US FDA issues guidance on Interim Product Reporting for Human Drug Compounding Outsourcing Facilities

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US Food and Drug Administration (FDA) has issued a guidance on Interim Product Reporting for Human Drug Compounding Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act. The guidance is intended for outsourcing facilities that compound human drugs. Now the outsourcing facilities may elect to register with FDA under section 503B.

If an outsourcing facility registers, it must report to FDA information about the drugs compounded at the outsourcing facility. This guidance focuses on  electronic submission of drug reporting information.

The Drugs Quality and Security Act (DQSA) adds new section 503B to the FD&C Act. Under section 503B(b), a compounder may elect to become an outsourcing facility by registering with FDA. Upon initially registering as an outsourcing facility, and twice each year which is once in June and once in December, an outsourcer that registers with FDA must submit to the Agency a report identifying the drugs compounded by the facility during the previous six-month period. For each identified drug, the outsourcing facility must provide certain information listed in section 503B(b).

An outsourcing facility can qualify for exemptions from the FDA approval requirements in section 505 of the FD&C Act by meeting the requirements described in the rest of section 503B. Outsourcing facilities will be inspected by FDA and must comply with other provisions of the FD&C Act, such as current good manufacturing practice (cGMP) requirements.

This guidance addresses the provisions in the DQSA regarding the drug reporting requirements  for registered outsourcing facilities. A separate guidance provides instructions on how outsourcing facilities should register with FDA. This guidance provides instructions for interim reporting until FDA can modify its electronic submission system to accept the electronic reports 55 for drugs compounded by outsourcing facilities. When FDA has modified its current electronic system, we will issue a new outsourcing facility product reporting guidance describing the updated format for long-term use, stated the regulatory authority.

Under section 503B each registrant must submit a product report to FDA. This report must identify all drugs compounded by the outsourcing facility during the previous six-month period and provide information on each drug. This includes: active ingredient and strength of active ingredient per unit, source of the active ingredient, the National Drug Code (NDC) number of the source drug or bulk active ingredient, if  available. The regulatory also insists information on the dosage form and route of administration, package description, number of individual units produced; and NDC number of the final product, if assigned.

FDA encourages companies wishing to compound as outsourcing facilities to register with it immediately. If a facility registers before June 2, 2014, FDA does not intend to immediately enforce the requirement to report product information at the time of initial registration, as long as the facility submits its report within two months after the date of that initial registration.

Section 503B(b)(3) of the FD&C Act requires outsourcing facilities to submit drug reporting information by electronic means unless the regulator grants a request for a waiver of such requirement.

Source: Pharmabiz

FDA allows marketing of four “next generation” gene sequencing devices

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Two devices aid in screening and diagnosis of cystic fibrosis

Today the U.S. Food and Drug Administration allowed marketing of four diagnostic devices that can be used for high throughput gene sequencing, often referred to as “next generation sequencing” (NGS). These instruments, reagents, and test systems allow labs to sequence a patient’s DNA (deoxyribonucleic acid).

The new technology also gives physicians the ability to take a broader look at their patients’ genetic makeup and can help in diagnosing disease or identifying the cause of symptoms.

“NGS is changing the way we look at genomics,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in FDA’s Center for Devices and Radiological Health. “Before NGS, sequencing genes associated with a particular disease was a long and costly process. Today, we have the capability to read and interpret large segments of DNA very quickly in a single test and this information-rich technology is becoming more accessible for use by physicians in the care of their patients.”

Two of the newly cleared devices are used to detect DNA changes in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which can result in cystic fibrosis (CF), an inherited chronic disease that affects the lungs, pancreas, liver, intestines, and other organs of those who inherit a faulty CFTR gene from both parents.

More than 10 million Americans are CF carriers and approximately 30,000 children and adults in the U.S. are affected with CF. Most children with CF are diagnosed by age 2 and the average life span for people with CF who live to adulthood is approximately 37 years.

The cleared devices include:

  • The Illumina MiSeqDx Cystic Fibrosis 139-Variant Assay, which checks specific points in the patient’s CFTR gene sequence to detect known variants in the gene. Information about which DNA changes are associated with symptoms of cystic fibrosis is found in the Clinical and Functional TRanslation of CFTR database (CFTR2 disclaimer icon ).
  • The Illumina MiSeqDx Cystic Fibrosis Clinical Sequencing Assay, which sequences a large portion of the CFTR gene to detect any difference in the CFTR gene compared to a reference CFTR gene.  

Data submitted by Illumina for their cystic fibrosis tests included comparisons of the sequence results to Human Genome Build 19, a reference representation of the human genome.  In addition, Illumina evaluated the performance of its instrument and reagent systems against a publically available quality-weighted human reference genome that was created through collaboration between the FDA and the National Institutes of Standards and Technology (NIST). 

FDA authorized sequencing devices provide labs with quality and performance information

The FDA also granted de novo petitions for the Illumina MiSeqDx instrument platform and the Illumina Universal Kit reagents, two devices that make up the first FDA-regulated test system that allows laboratories to develop and validate sequencing of any part of a patient’s genome. The Universal Kit reagents isolate and create copies of genes of interest obtained from patient blood samples, and the MiSeqDx platform analyzes the genes. The software compares the patient’s genomic sequence to a reference sequence and reports back any differences between the patient and the reference.  

“The FDA’s review of the MiSeqDx and sequencer and Universal Kit reagents provides clinical laboratories with information about the expected performance of the device and the quality of the results,” said Dr. Gutierrez. “This information was not previously available for next generation sequencers, and, with this platform, labs can develop tests for clinical use with greater confidence because they use FDA authorized devices.”   

The FDA reviewed the Illumina MiSeqDx instrument platform and the Illumina Universal Kit reagents through its de novo classification process, a regulatory pathway for some novel low-to-moderate risk medical devices that are not substantially equivalent to an already legally marketed device.

For the de novo petitions, the FDA based its decision on the demonstrated performance of the MiSeqDx instrument and Universal Kit reagent systems across numerous genomic segments spanning 19 human chromosomes.

Illumina MiSeqDx instrument platform, Universal Kit reagents, MiSeqDx Cystic Fibrosis 139-Variant Assay, and MiSeqDx Cystic Fibrosis Clinical Sequencing Assay are manufactured by Illumina, Inc. in San Diego, Calif.

Industry wants govt. to clarify its stand on PET ban to avoid confusion

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Pharmaceutical industry wants the government to take immediate steps to clarify its stand on the proposed ban on the use of plastic and PET containers for liquid formulations. The government needs to substantiate with scientific evidence how the use of PET containers for packing liquid formulations will be harmful to the patients so that the industry will not be in a state of confusion.

This demand comes in the wake of growing concern within the industry over the Drugs Technical Advisory Board (DTAB) recommendation to the DCGI on phasing out of the use of plastic and PET (Polyethylene Terephthalate) containers for liquid formulations from the market on a gradual base. Goa Pharmaceutical Manufacturer’s Association (GPMA) pointed out that a lot of projects focused on expansion of oral liquid preparation have been stalled across the country due to the uncertainty and lack of clarity on the use of PET bottles.

They fear that lack of timely intervention from the government in clarifying the matter will affect not only the business but also lead to severe shortage of paediatric preparations, formulations meant for geriatrics, women in reproductive age group and pregnant women which comes in PET containers. According to A K Burman, president, GPMA globally PET is used as a well expected packaging material, even in the regulated markets like US, UK Japan etc. He stressed that industry finds it a little confusing on why India needs to suddenly ban the use of PET especially in the absence of any scientific evidence support the ban.

“Expansion plans largely depend on its packaging aspect, thus the government should come forth with a proper explanation based on scientific data on an urgent basis. So as to ensure that no one suffers due to time lapse. We fear that if this issues is not addressed at the earliest in the long run , the patients may feel the brunt of the same,” he cautioned.

Source: Pharmabiz

FDA takes significant steps to address antimicrobial resistance

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The U.S. Food and Drug Administration today is implementing a plan to help phase out the use of medically important antimicrobials in food animals for food production purposes, such as to enhance growth or improve feed efficiency. The plan would also phase in veterinary oversight of the remaining appropriate therapeutic uses of such drugs.
Certain antimicrobials have historically been used in the feed or drinking water of cattle, poultry, hogs, and other food animals for production purposes such as using less food to gain weight. Some of these antimicrobials are important drugs used to treat human infection, prompting concerns about the contribution of this practice to increasing the ability of bacteria and other microbes to resist the effects of a drug. Once antimicrobial resistance occurs, a drug may no longer be as effective in treating various illnesses or infections.
Because antimicrobial drug use in both humans and animals can contribute to the development of antimicrobial resistance, it is important to use these drugs only when medically necessary. The plan announced today focuses on those antimicrobial drugs that are considered medically important (i.e., are important for treating human infection) and which are approved for use in feed and water of food animals.
In a final guidance issued today, the FDA lays out a road map for animal pharmaceutical companies to voluntarily revise the FDA-approved use conditions on the labels of these products to remove production indications. The plan also calls for changing the current over-the-counter (OTC) status to bring the remaining appropriate therapeutic uses under veterinary oversight. Once a manufacturer voluntarily makes these changes, its medically important antimicrobial drugs can no longer be used for production purposes, and their use to treat, control, or prevent disease in animals will require veterinary oversight.
The FDA is asking animal pharmaceutical companies to notify the agency of their intent to sign on to the strategy within the next three months. These companies would then have a three-year transition process.
“Implementing this strategy is an important step forward in addressing antimicrobial resistance. The FDA is leveraging the cooperation of the pharmaceutical industry to voluntarily make these changes because we believe this approach is the fastest way to achieve our goal,” said FDA Deputy Commissioner for Foods and Veterinary Medicine Michael Taylor. “Based on our outreach, we have every reason to believe that animal pharmaceutical companies will support us in this effort.”
In order to help phase in veterinary oversight of those drugs covered by the guidance that are intended for medically appropriate uses in feed, the FDA also has issued a proposed rule to update the existing regulations relating to Veterinary Feed Directive (VFD) drugs. The use of VFD drugs requires specific authorization by a licensed veterinarian using a process outlined in the agency’s VFD regulations. The VFD proposed rule is intended to update the existing VFD process and facilitate expanded veterinary oversight by clarifying and increasing the flexibility of the administrative requirements for the distribution and use of VFD drugs. Such updates to the VFD process will assist in the transition of OTC products to their new VFD status.
“This action promotes the judicious use of important antimicrobials to protect public health while ensuring that sick and at-risk animals receive the therapy they need,” said Bernadette Dunham, DVM, Ph.D., director of the FDA’s Center for Veterinary Medicine. “We realize that these steps represent changes for veterinarians and animal producers, and we have been working — and will continue to work — to make this transition as seamless as possible.”

FDA allows marketing of first device to relieve migraine headache pain

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The U.S. Food and Drug Administration today allowed marketing of the Cerena Transcranial Magnetic Stimulator (TMS), the first device to relieve pain caused by migraine headaches that are preceded by an aura: a visual, sensory or motor disturbance immediately preceding the onset of a migraine attack.
Migraine headaches are characterized by intense pulsing or throbbing pain in one area of the head accompanied by nausea and/or vomiting and sensitivity to light and sound. A migraine can last anywhere between four and 72 hours when untreated. These debilitating headaches affect approximately 10 percent of people worldwide and are three times more common in women than in men. About one third of people with migraines experience an aura.
“Millions of people suffer from migraines and this new device represents a new treatment option for some patients,” said Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health.
The Cerena TMS is a prescription device used after the onset of pain associated with migraine headaches preceded by an aura. Using both hands to hold the device against the back of the head, the user presses a button to release a pulse of magnetic energy to stimulate the occipital cortex in the brain, which may stop or lessen the pain associated with migraine headaches preceded by an aura.
The FDA reviewed the data for the Cerena TMS through the de novo premarket review pathway, a regulatory pathway for some low- to moderate-risk medical devices that are not substantially equivalent to an already legally marketed device.
The FDA reviewed a randomized control clinical trial of 201 patients who had mostly moderate to strong migraine headaches and who had auras preceding at least 30 percent of their migraines. Of the study subjects, 113 recorded treating a migraine at least once when pain was present. Analysis of these 113 subjects was used to support marketing authorization of the Cerena TMS for the acute treatment of pain associated with migraine headache with aura.
The study showed that nearly 38 percent of subjects who used the Cerena TMS when they had migraine pain were pain-free two hours after using the device compared to about 17 percent of patients in the control group. After 24 hours, nearly 34 percent of the Cerena TMS users were pain-free compared to 10 percent in the control group.
The study did not show that the Cerena TMS is effective in relieving the associated symptoms of migraine, such as sensitivity to light, sensitivity to sound, and nausea. The device is for use in people 18 years of age and older. The study did not evaluate the device’s performance when treating types of headaches other than migraine headaches preceded by an aura.
Adverse events reported during the study were rare for both the device and the control groups but included single reports of sinusitis, aphasia (inability to speak or understand language) and vertigo (sensation of spinning). Dizziness may be associated with the use of the device.
Patients must not use the Cerena TMS device if they have metals in the head, neck, or upper body that are attracted by a magnet, or if they have an active implanted medical device such as a pacemaker or deep brain stimulator. The Cerena TMS device should not be used in patients with suspected or diagnosed epilepsy or a personal or family history of seizures. The recommended daily usage of the device is not to exceed one treatment in 24 hours.
The Cerena TMS is manufactured by eNeura Therapeutics of Sunnyvale, Calif.