A New Plan for Drug Shortages to Build on FDA’s Success

By: Capt. Valerie Jensen, R.Ph. 

I’ve led FDA’s efforts to address hundreds of drug shortages for more than 10 years. During that time, we’ve made progress. Just last year, we cut the number of new shortages by more than half. But more work needs to be done. 

In an effort to enhance FDA’s current approach to drug shortages and bring new ideas to reduce the number of patients who are affected, we provided Congress today with a strategic plan aimed at enhancing efforts to prevent and reduce drug shortages. FDA is actively working, as required by the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012, to address the public health threat caused by critically needed medications being unavailable for patients. And we will continue that work and build on our progress. 

An important part of our work is understanding the impact on patients. I’ve talked with many patients and caregivers about the effects of drug shortages. It deeply saddens me to hear a mother talk about her new baby boy, born prematurely, who is struggling to survive due to the scarce supply of drugs to meet his nutritional needs. Or a husband whose wife has been battling cancer and her doctor says the hospital is running out of the medication needed to properly treat her. 

I’m often asked, “Why do drug shortages persist?” and “Why are so many lifesaving drugs in shortage?” The majority of these problems stem from quality and manufacturing problems. Therefore, the answers boil down to quality manufacturing. 

While “quality manufacturing” may sound like a simple concept, getting there is a complex process – and one in which FDA and outside stakeholders have important roles to play. 

The strategic plan includes a number of new ideas to address shortages. Many of these strategies focus on enhancing FDA’s response and communication when we become aware of quality or manufacturing issues that could lead to a shortage. Other strategies that FDA is considering include the development of new risk-based approaches to identify early warning signals for manufacturing and quality problems that could lead to production disruptions.

In addition, the strategic plan identifies some preventive measures companies can take that place a greater emphasis on manufacturing quality and stability of supply, thereby eliminating the root causes of most shortages. 

Better manufacturing quality will help eliminate drug shortages over the long-term. But when a manufacturing disruption is likely to occur, early notification by manufacturers is critical. Along with the strategic plan, therefore, FDA is today issuing a proposed regulation implementing the expanded early notification requirements included in FDASIA. This regulation would require that all manufacturers of certain medically necessary prescription drugs give FDA advance notice of a permanent discontinuance or a temporary interruption of manufacturing. It would also extend this requirement to manufacturers of biologic products. 

Advance notification of a potential shortage allows FDA to work closely with manufacturers on the underlying issues, and in many cases, we are able to prevent the shortage. 

FDA envisions all stakeholders coming together to ensure patients have access to the safe, effective, and high-quality medications they rely on and deserve, and we believe the strategic plan we presented to Congress today will make great strides in ensuring that happens.

Capt. Valerie Jensen, R.Ph., is the Associate Director of the Drug Shortages Program in FDA’s Center for Drug Evaluation and Research


FDA and Partners Launch e-Learning Course on Evaluating Drug Promotion

By: Thomas Abrams 

You probably have seen many consumer advertisements for prescriptions drugs–on TV, in magazines, or online. While those ads are expensive, did you know that in 2010, pharmaceutical companies actually spent more money advertising to health care professionals than they spent advertising to consumers? Here at FDA, our Office of Prescription Drug Promotion (OPDP) monitors the information that pharmaceutical companies give to health care professionals (HCPs) about prescription drugs. We want to make sure the information your doctor or prescriber receives is truthful and not misleading, because they may use it when deciding what medicines to prescribe to you, their patient. 

We have just launched with Medscape an e-learning course and case studies as part of Bad Ad, a program designed to raise awareness among HCPs and students in various health programs about drug ads and promotional materials that might be untruthful or misleading, and how to report it to FDA. The course offers Continuing Medical Education (CME) credit for physicians and Continuing Education (CE) credit for other HCPs. Although the target audience for the course is HCPs, anyone can take the course. 

In addition, because students are actively engaged in forming clinical practice habits that may last throughout their careers, reaching them now with Bad Ad information could have a strong impact on how they view prescription drug promotion. To help them become discerning readers of drug promotional information, we in OPDP have developed several case studies based on FDA Warning and Untitled letters issued to drug companies. The case studies, which represent common problems, can be downloaded from the Bad Ad website. 

We encourage medical, pharmacy, nursing and other health care related schools to incorporate these cases into their coursework. The cases cover a range of promotional materials including a website, journal ad, and TV ad, and touch upon numerous promotional practices that don’t comply with our regulations. Through the case studies, students will have an opportunity to evaluate and discuss these real-life examples of misleading drug promotion. 

Our new e-learning courses and cases studies are the latest of many ways FDA works to help ensure that your health care professionals have truthful and accurate information when making decisions that affect your health and safety. 

Thomas Abrams is the director of FDA’s Office of Prescription Drug Promotion in the Center for Drug Evaluation and Research

Keeping Animal Foods Safe

By: Daniel McChesney, Ph.D. 

Animals are an important part of our lives. Whether we’re talking about a family’s pet or a farmer’s livestock, we at FDA are committed to doing all we can to keep the foods they eat free of contamination. 

To this end, we have proposed the Preventive Controls for Food for Animals rule to establish good manufacturing practices for facilities and personnel involved in manufacturing, processing, packing and holding animal food. It would require facility owners to have a food safety plan and to have controls in place to minimize any potential hazards. 

This proposed rule pulls together the work we’ve done over the past decade to craft a safety system for animal food and will give us new tools to do this important work. The research and findings of the agency’s Animal Feed Safety System Working Group helped create the foundation for the proposed regulations. 

Historically, we have put most of our efforts into responding to safety issues involving animal food as they arise. And while regulations have been crafted to address such threats as the brain-wasting bovine spongiform encephalopathy (aka “mad cow” disease), this regulation moves towards a comprehensive, risk-based regulatory framework to keep all animal foods safe. 

And you can see by looking at some of the crises in recent years this is clearly an important public health issue, one that affects both animals and people. 

Everyone still remembers the massive recall of pet foods in 2007 after melamine, a chemical used to make plastic, was intentionally added to ingredients produced in China, killing pets across the country. 

Just last year, 30,000 tons of dry dog and cat food were recalled following an outbreak of Salmonella tied to a South Carolina facility. The Centers for Disease Control and Prevention reported that 47 people in 20 states and two in Canada fell ill from coming in contact with the contaminated food. 

Globally, public health agencies have for years dealt with the presence of dioxin – linked to cancer and developmental problems in people – in animal food ingredients, and those episodes led to multiple food recalls. 

While FDA moved quickly in response to these and other crises tied to contaminated pet foods, the agency’s focus changed with the enactment in 2011 of the FDA Food Safety Modernization Act. Congress charged FDA to take a more preventive, risk-based regulatory approach. 

While FDA has proposed four other rules this year that were mandated by the food safety law, we chose to handle safety issues involving animal foods separately. Animal and human foods are produced differently, and animals and people are vulnerable to different hazards. 

Also, the rule deals with the nutrient content of animal foods to satisfy a need that is unique to animals. If humans eat a food that’s not particularly nutritious, we can choose something else later. Animals obviously don’t have that option, and they usually get the same food for every meal, so these foods must be complete, nutritionally balanced products.

The bottom line is that we want the foods that animals eat to be safe. We want you to be safe if you’re handling pet food or eating foods derived from animals. This rule will help us do that. You are welcome to read the rule and submit comments by visiting FDA’s official docket at www.regulations.gov or www.fda.gov/fsma

Daniel McChesney, Ph.D., is Director of the Office of Surveillance and Compliance at FDA’s Center for Veterinary Medicine.

As nanotechnology is being used to develop new drugs, FDA is working to ensure quality, safety, and effectiveness

By: Celia N. Cruz, Ph.D. 

Nanotechnology is a new and exciting field that offers scientists the opportunity to control matter at very small dimensions, opening many possibilities for making all kinds of new products. This technology operates on an incredibly small scale that measures things in units called nanometers. One nanometer is one billionth of a meter. It’s hard to even imagine how small that is, but here’s one way to do it: A human hair is about 100,000 nanometers wide. 

Wow, that’s small! But nanotechnology promises big things! There are already many products made using materials at the nanoscale, including new kinds of clothing, packaging materials, and light-weight, but strong, building materials. 

Why are we at FDA’s Center for Drug Evaluation and Research (CDER) writing about it? Because medical products can also be made using materials at the nanoscale. In fact some are already available, including certain sunscreens, in which the nanomaterials are used to provide UV protection while remaining transparent on the skin, and in drugs to treat cancer, including Doxil and Abraxane. Use of nanomaterials can enhance delivery of drugs to their biological target or help scientists customize them for a particular type of patient. 

Materials at the nanoscale can have different chemical, physical, or biological properties compared to their conventionally-scaled counterparts. Scientists can use these features to enhance the properties or the quality of a drug. But because such properties can affect the quality, safety, or effectiveness of a drug, FDA is studying these issues related the use of this powerful new technology in medical products. 

Recently, to help us better understand the potential impact nanotechnology could have on a drug’s quality, safety, or effectiveness, CDER’s Nanotechnology Risk Assessment Working Group (Nano Group) finalized a series of risk assessment and risk management exercises to identify potential risks associated with a drug product that contains nanomaterials. A key goal was to determine if our current regulatory processes are adequate to identify any potential risks and reduce those risks. 

Some members of the Nanotechnology Working Group in the CDER labs where characterization of gold nanoparticles is underway. Left to right, front row: Katherine Tyner, Ph.D. Office of Clinical Pharmacology; Celia N. Cruz, Ph.D. Office of New Drug Quality Assessment; middle row: Olen Stephens, Ph.D. Office of New Drug Quality Assessment: Don Henry, Office of Pharmaceutical Science; Abigail Jacobs, Ph.D. Office of New Drugs; back: Paul Brown, Ph.D. Office of New Drugs.

The CDER Nano Group consisted of a multidisciplinary team of scientists that could provide a complete evaluation of the use of nanomaterials in the types of drugs regulated in the Center. We first performed a thorough risk assessment of all stages in the lifecycle of a drug containing nanomaterials to capture any real or perceived hazards related to the nanomaterials. To complete the exercise, we evaluated the common ways a person could be exposed to nanomaterial in a drug product ― swallowing a drug, having it injected, applied to the skin, or inhaled. In addition, we evaluated unintentional and accidental exposure. 

Once all the potential risks were identified, we undertook a risk management exercise to examine the regulatory process we use to evaluate drugs. We then considered whether the identified potential risks in the first exercise could be sufficiently managed by the existing review processes we use to help protect patients from harm. 

Our risk management exercise determined that our current regulatory review processes indeed can adequately protect the public from potential risks associated with the use of nanomaterials in drug products. We also identified areas that could benefit from improvement. These areas include increased nanotechnology regulatory science research and up-to-date training of the review staff who evaluate marketing applications for drug products developed using nanomaterials. FDA does not make a categorical judgment that nanotechnology is intrinsically safe or harmful. Rather, for nanotechnology-derived and conventionally-manufactured products alike, FDA considers the characteristics of the finished product and, as applicable, its safety, effectiveness, or other product attributes. 

Historically, FDA has successfully adapted to novel technologies, and the robust review process we use will continue to capture the potential risks associated with this new technology. To share the findings of the nanotechnology risk assessment and management exercises, in January 2014, FDA will co-sponsor a workshop with the US Pharmacopeia, the International Society for Pharmaceutical Engineering, the American Association for Pharmaceutical Scientists, and the Society of Toxicology to review and share experience gained during the development and review of medical products containing nanomaterials. With these and other activities, FDA will continue to work to ensure that safe, effective drugs are available to the American public. 

Celia N. Cruz, Ph.D. is Senior Reviewer, Chemistry, Manufacturing and Controls, at FDA’s Center for Drug Evaluation and Research

Help Us Find Out Why Jerky Treats Are Making Pets Sick

By: Linda Tollefson, D.V.M. 

As a veterinarian and lover of animals, I find that working at FDA is a dream job in many ways. In the Foods and Veterinary Medicine program, there are veterinarians in many different jobs that all have to do with keeping both people and animals safe. 

Within the program, FDA’s Center for Veterinary Medicine (CVM) is a working testimonial to animals and their companion people. Desks and office doors are covered with photos of pets — dogs and cats of course, horses for sure, and even our favorite reptiles, birds, cows, pigs, sheep and a few great goats. Water cooler conversations are full of stories about the antics of our friends and family members (with and without fur, fins or feathers) and the challenges of caring for an aging animal. 

That’s why it means so much to us when we are able to target what is making an animal sick, and why it hurts, both personally and professionally, when the cause of illness eludes us despite global efforts to track it down. 

How to Report a Complaint about Jerky Pet Treats

As of September 24, 2013, over 3,600 dogs and 10 cats have reportedly become ill from eating jerky pet treats, nearly all of which were imported from China. While most pets have fully recovered, approximately 580 of these pets have died. The mystery that CVM is trying to solve is this: What is causing the reported illnesses and deaths in dogs (and some cats) that have eaten jerky pet treats made in China? 

The Center has been investigating these illnesses and deaths since 2007, working with experts in academia, industry, foreign governments and state labs. CVM’s Office of Research has been working with the Veterinary Laboratory Investigation and Response Network (Vet-LIRN), a consortium of animal health labs nationwide, to examine both animal diagnostic and tissue samples from pets that have become ill and the jerky pet treats themselves. 

Researchers in CVM labs, working together with other labs across the country, have tested jerky pet treats for microbiological contaminants, heavy metals and elements, pesticides, rodenticides, molds, antibiotics and other compounds. We’ve also analyzed hundreds of medical records and lab results, including examining and testing fluids and tissues of sickened pets. FDA inspection teams have visited manufacturing plants and suppliers in China and met with representatives from the Administration of Quality Supervision, Inspection and Quarantine (AQSIQ), the Chinese regulatory agency responsible for pet food, to discuss U.S. requirements for pet food safety. Jerky pet treats from pet owner’s homes have been tested and compared with store samples. We’ve even made our own jerky to try to duplicate the commercial process. 

So why don’t we know what exactly is causing these illnesses? We’re not sure, but we know that we need more information about the pets that are getting sick. In order to get that information, we need the help of pet owners and veterinarians. To that end, we have issued a “Dear Veterinarian” letter asking veterinary practitioners who treat animals they suspect may have been sickened by eating jerky treats to report these cases to CVM through the FDA Safety Reporting Portal right away so that we can suggest certain tests (and cover the cost of these tests in many cases) when appropriate. We are working with our partners in Vet-LIRN labs across the country to test urine, blood and tissue samples from ill pets that may have been sickened by jerky treats. This collaboration helps leverage our resources and pool scientific expertise for the greatest effect. 

Despite extensive media coverage of the illnesses associated with these products and our own outreach efforts including through the CVM web site, we know there are still pet owners who are unaware of this issue. In response, FDA has developed a Fact Sheet for pet owners that can be made available at veterinary hospitals, pet supply stores, other stores selling pet food, and anywhere pet owners visit. The Fact Sheet explains what symptoms to look for, how to contact your local FDA office, and the status of our jerky pet treat investigation so far. We hope that these tools will help prevent more pets from becoming sick and will provide us with the clues we need to crack the case. 

What we do know is that our pets bring joy to our lives. It’s our mission, both as public servants and animal lovers, to find – and eliminate – the cause of these illnesses. 

Linda Tollefson is Associate Commissioner for FDA’s Office of Foods and Veterinary Medicine

Fishing for a solution

By: Stacey DeGrasse

My collaboration with fishermen began in 2005, when I was dispatched to New England to test the safety of shellfish harvested from federal waters infested by a type of algae that produces toxins. Shellfish that ingest the toxin are not harmed, but if the toxins reach high enough levels, they can make humans who eat the shellfish extremely ill.

The assignment given to me and three other scientists from the Food and Drug Administration: Determine if it was safe for fishermen to continue harvesting clams and other shellfish in the area without endangering consumers.

The high toxin levels we measured in the ocean areas experiencing the expansive bloom of Alexandrium fundyense algae prompted the closure of 15,000 square miles of harvest area to commercial clam fishermen. While it was gratifying to know we were preventing toxic shellfish from harming consumers, it was heartbreaking to look into the eyes of hardworking fishermen and know what the decision meant to their livelihoods.

Years before, in 1990, another Alexandrium bloom had closed to shellfish harvesting the massive Georges Bank, which begins 62 miles off the coast of New England and extends to Nova Scotia. The additional closing in 2005 plunged the clamming industry into crisis.

At that moment, I became determined to play a role in developing a strategy that would someday allow the fishermen to return to traditional fishing grounds while still protecting the public.

I joined colleagues, including FDA’s Paul DiStefano and Steve Conrad, who shared the same goal. Years of research led to a possible solution. The algal blooms come and go, so perhaps the answer was for fishermen to test the clams as they harvested them at sea. That way, the fishermen wouldn’t spend time and money many miles offshore, only to arrive at the docks for their product to be tested by government officials and discover they had returned with contaminated clams they’d have to pay to discard.

We worked with test kit manufacturers to adapt a test originally designed for lab scientists so it could be used by fishermen at sea. Our efforts simplified the kit. Still, the test took about an hour and a half and required precise steps, including keeping track of standards, samples, reagents, timed incubations and data collection. The fishermen would need to do all of this far offshore, sometimes under extreme conditions.

There was a lot of skepticism. First, how would the fishermen react to listening to days of lectures from a young, academically trained, government scientist? Could they accurately conduct these tests that sometimes even challenge lab scientists?

The fishermen, it turned out, are self-taught scientists eager to learn more in an academic setting. In fact, I soon learned that they have spent more time observing science at sea than I have done with my Ph.D. in oceanography. Their observational skills are keen, and they taught me as much about oceanography as I taught them during training sessions on land and at sea.

They shared with me their empirical knowledge about climatological and environmental effects on algal blooms, declines in clam populations due to temperature increases, and changes in whale behavior – to name a few.

While I enjoyed putting on my foul weather gear and participating in the hard work of dredging and shucking clams and testing them for toxins, the most memorable times came when fishermen told me sea stories. Topics ranged from harrowing events at sea to the most unusual organisms and objects they had pulled from the sea. I realized during those exchanges that we all had one thing in common – a love and respect for the sea and all that it offers.

The training worked. As of this year, a large portion of Georges Bank has reopened to commercial clam fishermen who agree to follow the biotoxin control strategy, which includes taking FDA-training to conduct onboard tests of their catch and submitting dockside shellfish samples for a second test conducted by state authorities.

I came to FDA rather than pursuing an academic position because I hoped my research would have immediate applications. My hopes have been fulfilled; it is extremely gratifying to see that our research has made a positive impact on the economy and on fishermen’s livelihood, while ensuring safe seafood for the public.  

Stacey DeGrasse is a research biologist in FDA’s Office of Regulatory Science, Division of Analytical Chemistry, Spectroscopy and Mass Spectrometry Branch