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  • Beware EUA Deprioritization!

    As the end of the COVID pandemic appears into view, the Center for Devices and Radiological Health (CDRH) appears to be taking steps toward shedding at least part of its Emergency Use Authorization (EUA) caseload.

    Under Section 564(a)(1) of the Federal Food, Drug, and Cosmetic Act, FDA has discretion whether to issue an EUA.  Under Section 564(c), FDA may only issue an EUA if the following criteria are met:

    • The product may be effective in diagnosing, treating, or preventing the disease or condition.
    • The known and potential benefits outweigh the known and potential risks.
    • There is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating such disease or condition.

    CDRH is increasingly declining to review EUA requests and terminating pending EUAs.  Two rationales are typically offered.  One rationale is that, given the volume of EUAs, a particular EUA is simply not a priority.  CDRH usually provides little or no additional information about why a product is not a priority.

    A second rationale is that that there are already adequate supplies available in the market.  Based on this finding, the requirement in the last bullet, above, is not met and an EUA cannot issue.

    Even if CDRH has issued prior EUAs in a product category, supply conditions may change.  Indeed, the issuance of prior EUAs may have helped better supply the market.  CDRH’s position is that it cannot continue issuing EUAs if there are adequate alternatives in the market.

    CDRH has adopted deprioritization across a range of product categories.  Diagnostics have been particularly hard hit, but they are not alone.

    Here are three examples:

    • In the past few months, CDRH deprioritized antibody serology tests for COVID. It then proceeded to terminate pending EUAs and declined to accept new ones.
    • A PCR test for COVID may still receive an EUA if indicated for, e.g., point of care, but CDRH has deprioritized some tests on the ground that they were indicated only for laboratory use.
    • The umbrella EUA for face masks does not extend to masks made with antimicrobials. In theory, it should be possible to obtain an individual EUA for an antimicrobial face mask.  The reality is that CDRH is unwilling to expend resources reviewing such an EUA; they are deprioritized.

    There is little or nothing that can be done to challenge FDA’s prioritization decisions.  Section 564 gives the agency very broad discretion.  Therefore, if firms are considering pursuit of an EUA, they should be wary.  To avoid wasting money, firms need to assess the deprioritization risk carefully.

    Of course, it is not that easy to assess this risk, especially when FDA institutes deprioritization based on changing market conditions.  Also, not all product categories are treated the same way.  In some, CDRH may suddenly simply stop accepting new EUAs.  In other categories, CDRH may be skeptical but still be willing to authorize a product.  For instance, in some cases, they may be willing to review an EUA if (and only if) a manufacturer has the capability to produce in high volume or for a non-laboratory setting.

    CDRH could help everyone better assess deprioritization risk by creating a public database of deprioritized product categories, with designations as to whether they are entirely or only partially subject to deprioritization.  If not a database, CDRH could perhaps at least provide prioritization updates on their EUA FAQ web page.  This increased transparency would help firms better align themselves to CDRH’s priorities.

    Bottom line:  In every new EUA project, firms should factor in deprioritization as one of the risks to be concerned about.  Even after a firm expends considerable resources, a subsequent shift in CDRH’s priorities could prevent a product from obtaining an EUA.

    In the world of EUAs, caveat emptor rules the day.

    Categories: COVID19 |  Medical Devices

    Getting Into the Weeds of USDA’s Hemp Production Program Regulations

    It seems as if the “hemp” debate has been raging forever.  Yet only a little over two years have passed since enactment of the Agricultural Improvement Act of 2018, the “Farm Bill,” in December 2018 that amended the Agricultural Marketing Act of 1946 directing the Department of Agriculture (“USDA”) to establish the regulatory framework for a domestic hemp production program.  Now USDA has issued the final regulations governing that program at lightning speed compared with other federal cannabis-related initiatives.  Establishment of a Domestic Hemp Production Program, 86 Fed. Reg. 5596 (Jan. 19, 2021).  USDA’s Agricultural Marketing Service (“AMS”), the delegated authority to administer the domestic hemp production program, received almost 6,000 comments after issuing an interim final rule on October 31, 2019.  Agricultural Marketing Service, Establishment of a Domestic Hemp Production Program; Document IDs AMS-SC-19-0042-0001 & AMS-SC-19-0042-4666, Regulations.gov (last visited Feb. 23, 2021).

    The Farm Bill mandates that USDA establish and administer a national hemp production program.  As a reminder, “hemp,” as defined in the Farm Bill and final rule, is “the plant species Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis.”  7 C.F.R. § 990.1; see also 7 U.S.C. § 1639o(1).  Cannabis with a THC level exceeding 0.3 percent is marijuana, a schedule I controlled substance under the federal Controlled Substances Act.  Plants and plant material exceeding 0.3 percent THC concentration must be disposed of by a DEA-registered reverse distributor or law enforcement officer.  86 Fed. Reg. 5604.  In the alternative, non-conforming plants and materials can be “remediated” plowing the plants, composting into “green manure” for use on the same land, tilling, disking, burial, or burning.  Id.

    The Farm Bill allows States and Indian Tribes wishing to exercise primary authority over hemp production within their territory to submit their own production plans for USDA approval.   USDA has approved 45 State and Tribal plans though not all States and Tribes have implemented their programs.  86 Fed. Reg. 5596.  USDA has also accepted production applications under its program since October 2019 and has issued 380 producer licenses.  86 Fed. Reg. 5608.  Licenses issued prior to final rule’s publication will remain in effect until their original expiration.  Id.  USDA will not issue production licenses to producers within States or Tribal territories that have a production plan pending for USDA approval and will deny applications from individuals in States or Tribes with USDA-approved plans.  Id.

    The Farm Bill set general requirements on licensing, recordkeeping about the land where hemp is produced, testing for delta-9-tetrahydrocannabinol (“THC”), disposing of non-conforming plants, and conforming to compliance provisions and procedures for handling violations.

    USDA Hemp Production Program

    Hemp production in States or Tribal territories lacking a USDA-approved State or Tribal plan must comply with USDA hemp program requirements.  Producers must hold a valid license prior to producing hemp.  7 C.F.R. § 990.21(a)(1).  Applicants must provide contact information and a current criminal history report.  7 C.F.R. § 990.21(3).  A completed application serves as consent to comply with USDA requirements.  7 C.F.R. § 990.71(a)(3).  Persons with a state or federal felony conviction related to controlled substances are ineligible to produce hemp for ten years following the conviction date.  7 C.F.R. § 990.20(b).  Licenses are valid for three years and must be renewed prior to expiration.  7 C.F.R. § 990.21(a)(6), (b).  Producers of hemp for research must also obtain a USDA license.  7 C.F.R. § 990.21(d)(1) (effective Mar. 22, 2021).  Only research institutions registered with DEA to handle marijuana can maintain hemp testing over the acceptable THC level to the end of their study; all other licensees must ensure the disposal of non-conforming plants.  7 C.F.R. § 990.21(d)(2) (effective Mar. 22, 2021).

    Producers must

    1. Report hemp crop acreage to USDA’s Farm Services Agency (“FSA”) within 30 days of planting hemp;
    2. Provide street address and geospatial location where hemp will be produced, and acreage or indoor footage dedicated to hemp production and hemp license; and
    3. No earlier than 30 days prior to harvesting, have a trained agent collect samples from the flowering tops of the plant for THC level testing. 7 C.F.R. § 990.23; .24 (effective Mar. 22, 2021).

    Hemp cannot be harvested prior to samples being taken.  7 C.F.R. § 990.24(e).

    Producers cannot harvest any later than 30 days after sample collection and failing that, test a second pre-harvest sample of the lot.  7 C.F.R. § 990.26(a); (b) (effective Mar. 22, 2021).  Only lots with the acceptable THC level may enter commerce; plants exceeding that THC level are marijuana and must be disposed of by a DEA-registered reverse distributor or law enforcement or remediated on-site.  7 C.F.R. § 990.26(d); .27(a) (effective Mar. 22, 2021).  Producers must notify USDA of their intent to dispose of or remediate non-compliant plants and submit verification.  7 C.F.R. § 990.27(b) (effective Mar. 22, 2021).

    Laboratories must:

    1. Ensure the validity and reliability of test results;
    2. Have effective disposal procedures for non-conforming plants;
    3. Test samples for total THC using post-decarboxylation or other USDA-approved methods; and
    4. Hold a DEA registration to test after December 22, 2022. 7 C.F.R. § 990.25(a); (e); (g) (effective Mar. 22, 2021).


    Producers must maintain records of hemp plant acquisition, production and handling, and storage, as well as disposal and remediation of non-conforming cannabis plants.  7 C.F.R. § 990.32(c) (effective Mar. 22, 2021).  They must maintain records and reports for at least three years, and records must be available for inspection by USDA employees and representatives.  USDA inspectors and representatives must have access to any premises where hemp plants may be held.  7 C.F.R. § 990.32(d) (effective Mar. 22, 2021).


    Producers must report disposal or remediation within 30 days after completion.  Reports must include producer’s name and address, license number, geospatial location, or other valid land descriptor for the production area subject to disposal or remediation and date of completion.  7 C.F.R. § 990.71(b) (effective Mar. 22, 2021).  Producers must also annually report lot, location type, geospatial location, total planted acreage, total acreage disposed and remediated, and total harvested acreage.  7 C.F.R. § 990.71(c) (effective Mar. 22, 2021).  Producers are also responsible for ensuring that laboratories testing samples report test results to USDA (informal testing conducted throughout the growing season for THC concentration need not to be reported to USDA).  7 C.F.R. § 990.71(d) (effective Mar. 22, 2021).  The test report must contain for each sample tested:

    • Lot identification number for the sample;
    • Laboratory name;
    • Date of test and report;
    • Identification of any pre-harvest or post-harvest retest; and
    • Test result. Id.


    USDA may audit hemp producers’ records for completeness and accuracy, and conduct on-site visits to farms, storage facilities, and locations affiliated with licensees’ hemp operation.  USDA audits may be conducted every three years and can focus on current crop year and previous crop years.  7 C.F.R. § 990.28(a), (b).  USDA will provide reports to producers within 60 days of an audit’s conclusion.  USDA requires a corrective action plan to correct a negligent violation, which USDA will approve or deny within 60 days of receipt.  7 C.F.R. § 990.28(d).  USDA may also revoke a producer’s USDA license for one year or until the producer becomes compliant.  7 C.F.R. § 990.28(d) (effective Mar. 22, 2021).


    Producers are not subject to more than one negligent violation per calendar year.  7 C.F.R. § 990.29(a) (effective Mar. 22, 2021).  Negligent violations include failure to provide an accurate legal description of land where hemp is produced, production of hemp without a license, and production of cannabis that exceeds the acceptable hemp THC level.  7 C.F.R. § 990.29(a)(1)-(3).  USDA issues a notice of violation for each negligent violation requiring a corrective action plan from the producer.  Corrective action plans will be in place for a minimum of two years and include:

    • The date by which the producer will correct violations;
    • Steps the producer will take to correct violations; and
    • Procedures that will demonstrate compliance that must be submitted to USDA. 7 C.F.R. § 990.29(b).

    USDA will revoke the license of producers who commit negligent violations three times within five years, and they will be ineligible to produce hemp for five years.  7 C.F.R. § 990.29(e).

    If USDA determines that a producer has violated the terms of their license or the regulations with a “culpable mental state greater than negligence,” it will immediately report the licensee to the U.S. Attorney General and the chief law enforcement officer of the State or Indian territory where the production is located.  7 C.F.R. § 990.29(f)(1).

    USDA may issue a notice of suspension to a producer if they have violated a provision of the regulations or failed to comply with a written order from USDA related to negligence.  7 C.F.R. § 990.30(a).  Producers whose license has been suspended may appeal the suspension but cannot produce hemp during the suspension.  7 C.F.R. § 990.30(c), (d).  Producers whose licenses have been suspended and not restored on appeal may have their license restored after a waiting period of one year from the suspension date.  7 C.F.R. § 990.30(e).  USDA may also require a producer whose license has been suspended to operate under a corrective action plan to fully restore their license.  7 C.F.R. § 990.30(f).

    USDA will revoke a license immediately if the licensee:

    • Pleads guilty to, or is convicted of, any felony related to a controlled substance;
    • Made any materially false statement to USDA or its representatives with a culpable mental state greater than negligence; or
    • Is found to be growing cannabis exceeding the acceptable hemp THC level with a culpable mental state greater than negligence or has negligently violated the regulations three times in five years. 7 C.F.R. § 990.31.

    Producers can appeal license denials, suspension, and revocations.  7 C.F.R. § 990.40; .41.  The regulations, under 21 C.F.R. § 990.42, also set forth the process for States and Tribes to appeal USDA actions on their hemp production plans.

    State and Tribal Hemp Production Programs

    The USDA final rule, tracking the Farm Bill, requires USDA-approved State and Tribal programs to include many of the same components as USDA’s program.  USDA exercises oversight of State and Tribal programs first by reviewing and approving their plans, then by conducting audits to ensure compliance with the Farm Bill and final rule.  States and Indian Tribes must submit their program plan to USDA for approval before implementation.    

    State and Tribal plans must collect, maintain, and report to USDA, for each licensed or authorized producer, contact information, a legal description of the land on which the producer will produce hemp including geospatial location, and the producer’s license number and status.  7 C.F.R. § 990.3(a)(1).

    In addition, State and Tribal plans must include procedures for:

    • Sampling hemp, requiring agents to collect hemp within 30 days prior to harvest for THC testing. 7 C.F.R. § 990.3(a)(2)(i) (effective Mar. 22, 2021);
    • Identifying through testing whether the hemp sample contains THC concentration exceeding the acceptable hemp THC level by validated testing methods using post-decarboxylation or similar methods (only DEA-registered laboratories registered may test hemp after December 22, 2022). 7 C.F.R. § 990.3(a)(3) (effective Mar. 22, 2021);
    • Disposing of or remediating cannabis plants if the tests exceed the acceptable THC level by DEA-registered reverse distributors, law enforcement or remediation on-site. 7 C.F.R. § 990.3(a)(6) (effective Mar. 22, 2021); and
    • Conducting annual inspections of a random group of producers to verify compliance. 7 C.F.R. § 990.3(a)(7) (effective Mar. 22, 2021).

    USDA Approval and Audits

    USDA must approve or disapprove State and Tribal plans within 60 days of receipt.  States and Tribes must submit amended plans if, after disapproval, they still wish to have primary regulatory authority over hemp production within their territory.  7 C.F.R. § 990.4(a), (b).

    USDA may audit State and Tribal programs to determine compliance with their approved plans every three years but can adjust audit frequency based on performance, compliance issues, or other relevant factors identified and provided to State/Tribal governments.  7 C.F.R. § 990.5(a).  USDA audits can include:

    • Resources and personnel administering and overseeing programs;
    • Licensing and compliance review of hemp producers;
    • Sampling and lab testing requirements and components;
    • Disposal and/or remediation of non-conforming plants to ensure correct reporting;
    • Results of and methodology used for annual inspections of producers; and
    • Information collection procedures and accuracy. 7 C.F.R. § 990.5(b) (effective Mar. 22, 2021).

    USDA will provide reports to State and Tribal governments within 60 days after completing audits.  USDA will advise of non-compliance and corrective measures required to bring programs into compliance.  States/Tribes will develop a corrective plan that must be reviewed and approved by USDA.  7 C.F.R. § 990.5(c)(1).  If USDA determines the State or Tribe is non-compliant after the second audit, it may revoke approval for one year or until the program becomes compliant.  7 C.F.R. § 990.5(c)(2).


    States and Tribes with approved plans must submit a monthly report to USDA providing contact information and license status for every producer.  Monthly reports to USDA must contain:

    1. For each new licensed producer who is an individual, their full name, license or authorization identifier, business entity Employee Identification Number, address, telephone number, and email address;
    2. For each new licensed producer that is an entity, their full name; business address; license or authorization identifier; and full name, title, and email address of each employee for whom the entity is required to submit a criminal history report;
    3. For producers in prior reports whose reported information has changed, the previously reported information and the new information;
    4. Status of each producer’s license; and
    5. Indication, if applicable, of no changes during the current reporting cycle. 7 C.F.R. § 990.70(a) (effective Mar. 22, 2021).

    States and Tribes must also submit monthly reports notifying USDA of any occurrence of non-conforming plants or plant material and the disposal or remediation record by the producer.  Disposal and remediation reports must include:

    1. Producer’s name and address;
    2. Producer’s license or authorization identifier;
    3. Location, such as lot number, location type, and geospatial location or other descriptor for the production area subject to disposal or remediation;
    4. Disposal or remediation completion date; and
    5. Total acreage. 7 C.F.R. § 990.70(b) (effective Mar. 22, 2021).

    State and Indian Tribes must also report annually to USDA the total acreage planted, harvested, and disposed/remediated within their territory.  7 C.F.R. § 990.70(c) (effective Mar. 22, 2021).

    Producers are responsible for ensuring labs testing their samples report results to USDA.  (Informal testing conducted throughout the growing season monitoring THC concentration do not need to be reported to USDA).  Test result reports must contain:

    1. Producer’s license or authorization identifier;
    2. Producer’s name and address;
    3. Lot identification number for the sample;
    4. Laboratory name and, no later than December 31, 2022, laboratory’s DEA registration number;
    5. Date of test and report;
    6. Identification of a pre-harvest or post-harvest retest; and
    7. Test results. 7 C.F.R. § 990.70(d) (effective Mar. 22, 2021).


    State and Tribal plans must include enforcement provisions for “negligent” and “culpable” producer violations as well as felonies.  7 C.F.R. § 990.6(a)-(e).  The plans must prohibit anyone who materially falsifies any application information from program participation.  7 C.F.R. § 990.6(f).  Hemp producers cannot receive more than one negligent violation per calendar year.  7 C.F.R. § 990.6(b) (effective Mar. 22, 2021).  As with USDA requirements, negligent violations include:

    • Failing to provide a legal description of land where hemp is produced;
    • Producing hemp without a license; and
    • Producing cannabis exceeding the acceptable hemp THC level. Id.

    For each negligent violation, the State/Tribe must require a corrective action plan for a minimum of two years that includes the date by which the producer will correct negligent violations and the producer’s regular reporting on compliance.  7 C.F.R. § 990.6(c).  Producers who negligently violate their license three times within five years will have their license revoked and are ineligible to produce hemp for five years.  7 C.F.R. § 990.29(e).

    State/Tribal programs must also contain provisions relating to producers who commit violations with a “culpable mental state greater than negligence.”  86 Fed. Reg. 5606.  Programs must immediately report  licensees to the U.S. Attorney General, and the chief law enforcement officer of the State or Indian territory.  7 C.F.R. § 990.6(d).  State and Tribal programs must prohibit any person with a State or Federal controlled substance-related felony conviction from participation in hemp production for ten years from the conviction date.  7 C.F.R. § 990(e).

    It will be interesting to see how USDA will administer its own hemp production program while overseeing numerous State and Tribal programs.  As noted, the final rule is effective March 22, 2021.

    “Tongue and Done” – Just . . . No.

    Yesterday’s FDA Warning Letter, Press Release, and accompanying public relations campaign related to AcelRx’s promotional material for Dsuvia (sufentanil) are remarkable for exactly the reasons FDA intended them to be remarkable: these actions all signal to industry that despite anemic levels of FDA enforcement related to Rx drug promotion, when it comes to opioids, FDA is paying attention and ready to take action.  In addition to the Press Release, FDA’ers tweeted about the Warning Letter, including the following tweet (of three) by Dr. Janet Woodcock:  “False or misleading promotional communications will not be tolerated.  The agency is focused on reducing harm by decreasing exposure to opioids, while still enabling appropriate access for patients with medical need.”  FDA, in what appears to be a new approach, has already updated the OPDP 2021 Warning Letter website to include CDER’s press release, in addition to posting the Warning Letter and underlying promotional material.

    It should come as no surprise that the media blitz and OPDP’s first letter of 2021 relate to opioid promotion.  Before retirement, Tom Abrams, former Director of OPDP, regularly stressed OPDP’s enforcement priorities and, included among them, was promotion for drugs that have serious risks.  Just last month, Acting Director of OPDP, Katie Gray, provided an interview where she explicitly stated, in response to a question on which promotional materials were priorities, that OPDP would focus “on promotional materials for high-risk drugs, such as opioids. We want to make sure the promotional materials accurately convey the risks associated with these drugs, convey responsible use of opioids, and do not inadvertently contribute to the opioid epidemic.”  The last time an OPDP Warning Letter was accompanied by an FDA Press Release was back in December 2019, relating to a treatment intended to prevent relapse to opioid dependence.

    Back to the Dsuvia Warning Letter – there are a number of key takeaways for industry.  It is apparent that the letter was triggered, in this particular instance, by the use of the pithy tagline, “Tongue and Done” that emphasizes simplicity in administration.  Given FDA’s history with this product, and that administration was one of the issues cited as part of a complete response letter – it is not surprising that this type of promotion was likely to garner the agency’s attention.  (As an aside, knowing how much former FDA Commissioner Scott Gottlieb enjoys our song references, these bloggers spent an inordinate amount of time looking for clever references to music videos that would relate to this tagline.  Not surprisingly, after watching a few too many Kiss videos – featuring Gene Simmons – we abandoned the exercise.  Hence the name of this blogpost.)

    Putting the tagline trigger aside, FDA also called out the company’s failure to include information on the maximum dosing within a 24 hour period, despite otherwise calling out the ability to re-dose Dsuvia within an hour.    This is a practical concern, not simply for opioids, as there is a safety suggestion implied with re-dosing statements.

    Industry should pay close attention to other FDA comments in the Warning Letter with regard to the presentation of risk and benefit information.  The allegations relating to how the company presented the full indication and limitations for the product, as well as Important Safety Information, should be scrutinized as the techniques employed are often used by others.   From the Warning Letter:

    “the full indication with the limitations of use are intermingled with risk information in a paragraph format in a much smaller font size and a plain white background, and are accessible only if viewers “scroll” down the banner. Therefore, this does not mitigate the misleading impression.”

    These bloggers find it shocking that FDA would object to presenting the full indication, particularly one that is longer and includes limitations of use, with safety information and that FDA would particularly call out that it was against a plain white background.  One of the core tenets of any ad is ensuring that the full indication and safety information are legible – and FDA has a long history of calling out instances when safety information was minimized because it was presented against a colored background.   In fact, this very issue was addressed in FDA’s Draft Guidance on Presenting Risk Information, dating back to 2009, in a section on Contrast:

    “Contrast between text and background should not highlight the benefit information more than the risk information. Example 18: If benefit information in a piece is presented in white letters on a black background, risk information should be presented with similar contrast. If the piece presents risk information in a way that would make it difficult to discern (e.g., using white letters on a light gray  background or gray letters on a black background), the presentation may be considered false or  misleading. Even if the background is a color designed to attract attention, the contrast influences the prominence of the words once attention has been gained. In fact, printing words in some attention-grabbing colors (e.g., red) may make the words difficult to read.  Similarly, the placement of risk information over pictures or other visual elements with multiple colors can cause this information or portions of this information to lack prominence and be difficult to read. Furthermore, a print piece that superimposes risk information over a visual image could compromise the accuracy of the piece as a whole by drawing attention away from the risk information.

    While it may be fair to point out in the Warning Letter that the safety information was only visible after scrolling within the digital banner ad, it is absurd to think that by providing safety information in black font against a plain white background that the company has somehow minimized risk.

    In looking at the banner ad, it looks like the company employed a “20%” approach to the inclusion of safety information.  This approach includes a scroll bar for the user to obtain additional safety information, but devotes 20% of the visual field to safety information as balance.  In this Dsuvia banner ad, that amount of space was not enough to present the full, all caps title from the Boxed Warning.  Although somewhat consistent with how industry treats digital banner ads (although arguable that 20% of an ad would be sufficient balance for an opioid with significant safety concerns and a REMS), companies should be mindful, not only of spacing, but of the substantive safety information in view.

    FDA also cited both the digital banner as well as a print flyer for failing to present information relating to the Boxed Warning, Contraindications, Warnings and Precautions, and Adverse Reactions “with a prominence and readability reasonably comparable with the presentation of information relating to the benefits” of the drug.  FDA cites “typography, layout, contrast, headlines, paragraphing, white space, and other techniques” as affecting readability and emphasis. FDA also highlights that “risk information is relegated farther down in paragraph format with less prominence.”

    The key takeaways here are not new:  minimizing safety, particularly for a drug with serious risks, will likely trigger FDA enforcement (no matter how sleepy OPDP may seem).  The issues cited by OPDP are those clearly outlined in its 2009 Draft Guidance – which was not exactly revolutionary at the time it was originally published and simply summarized points made in prior DDMAC Warning and Untitled Letters.  Many of the techniques utilized by AcelRx, and objected to by OPDP, are those employed across industry.  One has to question whether lack of OPDP enforcement has led, to a certain degree, to industry falling back into old habits –  with safety information “below the line,” at the end of a piece, in small font with running text.  While it may have been the nature of this promotion in the midst of the opioid crisis that stirred FDA to action, the issues OPDP called out are nevertheless ones even non-opioid manufacturers might want to reconsider in light of this letter.

    ACI’s 36th FDA Boot Camp (Virtual Conference)

    The American Conference Institute’s (“ACI’s”) popular “FDA Boot Camp” – now in its 36th iteration – is scheduled to take place from March 24-25, 2021 (Eastern Time).  The conference is billed as the premier event to provide folks with a roadmap to navigate the difficult terrain of FDA regulatory law.  And like a lot of conferences over the past year, the ACI conference format has changed from a live, in-person event to an interactive, virtual conference.

    ACI’s FDA Boot Camp will provide you not only with the essential background in FDA regulatory law to help you in your practice, but also key sessions that show you how this regulatory knowledge can be applied to situations you encounter in real life. A distinguished cast of presenters will share their knowledge and provide critical insights on a host of topics, including:

    • The organization, jurisdiction, functions, and operations of FDA
    • The essentials of the approval process for drugs and biologics
    • Clinical trials for drugs and biologics
    • The role of the Hatch-Waxman Act in the patenting of drugs and biologics
    • Labeling in the drug and biologics approval process
    • cGMPs and other manufacturing concerns relative to products liability
    • Proactive adverse events monitoring and signal detection
    • Recalls, product withdrawals, and FDA oversight authority

    Hyman, Phelps & McNamara, P.C.’s Kurt R. Karst is co-chairing the conference and will also present at a session titled “Understanding the Relevance of New FDA Initiatives and Policies and How They May Redefine the Life Sciences Industry in the Aftermath of COVID-19.”

    FDA Law Blog is a conference media partner. As such, we can offer our readers a special 10% discount. The discount code is: D10-874-874EX05.  You can access the conference brochure and sign up for the event here.  We look forward to seeing you (virtually, of course) at the conference.

    HP&M’s Food, Beverage & Supplement Wrap Up: January 2021

    Welcome to the latest edition of HPM’s monthly wrap up of food, beverage and supplement news, including regulations, guidances, events, and whatever else is catching our eye. It’s been quite a January, hasn’t it?

    Food & Beverage

    • Transition: As of this writing, Janet Woodcock is Acting Commissioner of Food and Drugs; Norris Cochran is Acting Secretary of Health & Human Services; and Kevin Shea is Acting Secretary of Agriculture.
    • Whither regulation of bioengineered animals? USDA and HHS officials signed an MOU under which USDA would take the lead on regulation of bioengineered animals intended for agricultural purposes. Then-Commissioner Hahn quickly disavowed the MOU via Twitter, thereby suggesting that the future of that initiative is uncertain.
    • Another source of protein. EFSA has declared mealworms safe for human consumption. This is their first opinion on insects as a novel food and could help drive the category forward.
    • Uniformity is good. The FDA announced that January 1, 2024, will be the uniform compliance date for final food labeling regulations that are issued in calendar years 2021 and 2022. This action does not change existing requirements for compliance dates contained in final rules published before January 1, 2021.
    • Traceability is good too. The FDA published FAQs about the FSMA Food Traceability Proposed Rule to assist those considering submitting comments (due Feb. 21, 2021). FDA also updated its Food Traceability List to provide some clarity (without changing any of the listed foods).
    • Not-so Short Form. On January 8, 2021, California’s Office of Environmental Health Hazard Assessment (OEHHA) announcedproposed amendments to Proposition 65 warning regulations that would limit use of the short-form version of the safe harbor warning. Check out Riëtte’s blog post for more information.


    • Another try at CBD: Legislation was again introduced in Congress that would make lawful the use of hemp and its derivatives (including CBD) as dietary ingredients in a dietary supplement, provided that the supplement complies with all other applicable requirements. Hat tip to CRN, which posted the bill on its website.
    • And another NAD decision on “natural”: NAD took issue with the word “natural” in a brand name used for products in which the key ingredients are not naturally derived. Other aspects of the decision also make it a worthwhile read.

    More on Cannabis

    Other things that caught our eye:


    Categories: Dietary Supplements |  FDA News |  Foods

    ACI’s Advanced Legal, Regulatory, and Compliance Forum on OTC Drugs (Virtual Conference)

    The American Conference Institute (“ACI”) is sponsoring its Advanced Legal, Regulatory, and Compliance Forum on OTC Drugs Conference on February 26, 2021 (Eastern Time).  Like a lot of conferences over the past year, the ACI conference format has changed from a live, in-person event to an interactive, virtual conference.

    Hear from leading OTC industry counsel and regulatory executives who will provide timely analysis and best practices for:

    • Preparing for monograph reform under the CARES Act
    • Substantiating COVID-related claims
    • Identifying labeling and manufacturing missteps for imports, to avoid costly hold ups at the border
    • Leveraging lessons from recent Rx-to-OTC switch success stories to overcome complex legal and regulatory hurdles
    • Navigating recalls and adverse events protocols

    Hyman, Phelps & McNamara, P.C.’s Deborah L. Livornese will be speaking at a session titled “How to Prepare for a Modernized OTC Drug System under the CARES Act.”

    FDA Law Blog is a conference media partner. As such, we can offer our readers a special 10% discount. The discount code is: D10-826-826DX01. You can access the conference brochure and sign up for the event here.  We look forward to “seeing you at the conference.”

    OIG PBM Rebate Rule Delayed – Twice

    In late November, the OIG published a final rule that excludes from the Federal healthcare program safe harbor for discounts rebates paid to Medicare Part D plans, or their PBMs (see our post here).  The rule also establishes two new safe harbors: one for rebates paid to Medicare Part D plans and Medicaid Managed Care plans, or their PBMs, if the rebates are passed through by the plan or PBM to the dispensing pharmacy; and another for service fees paid to PBMs.  Together, these safe harbor amendments were intended to force PBMs to pass manufacturer rebates through to pharmacies to lower the out‑of‑pocket costs of government beneficiaries at the pharmacy counter.  The exclusion from the discount safe harbor had a delayed effective date of January 1, 2022, while the two new safe harbors were scheduled to go into effect on January 29, 2021 (last Friday).  However, since Friday, both the discount safe harbor exclusion and the new safe harbors have now been delayed further.

    On Friday, just under its deadline, the OIG issued a “correction” to the two new safe harbors delaying their effective dates until March 22, 2021.  The delay was pursuant to the regulatory freeze issued by the White House on inauguration day, which, among other things, directed federal agencies to consider delaying published rules that have not yet become effective for 60 days, and longer where necessary, to permit the agency and OMB to review factual, legal, and policy issues raised by the rule.

    On Saturday — the very next day — the new discount safe harbor exclusion was also delayed, this time by court order.  Earlier this month, before the change in administration, the Pharmaceutical Care Management Association (PCMA), a trade association of PBMs, had sued HHS to vacate the rule on procedural and substantive grounds.  Saturday’s Order delayed the effective date of the exclusion one year from January 1, 2022 to January 1, 2023, “pending the duration of HHS’ review of the November 20, 2020 rule,” with the consent of the parties.

    The fate of these safe harbor amendments under the Biden administration is in doubt.  As we pointed out in our previous post, the safe harbor amendments would reduce coinsurance for some federal program enrollees but would preclude PBMs from using rebates to reduce premiums across all enrollees.  The Congressional Budget Office estimated that the impact would be to increase Medicare and Medicaid spending by $177 billion over 10 years.  This Administration, like the previous one, has committed to reducing drug prices, but can be expected to favor price reduction measures that do not increase costs to the government.

    Conducting Virtual Inspections: EMA and MHRA do it, CMOs do it, why won’t FDA do it?

    At a conference sponsored by the Parenteral Drug Association on January 27, speakers demonstrated that:

    • Industry has developed best practices for auditors or regulatory inspectors to conduct virtual inspections of drug-manufacturing facilities (virtual inspections are those in which the auditor or inspector is not physically on-site, but, instead, conducts the inspection remotely through audio or video streaming techniques, or both).
    • Advanced technology is available and is easily controlled by remote auditors in such a fashion as to replicate the physical presence on-site of an inspector or even a team of inspectors.
    • Sponsors of approved applications for drugs regularly conduct virtual audits of their Contract Manufacturing Organizations (CMOs).
    • Other drug-manufacturing regulatory agencies worldwide routinely conduct virtual inspections, and have done so since COVID-19 began to shut down travel of inspectors.

    As we have previously reported (here, here, and here) and as my colleague Mark Schwartz wrote in a Bloomberg article, numerous FDA approvals of critically needed drugs are being blocked because FDA is insisting that the approvals must await in-person inspection of the facilities manufacturing either drugs or the Active Pharmaceutical Ingredients that are essential components of pharmaceuticals.  And yet FDA has not promulgated guidance or publicized policies on virtual FDA inspections so that the unnecessary blockade of drug approvals can be lifted.  FDA has claimed it has performed virtual inspections of food-manufacturing facilities, but has not claimed that it has performed a single virtual inspection of a drug-manufacturing facility.  By contrast, the European drug manufacturing regulatory body (the European Medicines Agency, or EMA) and its British counterpart (the Medicines and Healthcare products Regulatory Agency, or MHRA) have been performing such inspections since March.

    At the PDA webinar, which was attended by more than 350 individuals involved in drug manufacturing (and also apparently by some FDA officials: let’s hope they recognize the ease and promise of virtual inspections), presentations described the procedures that drug manufacturers should establish for the conduct of virtual inspections (including that video and audio should be streamed in real time, without alteration or enhancement) and discussed the practices that inspected entities need to embrace (such as ensuring that adequate wifi capabilities are available in all areas which are subject to inspection).  (This blogpost will be updated to provide a link to the presentations, when they are available.)  One presenter, Peter Miller of Dynamic Compliance Solutions, demonstrated a 360camera that provides viewers of the video feed the same capabilities that an inspector or multiple inspectors would have if they were personally present at the inspected facility.  As you can see in the brief video, viewers can:

    • Instruct personnel on-site to move the camera to particular places or in certain directions;
    • Remotely pan or tilt the view provided by the camera as the remote inspectors wish, and, if there are multiple remote inspectors, each viewer can tilt or pan the camera to view different areas, people, or equipment as they wish (by left-clicking and rolling the mouse), and can zoom in and out;
    • Interview plant personnel; and
    • Demand to view specific documents through a flexible and high-resolution document camera.

    Which brings us to the immortal lyrics of Cole Porter, popularized by Ella Fitzgerald.  “Let’s Fall in Love” suggested that “birds do it, bees do it, even educated fleas do it,” and implied, “Why don’t we do it?”  The same question could be asked of FDA about virtual inspections.  (This blogger’s question is rhetorical, only, because offering his honest response would be based on speculation and the content of the answer would be undignified.)  It is clear that COVID is going to prevent adequate FDA on-site inspections for months, if not years, and yet . . .

    UPDATE: A copy of the presentations noted above is available here.

    Categories: cGMP Compliance

    FDLI Publishes New Book on IVD Regulation Co-Edited by HP&M’s Jeffrey Gibbs and Allyson Mullen

    While receiving less public attention than some other types of health care products, in vitro diagnostics (IVDs) have for years been playing an increasingly important role in health care.  The COVID-19 pandemic has highlighted what has long been the case: IVDs are indispensable to public health.  Whether used as companion diagnostics to guide therapeutic treatment, or liquid biopsy to identify tumors from blood tests, or to detect an infectious disease, or to help determine whether a patient has had a heart attack, or in thousands of other ways, IVDs are essential in medicine.

    There has not, however, been a single source that someone could consult to learn about how IVDs are regulated today.  To fill that void, the Food and Drug Law Institute (FDLI) has just released Diagnostics at a Crossroads: Navigating IVD Regulation in a Changing Environment, the first book in over a decade that addresses the world of IVD regulation.

    The book comprehensively covers diagnostic regulatory issues, from premarket issues, e.g., analytical testing, statistics, clinical studies, and pathways to the market, to post-market issues, such as Quality System Regulation and Medical Device Reporting.  And, of course, it addresses two of our favorite topics: laboratory developed tests (LDTs) (see, e.g., our earlier posts here, here, here, here, here, and here) and research use only (RUO) products.  The authors represent a range of disciplines and expertise.  To name just a few, they include Dan Schultz, former director of CRRH; Nina El-Badry of BARDA; and Sally Hojvat, who was Director of one of the IVD Divisions at CDRH and now consults with WHO; and several colleagues at Hyman, Phelps & McNamara, P.C., and other law firms.  The book also covers other topics critical to IVD manufacturers and investors, such as reimbursement – simply getting on the market isn’t often enough for a test to be commercially viable – and the evolving European regulatory model.

    More information about the book can be found here: https://www.fdli.org/IVD-book.

    With the ongoing leaps in technology the importance of IVDs will only continue to grow.  We expect that this book will be a valuable resource for those who are seeking to learn how to better understand and navigate the world of IVD regulation.

    New HHS Policy on Buprenorphine for the Treatment of Opioid Use Disorder – Finally, Treatment is More Accessible than Opioids…. UPDATE

    In the waning days of the Trump administration, the Department of Health and Human Services announced a fairly significant change in addiction medicine policy. The new policy permits physicians (and only physicians) more flexibility to prescribe buprenorphine – a much used and effective drug that treats opioid use disorder.  On a side note, it has always been a “head scratcher” that it was actually much easier to prescribe highly addictive opioids (like schedule II or schedule III narcotic controlled substances) than buprenorphine, which is used for the much-needed treatment for abuse of opioids.  Until HHS’s recent announcement, any physician seeking to treat opioid use disorder with buprenorphine was required to obtain an “X” DEA number (i.e., “X waiver” or “Data 2000 waiver”).  Unless appropriately board certified, this required an 8-hour training; advanced practitioners including physician assistants and nurse practitioners need 24 hours of training.  Prescribers were also limited to 30 patients at a time within their first waiver year, and 100 patients thereafter (after meeting additional notification requirements).

    We were waiting for — and wondering why — the Practice Guideline had not been been published in the Federal Register notwithstanding its release more than ten days ago, yet remained hopeful.  Enter the Biden Administration.  As published in The Washington Post, and carried by other news outlets, these practice Guidelines announced by the Trump administration in its final days “had significant legal and clinical concerns” and the Biden will not issue the Practice Guidelines that were previously announced.

    As the original blogpost stated, the attached Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder exempts from certain certification requirements under 21 U.S.C. § 823(g)(2) of the Controlled Substances Act (CSA) those physicians licensed under State law and who possess a DEA registration.  Note the following important limitations on the new HHS exemption:

    • The exemption only applies to physicians who may only treat patients who are located in the state or states in which they are authorized to practice medicine.
    • Physicians will be limited to treating no more than 30 patients with buprenorphine for opioid use disorder at any one time (but note: the 30-patient cap does not apply to hospital-based physicians, such as emergency department physicians).
    • The exemption applies only to the prescribing of drugs or formulations covered under the X waiver, such as buprenorphine, and does not apply to the prescription, dispensation, or use of methadone for the treatment of OUD (which – appropriately used — must be administered in a SAMHSA-certified program).
    • Physicians utilizing this exemption shall place an “X” on the prescription and clearly identify that the prescription is being written for opioid use disorders (and separately maintain information in the chart used for the patient being treated for OUD).
    • An interagency working group will be established to monitor the implementation and results of these new practice guidelines, as well as the impact on diversion.

    Notwithstanding the benefit of greater access to medication assisted treatment using buprenorphine in what appears to be a thoughtful, controlled and reasonable manner, it seems like, given the new administration’s unwillingness to publish them, at least this blogger will continue to wonder why it appears easier to obtain the addictive opioid than it is to obtain the medication assisted treatment (at least the prescribing of buprenorphine) for opioid addiction.

    HP&M’s Frank Sasinowski to Present at Kinexum’s “Wow or Yeow?! FDA Outlook for 2021 and Beyond”

    2020 was unprecedented and tumultuous due to simultaneous challenges of a once-in-a-century global pandemic, the resulting socio-economic fallout, and political polarization regarding policy responses to the pandemic, civil rights protests and presidential elections. The FDA has been pressured and challenged and responded with varying degrees of success and now faces an incoming administration that in many ways could not contrast more sharply with its predecessor.

    Join the all-star panel of FDA consultants and lawyers, including HPM’s own Frank Sasinowski in a discussion and Q&A of the 2020 experience and the FDA outlook for 2021 and beyond. To register, please click here.

    Most Favored Nation Drug Pricing Rule on Hold Awaiting Changes

    As we previously reported (see here and here), in three separate cases, federal courts blocked the implementation of the Most Favored Nation (MFN) rule for Medicare Part B drug payment.  (Our summary of the MFN rule is available here.)  In December 2020, the District Court for the Northern District of California and the District Court for the Southern District of New York issued nationwide preliminary injunctions, while the District Court for the District of Maryland issued a temporary restraining order.  Each order effectively blocked the MFN rule from taking effect on January 1, 2021.

    On January 13, 2021, Judge George J. Hazel granted a stay in the suit filed in the District Court for the District of Maryland.  As explained in the Joint Motion to Stay, the plaintiffs (the Association of Community Cancer Centers, the National Infusion Center Association, the Global Colon Cancer Association, and PhRMA) and government defendants agreed to stay the litigation until a new final rule is published in the Federal Register, based on “(1) Defendants’ agreement that they will not appeal the preliminary injunction issued by the Northern District of California; and (2) Defendants’ agreement that the performance period for any final regulation … shall not commence earlier than 60 days after publication of that regulation in the Federal Register.”  We note that, in a fourth lawsuit challenging the MFN rule, the government filed a Status Report on January 8, notifying the District Court for the District of Columbia that it will not appeal the nationwide preliminary injunctions issued by the District Courts in the Northern District of California and Southern District of New York.

    A new administration has taken over since these court developments.  Based on what we’ve seen so far, including the Biden White House’s “Regulatory Freeze Pending Review” memo issued on January 20, we can safely say the MFN Rule published in November 2020 will not take effect in the short term.  We can also confidently predict that, if and when a new MFN rule is introduced, it will be in the form of a proposed rule with an opportunity for public comment.  More difficult to predict is whether an international reference pricing model will fit into the overall drug price reduction strategies of the new administration and Congress.

    FDA Continues Discussion of AI/ML Software Medical Devices

    On January 12, 2021, FDA issued an Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD) Action Plan (“AI/ML Action Plan”) and a discussion paper on their Proposed Regulatory Framework for Modification to Artificial Intelligence/Machine Learning (AI/ML) – Based Software as a Medical Device (SaMD) (“Modifications Discussion Paper”).  FDA started its public discussion of AI/ML in 2019, as we blogged about here, with publication of an AI/ML-based SaMD discussion paper outlining a potential framework for regulation of AI/ML-based SaMD.

    The new AI/ML Action Plan describes feedback in response to the initial discussion paper and briefly describes a five-part action plan at a high level.  The Modifications Discussion Paper provides more detail on FDA’s thoughts related to modification of AI/ML-based SaMD and the “Predetermined Change Control Plan” that was introduced in the 2019 discussion paper.

    The AI/ML Action Plan describes the following actions and goals:

    • Develop an update to the proposed regulatory framework presented in the AI/ML-based SaMD discussion paper, including through the issuance of a Draft Guidance on the Predetermined Change Control Plan.

    • Strengthen FDA’s encouragement of the harmonized development of Good Machine Learning Practice (GMLP) through additional FDA participation in collaborative communities and consensus standards development efforts.

    • Support a patient-centered approach by continuing to host discussions on the role of transparency to users of AI/ML-based devices. Building upon the October 2020 Patient Engagement Advisory Committee (PEAC) Meeting focused on patient trust in AI/ML technologies, hold a public workshop on medical device labeling to support transparency to users of AI/ML-based devices.

    • Support regulatory science efforts on the development of methodology for the evaluation and improvement of machine learning algorithms, including for the identification and elimination of bias, and on the robustness and resilience of these algorithms to withstand changing clinical inputs and conditions.

    • Advance real-world performance pilots in coordination with stakeholders and other FDA programs, to provide additional clarity on what a real-world evidence generation program could look like for AI/ML-based SaMD.

    AI/ML Action Plan at 8.

    SaMD as a whole, and especially SaMD that uses AI/ML, is updated frequently.   Under the current regulatory framework, for class II devices subject to 510(k) premarket notifications, a new submission is required whenever software changes introduce new risks, impact risk controls, or significantly affects clinical functionality or performance specifications.  With AI/ML, software can be retrained using new data and, given the technology, these changes can be made more quickly than other types of design changes.  These types of changes often times improve performance or allow use of the software in expanded populations which, today, require a new regulatory submission.

    In the Modifications Discussion Paper, FDA proposes a total product lifecycle (TPLC) approach for regulation of AI/ML-based SaMD that would allow some modifications that currently require a new regulatory submission to be made without one.  The proposed TPLC approach would start with the incorporation of GMLPs into the device manufacturer’s quality system.  While the specifics are not yet defined, GMLPs would describe best practices such as data management, feature extraction, training and evaluation used in the development of AI/ML-based SaMD.

    The Modifications Discussion Paper then describes a regulatory pathway including an initial premarket evaluation of the AI/ML-based SaMD that includes both an evaluation of the safety and effectiveness of the device as well as an evaluation of “SaMD pre-specifications” (SPS) and an “algorithm change protocol” (ACP).

    An SPS would describe “anticipated modifications to ‘performance’ or ‘inputs,’ or changes related to the ‘intended use’ of AI/ML-based SaMD.” Modifications Discussion Paper at 10.

    An ACP would define “specific methods that a manufacturer has in place to achieve and appropriately control the risks of the anticipated types of modifications delineated in the SPS.” Id.   After initial FDA clearance, including the SPS and ACP, future modifications within the bounds of the cleared SPS and ACP could be made without a pre-market submission.

    The Modifications Discussion Paper also proposes a process for transparency and real‑world performance monitoring of AI/ML-based SaMD, including “periodic reporting to FDA on updates that were implemented as part of the approved SPS and ACP, as well as performance metrics for those SaMD.” Id. at 14.  Labeling to accurately and completely describe the modification and its impact on performance are also proposed.  Again, the Modifications Discussion Paper does not provide details on the mechanisms by which transparency would be achieved as it seeks to receive input from stakeholders.

    For some SaMD, we see a potential tradeoff between speed of the initial clearance and speed at which future changes may be made.  If the future path of the AI/ML-based SaMD is clear, spending extra time to develop an SPS and/or an ACP before the initial submission would allow future changes to be implemented without pre-market review, which will decrease time to market.  In cases where future modifications may not be well defined during initial review, developing an SPS and/or an ACP may delay initial submission without much gain down the road.

    Anticipating that changes may not always be known at the time of the initial submission, the Modifications Discussion Paper proposes a step where FDA can perform a focused review of the SPS and ACP for any modification that is outside of the SPS and ACP agreed to in the initial clearance.  The mechanism for this interaction and its timeframe are not yet defined.   For any AI/ML-based SaMD where development of an SPS and ACP at time of initial submission does not make sense or would be likely to cause delays that are not balanced by improved speed of future modifications, the traditional framework would still remain an option.

    While the unique characteristics of AI/ML may make it faster to implement a design change compared to other device types, the proposed framework may also be welcomed by industry for other types of devices.  A regulatory submission is currently filed at the end of development when verification and validation data supporting the final, finished device are complete for FDA review.

    Many manufacturers start with an initial regulatory application for a foundational device and then submit subsequent submissions to add new feature and uses, many of which are known from the beginning.  The Modifications Discussion Paper makes us wonder, if FDA can define a mechanism by which to allow modification of an AI/ML-based SaMD based on pre‑specifications and change protocols, would they consider a similar approach for other device types?

    In thinking about the current approach to FDA review, we recognize that, in using the pre-submission process, there are frequently multiple iterations of a protocol with the agency before agreement is obtained.  For device submissions that include data generated by following a protocol that had been subject to pre-submission interactions with FDA, FDA still scrutinizes the data and often raises questions or concerns during review of the study report in the pre-market application.

    It is hard to envision FDA becoming comfortable with granting marketing authorization based on authorization of specifications and a change plan without review of the test results to ensure the protocol was strictly followed, that all data meet the specification as it was agreed upon, that appropriate regression testing was also performed, and that any justified anomalies or adverse events are appropriate.  The proposed real-world performance monitoring will need to be robust to ensure FDA feels the types of issues it may have detected in premarket review would be detected quickly via the postmarket processes.

    As with the initial AI/ML discussion paper, the Modifications Discussion Paper is not a guidance or even a draft guidance, but is intended to further the AI/ML discussion by eliciting additional comments and feedback that the Agency can incorporate into guidance planned for later this year.

    Despite these matters being in the discussion phase, FDA has already granted marketing authorization via the De Novo pathway of a device incorporating artificial intelligence that utilized a predetermined control plan to incorporate future modifications (DEN190040); thus, it seems the Agency is committed to going in this direction for regulation of AI/ML-based SaMD.

    Interested parties are encouraged to provide feedback to the questions FDA has raised in the Modifications Discussion Paper to ensure that the process, when it is able to move out of the discussion phase, will provide a viable mechanism for today’s SaMD and innovations that are yet to come.

    Categories: Medical Devices

    Proposed Changes to Short-Form Version of Safe Harbor Proposition 65 Warning

    On January 8, 2021, California’s Office of Environmental Health Hazard Assessment (OEHHA) announced proposed amendments to Proposition 65 warning regulations that would limit use of the short-form version of the safe harbor warning.

    Proposition 65, California’s Safe Drinking Water and Toxic Enforcement Act of 1986, mandates that businesses that sell consumer products—including food, cosmetics, and OTC drugs—notify Californians about possible exposure via a clear and reasonable warning about certain chemicals that have been identified as substances that cause cancer or reproductive toxicity.

    Since the original warning requirements took effect in 1988, most Proposition 65 warnings simply stated that a chemical is present that causes cancer or reproductive harm, but they did not identify the chemical or provide specific information about how a person may be exposed or ways to reduce or eliminate exposure to it.

    New OEHHA regulations, adopted in August 2016 (and effective in August 2018) changed the “safe harbor warning” that was deemed to meet the requirements for a clear and reasonable warning.  Importantly, the new safe harbor warning was to identify at least one chemical that prompted the warning.  In addition, the warning statement would no longer state “contains” the chemical but instead “can expose you to” a Proposition 65 chemical.  The regulations did provide for a short-form version of the Proposition 65 warning.  The key difference between these two warning statements is that the long-form warning requires that the business specifically must name at least one Proposition 65 chemical that could result in exposure from the product’s use, whereas the short form warning requires only a statement of the potential health hazard.  For example, a long-form warning for a product containing a chemical listed as a carcinogen could read:

    ⚠WARNING: This product can expose you to chemicals including [name of one or more chemicals], which is [are] known to the State of California to cause cancer. For more information go to www.P65Warnings.ca.gov.

    A short-form warning for the same product could read:

    ⚠WARNING: Cancer – www.P65Warnings.ca.gov

    Not surprisingly, many businesses chose to use a short-form warning.  In its “Initial Statement of Reasons” OEHHA asserts that the short-form warnings are used in ways that were not intended and do not further the purposes of Proposition 65.  Specifically, the intent of the 2016 updates had been to provide consumers with more meaningful and informative warnings, avoid over-warning, and limit the use of the short form warning where the full-length warning will not fit on the label. Therefore, OEHHA is proposing amendments that limit and revise the use of short-form warnings.  Proposed changes include:

    • Allow the short-form warning only

    (a) on products with 5 square inches or less of “label space” and

    (b) when the standard warning will not fit.

    • Prohibit the short-form warning for internet and catalog sales. This prohibition would apply even if the actual product label is eligible and contains the short-form warning.
    • Add a requirement that the name of at least one chemical per relevant toxicity endpoint be included in the short-form warning; and
    • Include the words “Risk” and “Exposure” in the warning.

    Under the proposal, the new safe harbor warning for a product containing a potential carcinogen would read “ WARNING: Cancer Risk from [insert chemical name] Exposure – www.P65Warnings.ca.gov.”

    The existing minimum type size requirements under the current regulations would not change.  In addition to requiring more transparency concerning the identity of chemicals in the warning, OEHHA hopes the proposed changes will dissuade businesses from over-warning.

    OEHHA is accepting comments on the proposal through March 8, 2021.

    AMG v. FTC: A Moot Court-Worthy Conflict at the Supreme Court

    With a legal question that led to a classic oral argument where all nine Justices refused to tip their hands on how the case will turn out, the U.S. Supreme Court this week heard oral arguments in AMG Capital Management v. Federal Trade Commission.  The sole issue before the Court is the FTC’s authority to seek and obtain equitable relief from a court with regard to the meaning of a statutory scheme that both sides acknowledged is not expressly resolved by the wording of Section 13(b) of the FTC Act, 15 U.S.C. 53(b).  The operative language of that provision simply authorizes the FTC to seek, and a court to issue, “a permanent injunction.”

    You can read more about the background of this case in our previous posts here, here, and here.  At its base, though, the Justices clearly recognized that this issue is the classic – and moot court-worthy – conflict between a pure textual reading of the statute, versus examining the historical context of the provision built on decades of enforcement actions and court decisions both before and after the provision was enacted by Congress in 1973.  AMG primarily argued that because Congress explicitly included equitable relief in Sections 19 and 5(l), the failure to include that language in 13(b) must mean that Congress intended to exclude such relief from that provision. The FTC asserted that while the legislative history of the 13(b) is sparse, Congress employed the facially unclear “injunction” language in 13(b) with a backdrop that Congress intended that two pre-enactment Supreme Court rulings involving other federal agencies gave the FTC the same powers to seek equitable relief.  However, several Justices noted that soon after 13(b) was enacted, the FTC itself did not believe that this section authorized the FTC to seek equitable relief.

    Joel Marcus, Deputy General Counsel for Litigation argued for the FTC, and Michael Pattillo of MoloLamken argued for AMG.  One interesting sidenote is that the case is one of the extremely rare cases where the FTC is representing itself before the Court, rather than relying on the Solicitor General of the United States.

    Both sides’ arguments were excellent, as were their briefs, and as Justice Breyer commented during the argument, “Blue brief I think you’re right. Red brief I think you’re right. You can’t both be right. That’s right. Alright. You see, that’s the old joke but that’s where I am.”  Many commentators are right there with you, Justice Breyer.

    Chief Justice Roberts noted that the Court has changed over time the way that it interprets statutes.  He stated (and other justices agreed) that the Court interprets statutes in a “more disciplined” way than its prior approach, which he described as “freewheeling.” While he made this comment in the course of asking if the court should construe the statute in the environment in which it was passed, the Chief Justice did not explain what he meant by these terms.

    While we could look into a crystal ball and try to guess where the Court will land, we won’t – mainly because it would be a wild guess. We do, however, want to address an oversimplification that came up a few times during the argument, that being that employing 13(b) as a means to get relief is the “easier” or “more attractive” path for the FTC to take to get equitable relief when the FTC is deciding to choose among Section 13(b), Section 19 (15 U.S.C. § 57b) or Section 5(l) (15 U.S.C. § 45(l)) of the FTC Act.

    In contrast to Section 13(b), Sections 19 and 5(l) expressly authorize the government to obtain equitable relief.  The first provision requires the FTC to first obtain an administrative cease and desist order against a company or other person, before the FTC can go to court to get equitable relief.  The second provision is also quite limited because it too requires a prior cease and desist order or administrative rule before the FTC can go to court to seek equitable relief.  In contrast, 13(b) allows the FTC to go to court to enjoin allegedly unlawful conduct without providing any notice at all to the alleged violator.  This “lack of prior notice” contrast was noted by a number of the Justices in this week’s argument.

    Speaking as a former FTC staff attorney (Karin) and the former Director of the DOJ’s Office of Consumer Litigation (now called the Consumer Protection Branch) (John), we believe this contrast oversimplifies the strategic analysis that FTC Staff conducts when assessing which provision to employ to determine the path forward on every case.  We have clearly seen that FTC Staff considers a multitude of factors in their strategic analysis of whether to proceed against an alleged offender by bringing a 13(b) action in court as opposed to seeking an administrative cease and desist order without first resorting to a court.  For example, the FTC weighs primarily which of the two actions is most conducive to discovery issues and an expedited resolution.  In addition, the FTC considers how forthcoming the target of the investigation has been with information, whether the case presents a novel theory or otherwise complex issues or whether it’s “run of the mill”, what injunctive relief is necessary and how quickly it is needed, what equitable relief might be available, where assets are located (here or abroad).  In other words, FTC lawyers do not necessarily agree in every case that a 13(b) action, which the Court seemed to believe is always the faster and better alternative for the FTC, is the path the agency wants to follow.  And for defendants, there are other important distinctions between the two paths.  For example, injunctions obtained by the FTC in court are generally much more detailed and onerous on the defendants than most cease and desist administrative orders.

    Additionally, the concept that 13(b) is “easier” or “more attractive” seems to ignore the reality of the hundreds of cases the FTC has decided administratively.  See, e.g., In re POM Wonderful, LLC, 155 F.T.C. 1 (2013), aff’d as modified, 777 F.3d 478 (D.C. Cir. 2015) (FTC order clarifying policy on health claim substantiation); In re 1-800 Contacts, 2018 WL 6078349 (F.T.C. 2018) (FTC order resolving antitrust case alleging anticompetitive practices in the online contact lens market).

    As noted above, this is a case where it is impossible to predict the outcome.  It is possible that the Court will overrule its earlier precedent dealing with agencies’ authority to seek and obtain equitable relief.  It is also possible that the Court will decide to follow that precedent.  We also do not know if the Court will use this case as a vehicle to reexamine long standing precedent regarding what is and is not appropriate equitable relief.  But one thing is crystal clear: a ruling against the FTC will put a dagger in the agency’s enforcement of the FTC Act.  Absent a subsequent amendment of that statute, the FTC would lose what is probably its main enforcement weapon, namely obtaining monetary relief, to combat alleged violations of the FTC Act.

    As we have written before, this is not solely an issue for those dealing with the FTC.  Other federal agencies such as the SEC and FDA have also sought to obtain equitable relief under statutory schemes that authorize the agencies to bring lawsuits seeking injunctions.  It may well be true that the parameters of agencies’ authority to obtain such relief will depend on the specific wording of their governing statutes.  Nevertheless, the Court’s ruling could well impact other agencies.

    In light of the developing case law, FDA may also need to be more circumspect in seeking equitable relief when it (through the Department of Justice) files an injunction action under 21 U.S.C. § 332.  That provision authorizes courts to “restrain violations” of the Federal Food, Drug, and Cosmetic Act, but is silent on the court awarding equitable relief as part of the injunction.  We will let you know what the Supreme Court decides.

    An historical note.  Over fifty-five years ago, on November 8, 1965, the Supreme Court decided a false advertising case entitled FTC v. Mary Carter Paint Co.  The Beatles were in their heyday, at least in terms of performing concerts in this country.  The Selma to Montgomery freedom marches had occurred earlier that year.  And alas, the Cleveland Browns had won their last championship less than one year earlier.  It is hard to believe that this ruling was probably the last case decided by the U.S. Supreme Court involving the scope and powers of the Federal Trade Commission’s Bureau of Consumer Protection relating to deceptive practices.  The Court’s decision in AMG will likely come down sometime between mid-March and the end of June.

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