Category Archives: Regulatory

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.

28Aug/06

What’s More Sterile: the Band-Aid on Your Paper cut or Cardioplegia?

By Daniel R. Matlis

It’s a trick question. Technically both should be sterile. 

But you would think that cardioplegia, the solution used to stop the heart during bypass surgery, would be more stringently tested since it is infused directly into the heart.

According to a recent USA Today article, at least 11 cardiac surgery patients were stricken with an infection during a 10-month period from the end of December 2004 to September 2005, and three of them died at Mary Washington Hospital.  After a thorough investigation, tests confirmed the presence of several types of bacteria in the cardioplegia solution injected into patients’ hearts during surgery. 

I can already hear the cry from the trial lawyers: “Which Pharmaceutical Do We Go After? 

The answer? None, the reason is that the products leaving the Pharmaceutical companies were perfectly safe and sterile, but some drugs, including high-risk sterile preparations, are made in pharmacies under less-restrictive rules than those that drug companies follow.  Almost all hospital pharmacies do some type of drug making, called compounding. Pharmacist duties may range from low-risk procedures, such as grinding tablets to put them into liquid suspension, to high-risk work, such as making sterile treatments from scratch. 

I’m in favor of compounding, and cannot thank Andrew, my local pharmacist, enough for compounding prescriptions when my kids need them. Try to get a 3 year old to swallow an adult size tablet. It goes much smoother when it is ground and suspended in strawberry flavored syrup.

But there is a big difference between grinding tablets and preparing a sterile solution to be injected into the heart.  This is not an issue of qualifications, but one of oversight and facilities. Hospital pharmacies are regulated by each state, and the frequency and thoroughness of state inspections vary widely. The FDA’s role in oversight is hampered by questions of jurisdiction over what’s generally state matter. To make matters worse, in most states hospitals are not required to test the sterility or potency of products made in their own pharmacies or purchased from outside pharmacies.  So while a drug company could not sell saline solution without testing sterility, hospital pharmacies and their suppliers are not required to test for it. 

I am not a big proponent of government regulations, but this is a case of public safety and the proverbial “what’s good for the goose is good for the gander” theory of enforcement.  Having 50 different state statues regulating sterility and potency requirements for drugs is impractical, when the FDA has the mandate, know-how and capabilities to regulate them.  If hospital pharmacies and suppliers want to continue manufacturing sterile solutions, they ought to be held to the same standards as the Sesame Street Band-Aid I put on my kid’s “boo-boo”. 

28Aug/06

What’s More Sterile: the Band-Aid on Your Paper cut or Cardioplegia?

By Daniel R. Matlis

It’s a trick question. Technically both should be sterile. 

But you would think that cardioplegia, the solution used to stop the heart during bypass surgery, would be more stringently tested since it is infused directly into the heart.

According to a recent USA Today article, at least 11 cardiac surgery patients were stricken with an infection during a 10-month period from the end of December 2004 to September 2005, and three of them died at Mary Washington Hospital.  After a thorough investigation, tests confirmed the presence of several types of bacteria in the cardioplegia solution injected into patients’ hearts during surgery. 

I can already hear the cry from the trial lawyers: “Which Pharmaceutical Do We Go After? 

The answer? None, the reason is that the products leaving the Pharmaceutical companies were perfectly safe and sterile, but some drugs, including high-risk sterile preparations, are made in pharmacies under less-restrictive rules than those that drug companies follow.  Almost all hospital pharmacies do some type of drug making, called compounding. Pharmacist duties may range from low-risk procedures, such as grinding tablets to put them into liquid suspension, to high-risk work, such as making sterile treatments from scratch. 

I’m in favor of compounding, and cannot thank Andrew, my local pharmacist, enough for compounding prescriptions when my kids need them. Try to get a 3 year old to swallow an adult size tablet. It goes much smoother when it is ground and suspended in strawberry flavored syrup.

But there is a big difference between grinding tablets and preparing a sterile solution to be injected into the heart.  This is not an issue of qualifications, but one of oversight and facilities. Hospital pharmacies are regulated by each state, and the frequency and thoroughness of state inspections vary widely. The FDA’s role in oversight is hampered by questions of jurisdiction over what’s generally state matter. To make matters worse, in most states hospitals are not required to test the sterility or potency of products made in their own pharmacies or purchased from outside pharmacies.  So while a drug company could not sell saline solution without testing sterility, hospital pharmacies and their suppliers are not required to test for it. 

I am not a big proponent of government regulations, but this is a case of public safety and the proverbial “what’s good for the goose is good for the gander” theory of enforcement.  Having 50 different state statues regulating sterility and potency requirements for drugs is impractical, when the FDA has the mandate, know-how and capabilities to regulate them.  If hospital pharmacies and suppliers want to continue manufacturing sterile solutions, they ought to be held to the same standards as the Sesame Street Band-Aid I put on my kid’s “boo-boo”. 

02Aug/06

Can I make your pacemaker software run faster?

I recently read an article on the Free Software Foundation’s Website entitled “Regulatory compliance is no reason to lock up users” The author states that “Medical devices are (theoretically) programmed to a high standard of safety, and careless modification could cause great harm. Medical device manufacturers want to Tivo-ize their devices so that only they can upgrade the software on them. They claim that this is necessary for compliance with FDA regulations.”

The FDA gives manufacturers the freedom to choose what software to use in medical devices. But with this freedom comes responsibly. The Agency does not require or favor the use of commercial over free software in medical devices.  However, the Quality System Regulation (21CFR§820) does require that Medical Devices automated with computer software be subject to design controls.

FDA’s Guidance on Software Validation states that “where the software is developed by someone other than the device manufacturer (e.g., off-the-shelf software) …the party with regulatory responsibility (i.e., the device manufacturer) needs to assess the adequacy of the off-the-shelf software developer’s activities and determine what additional efforts are needed to establish that the software is validated for the device manufacturer’s intended use.”

The difficulty with Free Software is that it falls into software quality limbo.  After all there is no vendor to audit, or documented evidence that a quality system exists and was followed in the design and testing of the Free Software.

I know that auditing Off the Shelf Software vendors can be hard enough (I tried to audit Microsoft once), but in general you can perform an audit of your software provider to assess the quality systems they have established and to ensure that they are following their quality system. Whom do you audit for your open source code?

Nevertheless, this does not purge the use of Free Software in devices. It does put the burden for proving and documenting that the software meets the intended squarely on the shoulders of the Device Manufacturer. The level of diligence required for Free Software is not unlike that of Custom Software. The cost of the Open source Software (free) may offset the cost of this additional compliance burden, but that is a business decision each manufacturer must make.

Free Software has a place in our industry. You want to run your HTTP server on Apache, go ahead (after you have assessed the impact on you compliance program), but I would not recommend using open source software in Medical Devices.

Device Software is one area where reliability and safety should always come before speed.

After all making a pacemaker run faster is not always a good thing.

13Jul/06

Doctors Don’t Treat Populations, They Treat Individual Patients

This week, Scott Gottlieb, MD Deputy Commissioner for Medical and Scientific Affairs at the Food and Drug Administration made an interesting speech before the 2006 Conference on Adaptive Trial Design in Washington, DC.Dr Gotlieb commented how today’s clinical trials are highly empirical. Drugs are tested on general populations for a response and a treatment effect that is statistically not likely to be a chance result. This approach is rigorous and focused, but inflexible. According to Dr. Gotlieb, “another problem with the empirical approach is that it yields statistical information about how large populations with the same or similar conditions are likely to respond to a treatment. But doctors don’t treat populations, they treat individual patients. Doctors need information about the characteristics that predict which patients are more likely to respond well, or suffer certain side effect. The empirical approach doesn’t tell doctors how to personalize their care to their individual patients.” This results in a highly empirical approach to the practice of medicine. Gone are the days of: Take two off these and call me in the morning. Gottlieb comments “Doctors prescribe treatments knowing full well that only a certain percentage of their patients will receive a benefit from any given medicine.” This approach is akin to: Take all of these and call me if you have a side-effect. 

But with the demands for personalized medicine and the advent of Pharmaco-genomics, there are potentially better alternatives. By enabling more trials to be adapted based on knowledge about gene and protein markers or patient characteristics, we can help predict whether patients will respond well to a new medicine. “These new approaches to clinical trials can result in trial designs that tell us more about safety and benefits of drugs, in potentially shorter time frames, exposing fewer people to experimental treatments, and resulting in clinical trials that may not only be more efficient but are more attractive to patients and their physicians to enroll in.” said Gottlieb. This is only a first step in the process to develop more adaptive clinical trials. This process will lead to more targeted therapies and in turn, Ii is my hope, more personal and personalized medicine.