FDA Publishes First Performance Metrics for Third Party 510(k) Reviews

The US Food and Drug Administration (FDA) on Friday published the first of its quarterly performance reports for accredited third party reviewers for certain medical device submissions.

Background

FDA's third party accredited persons program was created by the 1997 FDA Modernization Act (FDAMA) as a means of making the review process for certain low-risk devices submitted under a 510(k) more timely and efficient.

Under the program, device makers can submit 510(k)s for eligible devices to accredited third parties that conduct the primary review of the submission before forwarding their recommendation to FDA, which makes a final determination on the recommendation within 30 days.

There are currently seven accredited third party reviewed under the program based in the US, China and Norway.

Performance Metrics

While FDA's third party accredited persons program has been operational for roughly two decades, the agency had not released performance data for individual third party reviewers until this year, after committing to do so in the recently reauthorized Medical Device User Fee Amendments (MDUFA IV).

However, under MDUFA IV, FDA only agreed to publish performance data for third party reviewers that have completed a minimum of five reviews during the reporting period, which at the time of the agency's first report includes just one third party reviewer: Regulatory Technology Services (RTS).

The report itself features a box plot detailing the performance of the individual third party reviewers for six different metrics:

1. Initial third party review time
2. Third party hold time
3. Total third party review time
4. Total FDA review time
5. Total time to decision from FDA
6. Total time to decision from third party receipt

The report also provides data on the combined performance of all seven third party reviewers.

In total, FDA says there have been 18 third party 510(k) submissions in FY2018, eight of which have been completed and found substantially equivalent to a predicate device, and ten of which are still pending a final decision by FDA.

Of the ten pending decisions, nine are still within the 30-day window for FDA to issue a determination, while one has been pending for more than 30 days.

For the third party reviews themselves, FDA says the average total time to decision from the time a third party reviewer receives a submission to when FDA issues its final determination is 80 days, with an interquartile range of 52 to 94 days and the longest review taking 172 days.

FDA Warns BD Over Changes Made to Blood Collection Tubes in Lead Testing Investigation

After examining the cause of the faulty lead test of four of Magellan Diagnostics LeadCare test systems last May, the Food and Drug Administration (FDA) warned Becton Dickinson (BD) on Thursday that it has not submitted a new lead test. 510 (k) for changes in his blood collection tubes.

At the beginning of the study, Jeffrey Shuren, director of the Center for Apparatus and Radiological Health (CDRH), said that the agency tried to determine the cause of the inaccurate test results, but still did not know these problems because of differences in blood. samples are collected, tubes are used to hold blood or a change in the way samples are processed.

As part of the investigation, the FDA inspected BD facilities in Franklin Lakes, New Jersey, where it produces Vacutainer blood collection tubes for three weeks in May and June.

"Our inspection has shown that BD has violated the law by making major changes to certain devices ... without notifying the FDA and not following good manufacturing practices," said Donald St. Pierre, Deputy Director of Evaluation. new products on CDRH. The FDA also stated that BD had not investigated a 2015 Magellan complaint regarding "observed negative bias" in test results with Magellan's LeadCare test systems when using Vacutainer tubes.

"Your company did not record this information in the complaints system, did not evaluate the complaint to determine whether this was a reportable event, or started an investigation into the complaint," the FDA wrote.

Although the FDA has stated that changes in the composition of rubber stoppers used with Vacutainer tubes may cause new interference with laboratory tests and lead to biased results, the agency said it was uncertain.

In a statement released on Friday, Richard Byrd, president of BD's pre-analytical systems, said the company was working with the FDA and thought the company was responding fully to the agency's inspection observations.

Update on BD spraying

On Friday, the FDA also announced that BD has stopped using rubber stoppers in its syringes, which reduces the power of the drug.

In September 2015, the FDA warned health professionals against the use of BD general-purpose syringes with compounded or reconditioned drugs stored in syringes due to the potential of drugs that interact with the rubber stopper in the syringe.

Although the FDA has approved approved syringes for general aspiration and injection of fluids, they are not authorized to be used as closed container storage systems for pharmaceuticals.

Now the FDA has declared that BD has stopped the rubber stopping material with regard to the power loss of the medicine and has returned with a rubber stopper used in other syringes.

Healthcare professionals should contact BD to determine if specific batches of syringes contain the new caps.

OPDP Letters: FDA Closes Out 2017 With Record Low

In the last days of 2017, the Office of Prescription Drug Promotion (OPDP) of the US Food and Drug Administration. UU (FDA) has sent a warning letter to over-the-counter pharmacist Avanthi, Inc. to omit risk information on a panel for the Lomaira weight loss drug (Phentermine hydrochloride, USP).

The warning letter brings to four the total number of compliance letters issued by the OPDP in 2017 (three warning letters and one untitled letter), a historical minimum for the agency.

While the number of letters sent each year by the OPDP has steadily declined since the late 1990s, while the office regularly published more than 100 letters per year, 2017 is the second time that the office has published fewer than 10 letters per year. 'action.

In 2015, the OPDP issued only nine action cards (two warning letters and seven untitled letters) and in 2016 the office issued 11 action cards (three warning letters and eight untitled letters). ) after a series of six letters the last weeks of the year.

Warning letter

According to the FDA, a panel sponsored by Avanthi, which appeared in the exhibition halls of the 2017 annual meetings of the Endocrine Society and the American College of Cardiology, failed to mention the risks of Lomaira.

The panel, which advocates "flexible dosing options" and makes other promotional statements such as "The power of three", does not mention any possible side effects, contraindications or warnings of the drug, such as the risk of abuse and dependence.

"By omitting the risks associated with Lomaira, including serious and potentially fatal risks, panel fairs provide material information about the consequences that may result from the use of the drug and create a misleading impression of the safety of the drug", wrote the FDA.

The FDA also notes that Lomaira is only indicated in the short term in patients with a body mass index of 30 kg / m2 or greater than or equal to 27 kg / m2, with other risk factors such as controlled hypertension , diabetes or hyperlipidemia.

In response, the FDA is asking Avanthi to stop labeling Lomaira and provide an action plan to broadcast "true, non-misleading and complete remedial messages" to the audiences who received the promotional material.

OPDP Letters: FDA Closes Out 2017 With Record Low

In the last days of 2017, the Office of Prescription Drug Promotion (OPDP) of the US Food and Drug Administration. UU (FDA) has sent a warning letter to over-the-counter pharmacist Avanthi, Inc. to omit risk information on a panel for the Lomaira weight loss drug (Phentermine hydrochloride, USP).

The warning letter brings to four the total number of compliance letters issued by the OPDP in 2017 (three warning letters and one untitled letter), a historical minimum for the agency.

While the number of letters sent each year by the OPDP has steadily declined since the late 1990s, while the office regularly published more than 100 letters per year, 2017 is the second time that the office has published fewer than 10 letters per year. 'action.

In 2015, the OPDP issued only nine action cards (two warning letters and seven untitled letters) and in 2016 the office issued 11 action cards (three warning letters and eight untitled letters). ) after a series of six letters the last weeks of the year.

Warning letter

According to the FDA, a panel sponsored by Avanthi, which appeared in the exhibition halls of the 2017 annual meetings of the Endocrine Society and the American College of Cardiology, failed to mention the risks of Lomaira.

The panel, which advocates "flexible dosing options" and makes other promotional statements such as "The power of three", does not mention any possible side effects, contraindications or warnings of the drug, such as the risk of abuse and dependence.

"By omitting the risks associated with Lomaira, including serious and potentially fatal risks, panel fairs provide material information about the consequences that may result from the use of the drug and create a misleading impression of the safety of the drug", wrote the FDA.

The FDA also notes that Lomaira is only indicated in the short term in patients with a body mass index of 30 kg / m2 or greater than or equal to 27 kg / m2, with other risk factors such as controlled hypertension , diabetes or hyperlipidemia.

In response, the FDA is asking Avanthi to stop labeling Lomaira and provide an action plan to broadcast "true, non-misleading and complete remedial messages" to the audiences who received the promotional material.

FDA Finds Quality Documents Stuck in a Shredder at Glenmark Facility

The United States Food and Drug Administration (FDA) UU has released a highly drafted form 483, sent last month to Glenmark Pharmaceuticals manufacturing facilities in Solan, India on Tuesday.

One of the seven observations on Form 483, first announced by the company on Nov. 28, noted that FDA inspectors found at least 13 quality documents "crushed into the teeth and internal moving parts of the crusher ". "

The FDA stated that the quality documents were not in the logbook as required by one of the site's standard operating procedures.

Further comments focused on the fact that the site did not thoroughly investigate unexplained lot spreads and failures, deficiencies in complaint files and lack of written procedures for production and process controls.

In one case, Form 483 indicates that the company attributed a batch error to the sample preparation error "by providing photographs of sample vials indicating alleged preparations of abnormal samples". The photographs included in the survey did not include stamps. of date ... The authenticity of the supporting photographs could not be verified by the investigators of the FDA. "

Glenmark stated that the manufacturing unit that received Form 483 contributes about 10% of the company's sales to the United States. UU And that the company "is in the process of providing a complete response to the observations."

House Adds Provision to Allow DoD to Approve Medical Products Outside of FDA

On Monday, the Rules Committee of the House of Representatives will adopt a provision that would expand the ability of the US Department of Defense to urgently approve medical products, according to the US Food and Drug Administration Commissioner. United (FDA) Scott Gottlieb for the provision to be rejected

According to the committee conference report on the National Defense Authorization Act for fiscal year 2018, the House will add the Senate amendment to authorize the Secretary of Defense to approve the emergency use of medical products outside of the US. UU., Expanding the capacity of the Department of Defense to approve these products.

"Participants agree that the traditional routes for the approval and authorization of the Food and Drug Administration of critical medical products for the care of combat victims are too slow to allow a rapid insertion and use of these products on the battlefield "said the report.

Speakers in the House noted "even higher survival rates due to severe combat injuries and injuries suffered by service members" as a reason to add the provision, although they said they expect the FDA to be consulted when evaluating medical products for the care of combat victims and use this new authority strictly for the approval of medical products for injuries and injuries on the battlefield. "

The FDA and the Department of Defense are already working together on the emergency use authorizations (EUA), including the DoD presentations, in accordance with the FDA's guidance on the use of said US as of January. For example, in 2014, the FDA issued an EUA to authorize the use of the EZ1 Real-Time DZ-PCR Assay of the Department of Defense for the detection of Ebola Zaire virus during the outbreak in West Africa.

The decision to add the provision to the House bill followed Gottlieb's comments earlier this week, which is rare for an agency that often says it will not comment on pending legislation, which must maintain such approvals within the scope of the FDA. The former commissioners of the FDA have also had problems with the provision.

And the move to carry it out in the House committee on Monday may not indicate that the change is final. Senator Patty Murray (D-WA) told Axios that an agreement had been reached with Senator Lamar Alexander (R-TN) to maintain US reviews under the FDA, but the DoD could pressure the FDA to expedite certain product reviews.

Pay-for-Delay Deals: FTC Notes Continued Decline Since SCOTUS Ruling

The total number of transactions in which brand-name drug companies pay to delay the entry of generic competitors continues to decline, and only 5 of 170 final 2015 settlements included generic compensation and entry restriction generic, the Federal Trade Commission (FTC) said in a report released on Wednesday.

Fiscal 2015 is the second full year of filings since the Supreme Court ruled FTC v. Canada. Actavis, Inc. in June 2013, when it concluded that a drug company's transfer to a generic competitor to settle a patent dispute could violate antitrust laws. The decline in fiscal 2015 follows a similar decline revealed in a report from the FTC last year.

"In accordance with the 2014 fiscal year, the number of settlements that can lead to late payment continues to decline significantly as a result of the Actavis decision, even though the total number of settlements filed with the FTC has increased," the report says.

During the 2015 financial year, the total number of definitive settlements was 170, compared to 140 in 2012, 145 in 2013 and 160 in 2014. However, the number of potential deferred payment agreements fell to 14 in 2015, from a high of 40 late payment settlements for fiscal year 2012.

Of these 14, 10 included compensation in the form of a cash payment only for litigation costs (one of which included a cash payment of more than $ 7 million), while the other four included a promise of non-commercialization. an authorized generic in competition with the generic manufacturer for a period.

Ten additional definitive regulations are classified by the FTC as containing "possible compensation" because it is not clear whether certain provisions in the agreements are equivalent to what should be considered compensation for the generic patent applicant.

"For example, an agreement containing a declining royalty structure, in which the generic's obligation to pay royalties is reduced or eliminated if a brand launches an authorized generic product, can have the same effect as an explicit commitment without MGAs. ", says the report. .

In addition, 126 of the 170 final regulations limited the ability of the generic manufacturer to market its product, but did not include explicit or possible compensation ...