FDA permits marketing of two devices that detect parathyroid tissue in real-time during surgery

FDA permits marketing of two devices that detect parathyroid tissue in real-time during surgery
Today, the U.S. Food and Drug Administration permitted marketing of two devices that provide real-time location of parathyroid tissue during surgical procedures such as thyroidectomy (surgery to remove all or part of the thyroid) and parathyroidectomy (surgery to remove one or more parathyroid glands).
“For some patients with parathyroid disease, treatment may mean a surgical procedure,” said Binita Ashar, M.D., director of the Division of Surgical Devices in the FDA’s Center for Devices and Radiological Health.  “Real-time identification of parathyroid tissue during surgery can provide surgeons… Continue reading.

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624982.htm?utm_campaign=11022018_PR_FDA%20authorizes%20devices%20to%20detect%20parathyroid%20tissue%20in%20during%20surgery&utm_medium=email&utm_source=Eloqua

November 2, 2018

Release

Today, the U.S. Food and Drug Administration permitted marketing of two devices that provide real-time location of parathyroid tissue during surgical procedures such as thyroidectomy (surgery to remove all or part of the thyroid) and parathyroidectomy (surgery to remove one or more parathyroid glands).

“For some patients with parathyroid disease, treatment may mean a surgical procedure,” said Binita Ashar, M.D., director of the Division of Surgical Devices in the FDA’s Center for Devices and Radiological Health. “Real-time identification of parathyroid tissue during surgery can provide surgeons with valuable information to help preserve healthy tissue or to remove diseased tissue.”

Disorders in the parathyroid tissue, which is tissue that borders the thyroid gland, are usually treated by surgeries to remove part of the thyroid gland or parathyroid tissue. Hyperparathyroidism, or the overproduction of parathyroid hormone, is the most common of parathyroid disorders and is diagnosed in approximately 100,000 Americans each year. For surgeons treating hyperparathyroidism or other disorders, parathyroid tissue can be visually difficult to locate and distinguish from nearby tissues during a surgery.

The Fluobeam 800 Clinic Imaging Device is used to assist in the imaging of parathyroid glands and can be used as a companion method to assist surgeons in locating parathyroid tissue visually during surgery. Parathyroid tissue emits a fluorescent glow when exposed to the device’s light source, avoiding the need for a contrast agent. The device was previously cleared as an imaging system used to capture and view fluorescent images for the visual assessment of blood flow as an adjunctive method for the evaluation of tissue perfusion.

The Parathyroid Detection PTeye System aids in detecting parathyroid tissue during surgery by using a probe that emits fluorescence light. Tissue detection is based on how the parathyroid tissue reacts to the fluorescent light. When parathyroid tissue is detected, the system provides an audio and visual display to indicate its presence.

Use of either device is intended to assist, not replace, experienced visual assessment in identifying the parathyroid tissue along with a biopsy to confirm thyroid tissue per standard of care. The systems are not intended to be used to confirm the absence of parathyroid tissue or glands and are only to be used to assist the surgeon in locating potential parathyroid tissue or glands.

For the Fluobeam 800, the FDA reviewed data from five peer-reviewed published studies, including one study that compared the rate of postoperative hypocalcemia (PH), or a temporary reduction in calcium in the blood, that occurs when healthy parathyroid tissue is inadvertently removed. In 93 patients who had surgery using the device, 5 percent experienced fluctuating PH following surgery compared with 21 percent of the 153 patients who had surgery without the device.

For the PTeye System, the FDA reviewed data from a single-blinded study of 81 patients who had surgery using the device. Results demonstrated that the PTeye could correctly identify the presence of parathyroid tissue as compared to histology 93 percent of the time and correctly identify the absence of parathyroid tissue as compared to intraoperative visualization by an expert 97 percent of the time, with an overall accuracy of 96 percent.

The Fluobeam 800 and the PTeye were reviewed separately but concurrently under the FDA’s De Novo premarket review pathway, a regulatory pathway for some low- to moderate-risk devices that are novel and for which there is no prior legally marketed device.

The FDA granted marketing authorization of The Fluobeam 800 Clinic Imaging Device to Fluoptics.

The FDA granted marketing authorization of Parathyroid Detection PTeye System to AiBiomed.

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Statement from FDA Commissioner Scott Gottlieb, M.D., on findings from the romaine lettuce E. coli O157:H7 outbreak investigation and FDA’s efforts to prevent future outbreaks

tatement from FDA Commissioner Scott Gottlieb, M.D., on findings from the romaine lettuce E. coli O157:H7 outbreak investigation and FDA’s efforts to prevent future outbreaks

Earlier this year, we experienced the largest E. coli O157:H7 outbreak the country has seen in the last decade, leaving hundreds sick and claiming the lives of five people who consumed contaminated romaine lettuce.
We’re committed to taking necessary actions to prevent future outbreaks like this and to improving the safety of leafy greens available in the marketplace. Since the next romaine growing season for the Yuma region is underway, it’s critical for all of us to understand what happened so we can identify the changes that can prevent future outbreaks and reduce the scope of any problems that could arise.
Since the first signs of the outbreak appeared…Continue reading

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624867.htm?utm_campaign=11012018_Statement_findings%20from%20the%20romaine%20lettuce%20E.%20coli%20O157%3AH7&utm_medium=email&utm_source=Eloqua

November 1, 2018

Statement

Earlier this year, we experienced the largest E. coli O157:H7 outbreak the country has seen in the last decade, leaving hundreds sick and claiming the lives of five people who consumed contaminated romaine lettuce.

We’re committed to taking necessary actions to prevent future outbreaks like this and to improving the safety of leafy greens available in the marketplace. Since the next romaine growing season for the Yuma region is underway, it’s critical for all of us to understand what happened so we can identify the changes that can prevent future outbreaks and reduce the scope of any problems that could arise.

Since the first signs of the outbreak appeared, our team has collaborated closely with our state, federal and local partners to determine the root cause of the outbreak. Today, the U.S. Food and Drug Administration is sharing an environmental assessment that details final findings from this investigation.

One of the investigation’s main objectives was to identify factors that potentially contributed to the introduction and spread of the strain of E. coli O157:H7 that contaminated the romaine lettuce associated with this outbreak. The FDA, the Centers for Disease Control and Prevention, and the Arizona Department of Agriculture launched an investigation of the outbreak, leading to the collection of samples in Yuma in order to help gather evidence needed to identify the source of the outbreak.

The environmental assessment issued today confirms the presence of E. coliO157:H7 in three samples of irrigation canal water collected as part of this investigation in the Yuma region. It considers that the most likely way the romaine lettuce became contaminated was from the use of water from the irrigation canal, since the outbreak strain was not found in any of the other samples collected in the region. How the water contaminated the lettuce is uncertain. But based on interviews with growers and pesticide applicators, possible explanations include direct application of irrigation canal water to the lettuce crop or the use of irrigation canal water to dilute crop-protection chemicals applied to the crops through both aerial and land-based spray applications. We cannot rule out other ways the lettuce became contaminated. It’s important to note that we have no evidence that any other product grown in Yuma was contaminated by this water.

When and how the irrigation canal became contaminated with the outbreak strain of E. coli O157:H7 is also uncertain. We know that a large concentrated animal feeding operation (CAFO) is located adjacent to this stretch of the irrigation canal where the samples were collected. This is one potential source. However, the investigation did not identify an obvious route for contamination of the irrigation canal from this facility. In addition, samples collected at the CAFO did not yield E. coli O157:H7. The investigation did not exclude other ways the irrigation canal could have become contaminated with this outbreak strain.

With the growing season underway in Yuma, we know just how important it is to continue collaborating closely with industry and our regulatory partners to ensure that leafy greens are safe. To assist with these efforts, our environmental assessment recommends a number of steps that can be taken to reduce the likelihood of another tragic outbreak from occurring in the future. Working with the produce industry to further reduce the risk of outbreaks is a key priority for the FDA.

Fully implementing the Food Safety Modernization Act (FSMA) is critical to these efforts. We must continue to advance FSMA’s Produce Safety Rule in collaboration with our state regulatory partners and ensure that we craft agricultural water standards that work across the incredible diversity of commodities and growing conditions. The FDA has resources available to help industry comply with FSMA requirements, including produce safety experts regionally located as part of the FDA’s Produce Safety Network and growers in the Yuma region can find the contact information for their area at this website.

Because leafy greens are a highly perishable commodity, the ability to traceback the route of a food product as it moves through the entire supply chain, or traceability, is critical to removing the product from commerce as quickly as possible, preventing additional consumer exposures, and properly focusing any recall actions. During the romaine investigation we found the typical traceback process to be particularly challenging because much of the finished lettuce product contained romaine that was sourced from multiple ranches As a result, our investigation involved collecting documentation from each point in the supply chain to verify the movement of product back to the Yuma area. Complicating this already large-scale investigation, the majority of the records collected in this investigation were either paper or handwritten.

Going forward, both FDA and industry need to explore better ways to standardize record keeping and determine whether the use of additional tools on product packaging could improve traceability.

We strongly encourage the leafy greens industry to adopt traceability best practices and state-of-the-art technologies to help assure quick and easy access to key data elements from farm to fork. We also strongly encourage the leafy greens industry to explore modern approaches to standardized record keeping and the use of additional tools or labels on product packaging that could improve traceability. We urge all segments of this industry and our government partners to review the findings of our environmental assessment and make necessary changes. For our part, the FDA is exploring ways to best tap into new technologies to significantly reduce the time needed for traceback investigations.

The agency is taking steps to improve our response times and provide actionable information to consumers as quickly as possible. We are also looking at our regulatory options and considering appropriate enforcement actions against companies and farms that grow, pack, or process fresh lettuce and leafy greens under insanitary conditions. We continue to explore additional ways to improve these processes and urge all segments of the leafy greens industry to review their operations in the same way.

As a next step, the FDA plans to collect and analyze romaine lettuce samples through a new special surveillance sampling assignment for contamination with human pathogens. This will help us determine whether products are safe to enter the U.S. marketplace. If samples are found to be contaminated, the FDA will follow-up with fresh-cut leafy greens processors and their growers or suppliers to determine if these foods were produced under insanitary conditions that render them harmful to consumers and take the appropriate action to remove them from the market.

We recognize and appreciate the efforts that the leafy greens industry has taken to date. But we know more must be done on all fronts to help prevent future foodborne illness outbreaks. I remain committed to investing in the FDA’s food program and applying our food safety expertise as we work to better safeguard the U.S. food supply. We want food to be safe because it promotes the American industries that grow and produce these products. That’s part of our dedication to these efforts. But first and foremost, we pursue food safety measures as key parts of our public health mandate to protect American consumers

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FDA warns patients and doctors about risk of inaccurate results from home-use device to monitor blood thinner warfarin

FDA warns patients and doctors about risk of inaccurate results from home-use device to monitor blood thinner warfarin

The U.S. Food and Drug Administration today is warning patients and doctors, who use at-home or in-the-office medical devices to monitor levels of the blood thinner, warfarin, that certain test strips used with the devices may provide inaccurate results and should not be relied upon to adjust the drug dosage. Roche Diagnostics issued a voluntary recall of certain test strip lots used with its CoaguChek test meter devices. The recall involves more than 1.1 million packages of CoaguChek XS PT Test Strips that were distributed nationwide from Jan. 12, 2018 to Oct. 29, 2018. Today, the FDA announced this action as…Continue reading 

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624904.htm?utm_campaign=11012018_PR_FDA%20warns%20of%20inaccurate%20test%20results%20for%20device%20to%20monitor%20warfarin&utm_medium=email&utm_source=Eloqua

 

November 1, 2018

Release

The U.S. Food and Drug Administration today is warning patients and doctors, who use at-home or in-the-office medical devices to monitor levels of the blood thinner, warfarin, that certain test strips used with the devices may provide inaccurate results and should not be relied upon to adjust the drug dosage. Roche Diagnostics issued a voluntary recall of certain test strip lots used with its CoaguChek test meter devices. The recall involves more than 1.1 million packages of CoaguChek XS PT Test Strips that were distributed nationwide from Jan. 12, 2018 to Oct. 29, 2018. Today, the FDA announced this action as a Class I recall, the most serious type of recall, which means use of these devices may cause serious injuries or death.

The FDA is warning patients and health care professionals that they should not rely on these test meter devices to monitor warfarin levels if they’re using test strips affected by the recall. Instead, they should have blood drawn from a vein and have their levels measured by a laboratory test or use an alternative meter device.

“These strips are widely used and we are working diligently to warn health care providers and the public about the dangers associated with this recall. Using faulty strips can lead to serious errors in medication dosage that could cause serious harm or death in some patients,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health. “We are also working with the company on the swift removal of the recalled strips and to ensure the new corrected strips are distributed to patients and health care providers as quickly as possible.”

Millions of Americans take the blood thinner warfarin (also known by the brand names Coumadin and Jantoven) to prevent and treat blood clots. The drug may be prescribed for patients with certain types of irregular heartbeats, blood clots in the legs or lungs, or certain medical device implants such as artificial heart valves. Achieving the correct warfarin dosage is crucial, and patients need regular monitoring to test how long it takes their blood to clot. The response is measured by a blood test to check the International Normalized Ratio, or INR. This test can be performed by an accredited laboratory on blood drawn from a vein or with a fingerstick blood draw using an INR test meter at home or in a doctor’s office.

The FDA’s warning concerning the CoaguChek XS PT Test Strips is based on medical device reports submitted by Roche Diagnostics to the agency indicating that the test strips may provide results that are higher than the actual INR. As a result of incorrect INR results, some patients may be prescribed an insufficient warfarin dose or instructed to interrupt warfarin use, which may increase the risk for dangerous blood clots. Approximately 90 medical device reports and two serious patient injuries involving strokes were reported to the FDA.

Incorrect INR results are of particular concern for individuals at an increased risk of blood clots including those with mechanical heart valves, atrial fibrillation (irregular heartbeat) who are at a high risk of stroke, or those who had a recent blood clot. It is important to note that problems with the CoaguChek XS PT test strips are not likely to be evident to the patient.

Roche Diagnostics attributes the cause of the problem to a recent re-calibration of the test strips to a different international standard that occurred earlier this year. They plan to provide new batches of re-calibrated test strips, based on the previous international standard, to their customers by the end of November; the FDA reviewed validation data submitted by the company for these recalibrated strips. The test strips are used with the CoaguChek XS plus, CoaguChek XS Pro, CoaguChek XS professional, CoaguChek XS PST and CoaguChek Vantus test meter devices.

Patients who are using CoaguChek meters should contact their health care provider to get information about alternative test methods and to address questions regarding their individual testing schedule. Patients should also contact their patient self-testing service providers to find out when they will be getting their corrected test strips. Health care providers and patients may contact Roche Diagnostics to learn more details about the recall.

All health care providers, patients and caregivers, are strongly encouraged to voluntarily report INR test meter problems directly to the FDA through MedWatch, the FDA’s voluntary reporting program. Problems should be reported whenever one suspects that there may be an issue with an INR test meter such as a malfunction or incorrect result, or that the meter caused or contributed to a serious injury or death.

The FDA is committed to continuing to communicate publicly on this issue and will provide updates related to this recall when available.

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FDA and USDA announce key step to advance collaborative efforts to streamline produce safety requirements for farmers

Image result for FDA and USDA announce key step to advance collaborative efforts to streamline produce safety requirements for farmers
As part of the U.S. Food and Drug Administration and the U.S. Department of Agriculture’s ongoing effort to make the oversight of food safety stronger and more efficient, the FDA and the USDA today announced the alignment of the USDA Harmonized Good Agricultural Practices Audit Program (USDA H-GAP) with the requirements of the FDA Food Safety Modernization Act’s (FSMA’s) Produce Safety Rule.
The new step is part of an ongoing effort to streamline produce safety requirements for farmers. The joint announcement was made by Agriculture Secretary Sonny Perdue and FDA Commissioner Scott Gottlieb, M.D., during a visit by the Secretary to the FDA’s White Oak campus in Silver Spring, Md.

june 5, 2018

Image result for FDA and USDA announce key step to advance collaborative efforts to streamline produce safety requirements for farmers

 

Release

As part of the U.S. Food and Drug Administration and the U.S. Department of Agriculture’s ongoing effort to make the oversight of food safety stronger and more efficient, the FDA and the USDA today announced the alignment of the USDA Harmonized Good Agricultural Practices Audit Program (USDA H-GAP) with the requirements of the FDA Food Safety Modernization Act’s (FSMA’s) Produce Safety Rule.

The new step is part of an ongoing effort to streamline produce safety requirements for farmers. The joint announcement was made by Agriculture Secretary Sonny Perdue and FDA Commissioner Scott Gottlieb, M.D., during a visit by the Secretary to the FDA’s White Oak campus in Silver Spring, Md.

“Government should make things easier for our customers whenever possible and these important improvements help accomplish that goal,” said Secretary Perdue. “Specialty crop farmers who take advantage of a USDA Harmonized GAP audit now will have a much greater likelihood of passing a FSMA inspection as well. This means one stop at USDA helps producers meet federal regulatory requirements, deliver the safest food in the world and grow the market for American-grown food. This is an important first step. We look forward to continuing to work with FDA, other government agencies and especially our state partners to ensure proper training of auditors and inspectors, and to help producers understand changes in the audit.”

While the requirements of both programs are not identical, the relevant technical components in the FDA Produce Safety Rule are covered in the USDA H-GAP Audit Program. The aligned components include areas such as biological soil amendments; sprouts; domesticated and wild animals; worker training; health and hygiene; and equipment, tools and buildings. The alignment will help farmers by enabling them to assess their food safety practices as they prepare to comply with the Produce Safety Rule. However, the USDA audits are not a substitute for FDA or state regulatory inspections.

“We’re committed to working with USDA to pursue our shared goal of advancing food safety in a way that is efficient and helps farmers meet our regulatory standards. By working together, our two programs can advance these efforts more effectively,” said Commissioner Gottlieb. “Today’s announcement will help FDA and states better prioritize our inspectional activities by using USDA H-GAP audit information to prioritize inspectional resources and ultimately enhance our overall ability to protect public health. Inspections are key to helping to ensure that produce safety standards are being met, but they only provide a snapshot in time. Leveraging the data and work being done by USDA will provide us with more information so that we can develop a clearer understanding of the safety and vulnerabilities on produce farms as well as concentrate our oversight and resources where they are most needed.”

The Produce Safety Rule, which went into effect on Jan. 26, 2016, establishes science-based minimum standards for the safe growing, harvesting, packing and holding of fruits and vegetables grown for human consumption. The rule is part of the FDA’s ongoing efforts to implement FSMA. Large farming operations were required to comply with the rule in January 2018. However, the FDA had previously announced that inspections to assess compliance with the Produce Safety Rule for produce other than sprouts would not begin until Spring 2019. Small and very small farms have additional time to comply.

The USDA Harmonized GAP Audit Program is an audit developed as part of the Produce GAP Harmonization Initiative, an industry-driven effort to develop food safety GAP standards and audit checklists for pre-harvest and post-harvest operations. The Initiative is a collaborative effort on the part of growers, shippers, produce buyers, audit organizations and government agencies, including USDA. The USDA Harmonized GAP audit, in keeping with the Initiative’s goals, is applicable to all fresh produce commodities, all sizes of on-farm operations and all regions in the United States. For more information visit: https://www.ams.usda.gov.

Today’s announcement builds on a formal agreement signed earlier this year outlining plans to increase interagency coordination regarding produce safety, inspections of dual-jurisdiction facilities and biotechnology activities. The FDA and USDA are committed to continuing to work collaboratively to ensure that the requirements and expectations of the USDA H-GAP Audit Program remain aligned with the FDA’s Produce Safety Rule.

Farmers who are interested in learning more about this alignment and what they can do to prepare for compliance with the Produce Safety Rule can contact their regional representative of the Produce Safety Network or find more information at FDA.gov.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

The U.S. Department of Agriculture (USDA) is made up of 29 agencies and offices with nearly 100,000 employees who serve the American people at more than 4,500 locations across the country and abroad. We provide leadership on food, agriculture, natural resources, rural development, nutrition, and related issues based on public policy, the best available science, and effective management. We have a vision to provide economic opportunity through innovation, helping rural America to thrive; to promote agriculture production that better nourishes Americans while also helping feed others throughout the world; and to preserve our nation’s natural resources through conservation, restored forests, improved watersheds, and healthy private working lands.

FDA updates the label of Tasigna to reflect that certain patients with a type of leukemia may be eligible to stop treatment after sustained response

FDA updates the label of Tasigna to reflect that certain patients with a type of leukemia may be eligible to stop treatment after sustained response

Discontinuation in treatment marks a first in chronic myeloid leukemia 

The U.S. Food and Drug Administration today updated the product label for the cancer drug Tasigna (nilotonib) to include information for providers about how to discontinue the drug in certain patients. Tasigna, first approved by the FDA in 2007, is indicated for the treatment of patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML). With today’s updated dosing recommendations, patients with early (chronic) phase CML who have been taking Tasigna for three years or more, and whose leukemia has responded to treatment according to specific criteria as detected by a test that has received FDA marketing authorization, may be eligible to stop taking Tasigna. Continue reading

 

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Statement from FDA Commissioner Scott Gottlieb, M.D., on newsteps to advance medical device innovation and help patients gain faster access to beneficial technologies

Statement from FDA Commissioner Scott Gottlieb, M.D., on newsteps to advance medical device innovation and help patients gain faster access to beneficial technologies

Enabling patients and providers to have efficient access to new and innovative medical products that meet the FDA’s gold standard for safety and effectiveness is a core part of our mission. We’re advancing these goals as part of the Medical Innovation Access Plan that I announced earlier this year. While we’ve unveiled parts of that plan already, we’ll be releasing its full detail shortly. As one part of that effort, we’re announcing some additional steps we’re taking right now to promote beneficial medical device innovation. Continue reading.
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Report from the EMA-FDA QbD pilot program

Image result for QBDReport from the EMA-FDA QbD pilot program

In March 2011, the European Medicines Agency (EMA) and the United States Food and Drug Administration (US FDA) launched, under US-EU Confidentiality Arrangements, a joint pilot program for the parallel assessment of applications containing Quality by Design (QbD) elements.

The aim of this program was to facilitate the consistent implementation of QbD concepts introduced through International Council for Harmonisation (ICH) Q8, Q9 and Q10 documents and harmonize regulatory decisions to the greatest extent possible across the two regions.

To facilitate this, assessors/reviewers from US and EU exchanged their views on the implementation of ICH concepts and relevant regulatory requirements using actual applications that requested participation into the program. The program was initially launched for three years. Following its first phase, both agencies agreed to extend it for two more years to facilitate further harmonization of pertinent QbD-related topics.

The program officially concluded in April 2016. During this period, the agencies received 16 requests to participate. One submission was rejected because the approach presented was not limited to QbD applications, and another application was not reviewed because it was never filed by the applicant.

In total, two Marketing Authorisation Applications (MAA)/New Drug Applications (NDA), three variation/supplements and nine scientific advice applications were evaluated under this program. One MAA/NDA was assessed under the parallel assessment pathway, with the rest following the consultative advice route. Based on the learnings during the pilot, FDA and EMA jointly developed and published three sets of Question and Answer (Q&A) documents.

These documents also addressed comments from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), which participated as an observer, offering input to further facilitate harmonization. The objective of these Q&A documents was to generate review guides for the assessors/reviewers and to communicate pilot outcomes to academia and industry.

Additionally, these documents captured any differences in regulatory expectations due to regional requirements, e.g. inclusion of process validation information in the dossier. The following topics were covered in each of the three Q&A documents: –

Q&A (1) published on Aug 20, 2013 included the following topics: (a) Quality target product profile (QTPP) and critical quality attributes (CQA), (b) Criticality, (c) Level of detail in manufacturing process descriptions, and (d) QbD for analytical methods1 –

Q&A (2) published on Nov 1, 2013 on Design Space Verification, that included definition, presentation, justification (including potential scale-up effects) and verification of design spaces both for active substances and finished products2 –

Q&A (3) published on Dec 19, 2014 included the following topics: (a) Level of detail in the dossier regarding Risk Assessment (RA), (b) Level of detail in the dossier regarding Design of Experiments (DOE) and Design Space3 R

 

Additionally, the FDA-EMA pilot provided the agencies an opportunity to harmonize regulatory expectations for the following precedent-setting applications that were reviewed under the consultative advice pathway: – The first continuous manufacturing (CM) based application submitted to both agencies.

Based on the learnings from this application, the following areas related to CM were harmonized: batch definition; control of excipients; material traceability; strategy for segregation of nonconforming material; real-time release testing (RTRT) methods and prediction models; and good manufacturing practice (GMP) considerations for RTRT, validation strategy, models, and control strategy. – A post approval supplement that included a broad based post-approval change management plan/comparability protocol.

Both agencies were harmonized on the expected level of detail in the protocol and considerations for implementation of a risk based approach to evaluate the changes proposed in the protocol. In line with the scope of the QbD pilot program, joint presentations of key findings were publically presented and discussed with stakeholders at different conferences.

These included the Joint EMAParenteral Drug Association QbD workshop4 organized in 2014 which also included participation from FDA and PMDA.

Overall, it is concluded that, on the basis of the applications submitted for the pilot, there is solid alignment between both Agencies regarding the implementation of multiple ICH Q8, Q9 and Q10 concepts. The FDA/EMA QbD pilot program opened up a platform for continuous dialogue which may lead to further communication on areas of mutual interest to continue the Agencies’ support for innovation and global development of medicines of high quality for the benefit of patients.

Both agencies are currently exploring potential joint activities with specific focus on continuous manufacturing, additional emerging technologies, and expedited/accelerated assessments (e.g. PRIME, Breakthrough). Additionally, EMA and FDA are hosting experts from each other’s organisations to facilitate dialog and explore further opportunities.

References: 1. EMA-FDA pilot program for parallel assessment of Quality-by-Design applications: lessons learnt and Q&A resulting from the first parallel assessment http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/08/WC500148215.pdf

2. FDA-EMA Questions and Answers on Design Space Verification http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/11/WC500153784.pdf

3. FDA-EMA Questions and answers on level of detail in the regulatory submissions http://www.ema.europa.eu/docs/en_GB/document_library/Other/2014/12/WC500179391.pdf

4. Joint European Medicines Agency/Parenteral Drug Association quality-by-design workshop http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2013/12/event_detai l_000808.jsp&mid=WC0b01ac058004d5c3

EMA/ FDA Mutual Recognition Agreement on drug facility inspections moving forward

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EMA/ FDA Mutual Recognition Agreement moving forward
A possible agreement between the EMA and the US FDA on mutual recognition agreement on drug facility inspections could already be signed in January 2017.

http://www.gmp-compliance.org/enews_05650_EMA–FDA-Mutual-Recognition-Agreement-moving-forward_15642,15660,15656,Z-QAMPP_n.html

A possible agreement between the European Medicines Agency EMA and the US Food and Drug Administration FDA on mutual recognition of drug facility inspections could already be signed in January 2017. This is noted in a report of the EU Commission: “The state-of-play and the organisation of the evaluation of the US and the EU GMP inspectorates were discussed. In light of the progress achieved, the conclusion of a mutual recognition agreement of Good Manufacturing Practices (GMPs) inspections by January 2017 is under consideration.”

But, according to the Commission, some issues are still not resolved – like, for example, the exchange of confidential information and the inclusion of veterinary products in the scope of the text.

The “Report of the 15th Round of Negotations for the Transatlantic Trade and Invesment Partnership” summaries the 15th round of negotiations for the Transatlantic Trade and Investment Partnership (TTIP) from 3rd to 7th October 2016 in New York.

////////EMA, FDA,  Mutual Recognition Agreement, drug facility inspections

GDUFA: FDA’s new Guidance on Self-Identification of Generic Drug Manufacturers

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GDUFA: FDA’s new Guidance on Self-Identification of Generic Drug Manufacturers

FDA’s new Guidance requesting generic drug manufacturers who want to export to the USA to self-identify has recently been published in a finalised form. Read more here about what types of generic drug manufacturers are affected and which company data are required by the FDA.

http://www.gmp-compliance.org/enews_05598_GDUFA-FDA-s-new-Guidance-on-Self-Identification-of-Generic-Drug-Manufacturers_15332,S-RGL_n.html

The GDUFA (Generic Drug User Fee Amendments) is a legislative package which came into force in 2012 and entitles the US-American FDA to collect fees from generic drug manufacturers, who strive for a marketing authorisation for the American market. An annual fee has to be paid after the successful registration.

The core of the document is the obligation to “Self-Identify” for those companies that have to submit essential site-related information to the FDA. The details of this self-identification are set in a Guidance for Industry entitled “Self-Identification of Generic Drug Facilities, Sites, and Organizations” published on 22 September 2016 by the FDA in the finalised form.

The Guidance describes the following elements:

1. Which types of generic facilities, sites, and organizations are required to self-identify?

2. What information is requested?

3. What technical standards are to be used for electronically submitting the requested information?

4. What is the penalty for failing to self-identify?

Hereinafter, you will find a short summary of these four topics:

1. Companies that manufacture finished generic medicinal products for human use or the APIs for them, or both are required to self-identify as well as companies that package the finished generic drug into the primary container and label it. Besides, sites that – pursuant to a contract with the applicant (generic drug manufacturer) – repack/redistribute the finished drug from a primary container  into a different primary container are also required to submit a self-identification as well as sites that perform bioequivalence/bioavailability studies. Last but not least, the obligation to self-identify also concerns sites that are listed in the application dossier as contract laboratories for the sampling and performing of analytical testing.

2. Essential data are: the D-U-N-S number (a unique nine-digit sequence specific for each site / each distinct physical location of an entity), the “Facility Establishment Identifier, FEI” (an identifier used by the FDA for the planning and tracking of inspections) and general information with regard to the facility (company owner, type of business operation, contact data, information about the manufacture of non generic drugs).

3. The HLS standard (Health Level Seven Structured Product Labeling) requested for generic applications (ANDAs)  has to be also used for the submission of self-identification information. A detailed description of this standard can be found in the Guidance “Providing Regulatory Submissions in Electronic Format – Drug Establishment Registration and Drug Listing“.

4. Companies that fail to self-identify do not have to expect an explicit penalty. However, such a failure leads to two drawbacks: first, the likelihood of a site inspection by the FDA prior to approval is higher. The second drawback which is much more serious is that all the APIs or finished drugs from a manufacturer who hasn’t self-identified are deemed misbranded. For the FDA, such products are not allowed for importation in the USA.

To the satisfaction of the FDA, the regulations set in the GDUFA and the provisions laid down in the new Guidance represent a major contribution to an enhanced transparency in particular of complex supply chains.

//////////GDUFA, FDA,  new Guidance,  Self-Identification, Generic Drug Manufacturers

FDA published generic user fee for 2017: for ANDA, DMF, and for Facility (API, FDF)

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http://www.raps.org/Regulatory-Focus/News/2016/07/26/25394/FDA-Lowers-ANDA-Fee-Rates-for-2017/

Generic drugmakers submitting abbreviated new drug applications (ANDAs) and prior approval supplements (PAS) will see their US Food and Drug Administration (FDA) fee rates drop in 2017, though all other rates, including those for drug master files (DMF) and facility fees will increase when compared to 2016.

For FY 2017, the generic drug fee rates are: ANDA ($70,480, down from $76,030 in 2016), PAS ($35,240, down from $38,020 in 2016), DMF ($51,140, up from $42,170 in 2016), domestic active pharmaceutical ingredient (API) facility ($44,234, up from $40,867 in 2016), foreign API facility ($59,234, up from $55,867 in 2016), domestic finished dose formulation (FDF) facility ($258,646, up from $243,905), and foreign FDF facility ($273,646, up from $258,905 in 2016).

The new fees are effective 1 October 2016 and will remain in effect through 30 September 2017.

FDA explained the increases and decreases in fees, noting that for ANDA and PAS fees, the agency is expecting an increase in the number of submissions estimated to be submitted in FY 2017 when compared to 2016. For 2017, the agency estimates that approximately 891 new original ANDAs and 439 PASs will be submitted and incur filing fees.

Fees for DMFs will increase, meanwhile, because of an expected decrease in the number of submissions estimated to be submitted in 2017 (FDA is estimating 379 fee-paying DMFs for 2017), when compared to the estimated submissions from 2016.

And all facility fees will increase in 2017 when compared to the previous year because of a decrease in the number of facilities that self-identified (the total number of FDF facilities identified through self-identification was 675, of which 255 were domestic facilities and 420 foreign facilities; while the total number of API facilities self-identified was 789, of which 101 were domestic facilities and 688 were foreign facilities), FDA said.

How FDA Calculates the Fees

In order to calculate the ANDA fee, FDA estimated the number of full application equivalents (FAEs) that will be submitted in FY 2017, which is done by assuming ANDAs count as one FAE and PASs (supplements) count as one-half of an FAE, since the fee for a PAS is one half of the fee for an ANDA.

The Generic Drug User Fee Act (GDUFA) also requires that 75% of the fee paid for an ANDA or PAS filing be refunded if either application is refused due to issues other than a failure to pay the fees.

And since this is the last year of this iteration of GDUFA (the next version is still in the works), the agency is allowed to further increase the fee revenues and fees established if such an adjustment is necessary to provide for not more than three months of operating reserves for the first three months of FY 2018, though FDA estimates that the GDUFA program will have carryover balances for such activities in excess of three months of such operating reserves, so FDA will not be performing a final year adjustment.

To pay the fees, companies must complete a Generic Drug User Fee Cover Sheet, available at http://www.fda.gov/gdufa and generate a user fee identification (ID) number. Payment must be made in US currency drawn on a US bank by electronic check, check, bank draft, US postal money order or wire transfer.

Federal Register Notice

See more at: http://www.raps.org/Regulatory-Focus/News/2016/07/26/25394/FDA-Lowers-ANDA-Fee-Rates-for-2017/#sthash.FNo99XHR.dpuf

/////////////FDA,  generic user fee,  2017, ANDA, DMF,  Facility, API, FDF

FDA publishes Technical Guide on Quality Metrics

The FDA has published a supplementing Guide on Quality Metrics. This is a very unusual step as the contents of the guide are planned to be integrated into the Guideline on Quality Metrics which hasn’t been finalised yet. Read more about the Technical Quality Metrics Guide.

see http://www.gmp-compliance.org/enews_05437_FDA-publishes-Technical-Guide-on-Quality-Metrics_15515,S-QSB_n.html

The FDA has published a supplementing Guide on Quality Metrics. This is a very unusual step as the contents of the guide are planned to be integrated into the Guideline on Quality Metrics which hasn’t been finalised yet.

The so-called FDA Quality Metrics Technical Conformance Guide should supplement the Guidance for Industry: Request for Quality Metrics published on 28 July 2015 which is currently still in the draft version. We have recently published a GMP News about a Quality Metrics Case Study at Aenova regarding a possible implementation. Now, the Technical Guide defines how the industry should submit Quality Metrics to the FDA. Technical standards and fields are defined. Basically, the FDA is oriented towards the data standards which are already established in other areas. FDA‘s so-called Study Data Technical Conformance Guide serves as a basis. Largely widespread in the industry, the XML format is used by the FDA and other authorities for the exchange of data and the submission of data within the marketing authorisation procedure (e.g. for eCTD).

Composed of 10 pages, the Guide primarily provides a definition of the variables necessary for the submission of Quality Metrics. The last page of the Guide refers to “Data Validation Rules”. Data Validation is defined as “a process that attempts to ensure that submitted data are both compliant and useful”. It should be ensured that the data are submitted in accordance with the required standard. The FDA recognises that the standardisation of data doesn’t ensure the quality of data, but it helps verify certain aspects of data quality thanks to automated checks. When finalising the Guidance for Industry on Quality Metrics, the FDA also wants to set validation requirements on the quality of data in the guideline and thus achieve that companies first perform a validation of their metrics before they submit them.

Source: FDA Quality Metrics Technical Conformance Guide

Figure 1: Types of images quality metrics.

////////FDA, Technical Guide,  Quality Metrics

FDA´s new policy regarding grouping of supplements for CMC changes

The US Food and Drug Administration’s (FDA) Office of Pharmaceutical Quality (OPQ) released a new document outlining how supplements can be grouped together and submitted concurrently for the same chemistry, manufacturing and controls (CMC) changes. Find out more about Policy and Procedures regarding the Review of Grouped Product Quality Supplements.

http://www.gmp-compliance.org/enews_05320_FDA%B4s-new-policy-regarding-grouping-of-supplements-for-CMC-changes_15173,Z-RAM_n.html

On April 19, 2016 the US Food and Drug Administration’s (FDA) Office of Pharmaceutical Quality (OPQ) released a new document outlining how supplements can be grouped together and submitted concurrently for the same chemistry, manufacturing and controls (CMC) changes to multiple approved new drug applications (NDAs), abbreviated new drug applications (ANDAs) and biological license applications (BLAs) submitted by the same applicant.

The agency says the goal of its new policy is to make the process more efficient and consistent when reviewing grouped supplements.The term “grouped supplements” is used to describe two or more supplements reviewed and processed using the procedures set forth in the new document, though FDA makes clear that supplements cannot be grouped if submitted by a different applicant or if the supplements provide for different CMC changes. “The supporting data necessary for the review of the CMC changes should be the same for each of the grouped supplements,” FDA says. “Any supplement that provides for the same CMC changes but necessitates the review of data that is unique to that supplement (e.g., product-specific data) should not be grouped.”

Supplements can be grouped when the following criteria are met:

  • The cover letter for the supplements clearly states the purpose of the proposed CMC changes and indicates that the supplement is one of multiple submissions for the same change.
  • Each supplement includes a list of the application numbers (NDA, BLA, and ANDA, as appropriate) and identifies the drug products that will be covered by the CMC changes.
  • The supplements have the same submission date on Form FDA 356h.

“On a case-by-case basis, the Center may also group supplements that do not meet some or any of the criteria described above, if grouping the supplements is advantageous to the review process,” FDA says.

Circumstances where this may occur include cases when an applicant submits a group of supplements for the same CMC change and then, at a later date, submits additional supplements for the same change and requests FDA officials to include the second set of supplements in the group.

The Regulatory Business Project Manager (RBPM) and Branch Chief (BC) of the relevant review division will decide on a case-by-case basis whether such changes will be allowed, though FDA notes that “consideration will be given to whether the goal date for the original group of supplements could still be met if the second set of supplements is added to the review.”

Additionally, seven new procedures were outlined by FDA in the MAPP (Manual of Policies and Procedures).

Source: Regulatory Affairs Proffessional Society – See more at:  OFFICE OF PHARMACEUTICAL QUALITY Review of Grouped Product Quality Supplements

//////// supplements, FDA, MAPP, supplements for CMC changes