FDA alerts health care professionals and patients not to use compounded drugs from Cantrell Drug Company; agency seeks action to stop production and distribution:
March 1, 2018;
The U.S. Food and Drug Administration is alerting health care professionals and patients not to use drug products produced by Cantrell Drug Company of Little Rock, Arkansas, including opioid products and other drugs intended for sterile injection, that were produced by the company and distributed nationwide. The agency is concerned about serious deficiencies in Cantrell’s compounding operations, including its processes to ensure quality and sterility assurance that put patient safety at risk. Administration of contaminated or otherwise poor quality drug products can result in serious and life-threatening injury or death.
FDA investigators most recently inspected Cantrell’s facility in June 2017, and observed poor compounding drug operations. Of particular concern, the FDA investigators observed insanitary conditions and violations of current Good Manufacturing Practice (CGMP) that could cause Cantrell’s drugs to become contaminated or made injurious to health. Because Cantrell produces drugs that are intended for sterile injection, the conditions identified — which can expose such products to contamination and render them unsterile — raise significant public health concerns. In response to the FDA’s recommendation, in July 2017, Cantrell recalled all drug products marketed as sterile and ceased sterile compounding. However, against FDA advice, the company resumed production and distribution without demonstrating that it had adequately addressed the problems identified.
FDA authorizes, with special controls, direct-to-consumer test that reports three mutations in the BRCA breast cancer genes:
March 6, 2018;
The U.S. Food and Drug Administration authorized the Personal Genome Service Genetic Health Risk (GHR) Report for BRCA1/BRCA2 (Selected Variants). It is the first direct-to-consumer (DTC) test to report on three specific BRCA1/BRCA2 breast cancer gene mutations that are most common in people of Ashkenazi (Eastern European) Jewish descent. These three mutations, however, are not the most common BRCA1/BRCA2 mutations in the general population.
Consumers and health care professionals should not use the test results to determine any treatments, including anti-hormone therapies and prophylactic removal of the breasts or ovaries. Such decisions require confirmatory testing and genetic counseling. The test also does not provide information on a person’s overall risk of developing any type of cancer. The use of the test carries significant risks if individuals use the test results without consulting a physician or genetic counselor.
The FDA reviewed data for the test through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device. Along with this authorization, the FDA is establishing criteria, called special controls, which set forth the agency’s expectations in assuring the test’s accuracy, reproducibility, clinical performance and labeling. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for this test.
FDA expands approval of replacement heart valve, smallest mechanical valve size approved in the world:
March 6, 2018
The U.S. Food and Drug Administration expanded the approval of a heart valve to include a size small enough to be used in newborn pediatric patients to treat heart defects. Specifically, the agency approved the Masters Series Mechanical Heart Valve with Hemodynamic Plus (HP) Sewing Cuff to include the 15-mm valve size, making it the smallest mechanical heart valve approved in the world.
Heart valve disease occurs if one or more of the four heart valves, which direct the flow of blood through the heart, fail to function properly. In pediatric patients, a malfunctioning heart valve is often the result of a congenital heart defect at birth. Each year, more than 35,000 babies in the U.S. are born with congenital heart defects, some of which will require heart valve surgery and, potentially, replacement heart valve surgery. However, prior to today’s approval, there have been limited replacement heart valve options available because of the patients’ small size. The Masters Series 15-mm HP valve represents an important treatment option for these patients.
The Master Series Mechanical Heart Valve is a rotatable, bileaflet (two-leaflet) valve designed for implantation in the aortic or mitral position. The bileaflet design consists of two semi-circular discs that open and close in response to blood pressure changes during the heartbeat, similar to a patient’s own valve.
The FDA evaluated clinical data from a single-arm study of 20 pediatric patients with serious heart failure ranging in age from 1.5 weeks to 27 months at the time of mitral valve implant. The data showed that one year after the implant procedure, the probability of survival was 69.3 percent and the probability of not experiencing a valve-related adverse event was 66.8 percent. Serious valve-related adverse events observed during the study through one-year follow-up included blood clots in the device and bleeding in the brain. Anticoagulation (blood thinning) therapy may be necessary after the procedure, to prevent clotting on the device, which can increase the risk of bleeding.
The Master Series Mechanical Heart Valve should not be used by patients unable to tolerate anticoagulation therapy.
FDA expands approval of Adcetris for first-line treatment of Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy:
March 20, 2018
The U.S. Food and Drug Administration approved Adcetris (brentuximab vedotin) to treat adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.
Lymphoma is a cancer that begins in the lymph system, which is part of the immune system that helps the body fight infection and disease. Lymphoma can begin almost anywhere in the body and can spread to nearby lymph nodes. The two main types of lymphoma are Hodgkin lymphoma (also called Hodgkin disease) and non-Hodgkin lymphoma. Most people with Hodgkin lymphoma have the classical type. With this type, there are large, abnormal lymphocytes (a type of white blood cell) in the lymph nodes called Reed-Sternberg cells. With early intervention, patients with Hodgkin lymphoma can usually experience long-term remission.
Adcetris combines an antibody and drug, allowing the antibody to direct the drug to a target on lymphoma cells known as CD30. Adcetris has also been previously approved by the FDA to treat cHL after relapse, cHL after stem cell transplant when a patient is at a high risk of relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after failure of other treatment, and primary cutaneous ALCL after failure of other treatment.
Common side effects:
Common side effects of Adcetris include low levels of certain blood cells (neutropenia, anemia), nerve damage causing numbness or weakness in the hands and feet (peripheral neuropathy), nausea, fatigue, constipation, diarrhea, vomiting and fever (pyrexia). In the above clinical trial, 67 percent of patients treated with Adcetris plus chemotherapy experienced damage to the peripheral nervous system (peripheral neuropathy). In addition, neutropenia occurred in 91 percent of patients treated with Adcetris plus chemotherapy, which was associated with a 19 percent rate of febrile neutropenia (neutropenia and fever). Preventative treatment with G-CSF, a growth factor for the bone marrow to produce white blood cells, is recommended with Adcetris plus chemotherapy for the first-line treatment of Stage III or IV cHL
Black Box warning
Adcetris has a boxed warning that highlights the risk of John Cunningham virus infection resulting in progressive multifocal leukoencephalopathy, or PML, a rare but serious brain infection that can result in death.
FDA authorizes first fully interoperable continuous glucose monitoring system, streamlines review pathway for similar devices:
March 27, 2018
The U.S. Food and Drug Administration permitted marketing of the Dexcom G6 integrated continuous glucose monitoring (iCGM) system for determining blood glucose (sugar) levels in children aged two and older and adults with diabetes. This is the first type of continuous glucose monitoring system permitted by the agency to be used as part of an integrated system with other compatible medical devices and electronic interfaces, which may include automated insulin dosing systems, insulin pumps, blood glucose meters or other electronic devices used for diabetes management. Today’s authorization also classifies this new type of device in class II and subjects it to certain criteria called special controls. This enables developers of future iCGM systems to bring their products to market in the least burdensome manner possible.
Continuous glucose monitoring systems that were first marketed had a different intended use and were evaluated through the FDA’s premarket approval pathway, the most rigorous review designed for the “highest risk” class III medical devices. However, the Dexcom G6 system is intended for a more seamless integration with other diabetes devices, and the FDA recognized this as an opportunity to reduce the regulatory burden for this type of device by establishing criteria that would classify these as “moderate risk” class II medical devices with special controls. With the authorization of the Dexcom G6, future iCGMs that meet the special controls criteria can go through a more streamlined premarket review.
The Dexcom G6 is a patch device, about the size of a quarter, that is applied to the skin of the abdomen and contains a small sensor that continuously measures the amount of glucose in body fluid. The device transmits real-time glucose readings every five minutes to a compatible display device such as a mobile medical app on a cell phone and will trigger an alarm when a patient’s blood sugar enters a danger zone soaring too high or dropping too low. If it’s integrated with an automated insulin dosing system, a rise in blood sugar would trigger the release of insulin from the pump. The patch device should be replaced every 10 days.
The FDA reviewed data for the device through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device. Along with this authorization, the FDA is establishing criteria, called special controls, which outline requirements for assuring iCGM devices’ accuracy, reliability and clinical relevance as well as describe the type of studies and data required to demonstrate acceptable iCGM performance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for this device.
Risks associated with use of the system may include hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) in cases where information provided by the device is inaccurate and used to make treatment decisions or where hardware or set-up issues disable alarms and alerts. Patients may also experience skin irritation or redness around the device’s adhesive patch.
FDA expands approval of Blincyto for treatment of a type of leukemia in patients who have a certain risk factor for relapse:
March 29, 2018
The U.S. Food and Drug Administration granted accelerated approval to Blincyto (blinatumomab) to treat adults and children with B-cell precursor acute lymphoblastic leukemia (ALL) who are in remission but still have minimal residual disease (MRD). MRD refers to the presence of cancer cells below a level that can be seen under the microscope. In patients who have achieved remission after initial treatment for this type of ALL, the presence of MRD means they have an increased risk of relapse.
B-cell precursor ALL is a rapidly progressing type of cancer in which the bone marrow makes too many B-cell lymphocytes, an immature type of white blood cell. The National Cancer Institute estimates that approximately 5,960 people in the United States will be diagnosed with ALL this year and approximately 1,470 will die from the disease.
Blincyto works by attaching to CD19 protein on the leukemia cells and CD3 protein found on certain immune system cells. Bringing the immune cell close to the leukemia cell allows the immune cells to attack the leukemia cells better. The FDA first approved Blincyto under accelerated approval in December 2014 for the treatment of Philadelphia chromosome (Ph)-negative relapsed or refractory positive B-cell precursor ALL. Full approval for this indication was granted in July 2017, and at that time, the indication was also expanded to include patients with Philadelphia chromosome-positive ALL.
Common side effects:
The side effects of Blincyto when used to treat MRD-positive B-cell precursor ALL are consistent with those seen in other uses of the drug. Common side effects include infections (bacterial and pathogen unspecified), fever (pyrexia), headache, infusion related reactions, low levels of certain blood cells (neutropenia, anemia), febrile neutropenia (neutropenia and fever) and low levels of platelets in the blood (thrombocytopenia).
Black Box warning:
Blincyto carries a boxed warning alerting patients and health care professionals that some clinical trial participants had problems with low blood pressure and difficulty breathing (cytokine release syndrome) at the start of the first treatment, experienced a short period of difficulty with thinking (encephalopathy) or other side effects in the nervous system.
Serious risks of Blincyto include infections, effects on the ability to drive and use machines, inflammation in the pancreas (pancreatitis), and preparation and administration errors—instructions for preparation and administration should closely be followed. There is a risk of serious adverse reactions in pediatric patients due to benzyl alcohol preservative; therefore, the drug prepared with preservative free saline should be used for patients weighing less than 22 kilograms.
FDA clears first contact lens with light-adaptive technology:
April 10, 2018
The U.S. Food and Drug Administration cleared the first contact lens to incorporate an additive that automatically darkens the lens when exposed to bright light. The Acuvue Oasys Contact Lenses with Transitions Light Intelligent Technology are soft contact lenses indicated for daily use to correct the vision of people with non-diseased eyes who are nearsighted (myopia) or farsighted (hyperopia). They can be used by people with certain degrees of astigmatism, an abnormal curvature of the eye.
The contact lenses contain a photochromic additive that adapts the amount of visible light filtered to the eye based on the amount of UV light to which they are exposed. This results in slightly darkened lenses in bright sunlight that automatically return to a regular tint when exposed to normal or dark lighting conditions.
Patients with the following conditions should not use these contact lenses:
- inflammation or infection in or around the eye or eyelids.
- any eye disease, injury or abnormality that affects the cornea, conjunctiva (the mucous membrane that covers the front of the eye and lines the inside of the eyelids) or eyelids.
- any previously diagnosed condition that makes contact lens wear uncomfortable.
- severe dry eye.
- reduced corneal sensitivity
- any systemic disease that may affect the eye or be made worse by wearing contact lenses
- allergic reactions on the surface of the eye or surrounding tissues that may be induced or made worse by wearing contact lenses or use of contact lens solutions
- any active eye infection or red or irritated eyes.
These contacts are intended for daily wear for up to 14 days. Patients should not sleep in these contact lenses, expose them to water or wear them longer than directed by an eye care professional. These contacts should not be used as substitutes for UV protective eyewear.
FDA approves first therapy for rare inherited form of rickets, x-linked hypophosphatemia:
April 17, 2018;
The U.S. Food and Drug Administration approved Crysvita (burosumab-twza), the first drug approved to treat adults and children ages 1 year and older with x-linked hypophosphatemia (XLH), a rare, inherited form of rickets. XLH causes low levels of phosphorus in the blood. It leads to impaired bone growth and development in children and adolescents and problems with bone mineralization throughout a patient’s life.
XLH is a serious disease affecting approximately 3,000 children and 12,000 adults in the United States. Most children with XLH experience bowed or bent legs, short stature, bone pain and severe dental pain. Some adults with XLH experience persistent discomfort or complications, such as joint pain, impaired mobility, tooth abscesses and hearing loss.
Common side effects:
The most common adverse reactions in adults taking Crysvita were back pain, headache, restless leg syndrome, decreased vitamin D, dizziness and constipation. The most common adverse reactions in children were headache, injection site reaction, vomiting, decreased vitamin D and pyrexia (fever).
FDA takes new steps to advance the development of innovative products for treating opioid use disorder:
April 20, 2018;
The U.S. Food and Drug Administration announced the latest action to encourage and support the development of treatment options for people with opioid use disorder (OUD). The agency has released the first of two new draft guidancesintended to aid industry in developing new medications for use in medication-assisted treatment (MAT) for opioid dependence. The first guidance, released today, explains the FDA’s current thinking about drug development and clinical trial design issues relevant to the study of sustained-release “depot” buprenorphine products (i.e., modified-release products for injection or implantation).
Use of MAT for opioid dependence relies on prescription drugs, including buprenorphine, methadone and naltrexone, to stabilize brain chemistry; reduce or block the euphoric effects of opioids; relieve physiological cravings; and normalize body functions. Regular adherence to MAT with buprenorphine helps patients gain control over their use of opioids, without causing the cycle of highs and lows, intoxication and withdrawal associated with opioid misuse or abuse. At proper doses, buprenorphine can also block the pleasurable effects of other opioids, making continued opioid abuse less attractive. Passive-compliance formulations (those that do not require taking a daily medication), such as sustained-release depots or implantable devices that release a continuous level of the drug, can provide effective treatment of opioid dependence that may also result in less misuse, abuse or accidental exposure compared to the self-administered formulations such as transmucosal tablets and films, which are absorbed through mucous membranes of the mouth.
This new draft guidance is an additional step the FDA is taking as part of the agency’s broad efforts to support the treatment of those with OUD. The FDA also intends to issue additional guidance that will provide a framework for the development of novel clinical endpoints that can form the basis of additional MAT product approvals. For example, in future guidance, the FDA intends to provide assistance to drug companies to help them develop a validated measurement of “craving” or “urge to use” illicit opioids to complement other endpoints and to determine how it supports the goal of sustained abstinence.