Stop the Presses: FDA Publishes Policy for Granting Requests to Conduct Expedited Reviews of NDA and BLA CMC Prior Approval Supplements

Stop the Presses: FDA Publishes Policy for Granting Requests to Conduct Expedited Reviews of NDA and BLA CMC Prior Approval Supplements

By Mark I. Schwartz

Late last month, CDER’s Office of Pharmaceutical Quality (OPQ) published a MAPP (Manual of Policies and Procedures #5310.3) outlining its policy for granting or denying expedited reviews of NDA and BLA Prior Approval Supplements (PAS) that involve chemistry, manufacturing and controls (CMC) changes overseen by OPQ.

Below are the pertinent highlights of the MAPP:

  • An expedited review in the context of this MAPP, is FDA-speak for seeking to assess and act on the PAS prior to the Prescription Drug User Fee Act (PDUFA) goal date associated with that PAS;
  • Normally, the sponsor is expected to make the request for expedited review, however, if the public need arises, OPQ may designate the CMC PAS for expedited review of its own initiative;
  • OPQ will only consider requests for expedited review that clearly state the basis for the request;
  • OPQ can designate a CMC PAS for expedited review at the time it receives the PAS or at any time thereafter. For instance, if OPQ receives a request for expedited review after the office has already processed the PAS, OPQ will consider the request and could still expedite the review of the PAS;
  • OPQ will not consider a request for an expedited review that involves a facility that is subject to an OAI recommendation, unless an expedited review will help address a public health concern;
  • OPQ will consider an expedited review request for a CMC PAS that falls into one of the following categories:
    • drug shortages;
    • special review programs such as the President’s Emergency Plan for AIDS Relief;
    • public health emergencies;
    • certain government purchasing programs;
    • statutory mandates or other legal requirements;
    • events that constitute extraordinary hardship on the applicant, such as a catastrophic event (eg, storm or fire damage), or the discontinuation of supply of an active ingredient or other material.

As it turns out, the categories for which OPQ will consider an expedited review request for a CMC PAS are not that dissimilar from the ones that the Office of Generic Drugs has previously indicated it will consider for expedited review of ANDAs, ANDA amendments, and ANDA supplements in its MAPP 5240.3, the most recent version of which was published on November 9, 2017. The only difference between the two MAPPs in that regard is that MAPP 5240.3 also includes the following categories, which are a function of the types of applications it reviews:

  • submissions containing certain patent certifications and exclusivity statements;
  • submissions for “sole source” drug products, i.e., “Submissions for drug products for which there is only one approved drug product listed in the Prescription Drug Product List (i.e., the “active section”) of the Orange Book and for which there are no blocking patents or exclusivities may receive a priority review, except when the approved drug product was approved pursuant to a suitability petition under section 505(j)(2)(C) of the Federal Food, Drug and Cosmetic Act.”

To summarize, the new MAPP 5310.3 for CMC PASs related to NDAs and BLAs is just a logical extension of the pre-existing MAPP 5240.3 for ANDAs, ANDA amendments and ANDA supplements. So, the next time your API supplier’s facility is knocked out by a torrential storm, you’ll know FDA’s position regarding the expedited review of your application or supplement!

{ Comments are closed }

Multiple Function Device Products – FDA Clarifies Its Approach

Multiple Function Device Products – FDA Clarifies Its Approach

By Adrienne R. Lenz —

On April 27, 2018 FDA released a draft guidance describing the regulatory approach and policy for multiple function device products. The draft guidance, Multiple Function Device Products: Policy and Considerations, is available here and has been issued in response to the 21st Century Cures Act section 3060(a) “Clarifying Medical Software Regulation.”

The term “function” is defined as “a distinct purpose of the product, which could be the intended use or a subset of the intended use of the product.” Draft Guidance at 4. The draft guidance is intended to clarify how FDA assesses the impact of functions that are not subject to FDA review when they are part of a multi-function product that includes at least one function that is subject to FDA review.

In short, the draft guidance indicates that FDA will not regulate functions of a multi-function product that do not meet the statutory device definition or are devices that are subject to an existing enforcement discretion policy. Also, though issued in relation to software functions, FDA states that they apply the same principles to the assessment of all multiple function products, not just those that contain software.

During review of premarket applications, FDA will assess the impact of “other functions” on a device function-under-review without reviewing the specifics of the other functions’ design and performance not related to the device function-under-review. In assessing the impact that these other functions may have on the device function-under-review, FDA will consider whether the other function(s) may impact the safety or effectiveness of the device function-under-review, by considering “whether there are shared computational resources, data dependencies, or any other type of relationship between the functions.” Id. at 9. If the other function(s) may impact the safety or effectiveness of the device function-under-review, FDA will consider whether there is an increased risk or adverse effect on performance.

Although sponsors may include information on other functions that positively impact the device function-under-review in their premarket submissions, FDA will only look for documentation on other functions in cases where the other function “could adversely impact the device function-under-review.” Id. at 11. A premarket submission for a multi-function device that includes other functions that could adversely impact the device function-under-review should include a description of the function, architecture and design information, risk analysis, requirements, and specifications. Also, FDA intends to include language in the submission summary (e.g., 510(k) summary) to indicate that “FDA assessed functions not subject to premarket review only insofar as they might adversely impact the safety and effectiveness of the functions subject to FDA premarket review.” Id. at 12.

This draft guidance should help those developing multiple function products to better understand how to limit their submissions to data and documentation for other functions only when they could adversely impact the device function-under-review. The boundaries have not always been clear in the past.

On the postmarket side, general control requirements are not applicable to non-device functions and will not be enforced for functions for which FDA does not intend to enforce applicable regulatory controls.

This area of device regulation has always been somewhat murky. The draft guidance is a positive step forward in providing clarity, even if it does not break new ground.

{ Comments are closed }

PEG 3350 Rx ANDA Holder Gets Things Moving in the D.C. Circuit

PEG 3350 Rx ANDA Holder Gets Things Moving in the D.C. Circuit

By Sara W. Koblitz

On April 27, 2018, Petitioners Breckenridge Pharmaceutical, Inc. and Nexgen Pharma, Inc. filed a Petition for Review in the United States Court of Appeals for the District of Columbia Circuit. The Petition seeks review of a final FDA order published in the Federal Register on April 2, 2018 (the “Order”). The Order denied requests for a hearing and withdrew approval for ANDAs for prescription polyethylene glycol 3350 (PEG-3350). The Order was initially effective May 2, 2018 but was stayed by FDA in response to several petitions for stay to the Agency. Currently, the Order goes into effect on November 2, 2018 – but FDA may not have the final say on this issue. Breckenridge/Nexgen’s asks the D.C. Circuit to set aside the Order as clearly erroneous, arbitrary and capricious, an abuse of discretion, and not supported by substantial evidence.

The Petition for Review is not a surprise. Breckenridge/Nexgen was one of several Rx ANDA holders participating in the Agency proceedings. Additionally, it and the other Rx ANDA holders had included in their petitions for stay to the Agency arguments that a stay was required to permit judicial review.

While FDA granted a stay until November 2, 2018, the Agency rejected the Rx ANDA holders arguments that a stay was required under 21 U.S.C. § 10.35 (e), because the criteria in (e)(1)-(4) were met.. Instead, FDA reasoned that the Agency petitioners had established that a stay was “in the public interest and in the interest of justice,” and therefore a discretionary stay was warranted—but not required. Breckenridge/Nexgen challenge both FDA’s Order and FDA’s stay determination.

Because a Petition for Review only starts the process for judicial review, it does not set forth the substance of the arguments that Breckenridge/Nexgen will make to the D.C. Circuit. That said, the Agency proceedings have been pending for some time, so the arguments are not unfamiliar to dedicated FDA Law Blog readers (indeed, we blogged on these issues here, here, here). For those of you who need a refresher on the regulatory history of laxatives, here’s a quick recap: in April 2007, FDA approved an NDA for an Rx-to-OTC switch for MiraLax. Five ANDAs based on MiraLax as the RLD had already been approved, so FDA issued a letter to the ANDA holders explaining that FDA believes their prescription products, which bear the “Rx only” symbol, are misbranded and may not be lawfully marketed. To lawfully market PEG-3350, according to the FDA letter, the ANDA holders must file new ANDAs referencing the OTC version of MiraLax and update the labeling to OTC labeling. FDA published a Notice of Opportunity for a Hearing in the Federal Register on October 24, 2008 (73 Fed. Reg. 63491) proposing to withdraw approval of the prescription PEG 3350 ANDAs. Four ANDA holders submitted timely requests for a hearing and supporting evidence, but FDA denied a hearing in both its proposed order of May 2014 and its final order of April 2018.

In a joint Petition for Stay at the agency level, Breckenridge/Nexgen argued that the final order irreparably harms their business and should be vacated. They explain that there is a meaningful difference between the Rx and OTC versions of PEG-3350 – duration of use, as well as reimbursement – and raise procedural errors and misstatements during the administrative process. Because the Order refused to consider all information submitted in 2014 and did not address Breckenridge/Nexgen’s arguments regarding outstanding factual issues with respect the scope of the Rx-to-OTC switch, those arguments may very well be made before the D.C. Circuit. Two Rx ANDA holders also filed petitions for stay with the Agency. Our firm represented one of those Rx ANDA holders.

As of the writing of this post, no briefing schedule has been set. The court has set May 31, 2018 as the date for Petitioner procedural motions.

{ Comments are closed }

USDA Publishes Proposed Rule for National Bioengineered Food Disclosure Standard

USDA Publishes Proposed Rule for National Bioengineered Food Disclosure Standard

By Ricardo Carvajal

USDA announced the publication of its much awaited proposed rule establishing a National Bioengineered Food Disclosure standard as mandated by Congress almost two years ago (for more on that law, see our prior posting here).  The rule is scheduled to publish in the Federal Register on May 4, but for those who can’t wait, it’s available in prepublication form.  We’ll follow up with a posting on key aspects of the proposed rule, but one thing bears emphasis now: the deadline for comments is July 3, 2018, and USDA has stated that the comment period will not be extended.  It therefore behooves those with an interest in the rule to make the timely submission of comments a top priority.

{ Comments are closed }

GAO Report: USDA/FSIS Should Update Some of Its Food Safety Standards

GAO Report: USDA/FSIS Should Update Some of Its Food Safety Standards

By Riëtte van Laack

In 2015, Senators D. Feinstein, R. Durbin and K. Gillibrand asked GAO to investigate the U.S. Department of Agriculture’s (USDA’s) Food Safety and Inspection Service (FSIS) pathogen standards for meat and poultry products and identify any steps that FSIS could make to address food safety. On April 18, 2018, GAO published its report of the two year investigation, Food Safety: USDA Should Take Further Action to Reduce Pathogens in Meat and Poultry Products.

Though the U.S. food supply is considered safe, the Centers for Disease Control and Prevention estimates that foodborne pathogens cause about 9 million illnesses each year. Two million of the illnesses are associated with Salmonella and Campylobacter.

GAO recognized that FSIS has taken a number of actions to address food safety, but concluded that it can do some things better. Among other things, FSIS has established performance standards for Salmonella and Campylobacter for some meat and poultry products. These standards are used to reduce contamination in meat and poultry before the products are sold. FSIS began setting these standards in 1996. At that time, the standards were set at industry-wide prevalence levels, not at levels that may protect human health. Since then, FSIS has changed its procedures and developed more science-based performance standards.

Over time, FSIS developed performance standards for Salmonella on beef carcasses, ground beef, pork carcasses, chicken carcasses and parts, comminuted chicken, turkey carcasses, and comminuted turkey. FSIS also developed performance standards for Campylobacter on chicken carcasses and parts, comminuted chicken, turkey carcasses, and comminuted turkey. Although some of the standards such as the standards for chicken have been updated, the standards for pork carcasses, beef carcasses and ground beef have not been updated since 1996 and there are no time frames for updating them. Moreover, for some commonly consumed products, such as turkey breasts, ground pork and pork chops, FSIS has never set standards. It was not clear to GAO how FSIS decides for which products it sets standards and when it updates standards.

The GAO made two recommendations regarding the performance standards: (1) document the process for deciding which products are considered for new standards (so as to better ensure that such decisions will be risk-based), and (2) set time frames for determining which updates or standards are needed for ground beef, beef carcasses, pork cuts, and ground pork.

Although FSIS agreed with the recommendations, its response included some comments. For example, FSIS indicated that it made a risk-based decision to not develop performance standards for turkey breast. Salmonella levels in turkey carcasses are typically low and consumption of turkey is relatively low, such that there appears minor exposure to pathogens from turkey parts.

As part of the audit, GAO also examined steps FSIS has taken to address challenges in reducing pathogen levels in meat and poultry that were identified in a 2014 GAO report. In that report, GAO found that the level of pathogens in poultry products can be affected by practices on farms where poultry are raised. Even though FSIS has no authority over such farm practices, GAO recommended that FSIS issue guidelines on the effectiveness of practices for controlling Salmonella and Campylobacter on farms. In response, FSIS did in fact revise its guidelines to include information on the effectiveness of on-farm practices for controlling pathogens in poultry and beef cattle. The draft guidelines for controlling Salmonella in pigs, however, do not contain such information. GAO recommends that FSIS include such information in the final guidance.

Senators Feinstein, Durbin, and Gillibrand sent the GAO report with four of their own questions (about timing of new performance standards and other actions recommended actions by GAO as well as a question about use of whole genome sequencing) in a letter to Secretary of Agriculture Sonny Perdue.

{ Comments are closed }

Don’t Say They Didn’t Warn You: FDA and FTC Issue 13 Warning Letters to Companies Selling E-Liquid Resembling Kid-Friendly Foods

Don’t Say They Didn’t Warn You: FDA and FTC Issue 13 Warning Letters to Companies Selling E-Liquid Resembling Kid-Friendly Foods

By Gugan Kaur

FDA is continuing the crackdown on the sale of tobacco products to minors (see our post here regarding recent FDA actions). On May 1, 2018, FDA and FTC issued 13 joint warning letters to manufacturers, distributors, and retailers for misleadingly labeling or advertising nicotine-containing e-liquids as kid-friendly food products, such as juice boxes, candies, and cookies.

The Federal Food, Drug, and Cosmetic Act (FDCA) provides that a tobacco product shall be deemed misbranded if, in relevant part:

1) its labeling is false or misleading (section 903(a)(1)), or

2) if, in the case of any tobacco product distributed or offered for sale in any State, its advertising is false or misleading in any particular (section 903(a)(7)(A)) or it is sold or distributed in violation of certain regulations, such as regulations prohibiting sale to minors (section 903(a)(7)(B)).

Section 201(rr)(4) of the FDCA prohibits a tobacco product from being marketed in combination with any other article or product regulated under the FDCA (including a drug, biologic, food, cosmetic, medical device, or a dietary supplement).

In terms of FTC authority, Section 5 of the FTC Act prohibits unfair or deceptive acts or practices in or affecting commerce. This prohibition includes practices that present unwarranted health or safety risks.

FDA and FTC found that companies violated the provisions outlined above by using false or misleading labeling and/or advertising that cause e-liquids to imitate food products, particularly ones that are marketed toward and appeal to minors. The batch of 13 warning letters all cited violations to both misbranding violations (under section 903(a)(1) of the FDCA) and unfair or deceptive acts or practices (Section 5 of the FTC Act). In addition, 6 warning letters also cited a violation of section 903(a)(7)(B) of the FDCA for sale of e-liquid products to minors and 1 warning letter cited a violation of section 201(rr)(4) of the FDCA for marketing a tobacco product in combination with a food product.

The warning letters mention that children are at particular risk for ingesting e-liquid products when the products have labeling and/or advertising that cause the product to imitate food products typically marketed toward and appealing to children. The warning letters also make the point that children are at particular risk because exposure to nicotine in the e-liquid can result in acute toxicity and, further, that severe harm can occur, including seizure, coma, respiratory arrest, and death from cardiac arrest.

The issuance of this batch of warning letters is just the most recent part of FDA’s ongoing efforts to enforce regulations specifically aimed at addressing youth access to tobacco products. We anticipate more FDA actions in the future and will continue to provide updates.

{ Comments are closed }

Sale of E-Cigarettes to Minors Prompts FDA to Light a Fire under the Industry

Sale of E-Cigarettes to Minors Prompts FDA to Light a Fire under the Industry

By Gugan Kaur

On April 24, 2018, FDA released a statement regarding new enforcement actions and a Youth Tobacco Prevention Plan aimed to help stop minors from using e-cigarette products.

Under the Family Smoking Prevention and Tobacco Control Act (“Tobacco Control Act”), a “tobacco product” is defined as “any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product.” The Tobacco Control Act gave FDA the express authority to regulate cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco. Any other “tobacco product” could be regulated by FDA only if the Agency issued regulations “deeming” such products to be subject to the Tobacco Control Act. As discussed in our previous post, on May 10, 2016, FDA published the final “deeming regulation” asserting authority over all tobacco products meeting the broad statutory definition of a “tobacco product.” This authority extends to electronic nicotine delivery systems (ENDS), which may be described with terms such as vapes, vaporizers, vape pens, hookah pens, e-cigarettes, or e-pipes. ENDS products typically use a liquid (“e-liquid”) that contains nicotine. This e-liquid is heated into an aerosol that can be inhaled by the user. ENDS products may be manufactured to look like traditional tobacco products or may resemble items such as pens or USB drives.

FDA cites the following CDC statistics regarding the use of ENDS products by minors:

  • More than 2 million middle and high school students were current users of e-cigarettes in 2016
  • 11% of high school and 4.3% of middle school students were current users of e-cigarettes in 2016
  • E-cigarette use rose from 1.5% to 16.0% among high school students and from 0.6% to 5.3% among middle school students from 2011 to 2015

We have previously discussed FDA’s comprehensive plan for tobacco and nicotine regulation announced last July (here). FDA’s most recent enforcement activity is more narrowly focused on the use of ENDS products by minors, and singles out one ENDS product in particular. In its April 24 statement, FDA outlined a series of enforcement and regulatory steps.

First, FDA announced that on April 6, 2018 it initiated a large-scale, undercover, nationwide blitz that will continue until the end of April 2018. This blitz focuses on the sale of e-cigarettes (specifically products under the JUUL brand) to minors at both brick-and-mortar and online retailers. The Agency’s efforts have already revealed numerous violations according to the FDA. This blitz, in addition to other compliance checks, has resulted in FDA issuing 40 warning letters for the illegal sale of e-cigarettes, specifically JUUL products, to minors.

Second, FDA contacted eBay regarding several listings for JUUL products on the website. According to FDA, eBay removed the listings and voluntarily implemented measures to prevent against re-listing of the items. It is possible that other online retailers with e-cigarette products, specifically JUUL products, may receive similar communications from the Agency.

Third, on April 24, 2018, FDA sent an official request for information to JUUL Labs, requesting the company submit information, such as documents related to product marketing; research on the health, toxicological, behavioral or physiologic effects of the products, including youth initiation and use; whether certain product design features, ingredients or specifications appeal to different age groups; and youth-related adverse events and consumer complaints associated with the products. FDA is planning on sending additional letters to other manufacturers and has asserted that companies that do not comply will be in violation of the law and subject to enforcement.

Fourth, the Agency announced that it is planning to take enforcement actions against companies that are marketing products in a way that is misleading to minors.

Finally, FDA is also continuing its efforts on science-based campaigns to educate minors about the dangers of all tobacco products, including e-cigarettes.

FDA Commissioner Gottlieb makes clear the focus of the Agency is ENDS products marketed and sold to minors. For adults, FDA believes that ENDS products may offer a potentially lower risk alternative for adult smokers, providing them with access to nicotine without the additional risks associated with the combustion of tobacco. However, the Agency states the viability of ENDS products serving this purpose is undermined if they attract minors.

The steps outlined above are just the first of those the FDA plans to pursue as part of the Youth Tobacco Prevention Plan, and additional steps will be announced in the future. FDA’s message to all tobacco product manufacturers and retailers is clear: the Agency is watching closely.

{ Comments are closed }

A Tale of Two Guidances: FDA Issues Final Next Generation Sequencing Guidances

A Tale of Two Guidances: FDA Issues Final Next Generation Sequencing Guidances

By Allyson B. Mullen

On April 13, 2018, FDA issued the final guidance documents “Considerations for Design, Development, and Analytical Validation of Next Generation Sequencing (NGS) – Based In Vitro Diagnostics (IVDs) Intended to Aid in the Diagnosis of Suspected Germline Diseases” (hereinafter the NGS Guidance, available here) and “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics” (hereinafter the Databases Guidance, available here). We previously blogged on the draft guidance documents issued in July 2016 here. As we discussed in our earlier post, these guidances have the possibility to be incredibly important to the IVD industry given the tremendous potential that sequencing holds.

The two guidances could hardly have undergone more different degrees of revision since their drafts were issued. The Databases Guidance received no substantive changes as compared to the draft. On the other hand, the NGS Guidance has undergone significant changes as compared to its draft, including its name. The draft NGS Guidance was originally named the “Use of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases.” NGS test developers will want to ensure they closely read the final NGS guidance to understand the full extent of its changes. Below we discuss several of the significant substantive changes to the NGS Guidance.

It is important to note that FDA provided no explanation for the changes to the NGS Guidance. Unlike the case with regulations, where FDA describes the reasons for revisions, guidances keep readers guessing as to why FDA’s thinking has shifted.

One of the major changes to the scope of the guidance is that it now applies only to NGS-based IVDs intended to diagnose suspected germline diseases in symptomatic patients. The guidance specifically states that it “does not address tests intended for use in the sequencing of healthy individuals.” The original guidance did not limit the scope of the guidance to only symptomatic individuals. This is an important change that will limit the scope and impact of the guidance to industry.

The guidance does, however, include several new helpful sections, including one regarding recommendations for reviewing changes to device design and production. This section pertains to all changes, including those that may or may not require premarket review. The guidance provides general guidance regarding assessing changes, including revalidation. The guidance also includes a new Appendix A. This appendix includes illustrative examples to aid in the guidance’s recommendations regarding analytical tests.

Finally, the NGS Guidance includes a notably shorter discussion of the possible exemption of NGS-based tests for germline diseases as compared to the draft. The draft had a full section regarding the possibility of an exemption for such tests. The final NGS Guidance still leaves open the potential for NGS-based tests being exempt from premarket notification. But, with a much more limited discussion in the final guidance it may be a signal that the Agency believes it is less likely that these tests will actually be exempt once classified. The guidance continues to state that it anticipates that the de novo pathway is the appropriate premarket pathway for these IVDs.

The extent of changes to the final NGS Guidance likely reflect that the Agency’s understanding and view regarding these tests is continuing to evolve. That will almost certainly remain the case for years to come. This is an area we will continue to watch closely and look forward to seeing FDA’s first de novo authorization for an NGS test to diagnose a germline disease.

{ Comments are closed }

FDA Denies Petition to Ban Caffeine Because the Requested Action Is Not Necessary; Issues Guidance Instead

FDA Denies Petition to Ban Caffeine Because the Requested Action Is Not Necessary; Issues Guidance Instead

By Riëtte van Laack

In 2014, the Center for Science in the Public Interest (CSPI) filed a Citizen Petition requesting that FDA ban the retail distribution of highly concentrated caffeine marketed as a dietary supplement and specify limits on the forms in which caffeine may be sold.   On April 16, 2018, on the same day that FDA issued guidance regarding highly concentrated caffeine in dietary supplements, FDA denied the petition.

FDA denied the Petition because, as explained in the denial, the Agency does not think that the requested actions (involving rulemaking) are necessary. It points to the guidance and “publication of information directed toward industry and consumers, through which [FDA] communicated about the legal status of” highly concentrated caffeine products.

In the guidance, FDA explained that it generally considers products containing potentially lethal amounts of pure or highly concentrated caffeine in powder or liquid form sold in bulk to be adulterated under FDC Act § 402(f)(1)(A). As discussed in the guidance, FDA’s concern relates to the difficulty of separating out a safe amount (serving) of caffeine. FDA has taken the position that labeling the product with instructions at to a safe serving size and warning statements do not mitigate the risk; notwithstanding the provision of a warning, directions, and dosing cups or other tools, the highly concentrated bulk caffeine product continues to present a significant or unreasonable risk of illness or injury.

The guidance also provides some examples of caffeine products that, according to FDA, do not present a significant or unreasonable risk of illness or injury. Assuming that the product otherwise complies with all applicable legal requirements, FDA likely will not consider caffeine supplement in solid dosage form or premeasured packets or containers that do not provide an excessive amount (not defined) of caffeine per dosage form adulterated. Even though such products may be highly concentrated, the dosage form eliminates the need to measure the serving and thus avoids the risk of inaccurate dosing. To avoid an adulteration charge for bulk powdered or liquid caffeine product, the caffeine concentration must be low so that a serving error or misunderstanding about dosing would not normally be expected to lead to a toxic/life threatening situation.

In the Federal Register notice, FDA justified issuing the guidance as final guidance; according to the Agency, the threat to public health posed by pure and highly concentrated caffeine products made prior public participation not feasible.

It is reasonable to expect that the Guidance will have the effect of discouraging the marketing of highly concentrated caffeine products sold in bulk form. Thus, it appears that even though FDA denied the Petition, CSPI effectively got what it requested and the Agency avoided having to go through notice and comment rulemaking.

{ Comments are closed }

FDA’s Proposed Expansion of the Abbreviated 510(k) Program

FDA’s Proposed Expansion of the Abbreviated 510(k) Program

By Jeffrey K. Shapiro & Rachael E. Hunt

Earlier this month, FDA issued a draft guidance: Expansion of the Abbreviated 510(k) Program: Demonstrating Substantial Equivalence through Performance Criteria. This draft guidance would expand use of the Abbreviated 510(k) pathway as follows: “The intent of the guidance is to describe an optional pathway for certain, well understood device types, where a submitter would demonstrate that a new device meets FDA-identified performance criteria to demonstrate that the device is as safe and effective as a legally marketed device.” Id. at 2.

The current Abbreviated 510(k) program allows a sponsor to demonstrate some of the performance characteristics necessary to support a finding of substantial equivalence by showing conformity to FDA-recognized consensus standards. In this guidance, FDA acknowledges that the current substantial equivalence analysis, which requires direct comparison testing can sometimes be very burdensome. For example, it is difficult to conduct comparison testing when a predicate device is not marketed or where it is prohibitively expensive. Another example is a device that relies on multiple predicate devices for different performance and technological characteristics may be required to conduct multiple comparative tests.

The draft guidance proposes an Expanded Abbreviated 510(k) program, in which sponsors would be able to utilize the same mechanisms available in the current Abbreviated 510(k) program to allow a demonstration of all performance characteristics. In some circumstances, no direct comparison testing would be required. A predicate device would still be identified, but testing of the proposed device would be conducted against objective performance criteria.

FDA plans to issue guidance documents to establish such performance criteria and identify the types of eligible devices. This guidance may include identification of products by product code, appropriate intended uses, appropriate indications for use, and expectations for technological characteristics.

This initiative should be considered a modest, but useful, tweak to the 510(k) program. While it may eventually ease testing burdens on well‑understood device types, FDA may require some time to issue a full panapoly of product-specific guidances. We suspect, though, that FDA has some devices in mind that it will address relatively quickly. Most device types will likely not be eligible for the program.

Anyone interested in submitting comments on the draft guidance must do so by July 11, 2018.

{ Comments are closed }