Pharmaceutics Workshop

Microenvironmental pH Modulation in Solid Dosage Forms: Chemical Stability, Dissolution, and Oral Absorption

Drugs:  Manufacturing, Analyses and FDA Regulations

Friday May 18, 2007  –  8:30 a.m. to noon

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[ PLEASE... If you plan to attend, please fill out our participant survey ]

The workshop is intended to be a forum for the presentation of the critical factors that determine consistent quality of pharmaceutical products, the science behind the manufacturing process, appropriate analytical methods and evaluation of the science behind the regulatory requirements and recommended changes in the regulatory field. Topics to be covered by the Workshop are:

  • Current opinion on regulatory requirements for Drug Substances (Active Pharmaceutical Ingredients)
  • Critical factors in ensuring batch to batch consistency in Drug Product manufacturing, bioavailability and stability
  • Formulation, correlation of dissolution to bioavailability (in immediate release and extended release products), dissolution methods
  • Current "Chemistry Manufacturing and Controls" (CMC) regulatory requirements, the rationale for the requirements (from industry / academia and regulators perspectives)
  • Critical factors missing in current CMC regulations.


Workshop chairperson:  Dr. Zelleka Getahun, FDA,  [ bio ]




8:40 AM

Dr. Katie Hunt, President, ACS  (special guest speaker) [ bio ]

“Re-igniting our Commitment to Science and Technology: Education, Collaboration and Innovation!”

9:00 AM

Dr. Richard C. Adams, Center for Drug Evaluation and Research, FDA [ bio ]

“Chemistry, Manufacturing, and Controls (CMC) Requirements for Multi-source (Generic) Drug Products: Up to the Task?”

9:40 AM

Dr. James S. McElvain, Amgen Inc.

[ bio ]

“Leveraging Scientific Knowledge and Experience into Pharmaceutical Regulatory Submissions: An Analytical Perspective”

10:40 AM

Dr. Munir A. Hussain, Bristol-Myers Squibb Co. [ bio ]

“Microenvironmental pH Modulation in Solid Dosage Forms: Chemical Stability, Dissolution, and Oral Absorption”

11:20 AM

Dr. Reza A. Fassihi, Temple University [ bio ]

“Development of a sensitive and reliable dissolution procedure unconventional drug delivery systems”


The Speakers:

Richard C. Adams is Deputy Director, Division of Chemistry II, Office of Generic Drugs, Center for Drug Evaluation and Research (CDER).  Prior to joining CDER, he worked with the Central Research Facility of Pfizer, Inc. having responsibilities in Discovery Research, Production Process Development, and Process R & D.  He later became a chemistry reviewer, Team Leader, and Deputy Director for CDER.  He has served on numerous office and center technical committees and ad hoc working groups and has chaired the Center Stability Technical Committee.


James S. McElvain is Director and Head of the Analytical Chemistry Department at Amgen Inc. in Thousand Oaks, California. His primary responsibilities involve directing and overseeing the development and implementation of analytical methodology to quantitate and characterize novel small molecule and peptide therapeutics during R&D product development. Prior to joining Amgen, Dr. McElvain held positions at Hoechst Marion Roussel in Kansas City, MO engaged in developing automated bioanalytical methods using LC-MS for pharmaceutical development candidates. He has a B.S. degree in Biochemistry from California Polytechnic State University in San Luis Obispo and M.S. and Ph.D. degrees in Biochemistry from Washington State University. Dr. McElvain has served as a member and past chair of the PhRMA Analytical Technical Group (ATG) as well as serving as a member of the PhRMA Technical Leadership Committee (TLC).  


Munir A. Hussain is a Senior Research Fellow at Bristol-Myers Squibb Company, New Brunswick, New Jersey. He received his B.S. in pharmacy from the University of Baghdad, Iraq and his Ph.D. in pharmaceutical sciences from the University of Kentucky in 1983.  He holds adjunct professor appointments at the School of Pharmacy, Duquesne University; College of Pharmacy, University of Kentucky; School of Pharmacy, Temple University; College of Pharmacy, University of Tennessee; and served as a board member, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University. He serves as a member on many graduate students’research committees. He is a member of the editorial boards of the Journal of Pharmaceutical Sciences, Journals of Pharmaceutical Development and Technology and AAPS PharmSciTech. He is the author/co-author of over 95 refereed publications in different areas of pharmaceutical sciences, 90 abstracts/national and international seminars, and 13 issued patents.  He is a Fellow of the American Association of Pharmaceutical Scientists (1993).  His research interests include drug delivery, preformulation, dissolution, formulation development and scale-up, and mechanisms of degradation and stabilizations of drugs.


Reza A. Fassihi is is professor of biopharmaceutics and industrial pharmacy at Temple University, school of pharmacy where he has taught and done research in the pharmaceutical sciences. He received his B.S. in pharmacy and his Ph.D. in Pharmaceutics from Brighton University in England in 1978 and was awarded a gold medal for his research work. He has worked as an assistant professor (1979-1982), a postdoctoral fellow at Brighton University (1983), a Senior Scientist at Welsh School of Pharmacy (1984), Senior Lecturer at Rhodes University in South Africa (1984-1986), and has been Professor and Head of Department, school of pharmacy, University of the Witwatersrand in Johannesburg (1986-1992) where he was awarded with gold medals by both the Academy of Pharmaceutical Sciences of South Africa and the Society of Cosmetic Chemists.

In 1991 he was a visiting professor at Cincinnati University and in 1992 he joined Temple University where he has served as professor, director of graduate programs, has chaired various committees and is Co-chair of PPF (Philadelphia Pharmaceutical Forum). He has been an invited speaker at various professional meetings and has presented seminars and workshops nationally and internationally and is a member of numerous societies. Dr. Fassihi has authored or coauthored more than 124 peer-reviewed professional papers on topics related to design, development, in-vitro and in-vivo evaluation, optimization and scale up operations of dosage forms, has numerous chapters in books, holds 6 US patents and has over 350 abstracts. He is a member of several professional organizations including the AACP, ACS, HPA, AAPS and CRS and is a Fellow of AAPS. He has trained 22 MS and PhD students and has mentored visiting scholars and postdoctoral fellows. Currently he has ongoing projects in various areas of drug delivery design targeting the upper and lower GI tract for achieving optimum therapeutic response. He acts as consultant to a number of pharmaceutical and nutritional manufacturers, government agencies, and has served as an expert witness on development and use of drugs and issues related to pharmaceutical products.


Special Guest Speaker:

Dr. Catherine T. “Katie” Hunt is Leader, Technology Partnerships for Rohm and Haas Company. Accelerating the pace of innovation in the company by fostering collaboration with industry, academia, national laboratories, government agencies and foundations is her main role. Since creating the unit in 2002, she has helped secure multi-million dollar grants from federal agencies to improve collaboration across all sectors. Dr. Hunt began her career as a senior scientist at Rohm and Haas Company after completing an NIH Postdoctoral Fellowship at Yale University. For more than 20 years she has held positions of increasing responsibility, from research scientist to plant laboratory manager to Director of Worldwide Analytical and Computational Competency Network and Technology Development. Dr. Hunt holds an A.B. in Chemistry (Cum Laude) from Smith College and a Ph.D. in Chemistry from the University of California, Davis. She has authored 13 papers and one book chapter on Metallothionein, a protein that binds heavy metals.

Dr. Hunt is President of the American Chemical Society, a fellow of the American Association for the Advancement of Science, and a member of the International Union on Pure and Applied Chemistry, and Sigma Xi. Dr. Hunt serves on the Board of Directors of the Council for Chemistry Research and is an organizing member of the Vision 2020 Nanotechnology Roadmap.

Over her professional career, Dr. Hunt has received many awards, including being one of just 25 women to represent the U.S. in the People to People Ambassador Program’s Women in Science Delegation to Cuba (2001). She is a past best-paper awardee from the Association of Nonwoven Fabrics Industry and a team recipient of her company’s S.J. Talucci Quality Award for developing a global, interactive analytical network. Recently, Dr. Hunt was named one of Pennsylvania's "50 Best Women in Business" by the commonwealth’s Department of Community and Economic Development, and was awarded the Smith College Medal from the Board of Trustees.


The Chairperson:

Zelleka Getahun is a Chemistry Reviewer in the Office of Generic Drugs (OGD) at the FDA. Her primary responsibility is evaluation of Abbreviated New Drug Applications (ANDA's) from the chemistry, manufacturing and controls perspective to assure that the drug product can be consistently and reproducibly manufactured to meet the requisite quality standards. This involves evaluation of the syntheses and controls of the active pharmaceutical ingredient, drug product formulation and manufacture, analytical methods for finished product release and stability monitoring. Her review experience covers various dosage forms for multiple therapeutic categories. Prior to joining OGD she has held positions at the University of Pennsylvania - Department of Biochemistry and Biophysics (peptide research), Dupont-Merck Pharmaceutical Co. (drug discovery research) and NIH (anti-mitotic drugs research); she has also served as an adjunct Assistant Professor (Organic Chemistry) at Temple University. She has a Ph.D. in Organic Chemistry from the University of Vermont (1987) and a B.Sc. in Chemistry (with a minor in Mathematics) from Addis Ababa University, Ethiopia (1980).



Special Remarks by Katie Hunt [ bio ] “Re-igniting our Commitment to Science and Technology: Education, Collaboration and Innovation!”   Chemistry is at a crossroads. It's time to re-ignite our commitment to Science and Technology. I believe that the keys to success in this endeavor are: Education of legislators, the public and the next generation; Collaboration to build a strong, vibrant and vocal technical community; and Innovation to recreate our companies, our schools and ourselves.

Education: Promoting Science and Engaging Students – Today's students are our future scientists, technologists and policy makers. Now, more than ever, we need to engage the next generation in the exciting and challenging field of science. "In the highly competitive, global economy of the 21st century, mathematics and science are no longer pursuits for the few. They are requirements for all" (A Commitment to America's Future: Responding to the Crisis in Mathematics and Science Education, Business-Higher Education Forum, 2005). It is time for us to actively promote Science and Technology on the local and national stage: from championing research investment to building technology partnerships, from mentoring students to promoting science fairs.

Collaboration: Building Strong Partnerships – No single company can do it alone; no scientific society can, or should, go it alone. We can best leverage our science and technology education and advocacy efforts by reaching out to other professional societies and forming strategic partnerships and coalitions.

Innovation: Recreating our Companies, our Schools and Ourselves – Investing in the physical sciences is an investment in the future! Incremental improvements are important, but we will not "tweak" ourselves to greatness. Sustainable growth will be driven by ongoing investment in cutting-edge, step-out innovation.

Looking ahead – At a time when chemistry has so much to offer, I am pleased and honored to step to the plate as President of the American Chemical Society. Now is our opportunity to make a difference. Working together we can make the ACS Vision a reality: "Improving People's Lives through the Transforming Power of Chemistry!"


Talk 1 – Richard Adams [ bio ] “Chemistry, Manufacturing, and Controls (CMC) Requirements for Multi-source (Generic) Drug Products: Up to the Task?”   What is the task? How do specific components of the CMC requirements contribute to the overall mission? Pharmaceutical Equivalence issues.   Modified Release Generics with release mechanisms differing from the RLD.  Narrow therapeutic index/Critical care drug products: special cases: should they be treated as such?  Issues for problematic drugs.



Talk 2 – Dr. James McElvain [ bio ]   “Leveraging Scientific Knowledge and Experience into Pharmaceutical Regulatory Submissions: An Analytical Perspective” The principles of Quality by Design (QbD) have recently become a modern bellwether for pharmaceutical drug development that is being embraced by both the pharmaceutical industry and international regulatory authorities such as the FDA. The elements of QbD are fundamentally based on the concept that the quality of a new molecular entity should be designed into the product from the start and evolves as the product matures through its development lifecycle. This science and risk based philosophy to product development relies on the knowledge that grows as the compound progresses through nonclinical and clinical development. At the time of final market application filing and commercial launch, these well defined and thoroughly characterized pharmaceuticals are ideally positioned to meet the current and future needs of the patients that depend on these life saving medicines. Despite the relative novelty of the term "QbD" in modern pharmaceutical development, the principles of applying good science to understanding and controlling product quality have been a cornerstone of the pharmaceutical industry for many years. The focus of this presentation will highlight several key examples of how critical analytical knowledge and experience gathered during product development can be essential to ensuring successful regulatory submissions and maintaining overall product quality.



Talk 3 – Dr. Munir A. Hussain [ bio ]   “Microenvironmental pH Modulation in Solid Dosage Forms: Chemical Stability, Dissolution, and Oral  Absorption”.    Microenvironmental pH can affect solid dosage form performance, particularly stability and dissolution profile. Modulation of the microenvironmental pH through the use of pH modifiers can be a very effective tool in maximizing solid dosage form stability.  Judicial selection of the appropriate pH modifier, its concentration and the manufacturing process used to incorporate the pH modifier is necessary to enhance stability.  Microenvironmental pH modulation can also control the dissolution rate and oral absorption of both immediate and controlled release dosage forms of compounds with pH dependent solubility. Examples on the utilization of  microenvironmental pH control to enhance stability and dissolution/oral absorption will be presented.



Talk 4 – Dr. Reza Fassihi [ bio ]  “Development of a sensitive and reliable dissolution procedure unconventional drug delivery systems”. Development of a meaningful dissolution procedure and specifications for in-vitro and in-vivo applications (IVIVC) and assurance of product quality and batch-to-batch reproducibility in release profiles especially for modified release systems has been a challenge to both the pharmaceutical industries and the regulatory agencies. Both GI physiology and the physicochemical properties of the drug and behavior of the delivery system are important to the oral absorption. Dissolution study is particularly important for drugs that demonstrate absorption-rate limited or dissolution rate limited characteristics as defined by the Biopharmaceutics Classification System, BCS. In this respect a meaningful and discriminatory power of dissolution rate testing becomes critical and development of a sensitive, reliable in-vitro dissolution procedure for the quality of a product and prediction of its bioavailability is of primary goal and will be discussed in details.


Note: Opinions and comments expressed in this Workshop are those of the presenters only and do not necessarily reflect the views or policies of the FDA.


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