Friday, October 23, 2009

Beauty Is Only "Skin" Deep

Posted by Mary Liu at Friday, October 23, 2009

The term "beauty is only skin deep" is taken literally here at Kythera Biopharmaceuticals, Inc. in Calabasas, California. Throughout my 4 weeks here, I delved into the fascinating (not exaggerating) world of dermatologic drug products. I learned very quickly that the rules and regulations that apply to dermatologic products are quite different than those that apply to other medications.

My main project was to develop a formulation model that would not only be commercially viable, but also enhance the intellectual property (IP) of this product. I initially performed multiple literature searches, digging through articles to uncover clues and formulate educated hypotheses on a drug candidate Kythera is studying in disorders of pigmentation.

Formulation of a novel topical drug candidate, however, is no easy feat. Once I investigated possible formulation options, I realized that there is an entire set of related issues I had to address: IP, competition, manufacturing, pharmaceutics, and toxicology.

Thus, my wild adventure into the world of dermatologic products began...

The key question every dermatologic drug candidate needs to resolve prior to formulation development is: Can this drug molecule get into the skin? To answer this, two issues must be addressed: (1) size and (2) lipophilicity.

(1) 500 Daltons tends to be the upper limit of the size of a molecule that can penetrate through the stratum corneum. (A Dalton is a measure of molecular weight or mass equal to the mass of one hydrogen atom.) But that does not stop molecules like Protopic (Tacrolimus), which is over 800 Daltons, from being made into an ointment and applied directly to the skin. Recently, an article was published on topically applied cosmeceutical creams containing growth factors and cytokines. Growth factors range anywhere from 20 to 150 kDa (Kilodaltons), so how were they penetrating the skin? The answer may lie in the hair follicle, which has been studied for years by such experts as University of Michigan College of Pharmacy Pharmaceutics Professors Emeritus, Drs. Norm Weiner and Gordon Flynn. Their research, and that of other experts, studied how large molecules could penetrate the skin, and they discovered that transfollicular delivery, along with sebaceous glands, appeared to be most likely the route.

(2) A non-lipophilic drug molecule is not likely to penetrate through the stratum corneum layer of skin. (Lipophilic refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Stratum corneum is the outermost layer of the epidermis.) During my research, I found that various penetration enhancers can be added to the drug vehicle as well as novel drug delivery systems to encapsulate or surround the drug, such as liposomal delivery and molecular umbrellas.

Getting the drug molecule into the skin is just the first hurdle. If we create a formulation that successfully penetrates the skin and reaches the target site of action, then we have to start considering the possibility and consequences of systemic absorption and active metabolites. Based on discussions with a toxicology consultant, preliminary ADME (absorption, penetration, metabolism, elimination) studies could answer these concerns as well as provide a clue to the length of our toxicology study program.

The current commercial landscape is also another issue that we have to consider. Who are our potential competitors? What competing products are already in the marketplace? And from these questions, IP questions will inevitably follow. If other products are already in the marketplace, how will ours be better? What can we do to obtain IP protection and exclusivity in the market?

The majority of my time at Kythera was devoted to piecing together the answers to these questions, as well as to develop potential formulation pathways based on my own research and discussions with various experts in the fields of toxicology, IP, formulation, and penetration/absorption.

I spent the balance of my time at Kythera speaking with various functional leaders of the company (in regulatory, marketing, operations, quality assurance, etc.) to obtain a better understanding of the daily and long term operations of a pharmaceutical company. One valuable concept that I learned was that all roles are interconnected. One decision cannot be made without affecting another department within the company. Kythera grasped this concept from the beginning, reflected in the interior design of their office: glass walls on which people jot ideas, as well as open doors, which welcome a free flow of communication between people.

And although beauty may be skin deep, there's nothing else about this industry that is. The dermatologic drug industry is an increasingly crowded and competitive field. I learned from Kythera, however, that if you are driven, business-savvy, highly knowledgeable about your field, and think outside-the-box, you have great potential to be successful in this industry. This rotation has certainly opened my eyes to the plethora of job opportunities for PharmDs in the pharmaceutical industry — and possibly, a career in drug development for me.

Wednesday, October 21, 2009

Pharma: Sanofi-Aventis with a Global Perspective

Posted by Jeffrey Huang at Wednesday, October 21, 2009

Fellowship or residency: this is the question I have been struggling with so far this P4 year. Both post-doc programs are motivating in different ways and both hit different areas of my academic curiosity. At the University of Michigan College of Pharmacy, we are groomed for a clinical path. We have excellent professors who specialize in different areas of clinical pharmacy and we have experiential training that exposes us to many of these different areas. The curriculum is mostly patient-case based, and we have the opportunity to choose almost half of our P4 rotations in diverse inpatient settings.

These are tough odds for any student thinking about a different path, but here is my train of thought: I hope for a career in pharmacy that goes beyond the counters of a pharmacy and the walls of a hospital. International influences have just fallen into place for me so far in the pharmacy program, including International Society of Pharmacoeconomics and Outcomes Research (ISPOR), International Pharmaceutical Students’ Federation (IPSF) and the newly established Center for Global Health (CGH). And from speaking to different professors and faculty, the route to a pharmacy career that spans international borders is through the pharmaceutical industry.

In industry, the path for a pharmacist can span medical to commercial, research to advocacy. Today, I spoke with a director in the Pharmaco-economics and Reimbursement Department at Sanofi-Aventis. She was originally from the UK, had lived in France for the past four years, and has just recently moved back to the US. She loved the fact that she could move abroad in industry and integrate cultural differences and viewpoints within her work. I also had dinner with a Michigan alumna, now a second-year Rutgers Fellow. She described the various international sites and vendors she works with in her firm's global clinical operations department, and the opportunities she has to travel to these sites to help meet their needs. She’s expanded her reach beyond the US borders, and the opportunities that lay ahead for her are really exciting.

I remember my mother telling me the Chinese idiom 井底之蛙 (Frog in the Well) in sixth grade when she dropped the news that we were leaving Seattle to move to Taiwan. It is a story of a frog in a well whose only vision of the world is the circle of sky it sees from the bottom of the well. It is not until the frog finds the courage to climb out of the well that he realizes how vast the world is, and how much there is to discover outside of his small circle of comfort.

My advice to my classmates, other students at the College, and prospective PharmD students is to explore things outside of your comfort zone and keep your options open. Throw yourself into the unfamiliar and the unknown. I guarantee you will discover things about yourself that you would never have otherwise known. There are so many options for pharmacists beyond institutional and community settings, and even in these settings you can create a unique niche that fits your own aspirations and motivations.

I am quite certain now as I finish my last few days at Sanofi-Aventis that I will be pursuing a path in the pharmaceutical industry through the Rutgers Fellowship. I can easily see myself living abroad and practicing pharmacy on a global scale, and I hope my experience with ISPOR, IPSF, and the CGH will help create opportunities to explore this area.

Sunday, October 18, 2009

Connections of past reflections with new perspectives

Posted by Akin at Sunday, October 18, 2009

My current institutional pharmacy rotation at the Karmanos Cancer Center in Detroit has been meaningful. I was able to do a clinical inpatient rotation in August that was also in cancer, so this present rotation provides reinforcement of some of the major cancer topics that I have learned before, but now from the perspective of the dispensing side.

During my clinical rotation, I was able to work-up patients who were taking chemotherapy regimens and got to see how patients responded to the medication and how they generally appeared and felt during treatment. From this new perspective at Karmanos, I get to see the entire behind-the-scenes process starting from after an order is first written by a physician all the way to the finished medication being sent to either the outpatient infusion clinic or to the inpatient floors. The process involves prudent verification including triple and quadruple checks of dosing calculations, proper documentation, and preparation of drugs in the IV room.

I was given the chance to go under the hood and prepare some IV chemo myself. I was trained to use an interesting device called a Phaseal to prevent accidental spilling of the hazardous chemo. One of the days when I was in the IV room, a chemo vial was accidentally dropped and spilled on the floor. After the chemo spill was cleaned, a demarcated line on the laminated floor remained from where the medication had been even though the medication was cleaned within a few minutes of the spill. These agents are pretty powerful! I certainly wouldn’t want to get any on my skin.

If I could do my clinical cancer rotation again, knowing what I now know from this current institutional rotation, I think I would approach things a little differently. For example, seeing firsthand the power of some of the chemo, I think I would be a little more understanding of some of the patients who looked pretty miserable on the days that they were getting these agents. Another example is with dose recommendations. Now knowing how difficult it is for the techs to measure between the graduated lines on a syringe, I would probably be more likely to round doses to nice whole numbers.

I think I understand why pharmacy residents are required to staff on weekends at the hospital. It helps to understand the behind-the-scenes verification process when on rounding teams. Your contribution to the team can put into consideration things such as IV preparation, inventory, and Rx order travel time that physicians are unaware of. This rotation allows me to integrate past familiarity from previous rotations with current experiences. I’m enhancing my learning and fortifying knowledge so that I can remember key concepts for years to come.

Friday, October 16, 2009

Exploring a Different Side of Pharmacy

Posted by Kendra Yum at Friday, October 16, 2009

Last Friday, I listened to two physicians speak to pharmacists about reinventing health care in America. Their names? Howard Dean and Bill Frist.

They were the keynote speakers during Academy of Managed Care Pharmacy’s (AMCP) Educational Conference. I had the pleasure of attending the conference since I was presenting a poster project from my managed care summer internship in Seattle.

It was interesting to hear what these two well-known politician/physicians had to say about what may and should happen to America’s healthcare system. They presented various hot-topic questions: Would a public option introduce competition and efficiency into the healthcare market? Could it crowd out the private sector? Should there be a healthcare mandate? After a dynamic and lively presentation, an anonymous member of the audience posed a final question: “Would either of you be interested in joining the next season of Dancing with the Stars?”

In addition to hearing about the healthcare reform debate, the conference offered sessions related to emerging trends in the pharmaceutical pipeline, specialty products and managed care pharmacy. I had the privilege of meeting a number of student pharmacists from all across the nation. Many of them took part in AMCP’s Pharmacy & Therapeutics (P&T) competition, where students are charged with the task of analyzing a product dossier and preparing a P&T monograph and presentation.

To give you a glimpse of my managed care summer internship, I stayed in the beautiful city of Seattle and worked at Group Health Cooperative for nine weeks. I had the chance to contact prescribers and patients about the availability of a generic ophthalmic medication. I presented evidence-based information to clinicians which examined high-risk medications in the elderly. I also created and presented a drug monograph for Group Health Cooperative's P&T committee. I developed a project on medication safety, focusing on chemotherapy administration in the outpatient setting. Based upon reported medication errors, published recommendations, and discussions with clinical pharmacists, I helped identify opportunities for improvement and drafted a new policy on chemotherapy handling that included additional error-prevention safeguards.

A final remark about the AMCP conference: I had a GREAT time in San Antonio! I connected with many of the students and pharmacists at the conference on the riverboat tour, while visiting the historic Alamo, and over Tex Mex cuisine and some darn good margaritas!

Tuesday, October 13, 2009

Why Pharmacy?

Posted by Shannon Hough at Tuesday, October 13, 2009

When I was in high school, I babysat for my neighbors. The dad was a nephrologist, and they had two kids and a dog named Henle. Yep. As in the Loop of Henle. At about the same time, I started trying to figure out what I wanted to be "when I grew up". I knew I wanted to work in health care, but started thinking I might like to be a physician. So my neighbor gave me a summer job in his office. I did all sorts of wild and exciting things. I filed charts, picked up lunch, ran urinalysis and answered the phone ... with a lot of hand washing in between! Often times I also went through brown bags of patient medications, consolidating them onto a neat list for the physician to review. As I worked in the office longer, I found myself less interested in lab tests and how a physician determines a diagnosis, and more interested in how all of those drugs helped the patients. I chose pharmacy to impact how the use of medications can improve quality and/or quantity of life for a patient.

I am currently on an institutional rotation at Botsford General Hospital in Farmington Hills, Mich. Pharmacists at Botsford provide decentralized (read: they are not all in the basement) pharmacy services. I will have had the opportunity to rotate through four different weeks with different pharmacists and patient populations. At the halfway point, I have been doing a lot of pharmacokinetic and anticoagulation dosing services.

This month's rotation takes me back to why I chose pharmacy. Other than seeing my neighbor nephrologist every day, I’ve had the opportunity to monitor drug therapy to improve patient outcomes. Possibly one of the most rewarding and petrifying things that this rotation includes is a Cardiac Rehab lecture. I will also be giving a lecture about cardiac medications to patients who have recently undergone heart surgery next Monday. Stay tuned!

Thursday, October 1, 2009

The many hats we wear

Posted by Akin at Thursday, October 01, 2009

As a fourth pharmacy student, my duties extend far beyond experiential rotations. I must also be thinking about completing my PharmD investigational research project, preparing for an hour-long seminar presentation, applications/interviews, and student organization obligations to name a few… just enough time-consuming requirements to make P-4 year anything but a vacation.

Another duty we P-4s have is to mentor first-year pharmacy students (P-1s) who are assigned to us. They shadow us on our rotations for a few days each semester. It is our responsibility to be a source of advice and support to them whenever they need. I have two P-1s assigned to me this year. Some might consider this as a double burden, as most students have just one P-1 student. But I see this as an opportunity not only to be a mentor, but also more importantly to “show-off”. (Smile.) Additionally, I can use this opportunity to reflect on my own P-1 year, and to see how far I’ve come in three years.

My P-1s came to Mott Children's Hospital to see me on my pediatric rotation service -- each on different days. As they asked me questions about my daily P-4 activities and my career goals, I began to realize that it wasn’t so long ago that I was in their shoes asking those same questions. When they asked me about my own aspirations after graduation, I told them what I wanted to do. But when I told them that there are many ways to get there and that I wasn’t 100 percent sure which route was best for me, I was reminded that I, too, need more guidance. I hope to get that at the ASHP Midyear Clinical Conference in December, and from my own mentors who are faculty and alumni.

It is good to have P-1 buddies to whom I can (hopefully) provide some wisdom that will last long after I graduate. I look forward to several more opportunities for them to shadow me as the year goes on. I want to give a shout-out to Courtney and Victor. You both are very enthusiastic students. But, just wait ‘til P-2 year!