Category Archives: Business

05Oct/06

Life Sciences Industry is an Emerging Powerhouse in Pennsylvania

By Daniel R. Matlis
 

According to a recent study by the Milken Institute the life sciences industry is an emerging powerhouse for U.S. global economic competitiveness in the 21st century. In the study, Philadelphia ranked as the 3rd most vibrant biosciences cluster in the nation.
Pennsylvania’s $2 billion Biosciences Enterprise commitment, coupled with Governor Edward G. Rendell’s $2.3 billion Economic Stimulus Package is fueling research and development, attracting venture capital, and supporting early-stage investment.
 

Recently, I had the opportunity to speak with Rebecca Bagley, Deputy Secretary for the Technology Investment Office of the Pennsylvania Department of Community and Economic Development (DCED), to learn about what the Commonwealth is doing to attract and retain life science companies.
 

What is PA’s vision around life sciences?
 

Life science is a major focus cluster for the Commonwealth since Governor Rendell took office. One of the reasons we focus in that sector is the continuum of assets the Commonwealth has to offer. The spectrum includes world class universities; eight of the United States’ largest pharmaceutical companies are located within a 50-mile radius of Philadelphia; and a strong venture capital climate.
 

How does the Commonwealth benefit?
 

We benefit through jobs, research and development expenditures, leveraging of capital into the state, as well as attracting entrepreneurs which benefit the state in the long run. There are more than 125 bio-pharma [biological-pharmaceutical] companies and more than 2,000 biosciences-related companies located in Pennsylvania.
 

How have trends such as outsourcing and the flat world impacted life science firms in PA?
 

The Commonwealth has a focus on innovation and early stage companies, funded not only through a venture capital network but also through our Life Science Greenhouses, a network and resource for early stage capital.
 

We also have the large pharmaceutical companies which provide potential for partnership opportunities.
 

In life sciences, it is less likely that the manufacturing will go overseas because of Food and Drug Administration (FDA) restrictions and the specialties that are necessary compared to a call center. Biotechnology manufacturing is much more complex and therefore more difficult to relocate overseas; we have not seen this trend with bio-pharma.
 

We have seen a significant shift to overseas life science manufacturing to countries like Mexico, Brazil and China. How has this impacted PA?
 

With our focus on innovation and heavy research and development, Pennsylvania offers a great advantage to bio-pharma companies. The Commonwealth is targeting high tech, complex manufacturing.
 

What initiative does the state have to attract foreign companies to establish headquarters in PA?
 

Within the Governor Rendell’s budget this year, we have a $ 15 million allocation for World Trade PA, which will help focus our international activities with both recruiting and attracting early stage companies to relocate here. For example, the Science Center in Philadelphia is recruiting early stage Japanese companies. Historically our goal has been to attract established companies to set up their U.S. headquarters in the Commonwealth.
 

How does your approach differ when dealing with early stage versus established companies?
 

The Technology Investment Office focuses on early stage innovation and technology.  There are other offices with in the department along with the Governor’s Action Team which focus on attracting or recruiting the established companies to PA.
 

We have a strong relationship with Pennsylvania Bio. This ensures that companies based in Pennsylvania stay in the state as they grow and require larger facilities. To that end, DCED Secretary Dennis Yablonsky and the president of PA-Bio meet with companies in Pennsylvania to make sure that growing companies are familiar with the range of incentives the state has to offer.
 

We offer packages that include loans, grants and tax credits that can accommodate relocation of large companies. We also can assist with site selection. The Governor’s Action Team works closely with local entities to ensure the process is smooth.
 

What is the state doing to attract service organization that support life sciences to ensure there is a complete ecosystem within the state?
 

That has been our approach from the beginning. We build clusters to include large pharmaceutical companies, service providers and early stage companies together in one area to have a complete market place.
 

So why should life science companies consider Pennsylvania?
 

The assets we have in the Commonwealth to develop life science clusters are very attractive to companies. From world class universities, which can provide research at their fingertips, to the supportive venture capital environment, and an extremely supportive and proactive state government, which provides both incentives and focused initiatives for the life science industry, we have created an environment which makes it very encouraging for companies to operate in the Commonwealth. Additionally, we offer great quality of life, great schools, inexpensive housing and thriving communities.

ã 2006 by Axendia

30Sep/06

FDA Issues Final cGMP Guidance

By Daniel R. Matlis
                            
Yesterday, on the heels of the release of a critical Institute of Medicine Report, the FDA issued a Final Guidance for Industry on a Quality Systems Approach to Pharmaceutical CGMP Regulations. The guidance covers the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Veterinary Medicine (CVM) and the Office of Regulatory Affairs (ORA).

This new guidance appears to be an interim step on the long awaited rewrite of the 1978 GMPs, known as the “GMPs for the 21st Century Initiative”.
According to the FDA, this guidance aims to address the following issues:

  • A quality system addresses the public and private sectors’ mutual goal of providing a high-quality drug product to patients and prescribers. 
  • A well-built quality system should reduce the number of (or prevent) recalls, returned or salvaged products, and defective products entering the marketplace. 
  • It is important that the CGMP regulations are harmonized to the extent possible with other widely used quality management systems, including ISO 9000, non-U.S. pharmaceutical quality management requirements, and FDA’s own medical device quality system regulations.  This guidance serves as a first step to highlight common elements between the CGMP regulations and Quality Management Systems.  With the globalization of pharmaceutical manufacturing and the increasing prevalence of drug- and biologic-device combination products, the convergence of quality management principles across different regions and among various product types is very desirable.
  •  The FDA has concluded that modern quality systems, when coupled with manufacturing process and product knowledge and the use of effective risk management practices, can handle many types of changes to facilities, equipment, and processes without the need for prior approval regulatory submissions. Manufacturers with a robust quality system and appropriate process knowledge can implement many types of improvements.   In addition, an effective quality system, by lowering the risk of manufacturing problems, may result in shorter and fewer FDA inspections.
  • A quality system can provide the necessary framework for implementing quality by design (building in quality from the development phase and throughout a product’s life cycle), continual improvement, and risk management in the drug manufacturing process.  A quality system adopted by a manufacturer can be tailored to fit the specific environment, taking into account factors such as scope of operations, complexity of processes, and appropriate use of finite resources.

This announcement is a step in the right direction. However, as stated in every guidance document it “does not create or confer any rights for or on any person and does not operate to bind FDA or the public”.

Let’s see what the “GMPs for the 21st Century” brings.

20Sep/06

ImClone Loses Patent Decision for Cancer Drug Erbitux

By Leslie Gladstone Restaino, Esq.

ImClone Systems, Inc. is reeling from a court decision Monday invalidating ownership of a significant patent for the company’s cancer drug Erbitux. 

Yeda Research and Development Co., the licensing arm of the Weizmann Institute, filed suit in 2003, alleging that three researchers had not been properly designated as inventors on the patent which claims the use of certain antibodies to block a tumor grown protein, when used in combination with chemotherapy.  Aventis claimed that its scientists had already conceived of the use of the antibodies as tumor inhibitors when one of its scientists asked scientists at the Weismann Institute to test the idea in routine experiments.  Yeda claimed that Aventis scientists volunteered to supply the Weizmann scientists with an ingredient to do the experiments.  The New York District Court agreed with Yeda, crediting the invention solely to the Weizmann researchers.  In order to continue to sell Erbitux, Yeda may likely look to grant a license to ImClone, Aventis’ exclusive licensee of the patents, at a premium to the current terms of ImClone’s pre-existing agreement with Aventis.  Alternatively, Yeda may block ImClone’s ability to sell Erbitux for use in chemotherapy combination therapies.
 
This ruling underscores the need to correctly list patent inventors. Inventorship turns on conception.  Oftentimes however, researchers list all project participants on patent filings, mimicking the procedure used for article publication.  Where incorrect,  ownership can shift, or the patent invalidated. 
 
About the Author:
Leslie Gladstone Restaino is a Member of the Firm of  Sills Cummis Epstein & Gross, P.C in the Intellectual Property and Corporate Practice Groups. She concentrates her practice on the special business and legal needs of public and private life sciences companies. Ms. Restaino represents established pharmaceutical companies and start-ups in the life sciences industry throughout all phases of their life cycle and understands the business concerns of growing and established companies.

18Sep/06

Compounding Redux

By Daniel R. Matlis

Recently, I wrote an article calling for consistent federal regulatory requirements for the practice of compounding. Last month, the US District Court in Texas ruled against the FDA on this mater.

As I made clear in my previous article, I am a supporter of compounding. But in order to protect the public, it is imperative that the combination of FDA approved drugs into new compounds be tested for safety and effectiveness.

Critics may ask: Don’t two FDA approved compounds a safe new compound make?

Not always. Remember Fen-Phen?

Fen-Phen is the combination of fenfluramine or dexfenfluramine (marketed as Redux) and phentermine. All were prescription medications approved by the FDA as appetite suppressants. In 1996, physicians began prescribing the combination of Fen-Phen for use in weight loss programs. During that year, the number of prescriptions for Fen-Phen in the United States exceeded 18 million. The practice is known as “off-label use” since no studies are presented to the FDA to demonstrate the effectiveness or safety of the drugs taken in combination.

In July 1997, the New England Journal of Medicine published an article potentially linking heart valve disease with the use of Fen-Phen.  Later in that year, the FDA found that of 291 asymptomatic patients screened, about 30 percent had abnormal valve findings, primarily aortic regurgitation. Based on these data, the manufacturers agreed to withdraw the products from the market and FDA recommended that patients stop taking the drugs.

But this is not a recent phenomenon. In 1937 the manufacturer of “Elixir Sulfanilamide” was seeking a palatable solvent for its new sulfa drug. It decided to use a combination of diethylene glycol and water with raspberry flavoring.  Both the drug and the solvent are safe by themselves, but combined create they a lethal mixture that killed 107 people (mostly children) before the drug was recalled recalled.  Similar to Fen-Phen the combination compound had not been tested prior to release to the public.

By contrast before the introduction of Caduet, the combination of high blood pressure medicine Norvasc and high cholesterol Lipitor, the manufacturer conducted a double blind placebo controlled clinical trial of 1660 patients to evaluate the safety of the combination therapy.

I believe there are two approaches to address this issue; the first is to required safety testing for new compounds comprised of already approved drugs, regardless of who makes them, big Pharma or your neighborhood pharmacist.  This testing should focus on the safety and efficacy of the new compound.

The second alternative is to go the route of informed consent and experimental drugs.  I believe that doctors should have the right to prescribe compounded medicines, pharmacist the right to make then and patients the right to take them as long as we can evaluated all known risks and have meaningful  informed consent.

By the way, I checked with Andrew, my neighborhood pharmacist, and he will only mix in flavor for my kids prescriptions if the drug has been tested for safety in combination with the flavoring syrup.

06Sep/06

FDA Approves First Implantable Replacement Heart

The U.S. Food and Drug Administration (FDA) yesterday approved the AbioCor®, the world’s first completely self-contained, implantable Replacement Heart. 

This approval provides patients suffering from heart failure on both sides of their heart (bi-ventricular) and who have no other alternative, a viable option for extending the quality of their life.

“This device represents a significant advance in artificial heart technology and holds promise for critically ill heart patients who are not candidates for heart transplants due to age or other medical conditions,” said Daniel Schultz, M.D., Director, Center for Devices and Radiological Health, FDA. “We hope today’s approval will encourage the continued development of potentially life-saving technologies for critically ill patients.” 

The quest for an implantable artificial heart began in 1964 at the National Heart Institute (NHI), now the National Heart, Lung and Blood Institute (NHLBI). The goal was to create an Artificial Heart Program aimed at reducing death and disability from heart disease through the development of reliable cardiac assist and total replacement heart systems.

The AbioCor is intended to replace the severely damaged native heart for patients who are not eligible for a transplant and have no other treatment alternative. The AbioCor sustains the body’s circulatory system and is designed to extend the lives of patients who would otherwise die of heart failure, while also offering a probable benefit for a satisfactory quality of life. A post-market study is planned to allow Abiomed to monitor and optimize the introduction of the AbioCor into clinical use.

FDA based approval on the company’s laboratory and animal testing and on a small clinical study of 14 patients conducted by Abiomed. The study showed that the device is safe and has likely benefit for people with severe heart failure whose death is imminent and for whom no alternative treatments are available. In some cases the device extended survival by several months, allowing the patients to spend valuable time with family and friends. In two cases, the device extended survival by 10 and 17 months respectively, and one patient was discharged from the hospital to go home. 

AbioCor will be available under a Humanitarian Use Device (HUD) provisions and will be limited to a patient population in the United States under this approval, with no more than 4,000 patients receiving the technology each year. In order to ensure the highest standards of patient care, Abiomed intends to make the AbioCor available through a controlled roll-out at approximately five to ten heart hospitals in the United States, including qualified clinical trial sites and additional qualified centers once they have completed a comprehensive and rigorous training program which may take six to eight months. Under HDE approval, the FDA may request a panel review of the post-approval study data. 

AbioMed, maker of the Replacement Heart, will reportedly charge $250,000 for the device.

FDA’s approval of the First Implantable Replacement Heart marks the realization of a goal 25 years in the making.