Two of our favorite shows to cover during the fall conference season are the ISPE and AAPS annual meetings. Unfortunately, this year they came at exactly the same time. As ISPE kicked off earlier this week in San Diego, AAPS goers were flying into LA just up the coast.

Last week posed a scheduling quandary for anyone interested in Pharmaceutical Quality by Design and Process Analytical Technologies.  Three important meetings were taking place....of course, the AAPS annual meeting in Atlanta, but also the Eastern Analytical Symposium and....the American Institute of Chemical Engineers meeting in Philadelphia.

Building a “world class� organization requires true teamwork. However, in many situations this teamwork is just a myth. Most employees can recall almost a dozen negative teamwork stories for every positive one. Investing in total employee involvement (TEI) can help change this situation, according to David Gootnick at the AAPS show in San Diego.

Gootnick, Managing Partner and Director of David Gootnick Associates, a New York-based management training and development firm, is also a trained scientist, science educator and health management professional with a Ph.D. in business, specializing in management, psychology and communication. “Winning teams synergistically harness their members’ talents and energy. This makes it so that ‘1 + 1 = at least 3’ and often much more.�

In the scientific community everybody is a member of multiple teams, “maybe too many teams,� and is highly degreed. Sometimes this combination results in people confining themselves to their own jobs or roles, sacrificing the team aspects of the team, according to Gootnick. He also thinks that the structure, processes and dynamics of many groups prevents true teamwork.

However, you can’t just wish your group into greatness. You have to systematically identify and remove the obstacles for success. “We have identified 108 blockages or illnesses – anything that gets in the way – to successful teams. Ridding your team of these blockages is the key to improvement,� said Gootnick.

Gootnick has recognized four stages for determining where your team stands and its success. Stage one is the undeveloped stage or old paradigm. It is the stage where most of the blockages (20-75) occur. Stage two is the experimenting stage, where you find your group and dynamics. Stage three is where it all comes together and stage four is where you reach your goal. “You need to get as rapidly as possible from stage one to four, but it isn’t easy and you might have to change the team’s culture,� said Gootnick.

Typical blockages identified include: talking without listening; little concern for others; little shared understanding of goals; boss issuing edicts; no support; policies to keep people in line; and little or no team development. According to Gootnick, team building activities (TBA) drive out these blockages or provide therapy to the team illnesses.

“Every team needs a team code of conduct and more importantly, a mission. These should be the first team building activities,� said Gootnick. He also advocates the team identify key performance measures, clarify team roles and cross train.

A disciple and former student of Buckminster Fuller (one of the first futurists and global thinkers, as well as inventor of the phrase “synergy�), Gootnick extols the virtues of shared goals and vision. “You need total team training. The practice of just training the managers ended 20 years ago.�

Each team member also should have a guardianship role, according to Gootnick. This practice promotes responsibilities valued by the team. Examples of guardianships are communication, motivation, conflict quality, development, resource, blockage and customer. These responsibilities should be regularly (every three months) rotated. “The guardian alerts team members to a situation in their area and handles it when necessary. Therefore, team leadership roles are shared.�

In addition, the three C’s (communication, cooperation and coordination) will help teams get to the next stage faster. These characteristics help prevent some blockages such as hidden agendas, boredom, interpersonal disputes and powerlessness. The result is a successful team where the whole is greater than the sum of its parts. Some stage four team characteristics are: individuals dedicated to the team; trust; members understand the whole team system; and a deep sense of pride in team accomplishments.

With all the talk of outsourcing in the pharmaceutical industry, Gootnick had a different take, “Outsourcing is just failed internal teams.�

BS

In May of 2007, the FDA added the Critical Path Initiative (CPI) for generic drug development. Still in its infancy, the framework hopes to eventually clear some of the roadblocks in the generic development process.

Speaking at the AAPS show, Robert Lionberger, from the FDA Office of Generic Drugs, explained FDA’s role of challenge identifier, input gatherer and collaborative participant in the process. The goal is to smooth the process for faster approval of future generic drugs.

“Since 50-60% of prescriptions are being filled with generics, it was time to look at the impediments to their development,� said Lionberger.

The agency has identified roadblocks in characterization, design, bio-equivalency tests and scale up/manufacturing. “To make a copy, an ANDA sponsor might need better characterization than the original,� said Lionberger.

In the design phase, it is hard to identify the quality attributes of new/complex dosage forms. For example, inhalers, transdermal patches and modified release mechanisms have limited dissolution IVIVC tests to evaluate the proposed formulations and processes.

According to Lionberger, problems in scale up have led to wasted commercial batches and process variability. In addition, many times it may require the sponsor to reformulate the product or revise the process.

Therefore, the FDA has identified four areas of opportunity in the CPI for generic drugs:
• Improve the science underlying quality by design for the development and manufacture of generic drug products.
• Improve the efficiency of current methods for assessment of bioequivalence of systemically acting drugs.
• Develop methods for the assessment of bioequivalence of locally acting drugs.
• Develop methods for characterizing complex drug substances and products.

“Quality by Design tools will help in the design and manufacture of generic products,� said Lionberger. “Formulation and absorption modeling, as well as dissolution tests will be critical.�

According to Lionberger, the bio-equivalence of locally acting drugs (e.g., nasal, skin, GI tract) will have the biggest impact on generic competition. However, these also have the most challenging scientific issues. New methods sought for locally acting drugs include: in vitro tests for product equivalence; imaging techniques; target tissue sampling; new biomarkers; and new designs for clinical endpoint studies.

“The goal of bio-equivalence is finding a biomarker for local delivery,� said Lionberger. “These could help companies identify sooner those product candidates that are likely to fail, while directing more resources to develop promising candidates.�

BS

The American Association of Pharmaceutical Scientists (AAPS) has announced its 2007 AAPS Fellows, cited for making "remarkable scholarly and research contributions to the pharmaceutical sciences." They will be recognized at the group's annual meeting this week in San Diego, which Bill Swichtenberg will be attending.

Congratulations to each and every one of them.  (If PhRMA would like to launch a new P.R. campaign to improve the public image of the pharma industry, perhaps its marketing types could describe some of these individuals' work in its public affairs material.  It's definitely a nice counterpoint to all the sales and marketing news).

And, for those who remain skeptical about process analytical technologies (PAT), or who think Quality by Design is the FDA's latest "flavor of the month," consider that at least two of these Fellows are very closely involved in both these areas.

 More on each of the fellows below:

Kenneth R. Morris, Ph.D is currently a Professor and the Associate Head of the Industrial and Physical Pharmacy Department at Purdue University . He has worked in the academic, industrial, and governmental sectors in both the pharmaceutical and environmental disciplines. His main research contributions have been in the area of pharmaceutical materials science and engineering. These pursuits led Dr. Morris to develop advanced techniques to monitor processing stress-induced changes for use in developing predictive models, and he emerged as the academic thought leader in the areas of quality by design, PAT and other important pharmaceutical product development initiatives.

Moheb M. Nasr, Ph.D is the Director of the Office of New Drug Quality Assessment, Center for Drug Evaluation and Research , U.S. Food and Drug Administration. He is responsible for providing executive leadership, scientific expertise, and overall technical direction to 150 multidisciplinary pharmaceutical scientists, chemists, engineers, and medical professionals engaged in the regulatory and scientific evaluation of Chemistry, Manufacturing and Controls (CMC) for all Investigational new drugs, and new drug applications intended for human use. Throughout his distinguished career at the FDA, Dr. Nasr has exemplified the spirit of distinguished public service through outstanding scientific and scholarly contributions to improving human health.

Mansoor M. Amiji, Ph.D is a Professor and Associate Chairman of the Pharmaceutical Sciences Department at Northeastern University , and Co-Director of the Nanomedicine Education and Research Consortium (NERC). Over the past 15 years, Dr. Amiji has contributed to the development of novel approaches for surface modification of polymeric biomaterials to improve biocompatibility, micro- and nanotechnologies for target-specific drug and gene delivery, and newer generations of multifunctional nanostructures for biomedical and pharmaceutical applications.

Steven Baertschi, Ph.D is a Research Fellow in Analytical Sciences R&D at Eli Lilly and Company, Indianapolis , Indiana . Over the last 18 years he has made significant contributions to the pharmaceutical sciences in the areas of drug stability, stress testing/degradation chemistry, photostability testing, and the development of analytical methodologies. Dr. Baertschi’s work in delineating degradation pathways has demonstrated the importance of using a "chemistry-guided approach" to solving complex stability problems and to the development of stability-indicating methods.

Ajay K. Banga, Ph.D is Professor and Chair in the Department of Pharmaceutical Sciences at the College of Pharmacy and Health Sciences, Mercer University , Atlanta , Georgia . His research expertise is in non-traditional approaches for transdermal drug delivery. Dr. Banga has investigated transdermal iontophoretic delivery of water soluble drugs for several years and more recently is also using microneedles and other approaches for transdermal delivery of macromolecules. He has just published a theme section on transdermal delivery of proteins in Pharmaceutical Research as a guest editor.

Peter L. Bonate, Ph.D.is currently Senior Director of Pharmacokinetics at Genzyme. His research has involved the exploration of new modeling and simulation methodologies and their application to drug development. He was one of the pioneers in using linear and nonlinear mixed effects modeling of exposure-QTc interval data. Dr. Bonate has been or is currently on the editorial advisory boards of the Journal of Clinical Pharmacology , the AAPS Journal , and Pharmaceutical Research , and he has more than 40 publications in the field of pharmacokinetics and clinical pharmacology

Piet Herdewijn, Ph.D. is one of the founders of the International Society for Nucleosides, Nucleotides and Nucleic Acids and is a member of the Belgian Academy of Medicine. He has taught the course of medicinal chemistry for 20 years at the Katholieke Universiteit Leuven in Belgium and is the head of the laboratory of medicinal chemistry in the Rega Institute for Medical Research, Belgium . Dr. Herdewijn contributed to the medicinal chemistry of nucleosides, oligonucleotides and peptides with applications in the anti-infection and antitumoral field. He has published 500 articles in international journals on these topics and, more recently, he discovered nucleoside triphosphate mimics that are accepted as substrate by HIV reverse transcriptase.

Donhgho (Robert) Lu, Ph.D. joined the U.S. Food and Drug Administration/ONDQA in 2005. Prior to his FDA career, he was a full professor in pharmaceutics at School of Pharmacy , Temple University , and an associate/assistant professor at College of Pharmacy , University of Georgia . Dr. Lu’s academic research interests have included the development of gene delivery and controlled-release systems, and the syntheses of pharmaceutical compounds with enhanced targeting properties

Tobias Massa, Ph.D. has supervised the regulatory strategy and authoring of chemistry, manufacturing and control sections of 20 globally approved pharmaceutical products and over 150 investigational drug applications. He is currently responsible for managing the CMC regulatory strategy for a portfolio of over 50 products in development and 300 approved products globally for Bristol-Myers Squibb Company. In addition to his corporate responsibilities, Dr. Massa has had a leadership role in efforts to refine regulatory policy for the manufacture and control of synthetic and biological products. He has chaired numerous industry committees on topics such as submission content, change control, specifications, biologics regulations and utilization of biologics manufacturing facilities.

Carlo Rossi, Ph.D.started his research career in the chemistry of natural products field. In particular, he studied the holothurinogenins, toxic saponin principles produced by the Actinopyga agassizi , a marine animal that is very active against its predators. More recently, Professor Rossi turned his scientific interests on the pharmaceutics and drug delivery areas, where he continues to be active. Noteworthy is the research line by which he developed, in a close collaboration with a group of MDs, multifunctional composite microcapsules as potential artificial bio-hybrid organs as a final cure for the type I diabetes mellitus.

Mandip S. Sachdeva, Ph.D.is a professor and section leader for the pharmaceutics activity at Florida A&M, College of Pharmacy . He has made significant contributions to the knowledge and understanding in the area of drug delivery with special emphasis in inhalation/aerosol delivery as applied to lung cancer and topical delivery of neuropeptides. He has used a multidisciplinary approach of not only delivering novel anticancer agents by inhalation drug delivery but also looking into their mechanism of action to look for newer targets. During the last 20 years, besides developing new approaches for improved drug delivery to the lungs and through the skin, Dr. Sachdeva has identified new molecular pathways and mechanisms for therapeutic agents intended for the treatment of lung cancer and skin inflammation.

Robert M. Straubinger, Ph.D Dr. Straubinger’s research in the field of biopharmaceutics focuses primarily upon drug carriers, drug targeting, and drug delivery. His sustained research on the taxane anticancer agents represents a comprehensive exploration of biophysical factors that determine formulation stability, as well as the pharmacological consequences of formulation properties. This work is described in approximately 14 publications and several patents, and resulted in the development of improved, liposome-based formulations of taxol (paclitaxel) having reduced toxicity.

Shinji Yamashita, Ph.D.has conducted continuous research on oral drug absorption and has published many important articles in this field. He is best known for his pioneering work on the development of in vitro and in situSumie Yoshioka, Ph.D. has been involved in fundamental studies with particular emphasis on the difficult and complex area of solidstate stability for more than 25 years. Dr. Yoshioka has published over 100 papers in peer-review journals and provided important leadership in the application of such science to regulatory and health policy issues world-wide. Achievements in her research include: elucidation of the importance of the role played by the physical properties of molecules in the solid state in determining the tendencies for such systems to undergo both physical and chemical instability, and work on solid-state stability using nuclear magnetic resonance to quantitate various types of molecular motions and to demonstrate their role in promoting instability.