Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

	Dr. Lei Zhang of CDER’s Office of Translational Sciences gave an update at the AAPS Annual Meeting in Chicago yesterday regarding the agency’s regulatory science initiative, which was rolled out in August 2011. She noted that some of the same challenges facing regulators a few years ago continue to plague FDA drug reviewers, namely:

	-products are being developed more quickly using evolving sciences and technologies
	-unmet medical needs are growing
	-industry is shifting from a treatment focus towards a focus on disease prevention and long-term clinical outcomes
	-global drug development is leading to increased responsibilities for all.

	The agency is trying to address these challenges not only with increased regulatory collaboration, which we’ve been hearing about for a few years (e.g., EMA, TGA, overseas offices) but also with grant programs to encourage academic research into how drugs and devices are reviewed and evaluated at FDA.

	Both the University of Maryland and Georgetown University received FDA grants for such work earlier this year. The UMD team, 

, is holding monthly training programs with reviewers at FDA’s White Oak Campus as well as public information exchanges with the industry.

	The work being done largely follows a circular cycle, explained Zhang, in which knowledge gaps in key areas are identified, researched, and filled-all while identifying even newer gaps and then working to research and fill those.

	The UMD/Georgetown programs, along with other grant programs, are part of the Regulatory Science Initiative’s goals to identify standards, questions, and methods for improving internal drug reviews at FDA. The June 2012 FDASIA legislation (see Section 1124) also calls for improving medical product decision-making at the agency and is nudging the initiative further, she said.

Articles

Dr. Lei Zhang of CDER’s Office of Translational Sciences gave an update at the AAPS Annual Meeting in Chicago yesterday regarding the agency’s regulatory science initiative.

FDA Reg Science Initiative Moving Along with Academic Help

At this week’s AAPS 2012 Annual Meeting in Chicago, graduate students across the country are being honored for their research and work in bio/pharmaceutical innovation. 

 had the chance to talk with a few of the recipients.

Biotechnology winner David W. Woessner noted that his team’s work at the University of Utah on Synthetically Lethal Combinations for CML Therapy demonstrates the first development of a protein/peptide-based therapeutic for CML. “While current therapies in the clinic (tyrsosine kinase inhibitors) act on the ABL portion of the protein, we are demonstrating efficacy by targeting the BCR portion, necessary for oligomerization and activation of the tyrosine kinase. Additionally this work also exploits a combination therapy approach early in development,” he said.

Lakshmi Prasanna Kolluru who won for drug design and development focused her work on albumin-based theragnostic nanoparticles for tumor targeted drug delivery. Based Mercer University, the PhD candidate says she was inspired as a teenager by her cousin, a cancer patient suffering from the side effects of chemotherapy. “She was disturbed psychologically when she had lost her hair due to side effects and this spurred the interest in me to focus on cancer research. So, when my professor gave me the freedom to design a project, I opted to work on development of a delivery system that targets anti cancer drugs to tumor and reduces the side-effects of chemotherapy,” said Kolluru.

University of California San Francisco student Rachel Jean Eclov won for her research into 

Enhancers, in the category of Pharmacokinetics, Pharmacodynamics, Drug Metabolism and Clinical Pharmacology and Translational Research. “Previous research on MXR functionality has been mostly aimed at functional (coding) variants of MXR. My research is unique in that it looks for how other types of genomic variations can alter MXR expression and thus drug disposition. I utilize epigenetic tools to unravel how MXR expression can be tissue specific or transiently increased or decreased,” she explains. “I then consider how genetic variation in identified regulatory elements can alter the transcriptional properties of that element. Although other epigenetic research has been published, the majority of it is on variations in regulatory elements that cause developmental defects. My research uses epigenetics to identify genetic variations that impact the more subtle world of drug disposition where the effects of these variations are not as obvious but can be just as severe.”

Full interviews with the winners will appear in the PharmTech December issue. Below is a list of all the graduate students’ winning universities and paper titles:

AAPS Graduate Student Symposium in Analysis & Pharmaceutical Quality

"Quantification and Characterization of siRNA and its Metabolites in Biological Matrices"

“Investigating the Role of Polymer Concentration on the Physical Stability of Nifedipine-PVP Solid Dispersions”

“Assessment of Molecular Drug-polymer Interactions by Mid-infrared Spectroscopy as a Polymer Selection Tool for Formulating Amorphous Solid Dispersions with Optimal Physical Stability”

“High Performance Liquid Chromatographic Method and Selectivity Investigation for the Analysis of Nicotine in Biorelevant Release/Permeation Studies of Smokeless Tobacco”

AAPS Graduate Student Symposium in Biotechnology

“Synthetically Lethal Combinations for CML Therapy—Disrupting Dimerization of Bcr-Abl and Secondary Leukemia Specific Pathways”

“Modeling Pre-existing Immunity to Adenovirus as a Method to Identify Novel Formulations for a Protective Ebola Vaccine”

“Elucidation of Cellular Uptake Mechanism of Novel Ternary Anionic-siRNA Lipoplexes”

“A Highly Potent, Choroid-targeted, Transferrin-tumstatin Fusion Protein and an In Situ Forming Slow-release Hydrogel for the Treatment of Choroidal Neovascularization”

AAPS Graduate Student Symposium in Drug Discovery and Development Interface

“Mechanistic Evaluation of a Mitochondrial-targeted Small Molecule as a Novel Treatment for Pancreatic Cancer”

“Modulation of EGF-receptors Signaling by Small Peptidomimetics and its Implications in Breast Cancer Progression”

“Molecular Docking, Synthesis of Novel Quinazolin Analogues as Inhibitors of Transcription Factors NF-kappaB Activation and their Anti-cancer Activities”

“Design and Development of Albumin Based Theragnostic Nanoparticles for Tumor Targeted Drug Delivery”

AAPS Graduate Student Symposium in Formulation Design and Development

“Theranostic Tumor Homing Pegylated Nanocarrier Drug Delivery System for Treatment of Cancer”

“Understanding Polymer Properties Important for Crystal Growth Inhibition—Impact of Chemically Diverse Polymers on Solution Crystal Growth of Ritonavir”

“Self-assembled Dipeptide Nanotubes, Nanovesicles and Nanogels: Potential Vehicles for Targeted Tumor Drug Delivery”

AAPS Graduate Student Symposium in Manufacturing Science and Engineering

“Contact Drying in an Agitated Filter-Dryer: Experiments and Simulations”

AAPS Graduate Student Symposium in Physical Pharmacy and Biopharmaceutics-Sponsored by Bristol-Myers Squibb Company

“Surface Diffusion of the Organic Glass Nifedipine”

“Molecular Mobility as an Effective Predictor of the Physical Stability of Amorphous State”

AAPS Graduate Student Symposium in Pharmacokinetics, Pharmacodynamics, and Drug Metabolism and Clinical Pharmacology and Translational Research

“Expression and Activity of Drug Transporters in Human Ocular Barriers and Disease Related Changes: Implications for Transporter Guided Retinal Drug Delivery”

“Brain/Brain Tumor Pharmacokinetics and Pharmacodynamics of Letrozole”

-University of California, San Francisco
 

“In Vivo Characterization of ABCG2 Enhancers”

“Effect of Monocarboxylate Transporter Inhibition on the Oral Toxicokinetics/Toxicodynamics of γ-hydroxybutyrate (GHB) and γ-hydroxybutyrate (GBL)”

“Application of a Novel Microemulsion Formulation of Elacridar to Improve Drug Distribution into the Brain for Therapy of Glioblastoma”

“Modeling Effects of Dexamethasone on Disease Progression of Bone Mineral Density in Collagen-induced Arthritic Rats.”

At this week's AAPS 2012 Annual Meeting in Chicago, graduate students across the country are being honored for their research and work in bio/pharmaceutical innovation. Pharmaceutical Technology had the chance to talk with a few of the recipients.

Grad Student Research Sparks Innovation through AAPS Awards

	At this week’s AAPS 2012 Annual Meeting in Chicago, graduate students across the country are being honored for their research and work in bio/pharmaceutical innovation. Pharmaceutical Technology had the chance to talk with a few of the recipients.

	Biotechnology winner David W. Woessner noted that his team’s work at the University of Utah on Synthetically Lethal Combinations for CML Therapy demonstrates the first development of a protein/peptide-based therapeutic for CML. “While current therapies in the clinic (tyrsosine kinase inhibitors) act on the ABL portion of the protein, we are demonstrating efficacy by targeting the BCR portion, necessary for oligomerization and activation of the tyrosine kinase. Additionally this work also exploits a combination therapy approach early in development,” he said.

	Lakshmi Prasanna Kolluru who won for drug design and development focused her work on albumin-based theragnostic nanoparticles for tumor targeted drug delivery. Based Mercer University, the PhD candidate says she was inspired as a teenager by her cousin, a cancer patient suffering from the side effects of chemotherapy. “She was disturbed psychologically when she had lost her hair due to side effects and this spurred the interest in me to focus on cancer research. So, when my professor gave me the freedom to design a project, I opted to work on development of a delivery system that targets anti cancer drugs to tumor and reduces the side-effects of chemotherapy,” said Kolluru.

	University of California San Francisco student Rachel Jean Eclov won for her research into In Vivo Characterization of ABCG2 Enhancers, in the category of Pharmacokinetics, Pharmacodynamics, Drug Metabolism and Clinical Pharmacology and Translational Research. “Previous research on MXR functionality has been mostly aimed at functional (coding) variants of MXR. My research is unique in that it looks for how other types of genomic variations can alter MXR expression and thus drug disposition. I utilize epigenetic tools to unravel how MXR expression can be tissue specific or transiently increased or decreased,” she explains. “I then consider how genetic variation in identified regulatory elements can alter the transcriptional properties of that element. Although other epigenetic research has been published, the majority of it is on variations in regulatory elements that cause developmental defects. My research uses epigenetics to identify genetic variations that impact the more subtle world of drug disposition where the effects of these variations are not as obvious but can be just as severe.”

	Full interviews with the winners will appear in the PharmTech December issue. Below is a list of all the graduate students’ winning universities and paper titles:

	AAPS Graduate Student Symposium in Analysis & Pharmaceutical Quality
	-University of Georgia
	“Quantification and Characterization of siRNA and its Metabolites in Biological Matrices”

	-University of Minnesota
	“Investigating the Role of Polymer Concentration on the Physical Stability of Nifedipine-PVP Solid Dispersions”

	-Purdue University
	“Assessment of Molecular Drug-polymer Interactions by Mid-infrared Spectroscopy as a Polymer Selection Tool for Formulating Amorphous Solid Dispersions with Optimal Physical Stability”

	-Virginia Commonwealth University
	“High Performance Liquid Chromatographic Method and Selectivity Investigation for the Analysis of Nicotine in Biorelevant Release/Permeation Studies of Smokeless Tobacco”

	AAPS Graduate Student Symposium in Biotechnology
	-University of Utah
	“Synthetically Lethal Combinations for CML Therapy-Disrupting Dimerization of Bcr-Abl and Secondary Leukemia Specific Pathways”

	-The University of Texas at Austin
	“Modeling Pre-existing Immunity to Adenovirus as a Method to Identify Novel Formulations for a Protective Ebola Vaccine”

	-University of Connecticut
	“Elucidation of Cellular Uptake Mechanism of Novel Ternary Anionic-siRNA Lipoplexes”

	-University of Southern California
	“A Highly Potent, Choroid-targeted, Transferrin-tumstatin Fusion Protein and an In Situ Forming Slow-release Hydrogel for the Treatment of Choroidal Neovascularization”

	AAPS Graduate Student Symposium in Drug Discovery and Development Interface
	-University of Southern California
	“Mechanistic Evaluation of a Mitochondrial-targeted Small Molecule as a Novel Treatment for Pancreatic Cancer”

	-The University of Louisiana at Monroe
	“Modulation of EGF-receptors Signaling by Small Peptidomimetics and its Implications in Breast Cancer Progression”

	-University of the Pacific
	“Molecular Docking, Synthesis of Novel Quinazolin Analogues as Inhibitors of Transcription Factors NF-kappaB Activation and their Anti-cancer Activities”

	-Mercer University
	“Design and Development of Albumin Based Theragnostic Nanoparticles for Tumor Targeted Drug Delivery”

	AAPS Graduate Student Symposium in Formulation Design and Development
	-Florida A&M University
	“Theranostic Tumor Homing Pegylated Nanocarrier Drug Delivery System for Treatment of Cancer”

	-Purdue University
	“Understanding Polymer Properties Important for Crystal Growth Inhibition-Impact of Chemically Diverse Polymers on Solution Crystal Growth of Ritonavir”

	-F.M. University, Orissa, India
	“Self-assembled Dipeptide Nanotubes, Nanovesicles and Nanogels: Potential Vehicles for Targeted Tumor Drug Delivery”

	AAPS Graduate Student Symposium in Manufacturing Science and Engineering
	-University of Connecticut
	“Contact Drying in an Agitated Filter-Dryer: Experiments and Simulations”

	AAPS Graduate Student Symposium in Physical Pharmacy and Biopharmaceutics
	Sponsored by Bristol-Myers Squibb Company
	-University of Wisconsin, Madison
	“Surface Diffusion of the Organic Glass Nifedipine”

	-University of Minnesota
	“Molecular Mobility as an Effective Predictor of the Physical Stability of Amorphous State”

	AAPS Graduate Student Symposium in Pharmacokinetics, Pharmacodynamics, and Drug Metabolism and Clinical Pharmacology and Translational Research
	-University of Colorado
	“Expression and Activity of Drug Transporters in Human Ocular Barriers and Disease Related Changes: Implications for Transporter Guided Retinal Drug Delivery”

	- University of Cincinnati
	“Brain/Brain Tumor Pharmacokinetics and Pharmacodynamics of Letrozole”

	-University of California, San Francisco
	“In Vivo Characterization of ABCG2 Enhancers”

	-University at Buffalo
	“Effect of Monocarboxylate Transporter Inhibition on the Oral Toxicokinetics/Toxicodynamics of -hydroxybutyrate (GHB) and -butyrolactone (GBL)”

	-University of Minnesota
	“Application of a Novel Microemulsion Formulation of Elacridar to Improve Drug Distribution into the Brain for Therapy of Glioblastoma”

	-University of Buffalo, SUNY
	“Modeling Effects of Dexamethasone on Disease Progression of Bone Mineral Density in Collagen-induced Arthritic Rats”

At this week’s AAPS 2012 Annual Meeting in Chicago, graduate students across the country are being honored for their research and work in bio/pharmaceutical innovation.

	The best approach to deal with an observation with which a company does not agree is to prevent an FDA-483 observation in the first place. During the course of an FDA inspection, there will be many opportunities to ascertain the areas of interest and potential areas of concern of the investigator. The clearest opportunity to understand the true concerns of the investigator will be during the periodic wrap-up sessions, which should occur on a daily basis per 

 (IOM) Section 5.2.3, writes Parexel’s David Elder and Richard Wright, former FDA officials, in the current PharmTech issue.

	FDA investigators are human beings just like the rest of us and mistakes or misunderstanding can happen. The agency encourages the industry to use these communication opportunities to ask questions or request clarification, and if during the course of these communication opportunities it becomes apparent that there is an area of misinterpretation or misunderstanding, additional information or documentation should be presented quickly and clearly, they state. Read more of this answer in the October issue of 

The best approach to deal with an observation with which a company does not agree is to prevent an FDA-483 observation in the first place.

How to Handle an FDA-483 Observation When You Don’t Agree

	I’ll be in Chicago next week for the 2012 annual AAPS meeting and hope to see you there. Looking forward to this year’s hot topic conversations on the changing pharma sciences career, drug development at small companies, FDA’s regulatory science initiative, and drug shortages in the United States. These sessions are being led by key industry representatives and offer insight into key challenges facing bio/pharmaceutical developers and manufacturers. Plus, AAPS will be announcing the recipients of its graduate student awards, among other recognitions. If you can’t make it to the show, be sure to follow my tweets @PharmTechAngie. And if you are there, stop by our booth #5011.

I’ll be in Chicago next week for the 2012 annual AAPS meeting and hope to see you there.

AAPS 2012 Annual Meeting and Exposition Next Week

I've recently been inspired by a series of events, programs, and speeches on the importance of the discovery side of our industry. Over the summer, hundreds of individuals raised nearly $1 million in one week to save the laboratory site of Nikola Tesla, the late physicist and engineer whose work in the late 1800s and early 1900s formed the foundation for wireless and X-ray technology. The funds are to be used to purchase the land where Tesla worked and to build a museum in his honor. The interest and initiative taken by donors to keep a scientific legend's work alive is more than moving.  

New legendary scientists are being discovered every day. In September, I was lucky to be able to attend the PhRMA Research & Hope Awards ceremony in Washington, DC, where nine individuals were honored for their work in the fight against Alzheimer's disease, a disease that is not only plaguing healthcare systems and distressing caregivers worldwide, but that also presents complex scientific challenges. Also in September, 10 major biopharmaceutical companies formed a nonprofit called TransCelerate BioPharma, with the aim of accelerating the development of new medicines, with an initial focus on clinical trial execution.  

This month, our Executive Editor Patricia Van Arnum will be in Madrid to meet the winners of the CPhI Worldwide Pharma Awards, which recognize companies that are breaking new ground in the manufacturing of pharmaceuticals, drug delivery, and sustainable packaging. Across the Atlantic, I will be meeting the recipients of the AAPS Graduate Student, Innovation, and Research Achievement awards in Chicago. The recipients of the various awards are dedicating their studies to improving pharma analysis, formulation design, drug delivery, biotechnology, product performance, and more.  

All of the individuals working to identify new disease diagnostics and therapeutics, whether or not they are recognized on the global stage, serve as the backbone to this industry. For without new products to manufacture for patients in need, where would we be? 

Just where R&D lies in America's future may very well depend on federal spending and support. With the US presidential election around the corner, I thought it important to examine where the country's candidates stand on this issue. Much has been said along the campaign trails regarding manufacturing and innovation, but the candidates' specific views on R&D and related federal spending do not always make the headlines.  

Here are a few goals from Obama's court based on his FY2013 presidential budget proposal, which calls for $140.8 billion in overall federal R&D spending, an increase of $2 billion over the FY2012 enacted level: 			

Enhance innovation in the manufacturing sector by supporting investment in new products, processes, and industries, and by investing in cross-cutting technologies 

At NIH, level funding for biomedical research ($30.7 billion); focus more on translational studies; and to get more out of funds, aim to increase the number of new research grants by 7% 

Provide $2.2 billion for federal advanced manufacturing R&D at the National Science Foundation, and 23 other agencies, a 19% increase over 2012. This includes funding for the National Institute of Standards and Technology to advance research in smart manufacturing, nanomanufacturing, and biomanufacturing  

Improve the patent system and protect IP by giving the US Patent and Trademark Office full access to its fee collections and strengthening its efforts to improve and speed patent reviews

Help small businesses obtain early stage financing.   

Both President Obama and Governor Romney support basic stem-cell research (in addition, Obama removed the federal funding ban on broader embryonic stem-cell research in 2009), and both candidates support making the research and experimentation tax credit permanent. Obama would also like to increase the alternative simplified credit from 14% to 17%. 

Romney's official website includes his plan for American jobs and economic growth. The 160-page document includes language on R&D and basic research, but that language largely focuses on clean energy spending and technologies. The core policy sections of Romney's plan—tax, regulation, trade, energy, labor, human capital, and fiscal management—do not include medical research or science policy (other than from an educational standpoint), and my email request to the Romney campaign team about his take on NIH and FDA spending was not answered.  

Media reports from earlier this year note that Romney would like to shrink the NIH biomedical budget. As governor of Massachusetts, however, he did support the state's biotech and life-sciences industry.  

It will be interesting to see how the winning candidate's goals are carried out given that Congress largely controls the final federal budget. Let's hope that, no matter how Election Day turns out, that R&D still has a significant role. 

Will the next US President support the backbone of our industry?