NEWSLETTERS

Cirrus Pharmaceuticals Inc. is proud to introduce the newest addition to our team: Dr. Thad Stauffer. Dr. Stauffer received his PhD in Bioinorganic Chemistry in 1999 from North Carolina State University, after receiving both undergraduate degrees in Chemistry and Biochemistry from the College of Charleston in 1994. While pursuing his doctoral degree, Dr. Stauffer synthesized, characterized, and studied reactivity of several novel organosulfur compounds and their coordination complexes with a variety of transition metals. Most recently he worked as a Senior Scientist with Catalent Pharma Solutions, Inc. where he directed and executed characterization and investigation studies of Extractables & Leachables from a variety of packaging substrates, medical devices, and drug product formulations. Dr. Thad Stauffer and the newly-added Extractables & Leachables capability are a great asset to the Cirrus team and will offer a valuable service to our clients.

Q: You have a PhD in Bioinorganic Chemistry. How did you decide to specialize in Extractables & Leachables (E&L)?

My graduate work centered on the interaction of Vanadium with sulfur-containing active sites of various proteins. To this end, my lab work focused on the synthesis and characterization of small-molecule, vanadium-containing models of the more complex biological systems. I spent a great deal of time using a wide variety of analytical methodologies to characterize the chemical structure and reactivity of these molecules. The very nature of E&L requires the ability to interpret data from a variety of instrumentation to provide a complete picture of extractables and potential leachables from a given material. Once the opportunity presented itself, the transition to characterizing materials in E&L seemed like the logical next step in my career development.

Q: What does your experience, both in GMP pharmaceuticals and in Extractables & Leachables, bring to Cirrus?

I have had the opportunity to work in a GMP environment conducting E&L related projects for a number of years using numerous analytical techniques. During that time, I have gained experience in working with a wide variety of materials for a wide array of drug delivery systems. With my experience in E&L method development and validation, Cirrus will be able to perform E&L work in-house. That adds to the reasons for partnering with Cirrus for drug product development.

Q: Can you explain the current need for Extractables & Leachables technology in the pharmaceutical industry? Has the need for these studies increased over your time in the field?

Ten years ago, E&L was virtually unheard of. Historically, E&L work was really only required for inhalation and nasal drug products. However, over the past five years or so, the FDA’s requirement for E&L has steadily expanded to virtually all other dosage forms, including parenterals, opthalmics, and even topicals. The current paradigm is that E&L is a crucial requirement of any new application.

Q: What do you foresee being the future of Extractables & Leachables here at Cirrus?

Initially, as the program is being developed, I envision the E&L program at Cirrus as more of an analytical support function for the current projects that are in the early phases of development. However, I expect the group to expand quickly in light of the market developments mentioned previously; and, I envision the E&L group to be an integral part of the service-offerings at Cirrus. The corporate commitment at Cirrus has always been to add quality, meet customer timelines, and provide value to each customer. This same commitment has now been extended to the E&L arena. I feel that with this commitment our new E&L group can use those same philosophies to provide a much needed value-added service to Cirrus' existing customers, as well as Cirrus' expanding customer base. I look forward to working with the talented staff of professionals at Cirrus and also assisting customers with their E&L needs.

Cirrus Pharmaceuticals, Inc. is pleased to announce it has been qualified and designated by Solvay Fluor as its exclusive provider of batch release testing services to perform independent analyses of Solvay's Solkane^® propellants, HFA-134a and HFA-227 in the US.

Solvay is a world leader in the rapidly expanding fluorochemicals market. With this designation from Solvay, Cirrus now has the ability to conduct the analysis on Solkane^® propellants 134a and 227, using Solvay's proprietary test methods that were transferred and re-validated at Cirrus' facilities in the Research Triangle Park, NC.

This ability will allow Cirrus to provide clients with an independent quality review of Solvay's Solkane^® propellants for HFA testing purposes. This type of testing is an FDA requirement for release of a drug product into the U.S. market.
"Cirrus is very excited to be the designated by Solvay Fluor as the exclusive service provider to perform the release testing for Solvay's Solkane^® propellants. Solvay chose Cirrus due to its inhalation expertise and quality of services it provides its clients and with the increase in demand for HFA propellants due to the CFC phase out, this service sector of our business will help speed up product development and the registration process for our clients" said Uli Foley, Cirrus' Director, Business Development.

Cirrus Pharmaceuticals is a contract research and product development company located in Research Triangle Park, North Carolina, USA. Cirrus can assist or manage projects as needed by providing a broad array of R&D services including physical and chemical characterization, formulation development, stability testing, container/closure selection, process development, scale-up and technical transfer to manufacturing for inhaled, nasal, oral, parenteral, topical and transdermal products. Services can include submission-ready regulatory documentation and assistance with regulatory submission questions.

Solvay is an international chemical and pharmaceutical Group with headquarters in Brussels. It employs more than 28,000 people in 50 countries. In 2007, its consolidated sales amounted to EUR 9.6 billion, generated by its three sectors of activity: Chemicals, Plastics and Pharmaceuticals.

Cirrus Pharmaceuticals, Inc. is excited to announce the expansion of our current capacity for stability storage via the addition of 3 LUWA Walk-in Stability Chambers. These new additions include:

Chamber A with a set point of 25°C / 60% RH storage

(long-term conditions)

Chamber B with a set point of 30°C / 65% RH storage

(Intermediate conditions)

Chamber C with a set point of 40°C / 75% RH storage

(Accelerated Conditions)

Each of the chambers will contain 1,100 cubic feet of storage space. These chambers will be cGMP compliant meeting FDA and ICH guideline requirements for stability.

Additionally, the new chambers will be validated, temperature and humidity mapped, and continuously monitored with an alarm system.

The addition of these new LUWA chambers will complement the Cirrus Pharmaceuticals, Inc. current cGMP compliant storage capabilities which include:

• Reach-in stability chamber with set point 25°C / 60% RH
• Reach-in stability chamber with set point 40°C / 75% RH
• Refrigerators at 5°C
• Freezers at -20°C
• Frezers at -70°C

Cirrus' expanded storage capabilities will meet the needs of the continuously growing 100 plus current sponsors. With the additional chambers, Cirrus Pharmaceuticals, Inc. will be able to increase our current capabilities in the areas of Formulation Development, Method Development, Validations, Release Testing, and Stability Testing in support of Clinical Trials, IND and NDA submissions.

This exciting expansion is expected to be completed in Q4, 2008.

We've got space, you've got samples... Let's get them into our new chambers! Please contact BizDev@cirruspharm.com to get started.

Dr. Jay Holt is Director, Inhalation at Cirrus Pharmaceuticals. He joined Cirrus in January of 2000 and he has focused primarily on the management of metered dose inhaler (MDI) and other inhalation programs. He earned a B.S. in chemistry from North Carolina State University and a Ph.D. in organic chemistry from Georgia Tech. For the July newsletter, Dr. Holt was interviewed on his experiences at Cirrus and how his team contributed to the development and market approval of Sepracor's Xopenex HFA^®

- You've been at Cirrus since January of 2000. How have you seen Cirrus grow?

From a numerical standpoint, we’ve grown from a few employees to over a hundred, and we’ve outgrown three lab facilities. But I’ve been most impressed with the growth of talent in the company and the creative solutions that have resulted, ranging from high-throughput inhalation testing to very efficient business processes. During that time we also have greatly expanded our dosage form capabilities.

One of the most notable things about our growth is what has not changed. From the beginning, Cirrus has had a nimble, "get it done" approach that reflects our founders’ style and philosophy. We’ve strived to retain that culture as we’ve grown. So we can still turn around a confidentiality agreement within a day, generate a quotation for a full development program within a week, and change project direction on a dime when necessitated by the sponsor.

- How do you see Cirrus developing over the next couple of years?

Each year we build capacity in existing areas and add new equipment, instrumentation, and talent. For example, we're currently adding walk-in, fully GMP compliant stability chambers, and we're building an expertise in extractables – leachables testing. There is also a lot of excitement around an electronic notebook system that’s being developed and implemented in-house. I expect this style of growth to continue, which will likely mean another facility expansion in the near future.

- When you joined Cirrus, we had just signed a project with Sepracor to develop Xopenex HFA^®, a metered dose inhaler product that is now on the market. In what way did Cirrus contribute to the development of this product?

We contributed to many aspects of the development, including micronization optimization, salt selection, analytical method development, development of the HFA formulation using a statistical DOE approach, primary packaging selection, performance and ruggedness testing, stability studies, and support of the IND and NDA. We also developed and scaled up the manufacturing process and participated in the tech transfer to clinical and commercial manufacturing sites. This project exemplifies the scope of our expertise in MDI development, as well as the value that we can bring to a sponsor.

- How did you and your approach and collaboration contribute to the success of the product?

For Cirrus, speed and quality were key. We got off to a running start and executed our tasks in a very efficient manner. We also have to credit the sponsor for managing their program in a truly expert fashion. They were open to a very collaborative approach, and the project benefited from those synergies. For example, we used a risk-based approach to identify studies that, while not strictly required, were valuable to have in the back pocket during the regulatory review process.

- This project was initiated in 1999, the NDA was filed in mid 2004 and the product was approved in early 2005. The FDA approval time was the shortest in the industry for an HFA MDI. How do you think the structure of Cirrus contributed to the development of Xopenex HFA^®?

Cirrus operates as a matrix organization, which means we could adjust the mix of expertise and resources as the project evolved. For projects that span five years or more and range from pre-formulation to post-marketing support, there is a wide range of skills required, and our flexibility is well suited to meet those demands. I see the Cirrus teams using this leverage this every day, to make special contributions for a wide range of sponsors and dosage forms.

Cirrus Pharmaceuticals, Inc. is pleased to announce our latest addition to the Cirrus team, Dr. Leo Trevino. Dr. Trevino is our new Director of Drug Delivery. He received his Ph.D. in Chemistry from the University of Nice-Sophia Antipolis (Nice, France) and has over 20 years of experience in pharmaceutical research and development. Dr. Trevino's areas of expertise include colloidal drug delivery systems, emulsions, liposomes, foams, parenterals, and topical drug development. As a part of Dr. Trevino's first couple months at Cirrus we interviewed him on his industry experience, his position here at Cirrus, and where he sees Cirrus and the pharmaceutical industry going in the future.

Q: You have a wide range of skills and areas of expertise. You certainly have a wide range of career options. What made you want to work here at Cirrus?

A: Most importantly, it was the quality of leadership. During the interviewing process, I spoke with Jean-Marc (Bovet, Ph.D. – Executive Senior Vice President) and Lili (Bovet, Ph.D., MBA – Executive Vice President). It was very clear that Dr. Bovet is interested in the science, and the value that deep scientific understanding of formulation development brings to Cirrus's sponsors.

Q: Over the past twenty, twenty five years you’ve been involved in a variety of organizations with different areas of expertise. Out of all of these experiences, what do you consider your greatest achievement?

A: Definitely being a part of a very talented team that brought a product from the research phase to market. The product was an intravenous microbubble ultrasound contrast agent. As a team we overcame very difficult technical issues, and at some point even had to delay preclinical development due to some of these issues. In the end, we took the product from preclinical all the way through market approval and launch. It's a great feeling to know that you're contributing in a field that truly improves the quality of people's lives.

Q: And along the same lines, you've also seen a lot of other changes in the pharmaceutical industry. How have you seen drug development change over your career?

A: Over the past twenty plus years, I have seen two definite trends: increased regulatory scrutiny in the development process and increased competitive pressure - pressure from the growth of international competitors and increased public scrutiny of the pharmaceutical industry in general. People want to know more and more about the drugs that are being developed and put into the healthcare marketplace.

Q: And how do you see this playing out over the next couple of years?

A: I think what it comes down to innovation. In effect, we need to focus our collective intelligence to work and push ourselves a little harder if we want to complete a more competitive landscape.

Q: Well put! So how do you see Cirrus fitting into this progression of the drug development industry?

A: Cirrus is really already known as a preeminent drug delivery CRO for inhaled drug delivery – particularly in the pMDI domain. So I really see our future growth expanding that preeminence into other areas of product development, both in scope and in depth. Particularly with potential opportunities in DPI development, intranasal delivery, and new topical and transdermal applications. In all, Cirrus serves as a great model for how contract drug development should be done and I am very appreciative of the opportunity that I’ve been given to contribute to Cirrus’ success.

Cirrus Pharmaceuticals, Inc. is excited to announce our repeat participation at Respiratory Drug Delivery 2008 (RDD). RDD took place this year at the Westin Kierland Resort & Spa in Scottsdale , Arizona from May 11-15. The conference, with a record attendance of 783 industry leaders, featured in-depth discussions of many developing issues surrounding aerosol drug delivery.

At the conference Ramil Menzeleev, Ph.D. and Colleen Moore, two of Cirrus’ key method development scientists, presented on how using modern approaches to analytical chemistry can help increase productivity for unit dose level particle size distribution ( PSD ) characterization. By using LC-MSD as a platform for inhalation product development, significant amounts of time and money can be saved in pulmonary delivery product development projects. Typically, characterization using ACI and NGI are labor and time intensive due to the amount of time spent washing each plate and adjusting the sample to volume. However, by using the combination of the internal standard methodology, LC-MSD, and electronic notebook, Cirrus scientists have found a way to double the productivity of ACI experiments without the use of a robotic wash. At the RDD Poster Sessions, Dr. Menzeleev and Mrs. Moore had the opportunity to discuss this methodology with scientists from all over the world.

A link to the technical poster can be found here.