elsevier, Amsterdam, 2007.
- Zlota, A. A. “Understanding chemical reactor performance for successful scale-up and technology transfer”, invited presentation at the 10th Annual Technology Transfer Conference of the Institute for International Research, Orlando, Florida, 2006.
- Laughlin, S. M., Wilkinson, S. W., Bakale, R.P, Zlota, A. A. “(S)-amlodipine-malate”, US Patent application, 20060035940.
- Zlota, A. A. “Challenges in crystallization process scale-up”, invited presentation at the 6th Annual Polymorphism and Crystallization Conference of the International Quality and Productivity Center, San Diego, California, 2006.
- Senanayake, C. H., Tanoury, G. J., Wilkinson, S. W., Bakale, R. P., Zlota, A. A. “Method of resolving amlodipine racemate”, US Patent # 6,822,099 (2004).
- Zlota, A. A. “Chemical process scale-up using RC1 ™ and VisiMix ™ scale-up calculations: the Bourne IIIa case”, invited presentation at the 12th Mettler Reaction Engineering User Forum, 2004.
- Zlota. A. A. “Tools for rapid scale-up of crystallization processes”, presentation at the National Meeting of the American Institute of Chemical Engineers, San Francisco, 2003.
- Zlota, A. A. “Crystallization investigations using the RC1 ™, with VisiMix ™ and JMP ™”, invited presentation at the 10th Mettler Reaction Engineering User Forum, 2002.
- Zlota, A. A. “Using VisiMix TM to bridge between Lasentec TM protocols and the use of the FBRM probe in LabMAX TM and RC1 TM reactors”, invited lecture at the 2001 Lasentec TM User Forum.
- Zlota, A. A. “Towards a guide for the perplexed VisiMix TM user; successes and challenges in scale-up”, invited lecture at the First North American VisiMix TM Users’ Forum, 1999.
- Zlota, A. A. “Synergistic use of the RC1 TM, ReactIR TM and VisiMix TM for the safe and rapid scale-up of an exothermic heterogeneous chemical process”, Midwestern Pharmaceutical Chemical Process Consortium, 1996.
- Streib, W. E.; Zlota, A. A.; Caulton, K. G. “Molecular Structure of Cp*RuCl(PtBu2Me), Bull. Polish Acad. Sciences, 1994, 42 (2), 197, invited paper.
- Zlota, A. A.; Tilset, M.; Caulton, K. G. “Attempted oxidative generation of a dihydrogen complex”, Inorg. Chem. 1993, 32, 3816.
- Tilset, M.; Zlota, A. A.; Folting, K.; Caulton, K. G. “A loss of innocence? Charge-transfer interactions with Ph3PNPPh3 + as electron acceptor”, J. Am. Chem. Soc. 1993, 115, 4113.
- Calhorda, M. J.; Galvao, A. M.; Unaleroglu, C.; Zlota, A. A.; Frolow, F.; Milstein, D. “Rhodaoxetane: synthesis, structure and theoretical evaluation”, Organometallics, 1993, 12, 3316.
- Zlota, A. A.; Frolow, F.; Milstein, D. “Synthesis and X-ray structure of a simple metallaoxetane. Metal-based selectivity in oxidative addition”, J. Am. Chem. Soc. 1990, 112, 6411.
- Zlota, A. A.; Frolow, F.; Milstein, D. “Formation of iridialactones by CH2-O oxidative addition of propiolactone to Iridium(I)”, Organometallics, 1990, 9, 1300.
- Zlota, A. A.; Frolow, F.; Milstein, D. “Oxidative addition of Si-Cl bonds to electron-rich Ir I complexes”, J. Chem. Soc., Chem. Commun., 1989, 1826.
- Ashkenazi, P.; Weinberg, O.; Zlota, A. A.; Ginsburg, D. “Propellanes. Part LXXXIV. Reduction of [20.3.3]propellane-24,27-dione: the three isomeric [20.3.3]propellane-24,27-diols” , Recl. Trav. Chim. Pays-Bas, 1986, 105, 254.
- Zlota, A. A.; Ashkenazi, P.; Kapon, M.; Ginsburg, D. “Propellanes. LXXXVIII. Hydroxylation of 11,13-dioxo-12-methyl-12-aza[4.3.3]propella-3,8-diene with Osmium tetroxide”, Tetrahedron, 1986, 42 (12), 3199.
- Balaban, A. T.; Bota, A.; Zlota, A. A. “1,1-Bis[2-furyl]ethanes from 1-(2-furyl)-ethanols”, Synthesis, 1980, 136.
- Note: regular contributor (since 2004) to the “Highlights from the Literature: Some Items of Interest to Process R&D Chemists and Engineers” section of Organic Process Research and Development journal
Andrei A. Zlota, Course Testimonials (QbD and DoE)
“Dr. Zlota is an expert in the field of QbD and I highly recommend this course.”
“Dr Zlota provided an outstanding seminar. The material was well referenced, and presented in an engaging manner. I would highly recommend the course to anyone involved in developing a chemical process.”
“Andrei Zlota gave us a very interesting course. The topics were well balanced. Andrei answered every question with a high degree of competence and kindness. Thank you very much!”
"The excellence of the course is a tribute to the knowledge and understanding of the presenter, Dr. Andrei Zlota, whose ability and willingness to answer and discuss questions were remarkable."
“Andrei is very knowledgeable and also very pleasant to learn from. Looking forward to the DoE course.”
“For a practicing organic chemist QbD is a fairly abstract concept. This course does a wonderful job of conceptualizing the entire process and make it understandable. It is also well balanced in terms of showcasing the strengths and weaknesses. I found myself absolutely engaged for the full three days, even in the areas that I thought I wouldn't be.”
“An excellent course delivered by an expert in the field. Very worthwhile.”
“I liked the way it is structured, it is a systematic approach and in particular I liked the section related to scale-up approaches.”
“One of the best courses I have attended! The lectures were well presented with many relevant examples.”
“Dr Zlota is a good teacher. The topic is very interesting and the content is great. Thank you.”
“Very interesting course due to its practical approach to QbD. Very knowledgeable presenter.”
“Enlightening on a new approach (for me) to face process development.”
“Well presented and good examples. Excellent course!”
“A really huge amount of information explained in a clear and articulate way. An obviously very competent speaker.”
“Excellent course. Found the section on mixing and crystallisation to be very useful.”
“The QbD course helps to provide an understanding of not only the principles but how they can be realistically applied to various processes.”
“Excellent course structure with a lot of valuable insight into the subject of DoE. Surely a must for everyone in Process Design and Methodology based research.”
“Dr Zlota is a great lecturer who takes the time to make sure his audience is following what could be at times challenging material to understand.”
“Andrei does an exceptional job conveying key concepts and applications in this introductory DoE course.”
“This was a very good course. Dr. Zlota is very knowledgeable, and communicated very well.”
“Andrei is a great presenter, very knowledgeable, and talented.”
“I was very impressed with the diversity of topics covered, and Andrei’s mastery of multiple disciplines.”
“Nice thorough overview of QbD and applications to process development and validation. Good comparison of traditional vs. QbD approaches to development. I appreciated the topics of crystallization and ICH guidelines.”
“The QbD course was excellent. Very useful for practitioners and people new to the philosophy…always something new to be learned even if you have used QbD before.”
"Excellent course. Lots of information covered, but I feel it was pitched at a perfect level. I thought Andrei really made the course enjoyable-he is a fantastic teacher...highly personable and very patient answering all the questions posed to him!"
“The quality of this course is ‘built-in’ by the deep experience of the teacher and the numerous well-taken practical examples. Topics and knowledge are so well organized that learning comes very naturally.”
“Sincere thanks to Dr Andrei Zlota…. for the much appreciated on-site QbD training course that was very effectively delivered to us at our facility…. Amidst apparently conflicting directions concerning QbD from many quarters, Andrei Zlota was able to present a very clear, pragmatic and down to earth grounding in QbD principles and practice in terms of intrinsic benefits, regulatory requirements, tools and techniques as well as realistic guidance and direction borne of extensive and erudite first-hand experience and expertise. We highly recommend this training for anyone in the Pharma process chemistry sector seeking practical guidance on QbD best practice and evolving regulatory direction.”