Susan Dudley, PhD & Isabel Platt
Updated July 2013

 

Modern medicine offers amazing treatments against a wide range of diseases. Today, people can overcome and survive health conditions that would have been fatal only a few decades ago. Nevertheless, most of us would agree that preventing disease – and not getting sick in the first place – is still far better than having to undergo those treatments.

Disease is more likely to develop under certain circumstances. To the extent that we can control those circumstances, we have a better chance of staying healthy. And it turns out that this isn’t always as complicated as most people assume.

Following just seven simple principles can make a big difference in helping us maintain our overall health and lowering the probability of developing many of the diseases that are most debilitating and dreaded, like cancer, heart and lung diseases, stroke, and diabetes.

 

1. Avoid tobacco and tobacco smoke

Diseases related to cigarette smoking alone account for almost 1 of every 5 deaths in the United States each year.[i] The greater the total lifetime exposure to tobacco smoke, the greater the risk of developing smoking-related diseases such as lung cancer and emphysema.

The message is clear: don’t smoke, and keep away from the second-hand smoke produced when people near you are smoking cigarettes, cigars, or pipes. Also avoid other tobacco products, such as snuff or chewing tobacco.

Quitting tobacco has major and immediate health benefits. Even if you’ve tried and failed before, keep trying until you succeed. For help, call the National Cancer Institute’s smoking cessation quitline at 1-877-44U-QUIT or visit NCI’s smoking cessation Web site at smokefree.gov. The CDC provides a list of other resources to help you quit.

 

2. Limit alcohol consumption

Alcohol is the third leading cause of death in the US.[ii] These deaths result from drunk driving and other risky behaviors, and also from diseases caused by alcohol, including liver diseases and cancers of the breast, mouth, throat, esophagus, prostate, and liver. For example, women who consume more than 3 alcoholic drinks per week are 30% more likely to develop breast cancer than those who do not drink.[iii]

The Department of Agriculture’s 2010 Dietary Guidelines for Americans recommends drinking alcohol only in moderation, which they define as having no more than 1 drink per day for women, and no more than 2 drinks per day for men.[iv] This definition refers to the amount consumed on any single day, not an average over several days.

For more information on how alcohol can affect your health, visit the CDC website.

 

3. Eat a healthy diet

Although surveys confirm that most Americans believe they have healthy eating habits, obesity and other diet-related chronic diseases are on the rise.[v] [vi] A lack of nutrients may lead to diseases such as osteoporosis and anemia, while eating unhealthy foods can lead to high blood pressure, heart disease, diabetes, and other life-threatening conditions.

An ideal diet depends on a person’s age, sex, and activity level. In general, the US Department of Agriculture recommends diets that are low in sodium, solid fats, cholesterol, and added sugars, and high in nutrient-dense foods including fruits and vegetables, whole grains, low-fat milk products, seafood, lean meats, eggs, beans, nuts, and seeds.[vi]

Unhealthy food is easy to find, especially in the form of canned and processed foods. To avoid unhealthy amounts of sodium, fats, and sugar, it is important to monitor the nutrient labels on the foods we buy at the supermarket.

To learn more about constructing a healthy diet that is right for you, check out the choosemyplate.gov website and read more about the Department of Agriculture’s dietary guidelines.

 

4. Control your weight

Roughly two-thirds of Americans are overweight and nearly one-third qualify as obese, according to the U.S. Centers for Disease Control and Prevention.[vii] Surveys show that while most of us can recognize when others are overweight, we don’t pay attention to our own weight problems or those of our children. Being overweight makes us more vulnerable to many medical problems, including high blood pressure, diabetes, heart disease, stroke, gallbladder disease, osteoarthritis, severe lung and breathing problems, and endometrial, breast, and colon cancers.

While many physicians say that anyone can lose weight by eating less and exercising more, this simplified method does not work for everyone. However, there are many other ways to regain control over your weight. An important step is switching to a healthier diet, which includes choosing lower calorie foods, eating smaller portion sizes, cooking foods that are lower in fat, and paying careful attention to what you order at restaurants. Some restaurants list “heart healthy” choices, and many large chain restaurants provide information about calorie and fat content.

When you consistently choose lower-calorie, healthier foods, it may seem like you are able to eat more over the course of a day. These nutrient-dense foods allow you to consume fewer calories and get important nutrients including calcium, iron, potassium, and vitamins. For more information about “nutrient-dense” foods, read this article.

Overweight and obesity are determined by calculating body-mass index (BMI), which is based on height and weight. However, having a high BMI does not necessarily mean that you are at an unhealthy weight. Physical activity, genetics, and other lifestyle choices play a more important role in determining your body’s health.

If you want to try counting calories as a way to control your weight, try out the daily calorie needs calculator at cancer.org. You can also download the MyFitnessPal mobile app to log your daily calorie intake and exercise routine.

 

5. Exercise every day

Adding 30 minutes of moderate-intensity exercise to your daily routine can reduce the risk of heart disease, stroke, colon cancer, diabetes, and high blood pressure. Research indicates that exercise helps control weight, contributes to healthy bones, muscles, and joints, reduces falls among older adults, and helps to relieve arthritis pain. Exercise also reduces symptoms of anxiety and depression and is associated with better sleep.[viii]

Everyone can benefit from regular physical exercise, and regardless of age or fitness level, it’s never too late to start. You don’t need to be an athlete, and the activity you choose doesn’t need to be strenuous, involve a gym membership, or be competitive. The point is simply to get moving, elevate your heart rate, and keep it elevated during the course of the activity period.

Most people believe that they are getting more exercise in the course of their daily lives than they actually are. Experts advise adults to engage in moderate-intensity physical activities – like walking, biking, swimming, mowing the lawn, or dancing – for at least 30 minutes on 5 or more days of the week. Alternatively, experts advise vigorous-intensity physical activity – like high-impact aerobics, jogging or running, uphill biking, or swimming laps – for at least 20 minutes on 4 or more days per week. In addition to aerobic activities, it is important to include muscle-strengthening activities that include lifting weights, doing sit-ups, or doing yoga.[ix] If you can’t do all that, remember that any exercise is better than none at all. Find ways to exercise as you go about your daily tasks. Take the stairs instead of the elevator. Walk instead of driving as much as you can. Start slow and build up to longer exercise sessions.

Read here to learn how to begin an exercise routine that works for you.

 

6. Limit your sun exposure

Although the sun is a good source of vitamin D, too much exposure to the sun’s ultraviolet (UV) rays can cause skin cancer.

Skin cancer is by far the most common cancer type in the US, with more than 2 million people diagnosed annually.[x] In addition to dangerous basal and squamous cell cancers, about 60,000 new cases of malignant melanoma – the most serious form of skin cancer – are diagnosed each year, as well as more than 9,000 deaths from the disease.[xi]

Skin cancer can be prevented by consistently using sun protection (even on cloudy days) and avoiding artificial sources of UV radiation such as tanning beds and sun lamps. To learn more about sun safety, read this article.

 

7. Take advantage of effective disease screening

In spite of our best efforts to stay healthy, we may all develop diseases. But early detection can make a tremendous difference in how well diseases are treated. The US Preventive Services Task Force recommends several screening tests including mammograms, pap smears, colonoscopy, and cholesterol and blood pressure checks to detect and treat early signs of disease.

To learn more about when you should begin getting these screenings, see the Agency for Healthcare Research and Quality’s recommendations for women and men.

 

Making it happen

It is important to make an honest assessment about your health habits, because deciding where you realistically need to concentrate your efforts is essential to improving your health.

Take these suggestions one step at a time, and remember that improving your health comes with a great deal of effort, willpower, and a real commitment to make long-term changes in your health. Remember that you don’t have to do it all at once, and that an occasional lapse doesn’t mean you can’t start again. Every change becomes easier as it becomes more firmly incorporated into your familiar routine.

The resources listed in each of the sections above can provide you with some valuable assistance to get started and keep moving toward a healthier lifestyle and longer life. The results will certainly be worth the effort.



[i] Smoking and Tobacco Use: Tobacco-Related Mortality. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/tobacco_related_mortality/. Accessed July 12, 2013.

 

[ii] Alcohol and Public Health: Fact Sheets–Alcohol Use and Health. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm. Accessed July 12, 2013.

 

[iii] Alcohol Consumption Increases Risk of Breast Cancer Recurrence. American Association for Cancer Research. Available at: http://www.aacr.org/home/public–media/aacr-press-releases/press-releases-2009.aspx?d=1703. Accessed July 12, 2013.

 

[iv] Dietary Guidelines for Anericans 2010 – DietaryGuidelines2010.pdf. Available at: http://www.health.gov/dietaryguidelines/dga2010/DietaryGuidelines2010.pdf. Accessed July 12, 2013.

 

[v] IFIC Foundation 2008 Food & Health Survey. Available at: http://www.foodinsight.org/Content/6/IFICFdn2008FoodandHealthSurvey.pdf. Accessed July 12, 2013.

 

[vi] Dietary Guidelines for Anericans 2010 – DietaryGuidelines2010.pdf. Available at: http://www.health.gov/dietaryguidelines/dga2010/DietaryGuidelines2010.pdf. Accessed July 12, 2013.

 

[vii] FASTSTATS – Overweight Prevalence. Available at: http://www.cdc.gov/nchs/fastats/overwt.htm. Accessed July 12, 2013.

 

[viii] Exercise: 7 benefits of regular physical activity. Mayo Clinic. Available at: http://www.mayoclinic.com/health/exercise/HQ01676. Accessed July 12, 2013.

 

[ix] Physical Activity for Everyone: Guidelines: Adults | DNPAO | CDC. Available at: http://www.cdc.gov/physicalactivity/everyone/guidelines/adults.html. Accessed July 12, 2013.

 

[x] Skin Cancer Facts – SkinCancer.org. Available at: http://www.skincancer.org/skin-cancer-information/skin-cancer-facts. Accessed July 12, 2013.

 

[xi] CDC – Skin Cancer Statistics. Available at: http://www.cdc.gov/cancer/skin/statistics/. Accessed July 12, 2013.

By Jennifer Focht, BA

January 2013

Choosing a new physician can be a nerve-wracking task, but thanks to the Internet, information about the doctors you are considering is just a click away.

Many people use reviews and ratings of restaurants, movies, hotels, and products to help decide what to buy. Many web sites offer the same opportunity to read about physicians. Healthgrades.com, RateMDs.com, and DoctorScore.com are just a few that offer patients the opportunity to rate their physicians, and the rest of us the opportunity to see what they said. But, as is true for many online ratings of products or services – especially those that are anonymous, some of the people doing the rating are wildly enthusiastic and some are scathing. How much should you trust online reviews of doctors, and can you make sense of an enormous range of ratings for the same doctor?

Who posts online reviews?

Thirty-four percent of young adults use online ratings to choose a doctor compared with just 19% of seniors.1 Of those who do use these websites, only 6-8% say they have posted a review of their experience with a doctor. 2The vast majority of people do not rate or review their physicians on the Internet, so if you rely on these ratings you will have no information on the quality of care received by over 90% of patients.

What do reviews say?

Some reviews contain general statements about the patient’s experience or impression of his doctor (“He is wonderful”), while others comment more specifically on the doctor’s competence (“She mis-prescribed a medicine I’ve been taking for years”) and bedside manner (“She makes embarrassing things not embarrassing”). 3 Some reviews even offer opinions on the patient’s experience beyond the care directly provided by the physician, such as comments on the office, staff, and availability of appointments. 4 Most physician reviews on the Internet are positive,5 but one study found that patients are most likely to post a review after a negative experience with the doctor. 6 In general, people who respond to surveys on any topic, whether online, over the phone, or in writing are most likely to be the ones that feel most strongly about the subject, either positively or negatively. So, you’re most likely to see those extreme comments, and less likely to see neutral or lukewarm evaluations.

According to a recent study, individual doctors have an average of less than 3 reviews each (and some have no reviews at all). 7 Because each doctor has so few reviews, you can’t assume that the reviews accurately represent how most patients feel about the doctor. In addition, one extremely negative or extremely positive review can have a misleading impact on the doctor’s average rating.

Finally, it is important to remember that there is no guarantee that any review contains accurate information. 8 Just because an anonymous person posts that a particular physician is terrible (or great) doesn’t mean it is true. There is no way to control a doctor’s friend or family member from giving a great rating, or a competitor from giving a terrible rating. (Keep that in mind for restaurant and hotel reviews as well!) And, patients may rate on things that have nothing to do with the quality of their medical expertise, such as how nice they are or how long they had to wait past their scheduled appointment. Worse yet, some patients might give a poor rating to a physician who is actually providing excellent care, such as a doctor who refuses to prescribe an antibiotic for a cold or the flu (The Facts About Medication for Colds and the Flu). But, if there are many ratings that seem similar, or a clear pattern (such as numerous people posting weeks or months apart that they waited a long time to see the doctor), then you may want to take that into consideration.

Bottom Line:

Online reviews of doctors should only be taken seriously if there are many reviews and a clear “trend” in the comments (for instance, most reviewers complained about the receptionist but felt the doctor really listened to them). Even then, the reviews probably can’t tell you about the quality of medical care you will get unless the reviewers are knowledgeable and provide specific information that you can judge for yourself. Until you visit a doctor for the first time and see for yourself, there is limited information you can gather. And, just because a doctor went to a well-respected medical school doesn’t mean he or she has a good bedside manner or is punctual. If your doctor is a specialist, you will want to check that he is Board-certified (you can check here), but after that, the best information you can get about a doctor is from a patient you know personally and who has the expertise to make an accurate judgment. If you need to use online reviews, keep in mind all the limitations of that information.

by Diana Zuckerman, PhD and Jennifer Yttri, PhD

Posted on Health Affairs Blog January 25, 2013

Antibiotic resistance is a major concern confronting our health care system, and there is tremendous pressure on the Food and Drug Administration (FDA) to “do something” about it.  Unfortunately, the FDA is responding by approving drugs that are likely to do more harm than good.

FDA advisory committees are supposed to provide independent advice from experts across the country, but recent meetings have left observers wondering whether too many FDA advisory committee members are providing neither scientific nor independent advice, and whether the committee process itself is fundamentally flawed.  These concerns dovetail with essential questions about FDA objectivity and scientific judgment in its review of antibiotics.

For example, a few weeks ago, the FDA approved a new drug for multidrug-resistant tuberculosis (TB) — bedaquiline, to be sold under the name Sirturo — shortly after data reviewed by FDA scientists indicated a higher death rate for the new drug compared to the usual standard of care.  The FDA’s Anti-Infective Drugs Advisory Committee had publicly reviewed the TB antibiotic on November 28, 2012. (See Note 1)

The company’s clinical trial data compared the standard drug regimen to the new drug taken in conjunction with the standard drug regimen. This was a high priority, expedited review, so the company’s randomized, clinical trial wasn’t yet completed.  You can clearly see (as the committee could) that patients treated with bedaquiline in addition to standard therapy were 10 percent more likely to die than those receiving the standard therapy alone, and the survival gap between the new drug and standard therapies increased over time. (See Exhibit below, click to enlarge) The difference was statistically significant, and a 10 percent increased chance of dying is not something most doctors could justify to a patient when choosing an antibiotic.

At the FDA meeting, these risks were downplayed by the manufacturer, Janssen Therapeutics, whose spokesperson suggested that the higher deaths resulted from chance, not from the drug.  That seemed like an odd rationale, since the purpose of conducting this or any other controlled, randomized trial is to ensure that any statistically significant difference in mortality is due to the treatment, not chance. The FDA’s scientific staff had concluded that the new drug could be causing the larger number of deaths, and the Committee expressed their concerns.

Apparently worried about losing the support of the advisory committee, representatives from Janssen offered to immediately provide committee members with data from the longer-term follow-up of the same study, which had just been completed.  This offer seems reasonable but is against the FDA rules: all of the sponsor’s data to be discussed at the public meeting must be submitted 22 business days before the meeting, so that FDA scientists can review it and provide the data and the FDA’s written analyses to Committee members at least 14 business days before the meeting, and to the public 48 hours before the meeting.  The FDA rules are also reasonable, because FDA analyses sometimes disagree with the company’s methodology or interpretation, and advisory committee members rely on those FDA analyses for objective peer review.

The FDA rules were ignored at the November 28th meeting.  The Committee chair agreed to Janssen’s request, and FDA officials did too. Those new data, which had not been included in the FDA’s scientific analysis provided to the Committee, were more favorable to the drug than the data that the company had previously provided. Our notes from attending the meeting indicate that the death rate from the new drug was still higher but the difference was not statistically significant.  Regardless, the company’s enthusiastic presentation of the non-peer-reviewed data was accepted at face value by most committee members, who voted 11-7 that the new drug was safe. A few weeks later, the FDA approved the drug with great fanfare as the first new TB medication in 40 years.

Did the company’s new data objectively prove that this new TB drug is safe and effective?  It’s impossible to know, because the FDA has still not made those data available on the FDA web site or elsewhere for independent reviewers.  The law requires that advisory committee data be made public in advance of the meetings, so that anyone can review it.  In this case they were not public before the meeting, or before or since the FDA made its approval decision.

The desire to approve a new TB drug is understandable, and the FDA mandated that Sirturo carry a Black Box Warning regarding the higher death rate experienced by patients taking the drug. A Black Box Warning is an important safeguard, but does not justify approving an antibiotic under these circumstances.  Unfortunately, the questionable approval of bedaquiline is far from unique.

The day after the November 28th FDA meeting, the same advisory committee met to discuss telavancin, an antibiotic that is already on the market by the name of Vibativ for the treatment of complicated skin infections.  The drug has been found to cause birth defects in animals and potentially deadly kidney toxicity in humans. With many safer drugs available, telavancin has twice before been denied approval by the FDA for treating pneumonia.

These same adverse reactions remained concerns regarding the pneumonia trials submitted to the November advisory committee. However, unlike previous reviews for this same drug, the November advisory committee members were apparently overcome by wishful thinking.  They concluded that the hoped for but unproven potential benefit of telavancin for a small minority of patients was enough to warrant these high risks and recommended approval. As they had the previous day, the committee members speculated that the possible benefits to patients in severe need, such as those with MRSA (methicillin-resistant Staphylococcus aureus), outweighed the risk of death.  Unfortunately, the FDA scientific analysis of the evidence does not support that view.  Analysis of the company’s own studies showed that the sickest patients– those with diabetes, heart failure, and kidney failure– were most likely to die if they took telavancin compared to vancomycin.

These two committee meetings highlight a problem with the FDA’s accelerated approval process, and leave patients, consumers, and public health experts with growing questions about whether advisory committee meetings are merely a pretense that is being used by the FDA to justify decisions that are not based on science.

Question #1:  Why is a drug that lacks clear evidence of efficacy or safety the subject of the time-consuming and resource-intensive review of a public FDA advisory committee meeting?  Is it because the FDA is under so much pressure to approve new drugs, and especially antimicrobials, that they are afraid to make a decision without support from an outside advisory committee?

Question #2:   Why did the FDA allow data that were not vetted by their own scientists to be discussed and used as the basis of advisory committee recommendations?  A related question is whether this is only allowed for data that the company provides, but not for data provided by other reputable sources.  The most egregious comparison is the FDA’s advisory committee meeting on the birth control pill Yasmin, just a year before.  In that case, the well-respected former FDA Commissioner, Dr. David Kessler, had written a report that documented that Bayer covered up data describing the high risk of venous thromboembolisms (VTEs) among Yasmin patients, but the FDA would not allow Kessler’s report to be shared with the committee or discussed during the public meeting because it was submitted a few days before the meeting, which was “too late” to be included in the committee materials or FDA peer review.  In contrast, this time the Janssen data were allowed to be provided and discussed during the meeting itself.

Question #3:  Why are FDA advisory committee members recommending approval for drugs that are not proven safe or not proven effective?  Based on the one-sided enforcement of FDA rules described in #2, above, and the quick approval of bedaquiline just a few weeks afterward, one has to wonder.  The advisory committee recommendation in favor of telavancin further raises the question of whether advisory committee members are selected to recommend what someone at the FDA has already decided to do.

Feeling worried?  We are.  We don’t know what is going on behind closed doors at the FDA, but based on public meetings, policies regarding the analyses of safety data are vague and sloppy, with strong warning signs overlooked in the desire to push new drugs through the pipeline.  The FDA has clear guidelines for proving efficacy, but these standards are being loosened to accommodate surrogate endpoints that do not necessarily predict health outcomes. Science is being sacrificed for speed, and this puts patients at greater risk for exposure to drugs that are not proven safe.  We’ve given two recent examples but can provide dozens more.

The risks are very real.  The last two drugs considered for ventilator-acquired pneumonia, doripenem and tigecycline, were found to increase mortality in patients after they were approved for treatment of other infections.  The FDA denied approval to telavancin previously, but judging from their public meeting the FDA may now be bowing to pressure to approve more antimicrobials, regardless of the scientific evidence.

Even more disturbing, antibiotic drug development and review seem to be ingrained with indefensible scientific practices.  Drugs are assigned to priority review before Phase II and Phase III safety studies on humans are completed, and mortality is no longer considered an important outcome by the FDA. Instead, the FDA supports studies of drug efficacy based on test tube data rather than patient-centered outcomes, such as survival and better quality of life. This distinction is important to patients and their families, because an antimicrobial drug can kill more bacteria in a test tube and yet result in more rather than fewer deaths when used in patients.

Companies need to be held to higher standards when developing antibiotic drugs than the FDA currently requires. There is a lack of scientific rigor in clinical trials for drugs that are being recommended for approval.  Large numbers of patients who won’t benefit are being exposed to risky new therapies as part of clinical trials that are not always well designed and often do not measure the outcomes that matter to patients, such as survival. The hope of a benefit for a small group should not be reason enough to expose a large number of patients to increased harm.  We have seen how expediting drugs through the regulatory pipeline to reach these sick patients comes at a large cost in patients’ lives.

A few months ago, Congress passed a law that provides generous incentives for companies to develop new antimicrobial drugs, extending market exclusivity for five years.  Under this law, four drugs have already been given QIDP (Qualified Infectious Disease Products) status.  Another new regulation is being considered that would alter the review process to permit limited approval for drugs using another expedited process. As the FDA grants priority review and fast-track status, we need to ensure that they are based on solid clinical trials demonstrating drug efficacy and safety.

FDA guidelines need to do more to reduce the overuse of antibiotics. Overuse of one type of antibiotic drug can result in resistance to similar drugs, including even the newest drugs.  Pharmaceutical companies admit that use of older antimicrobials that were approved without appropriate studies is contributing to antibiotic resistance in critical pathogens and higher rates of mortality in patients. Based on their calculations, the rate of resistance to currently used antimicrobials will make drugs in development obsolete even before their patent exclusivity expires under QIDP. Instead of promoting the generation of new and improved drugs, the incentives being awarded by the FDA are restricting other companies from generating better drugs while approving those that have not been proven as effective or safe.

Something has to give. Public health advocates need to persuade the FDA to stick to the science when it makes approval decisions for anti-infective drugs. Approving drugs without proven safety, efficacy, and benefit (often with increased mortality in comparison to older drugs!) is only serving to put all of us at increased risk.

Note 1. Although “antibiotic” is the commonly used term, “antimicrobial” or “anti-infective” are more encompassing terms. All three are used interchangeably within this article.

by Thomas M. Burton, Wall Street Journal

January 18, 2013

 

The Food and Drug Administration is studying whether several medical devices already on the market, such as electroconvulsive therapy devices for depression and emergency defibrillators, require additional evidence to prove they’re safe.

As part of that re-evaluation, the federal agency on Thursday proposed that companies making so-called metal-on-metal artificial hip joints produce medical evidence demonstrating their safety in order to stay on the market. Also, the FDA said, any new metal-on-metal hip products will require human clinical evidence to gain approval for marketing.

The metal-on-metal hips, of which there are estimated to be hundreds of thousands implanted in patients, have tended to fail and require replacement more quickly than some other artificial hip joints, according to recent medical research. One 2012 article in the British journal Lancet concluded that “metal-on-metal total hip replacement failed at high rates” and that such devices “give poor implant survival” compared with others made of polyethylene or ceramic materials.

In a safety advisory Thursday, the agency said patients with symptoms suggesting their devices aren’t functioning properly should be considered for testing of possible metal ions in their bloodstream. The agency said metal particles can lead to symptoms including skin rashes, neurological changes such as hearing and vision impairment, and psychological status changes including depression.

There have been recalls of hip joints in the past five years from Johnson & Johnson’s JNJ +0.07%DePuy unit, Zimmer Holdings Inc. ZMH +0.53%and of a Smith & Nephew SN.LN -0.07%PLC metal hip-implant component.

The FDA’s overall evaluation focuses on types of medical devices that were on the U.S. market when a 1976 law created a regulatory system for medical devices. New versions of some of these devices have been cleared for sale in the U.S. without clinical studies being required by the FDA. The agency has been evaluating whether more medical evidence may be required for 26 of these types of devices. It has made proposals for handling 18 of those 26, but eight others remain to be decided.

These include certain electroshock devices, orthopedic-surgery screws and emergency defibrillators of the sort used by paramedics. There have been reports over the years of some defibrillators failing to power up when needed to save a patient’s life.

William Maisel, deputy science director of the FDA’s device center, didn’t offer a time frame for a decision on the eight remaining devices, but said, “We consider this a very high priority.” The devices at issue got cleared through an abbreviated process, known as 510K, in which a company need only prove that a device is basically equivalent to another one already on the market—and needn’t conduct an extensive clinical study.

Diana Zuckerman, president of the National Research Center for Women & Families, said: “There are so many shortcuts at the FDA device center that they often take a shortcut and approve a product with minimal safety testing.”

Dr. Maisel responded: “For the vast majority of devices under 510K, the system allows an efficient and scientifically thorough evaluation. We acknowledge that, as with metal-on-metal hips, there are devices that would be better off with” clinical studies.

Write to Thomas M. Burton at tom.burton@wsj.com

November 21, 2012

The Honorable Henry A. Waxman, Ranking Member
Energy and Commerce Committee
U.S. House of Representatives
2204 Rayburn
Washington, DC  20515

Re: Draft Proposal of the Delivering Antibiotic Transparency in Animals (Data) Act of 2012

Dear Congressman Waxman:

We thank you for the opportunity to provide comments on the discussion draft of legislation to enhance the reporting requirements pertaining to the use of antibiotics in food animals.

The National Research Center for Women & Families supports the Data Act, and we share your concerns about the current and growing risk of antibacterial resistance to medically important drugs as a consequence of agricultural practices.

The Data Act’s proposed changes to the Federal Food, Drug, and Cosmetic Act would provide needed data to help public health officials interpret trends in microbial resistance, and understand the relationship between drug use in food animals and antibacterial drug resistance in medical treatment.  It would also identify strategies to control antibacterial resistance in the future. We support this legislation and offer the following suggestions that should help to ensure a more complete reporting and monitoring of antibiotic use in food animals.

In light of recent reports, consistent with the November 19, 2012 Washington Post article,[1] we suggest including fish in the list of reportable animal species. A recent report from a collaborative group between the United States and Canada found that “resistance to tetracycline in one or more species of bacteria was reported as ‘frequent-to-almost always’” in the most frequently farmed species (including catfish, salmon, tilapia, and shrimp).[2] With the rise in consumption of fish, monitoring antibiotic use in aquaculture now may be a way to prevent widespread antibiotic resistance and serve as a way to promote a healthy image for farm-raised fish in the U.S.A. as compared to imported seafood.

Section 4(3)(D) Guidelines to amend list of antibacterial active ingredients important in human medicine
We strongly support the requirement that sponsors must report on new drugs with an antibacterial active ingredient designated as important in human medicine or sharing resistance patterns with antibacterial active ingredients important in human medicine. We suggest adding a third clause to this section to clearly state that the Secretary has the authority to require reporting of new drugs with antibacterial active ingredients that may become important in human medicine in the future.  Bacteria are constantly changing and antibacterial active ingredients used in human medicine must adapt accordingly.

Thank you for the opportunity to comment on this discussion draft of the Data Act and look forward to working with you on this important legislation.

National Research Center for Women & Families

For more information, contact Paul Brown at (202) 223-4000 or pb@center4research.org
or Jennifer Yttri at jy@center4research.org

 


[1] Butler C (November 19, 2012).  Eating fish is wise, but it’s good to know where your seafood comes from, Washington Post.  http://www.washingtonpost.com/national/health-science/eating-fish-is-wise-but-its-good-to-know-where-your-seafood-comes-from/2012/11/17/73483c5a-2cd9-11e2-9ac2-1c61452669c3_story.html

[2] Tuševljak, N., Dutil, L., Rajić, A., Uhland, F. C., McClure, C., St-Hilaire, S., Reid-Smith, R. J. and McEwen, S. A. (2012), Antimicrobial Use and Resistance in Aquaculture: Findings of a Globally Administered Survey of Aquaculture-Allied Professionals. Zoonoses and Public Health. doi: 10.1111/zph.12017

 

 

November 7, 2012

Chairman Harkin and Ranking Member Enzi of the HELP Committee, Chairman Upton and Ranking Member Waxman of the Energy and Commerce Committee, Senators Grassley, Feinstein, Alexander, Burr, Whitehouse, and Bennet, and Representatives Dingell, Pallone, Bilbray, and Matheson:

Re: Draft Proposal to Improve Drug Distribution Security
As members of the Patient, Consumer, and Public Health Coalition, we thank you for the opportunity to provide comments on the discussion draft of legislation to improve the safety of our drug distribution system.

We write on behalf of millions of consumers, patients, scientists, and public health advocates to express our strong support for a robust U.S. pharmaceutical distribution system that will protect patients and the public health from unsafe, diverted and counterfeit medicines. We are deeply concerned about the current and growing risk to the U.S. pharmaceutical supply, a threat that can best be addressed through a meaningful national system to track and authenticate pharmaceutical products as they move from manufacturer to wholesaler to pharmacy to patient.

As you consider the various policy options laid out in the current draft, we urge you to make choices that will address the existing weaknesses in the system in a timely and comprehensive way. Our detailed comments follow:

Timelines
Even the shortest timelines proposed in this draft will result in delays of up to a decade before a comprehensive system is in place to protect patients and consumers. That is too long. Industry has extensive experience piloting track and trace programs and operating them in other countries. We recommend that timelines in this section be shortened.

Section 2. Pharmaceutical distribution supply chain
The legislation would create an interim lot-level system. This is a reasonable approach as long as it is part of a clear and established path to achieving a system that will track drugs at the unit-level. A meaningful system that will protect patients from the risks of counterfeit, stolen or diverted drugs must include the placement of a unique serial number on each package, or unit, of medicine as well as the ability to track those medicines at the unit-level. We note that any counterfeit drug product that copies an existing lot number will not be routinely detected under this interim system, since it entails no proactive responsibility on any entity within the distribution system to verify serial numbers. On its own, a lot-level tracking system alone is not a sufficiently significant advance in patient safety to warrant the preemption of existing state laws that go further to protect patients from counterfeit, diverted or stolen drugs.

Returns
Returns have been identified by regulators and enforcement officials as a significant area of risk for the insertion of counterfeit, diverted or stolen drugs into the legitimate supply chain. Erasing a product’s prior transaction history when it is returned and resold removes a purchaser’s ability to determine a drug’s origin, representing a major weakness in the distribution chain. Furthermore, regulators require a full transaction history to fully and appropriately investigate a breach in the supply chain. Therefore, we recommend that any legislation forbids a break in a drug’s pedigree when it is returned.

Verification
We support the requirement for companies to verify returned products. Ensuring that returned units are authentic will help to secure the returns process, which can be an entry point to the distribution chain for suspicious products. We also support the requirement for companies to verify suspect products, but this requirement must include the ability to determine whether the unique serial number on a unit or case of pharmaceutical product corresponds to the information applied by the drug manufacturer.

Alert system
We also support the proposed alerts system for the industry and FDA, but urge that this policy require that the alert system created under Section 2 is comprehensive. Pharmacies should have the same responsibility as other members of the supply chain to issue alerts when they encounter credible evidence of a suspect or illegitimate product that could cause serious health implications for consumers or threats to the public health.

Section 3. Enhanced Drug Distribution Security
Section 3 should be made as strong as possible in order to evolve and expand consistent with Congressional intent to significantly advance patient safety and justify the preemption of strong existing state laws. The policy must establish a clear path to achieving the steps described in Section 3, including mechanisms for all participants in the U.S. pharmaceutical system to proactively authenticate medicines at the unit level. A unit-level system is essential to achieving a meaningful advance for drug distribution security and to protect the public health. Without a clear and assured path to a unit-level system in the shortest timeframe possible, the policy would fail to adequately protect patients and consumers, and it would also cause significant harm by replacing strong, current state standards with a weaker national system. 

FDA regulations for a unit-level system
The draft legislation would allow but not require FDA to issue regulations to create a unit level system. We strongly recommend that the development of regulations not be left to the discretion of FDA. Rather FDA should be required to write regulations within a specific timeframe. The proposed elements of the regulation are strong and should be maintained.

 Pharmacies cannot be exempted
We recommend that Congress remove the exemption on requiring pharmacies to participate in the enhanced unit-level system. A strong national system cannot exempt pharmacies because to do so would leave consumers and patients at risk from counterfeit or stolen drugs introduced into the chain at the point of dispensing or inserted into distribution through pharmacy sales. The distribution security of the pharmaceutical supply cannot be assured without the participation of all members of the distribution chain, including pharmacies.

 Default statutory mechanism to create a unit-level system
To ensure that FDA and stakeholders move to a unit-level system in a timely way, the default statutory provision in Section 3 that takes effect absent a final regulation is essential. We recommend that this language remain in its entirety because it creates a strong incentive to develop and release the regulations.

Pilot programs
Experience in California shows that industry will develop pilot programs in response to regulations or statutory requirements. That model is preferable to putting the burden for pilots on the FDA, which has neither budget nor authority to compel companies to participate in pilots. Therefore we recommend that the pilot language should be struck and development of future regulations not be contingent on the completion, or outcome of, pilots.

Avoid Preempting Strong State Protections
In a number of provisions in the legislation, Congress runs the risk of not only failing to protect patients, but also causing further harm.  Enacting a weak national system could preempt stronger state protections currently in place in some states, and also prevent states from seeking more effective or stronger safeguards in the future.  We recommend that in every area possible, Congress create federal standards that are a floor, so as to create no barriers to a state that seeks to respond quickly to address future risks from counterfeit or adulterated drugs entering the supply chain.

Center for Medical Consumers
Community Catalyst
Consumers Union
National Consumers League
National Research Center for Women & Families
National Women’s Health Network
U.S. PIRG
WoodyMatters
 

For more information, contact Paul Brown at (202) 223-4000 or pb@center4research.org

November 15, 2012

Marilyn Tavenner
Acting Administrator
Centers for Medicare & Medicaid Services
Department of Health and Humans Services
Room 445-G
Hubert H. Humphrey Building
200 Independence Ave, SW
Washington, DC 20201

Dear Ms. Tavenner:

As members of the Patient, Consumer, and Public Health Coalition, we strongly urge CMS to release the Sunshine Act final regulations as quickly as possible.  Earlier this year (February 2012), we submitted comments on the draft regulations and we are still waiting for the final rule, which is more than a year late and should not be delayed any longer.  Public interest groups and members of Congress agree that it is past time to release the regulations and start collecting information on industry payments to healthcare providers.

Recently, a Washington Post editorial included the Physician Payments Sunshine (PPSA) Act rules in its list of regulations the White House should have already acted on.  The editorial stated, “the health-care reform law stipulated that final rules for a sunshine provision on drug-company payments to physicians and teaching hospitals were to be issued by October 2011. They still have not been.”[1]

An Institute of Medicine (IOM) report (Conflict of Interest in Medical Research, Education, and Practice) stated that, “The public needs to be able to trust that physicians’ decisions are not inappropriately influenced by their financial relationships with industry.”[2] The Sunshine Act directly addresses that issue.  Its purpose is to restore trust in the medical profession and to protect patients and public programs.  The Administration should release the regulations immediately so this important patient safety and consumer protection legislation can be implemented.

The PPSA regulations (CMS-5060-P, RIN 0938-AR33) are designed to increase accountability and transparency in our health care system.  It is not possible to ensure that physicians’ decisions involving prescription drugs and medical devices are based on the best available science, but it is possible to make sure that patients are aware of the financial incentives that their physicians have received from drug and device makers.

American Medical Women’s Association
Annie Appleseed Project
Connecticut Center for Patient Safety
Jacobs Institute of Women’s Health
National Research Center for Women & Families / Cancer Prevention and Treatment Fund
Truth in Medicine
THE TMJ Association
Union of Concerned Scientists
U.S. PIRG
WoodyMatters

For more information, contact Paul Brown at (202) 223-4000 or pb@center4research.org


[1] Editorial November 8, 2012).  Lawmakers face a torrent of delayed decisions, Washington Post.  http://www.washingtonpost.com/opinions/lawmakers-face-a-torrent-of-postponed-decisions/2012/11/08/5994f11c-278a-11e2-b4f2-8320a9f00869_story.html

[2] Institute of Medicine (April 2009). Conflict of Interest in Medical Research, Education, and Practice.  http://www.iom.edu/~/media/Files/Report%20Files/2009/Conflict-of-Interest-in-Medical-Research-Education-and-Practice/COI%20report%20brief%20for%20web.pdf

October 31, 2012

The Honorable Edward J. Markey
Energy and Commerce Committee
U.S. House of Representatives
2108 Rayburn
Washington, DC  20515

Dear Congressman Markey,

As members of the Patient, Consumer, and Public Health Coalition, we thank you for your commitment to the health of patients and consumers by introducing the Verifying Authority and Legality in Drug (VALID) Compounding Act of 2012.  This bill would strengthen FDA oversight of compounding pharmacies in several essential ways, and is clearly needed to prevent tragedies such as the contaminated steroid injections that have already resulted in 356 cases of fungal meningitis and 28 deaths.

The current laws and regulations regarding compounding pharmacies have resulted in giant loopholes that allow medical products that are neither safe nor effective to be sold throughout the country, putting patients’ lives at risk.  We are very grateful to you for your leadership on this very important, life-saving bill.

The VALID Act would protect the activities of traditional small compounding pharmacies while ensuring that compounding pharmacies that are essentially operating as drug manufacturers are regulated by the FDA the same way as other drug manufacturers.  It would require pharmacies that engage in interstate commerce to register with the FDA and comply with minimum safety standards.  The bill would require compounding pharmacies to report deaths and other serious adverse events to the FDA in a timely manner, so that other patients would not be harmed. It would authorize the FDA to inspect pharmacy facilities, which is absolutely essential.  It would also require a warning to patients that compounded drugs have not been approved safe and effective by the FDA.

We look forward to working with you on the VALID Act, and share your desire to make sure that waivers are available when the public health is at stake, but are not used to undermine the integrity of the legislation.

The scandal around the lack of oversight of compounding pharmacies has alarmed lawmakers on both sides of the aisle.  We will make every effort to secure bipartisan support for this bill.

Cancer Prevention and Treatment Fund
Jacobs Institute for Women’s Health
National Consumers League
National Research Center for Women & Families
Our Bodies Ourselves
Union of Concerned Scientists

For more information, contact Paul Brown at (202) 223-4000 or pb@center4research.org

November 30, 2012

Chairman Tom Harkin                                                Ranking Member Mike Enzi
731 Hart Senate Office Building                                379A Senate Russell Office Building
Washington, DC 20510                                              Washington, DC 20510

Comments from Members of the Patient, Consumer, and Public Health Coalition
Re: FDA’s Recent HELP Committee testimony on pharmacy compounding

Dear Chairman Harkin and Ranking Member Enzi,

As members of the Patient, Consumer, and Public Health Coalition, we welcome the opportunity to provide our views regarding FDA Commissioner Margaret Hamburg’s November 15, 2012 testimony at the HELP Committee hearing, “Pharmacy Compounding: Implications of 2012 Meningitis Outbreak.”  HELP staff asked us to focus our comments on FDA’s recommendations for a proposed risk-based framework, and on FDA’s request for additional statutory authorities to regulate pharmacy compounding companies.

Commissioner Hamburg’s risk-based framework addresses many of the same issues that HELP staff asked stakeholders to address earlier this month.  Commissioner Hamburg’s comments also mirror many of the proposals in Congressman Edward Markey’s Verifying Authority and Legality in Drug (VALID) Compounding Act of 2012.  We generally support the VALID Act because it will give the FDA the clear regulatory authority it needs to prevent tragedies such as the contaminated steroid injections that have resulted in hundreds of cases of fungal meningitis and more than 30 deaths.

The compounding industry and others argue that FDA already has the authority it needs to regulate non-traditional compounding companies.  However, the uncertainty regarding the status of section 503A due to different interpretations of the law by the Fifth and Ninth Circuit Courts has led to non-uniform enforcement in the U.S.  Congress needs to take legislative action so that FDA has clear, unambiguous authority to apply the law uniformly nationwide. There should not be one set of laws for Texas, Louisiana, and Mississippi (the Fifth Circuit), and another for the rest of the country.  Congress should absolutely clarify the legal status of section 503A, which should be revised to delete the unconstitutional advertising provision.

Additionally, FDA’s authority to regulate pharmacy compounding companies has been challenged by compounders.  Commissioner Hamburg stated in her testimony that the New England Compounding Center (NECC) “has repeatedly disputed FDA’s jurisdiction over its facility.”  NECC claimed that the state of Massachusetts had jurisdiction, rather than the FDA.

At the recent House and Senate hearings on compounding, there was sharp criticism of the FDA for not using the authority it already has to shut down what was characterized as large-scale drug manufacturing by NECC under the guise of pharmacy compounding.  Although we agree that the FDA should have done more, the blame is similar to blaming an underfunded police department for a city’s high crime rate.  FDA has been underfunded for years, which means they do not have enough “cops on the beat” to adequately regulate the enormously diverse and complex medical products industry.  User fee agreements, which were meant to address budget shortfalls, may have exacerbated safety problems because user fees mandate that FDA meet industry performance goals that focus almost entirely on speed of approval for new medical products—not on safeguards, such as inspections, post-market surveillance, or enforcement.

At numerous hearings on the reauthorization of PDUFA and MDFUA, industry railed against stronger FDA oversight, and many Members of Congress echoed those pressures.  The tragic deaths from a preventable outbreak of fungal meningitis is an important reminder that essential regulations will save lives.  Rather than responding with constructive strategies to improve patient safety, some of the same people who demanded less FDA oversight are blaming the Agency for not aggressively regulating compounding pharmacies.

Risk-based Framework
Commissioner Hamburg began her risk-based framework remarks by stating her support for FDA’s long-standing policy that compounding should be performed by a licensed pharmacist or licensed physician, and that there must be a prescription or an order for individual patients who need a compounded drug.  We agree.

We also agree with the Commissioner’s following recommendations:

  • What are currently called compounding pharmacies include traditional and non-traditional, and non-traditional should be subject to Federal standards. Commissioner Hamburg was specific in identifying products that would be in the non-traditional category (sterile compounded drugs, large volume of drugs being produced, whether the drug is shipped interstate among other items).  While Commissioner Hamburg said that non-traditional compounding products should be subject to Federal standards and urged Congress to strengthen Federal standards, we believe that many of these non-traditional compounders are actually manufacturers and should be regulated as such.
  • Non-traditional compounders that are not manufacturers should be subject to greater oversight, such as current Good Manufacturing Practices (cGMP) that comply with FDA standards.
  • Certain drugs should not be compounded.  There should be no copies of FDA-approved drugs (except in the rare situation of shortages or to address urgent public health issues).
  • States should have a role in regulating traditional compounders and there is a legitimate role for traditional compounders (for example making doses appropriate for children or preservative-free doses).

Additional FDA Authority Requested
Commissioner Hamburg stated that the FDA’s ability to take action against compounding “has been hampered by gaps and ambiguities in the law, which have led to legal challenges to FDA’s authority.”  The Commissioner recommends that FDA have clear, full authority to collect and test samples of compounded drugs and be able to examine the records of compounders (such as prescriptions received and the volume of products shipped).  We agree. Compounding companies should not be able to stonewall the FDA.

The Commissioner stated that non-traditional compounders should register with the FDA.  We agree.  How can the FDA provide oversight, if the Agency is unaware that a company is engaged in compounding?

The Commissioner also urges Congress to explore requiring non-traditional compounders to report adverse events, and to fund inspections and oversight of non-traditional compounders with registration or other fees.  We strongly support adverse events reporting and registration fees to support inspections and oversight.

Stronger regulations are clearly needed to prevent tragedies such as those caused by NECC’s contaminated steroid injections. Current laws and regulations regarding compounding pharmacies are not as clear as they should be, and this has allowed medical products that are neither safe nor effective to be sold throughout the country, putting patients’ lives at risk.

Breast Cancer Action
Jacobs Institute of Women’s Health
National Consumers League
National Research Center for Women & Families
Union of Concerned Scientists
U.S. PIRG

 

For more information, contact Paul Brown at (202) 223-4000 or pb@center4research.org

November 2, 2012

Chairman Tom Harkin                                            Ranking Member Mike Enzi
731 Hart Senate Office Building                             379A Senate Russell Office Building
Washington, DC 20510                                          Washington, DC 20510

Comments from Members of the Patient, Consumer, and Public Health Coalition
Re: “Questions for Stakeholders Regarding Appropriate Regulation of Pharmacy Compounding”

Dear Chairman Harkin and Ranking Member Enzi,

Members of the Patient, Consumer, and Public Health Coalition welcome the opportunity to provide our views regarding pharmacy compounding.  Stronger regulations are clearly needed to prevent tragedies such as the contaminated steroid injections that have already resulted in 356 cases of fungal meningitis and 28 deaths.  Current laws and regulations regarding compounding pharmacies have resulted in giant loopholes that allow medical products that are neither safe nor effective to be sold throughout the country, putting patients’ lives at risk.

Changes to regulations should ensure that compounding pharmacies that operate as drug manufacturers are regulated by the FDA the same way as other drug manufacturers.  Pharmacies that engage in interstate commerce should be required to register with the FDA and comply with safety standards.  Compounding pharmacies should be required to report deaths and other serious adverse events to the FDA in a timely manner, so that other patients would not be harmed. There needs to be no question that the FDA has the authority to inspect pharmacy facilities. Legislation is also needed to require a warning to health professionals and patients that compounded drugs have not been approved safe and effective by the FDA.

Below, we address your specific questions:

Current Authorities FDCA 503A
The Federal Food, Drug, and Cosmetic Act could have and should have been used to prevent the New England Compounding Center tragedy from happening.

Section 503A of the FFDCA exempts compounded drugs from FFDCA requirements regarding drug adulteration, misbranding, and new drug approval, provided that certain conditions are satisfied.  NECC was manufacturing large quantities of the steroid.  This appears to be in violations of the FFDCA requirement that the company “does not compound regularly or in inordinate amounts (as defined by the Secretary) any drug products that are essentially copies of a commercially available drug product.”[1]

The uncertainty regarding the status of section 503A due to different interpretations of the law by the Fifth Circuit Court and the Ninth Circuit Court has led to non-uniform enforcement in the U.S.  Congress needs to take legislative action so that FDA has a clear, unambiguous law to There should not be one set of laws for Texas, Louisiana, and Mississippi (the Fifth Circuit), and another for the rest of the country.  Congress should absolutely clarify the legal status of section 503A, which should be revised to delete the unconstitutional advertising provision.

Regarding prescription language in (a)(2), the section on limited quantities must remain, but a more precise definition of “limited quantities” is needed.  The anticipatory language “based on a history of the licensed pharmacist or licensed physicians receiving valid prescription orders” would serve as a loophole that would make it too easy for companies to get around the prescription requirement.

The ban on compounding copies of commercially available drugs in (b)(1)(D) should be maintained.  As noted previously, NECC seems to have violated that restriction.

The 5% cap on interstate shipments in (b)(3) needs to be lowered.  Drug compounding has morphed from its original intention of preparing medications that are not commercially available, such as lower dosage drugs for children or drugs without dyes to prevent allergic reactions.  As a result, the restrictions on interstate shipments should be clearly stated and enforced. The Secretary should be able to develop a waiver process in case of drug shortages or to protect public health, but this must not serve as an easy loophole in the law.

As for retaining the memorandum of understanding, the question is: Has it been effective?  What is the MOU’s track record?  Has the MOU with the Secretary and individual states, which addresses “the distribution of inordinate amounts of compounded drug products interstate” resulted in investigations by state agencies?  It seems clear that it has not been effective, and therefore it is a moot point for The Secretary and the National Association of Boards of Pharmacy to develop a MOU to be used by the states to comply with the inordinate amounts provision.

Pharmacy licensing standards in states may or may not address compounding standards.  An important question is whether the states have the resources to enforce the standards.  Another problem is that a patchwork of 50 different standards, particularly when some companies are selling their products across state lines, makes it impossible to guarantee safety for all Americans, or to stop a bad actor from setting up a compounding business in the state with the weakest standards.

Good Compounding Practices
Federal requirements for compounding pharmacies should comply with United States Pharmacopoeia standards for compounding.   It seems obvious that there should be more stringent compounding practices for sterile compounding. Federal good compounding standards could be enforced with spot checks by the FDA and civil monetary penalties, or in major violations, the shutdown of production until the drug compounding company complies with the standards.

Scale of Compounding
Federal legislation should distinguish between traditional compounding (used for small quantities such as doses for specific children or preservative-free doses) and large-scale compounding that more closely approximates manufacturing.  As we stated earlier, by clearly defining the phrase “inordinate amounts,” the FDA should be able to distinguish between manufacturing and traditional compounding.  In addition, enforcing the requirement of individual prescriptions would also reduce the volume.  Volume, percentage of sales, standardization of drug products, and interstate sales should be part of the equation in determining whether or not a compounding company was a manufacturer.  FDA should also carefully scrutinize preservative-free doses, which have historically been defined as traditional compounding, and whether those might be more likely to become contaminated.  Earlier this week, FDA and CDC laboratories identified bacteria present in three separate lots of NECC-supplied preservative-free betamethasone, which is a topical steroid used for itching, inflammation, and sometimes as an intramuscular injection for allergic reactions.

Type of Compounding
The Federal legislation should differentiate between types of compounded products such as sterile and non-sterile, with sterile products subject to stricter standards and more frequent inspections.  Also, how the drug is used should be taken into account.  Drugs that are injected into the spine, which could travel throughout the nervous system, have a higher risk profile than drugs used to treat a specific area of the body such as a joint or a muscle area.  It is appropriate for facilities producing drugs with higher risks to be subject to more robust standards; however, all facilities should be subject to GMP.

Interstate Shipment
Interstate shipments should be regulated by the FDA.  We stated earlier that we question whether states have the resources to enforce regulations for compounding companies within their own borders.  It seems even less likely that states have the resources to ensure that out-of-state pharmacies comply with their laws.

Ingredients in Compounded Products
Federal regulations should require that bulk ingredients used in compounding come from FDA-registered establishments and with a certificate of analysis, or that the drug substance complies with the standards of the United States Pharmacopoeia or National Formulary monograph.

Registration of Listing
Most compounding pharmacies should be required to register with the FDA with an exception for pharmacies/pharmacists who prepare an extremely limited number of compounding drugs (doses for individual young patients/preservative-free doses).  Even compounding pharmacies that do not currently sell their products across state lines need to register with the FDA because they may well sell their products across state lines in the future, especially if they are compounding drugs that are in short supply.  Registration should cover the basic contact information and key information about the products compounded.  FDA has experience with registration of prescription drug companies and medical device companies that it can draw on to create a registration database for compounding companies.  Firms subject to registration should pay a modest user fee to cover FDA’s cost of establishing the registration program.  A registration program would not be overly burdensome for compounding companies and would allow the FDA to keep better track of compounding companies, which should improve public health.

The Prescription
It should be a federal requirement that compounded products be made in response to a prescription or in anticipation of a prescription (but only limited quantities) based on previous sales.  If there were a federal requirement that the prescription (or notation ordering a compounded drug product) explicitly called for the drug to be compounded, then that would eliminate any confusion by doctors or other health care professionals over whether the drug was compounded or not.  Did all of the physicians who ordered methylprednisolone acetate for their patients realize it was a compounded drug?  A related question is whether the doctors and medical facilities understood that compounded drugs were not tested to ensure that they were safe or effective.

Office Stock
There should be federal restrictions on compounding for office uses.  Ideally, the compounder should be required to reconcile prescriptions from the physician once the compounded product has been dispensed in the physician’s office, but will physicians actually take to time to do this?  The amount of compounded stock should be limited to match the number of prescriptions the physician has written.  Also, if it is a product that requires special handling (for example, refrigeration) its stock should be limited.  The labeling requirements for office use should mirror the labeling requirements for all compounded drugs, which should state explicitly that the FDA has not approved the safety or effectiveness of this drug.  There should be an allowance for compounding for research, teaching or chemical analysis as long as these products are not for sale or dispensing.

Standardized Drug Products
It may be appropriate for a pharmacy to compound standardized drugs products in the case of drug shortages, or to protect public health or well-being, or when a patient’s allergies require a preservative-free dose or when a small dose is needed for a child.  The drugs should not be copies of commercially available drugs.  Earlier this week, the FDA reported that the time-release method for a generic drug to treat depression did not work the same as the brand name drug and this compromised its effectiveness.  Any additional restrictions on compounded drugs that use standardized drug products would also apply to office stock.

Inspection Authority
FDA authority to inspect compounding pharmacies should be broadened and strengthened.  FDA should have access to all compounding records.  It is unacceptable that compounding pharmacists hindered FDA efforts to determine if an injectable drug used to reduce risks of premature birth was substandard and possibly made with unapproved Chinese ingredients.[2]  Compounding pharmacies should not be able to stonewall the FDA by stating that the compounding records are for state authorities. In addition, if compounding pharmacies ship products across state lines, then they should be inspected by the FDA, and they should also be inspected by the FDA if they are producing sterile drugs or drugs that have higher risks (such as drugs injected in to the spinal cord).  FDA should limit its inspections to larger compounding pharmacies and perhaps exempt pharmacies that only rarely compound products.

Compounded Product Labeling
There should be a disclaimer on the label of compounded drugs. We support the label requirements that were part of the 2007 Discussion Draft (Safe Drug Compounding Act). The label should state first and in bold letters: THIS DRUG IS NOT REQUIRED TO MEET THE SAFETY, EFFICACY, OR MANUFACTURING STANDARDS FOR FDA-APPROVED DRUGS.  It should then state that the drug was made specifically for the patient because a health care provider determined that no FDA-approved product is available for this specific need.  If it is a sterile product, the label should state: This drug was not prepared using FDA’s manufacturing standards for sterile drugs.  Additionally, the label should have the date when the drug was compounded, the name of the licensed compounding pharmacist or physician, and other relevant information from labeling including from medication guides.

Adverse Event Reporting
Compounding pharmacies should be required to report most adverse events to the FDA.  Exceptions could be made for minor side effects such as headache, upset stomach, dizziness, diarrhea, etc.  There should be special regulations for a subset of adverse events. For example, compounding pharmacies would have to report to the FDA within 5 work days from becoming aware of an event that required hospitalization or was a threat to health, since action would be needed to prevent an unreasonable risk of substantial harm to the public health.  They would have 10 days to report other adverse events. This is similar to the reporting requirements for medical device manufacturers.  The reporting requirements should not necessarily be limited to compounding pharmacies.  If a health care provider is aware of a significant A/E (major side effect, injury or death) caused by a compounded product they must report it also.

Federal and State Coordination and Communication
Based on the NECC tragedy, federal and state officials need to better coordinate their existing authorities.  The Massachusetts Department of Health recently released hundreds of pages of documents about violations at NECC going back to April 1999.[3]  Was FDA aware of all of these problems?  A related question is why the FDA did not follow up on their own warning to NECC in 2006, and whether they expected the state to do so.  If a specific federal requirement calls for coordinating enforcement and regulatory activities with state officials, it must be written in a clear manner and written so that FDA can pursue enforcement and regulatory activities with or without state officials.  We do not want an effort to coordinate enforcement to be a roadblock to enforcement.

Breast Cancer Action
Jacobs Institute for Women’s Health
National Consumers League
National Research Center for Women & Families
Union of Concerned Scientists
US PIRG
WoodyMatters

For more information, contact Paul Brown at (202) 223-4000 or pb@center4research.org

 

[2] Bogdanich W, Tavernise S (October 23, 2012). U.S. Concern Over Compounders Predates Outbreak of Meningitis. New York Times.

[3] Tavernise S, Pollack A (October 23, 2012). Documents in Meningitis Case Show Complaints in 1999. New York Times.