Hyman Phelps & McNamara, P.C. is pleased to announce that Sara Koblitz has been promoted to Counsel at the firm.

Sara joined HPM in 2017 and advises clients on a broad range of FDA regulatory issues with a particular focus on Hatch-Waxman patent and exclusivity, biosimilars, and the Orange Book. Sara also counsels clients in various stages of product development and guides clients through applicable regulatory requirements with respect to applications and submissions, promotional issues and post-marketing requirements.  Sara’s full bio can be found here.

“Sara is an invaluable member of the firm and our clients rely on her expertise and judgment,” said HPM Managing Director J.P.Ellison.  “HPM is proud to recognize Sara’s significant contributions to the firm and its clients.”

Recently, the Drug Enforcement Administration (“DEA”) published a notice of proposed rulemaking (“NPRM”) that provides much needed clarity on the requirements for how emergency medical services handle controlled substances.  The NPRM would codify its regulations consistent with the Protecting Patient Access to Emergency Medications Act of 2017 (“the Act”).  Registering Emergency Medical Services Under the Protecting Patient Access to Emergency Medications Act of 2017, 85 Fed. Reg. 62,634 (Oct. 5, 2020). Electronic comments on the proposed rulemaking must be submitted, and written comments postmarked, on or before December 4, 2020.

The Act amends the federal Controlled Substances Act (“CSA”) allowing for a new DEA registration category of emergency medical services (“EMS”) agencies, establishing registration standards and controlled substance delivery, storage and recordkeeping requirements for EMS agencies.

Currently, EMS vehicles have generally obtained controlled substances pursuant to physician instructions under the hospital’s DEA registration.  An EMS vehicle owned and operated by a hospital handles controlled substances under the hospital’s registration and obtains controlled substances from the emergency room as an extension of the hospital pharmacy.  In the alternative, an EMS agency acts as the hospital’s agent under the hospital registration and the hospital supplies controlled substances to EMS vehicles.

Many EMS agencies utilize the ‘‘hub-and-spoke’’ model whereby they have a main, centralized location that manages satellite stationhouses located throughout an area to timely respond in medical emergencies.  DEA is proposing to allow EMS agencies to obtain a single registration in each state where they operate rather than requiring them to obtain a separate registration at every location within that state.  DEA also proposes to allow hospital-based EMS agencies to operate under the hospital’s registration to administer controlled substances without being separately registered.

The Act authorizes EMS agencies to designate unregistered locations where controlled substances could be delivered and stored, requiring registered EMS agencies to notify DEA at least 30 days before delivery.  DEA proposes requiring notification designated locations through the agency’s website.  (An EMS agency must still obtain a DEA registration for the location where it receives controlled substances from outside the agency).  An EMS agency that has identified designated locations to DEA may deliver controlled substances to the locations after notifying DEA unless DEA objects.

DEA is proposing to allow EMS agencies to identify stationhouses as designated locations.   Only an agency location meeting the definition of a stationhouse, i.e., an enclosed structure housing EMS vehicles in the state where the EMS is registered which are used for emergency response, can be a designated location.  A building housing public fire and rescue equipment constitutes a stationhouse and can be selected as a designated location by a DEA-registered EMS agency.

DEA is proposing to codify where registered-EMS agencies may store controlled substances.  Permissible locations include the agency’s registered and designated locations, as well as EMS vehicles.  The Act, and DEA’s proposed regulation, define EMS vehicles as ambulances, fire apparatus, supervisor trucks, and other EMS agency vehicles used to provide or facilitate emergency medical care, and that transport controlled substances to and from registered and designated locations.  Controlled substances can be supplied to, and stored in, EMS vehicles under the control of the consultant practitioner’s registration or hospital’s registration.  DEA proposes allowing registered EMS agencies to store controlled substances in EMS vehicles at the registered location, a designated location, traveling between those locations or responding to an emergency.

DEA proposes to require EMS agencies to maintain records of the EMS personnel whose state license authorizes them to administer controlled substances in compliance with state law.  DEA observes that as states have different requirements for the authority to handle controlled substances, maintaining records of employees authorized to handle controlled substances will assist DEA to identify the source of any diversion at EMS agencies.

Because EMS personnel may not have time after an emergency response to return to the stationhouse to restock their vehicle, DEA is proposing to allow nonhospital-based EMS agencies to receive controlled substances from a hospital.

DEA is proposing that EMS agencies maintain records at each registered and designated location where it receives, administers and otherwise disposes of controlled substances.  Delivery records must include controlled substance name, finished form, unit quantity in commercial containers, date, and agency location address where controlled substances are delivered.  EMS personnel must document each administration with drug, date and patient.  DEA notes that these requirements are necessary because EMS personnel lack independent authority to administer controlled substances.

DEA proposes that designated EMS agency locations notify the agency’s registered location within 72 hours of receiving controlled substances from a hospital for restocking an EMS vehicle following an emergency response.  EMS agencies operating under a hospital-based registration receiving restock from the hospital would be exempt from this requirement because the hospital would have a record of the controlled substances delivered to the EMS agency operating under the hospital’s registration.

Recognizing that EMS agencies have unique security concerns, DEA is proposing to implement physical security requirements for EMS agencies similar to requirements for practitioners.  DEA proposes to allow EMS agencies to store controlled substances in a securely locked, substantially constructed cabinet or safe that cannot be readily removed at a registered location, designated location or in an EMS vehicle.

DEA proposes to also allow EMS agencies to store controlled substances in automated dispensing system (“ADS”) machines.  An ADS machine is “a mechanical system that performs operations or activities, other than compounding or administration, relative to the storage, packaging, counting, labeling, and dispensing of medications, and which collects,

controls, and maintains all transaction information.” 21 C.F.R. § 1300.01.  An ADS machine at an EMS agency’s registered or designated location would serve as a storage container before controlled substances are placed into EMS vehicles, and would facilitate monitoring transactions.  Further, DEA proposes that an EMS agency can store controlled substances in an ADS machine if:

(1) The ADS machine is located at a registered or designated location;

(2) The agency does not allow any entity other than the registered agency to install and operate the ADS machine;

(3) The ADS machine cannot directly dispense controlled substances to an ultimate user; and

(4) The agency operates the ADS machine in compliance with state law.

While the Act allows for controlled substance deliveries between EMS registered and designated locations, DEA is proposing that deliveries to registered or designated locations can only be accepted by the agency medical director or a person the medical director designates in writing.  DEA is proposing to require the medical director or designated person receiving the controlled substances to maintain records with their signature, title, date and quantity received.

DEA proposes to allow EMS professionals of registered EMS agencies when providing emergency services to administer controlled substances outside the physical presence of the medical directors or authorizing medical professional under their state license.  EMS professionals outside the physical presence of a medical director or authorizing medical professional must have authority to administer controlled substances pursuant to a standing or verbal order issued and adopted by agency medical directors.

Agencies have given EMS personnel autonomy to administer controlled substances in emergencies by establishing standing orders.  Under the Act, a standing order is “a written medical protocol in which a medical director determines in advance the medical criteria that must be met before administering controlled substances to individuals in need of emergency medical services.” 21 U.S.C. § 823(j)(13)(M).  DEA proposes to incorporate that definition into its regulations.  The proposed regulation also allows standing orders developed by state authorities to be issued and adopted by an EMS agency medical director.  Only the medical director of an EMS agency has the authority to issue and adopt a standing order.  EMS agencies must maintain a record of the standing orders issued and adopted at their registered location.

In the absence of standing orders, EMS personnel can receive and administer under verbal orders.  A verbal order is an oral directive communicated directly to an EMS professional to contemporaneously administer a controlled substance to individuals in need of emergency medical services outside the presence of the medical director or authorizing medical professional.  21 U.S.C. § 823(j)(13)(N).  Authorizing medical professionals include emergency or other physicians, or other medical professionals (including advanced practice registered nurses or physician assistants) acting within the scope of their DEA registration whose practice under their state license includes authority to provide verbal orders.  21 U.S.C. § 823(j)(13)(A).

DEA is proposing consistent with the Act that an EMS professional can administer controlled substances outside of a practitioner’s presence when providing emergency medical services if authorized by state law and pursuant to a verbal order.  The authorization must be provided by a medical director or authorizing medical professional in response to an EMS professional’s request for a specific patient.

Of all scenarios for obtaining, administering and securing controlled substances within the CSA’s closed system, doing so by EMS agencies and personnel in emergency situations require the most flexibility.  The Act, and now DEA’s proposed regulations, provide adequate clarification and needed flexibility for EMS agencies in different scenarios to handle controlled substances in emergency situations without increasing risk that the drugs may be diverted.

Hyman, Phelps & McNamara, P.C. (“HP&M”) has been named the FDA Law “Law Firm of the Year” by the folks over at U.S. News & World Report, who teamed up with Best Lawyers for the 2021 “Best Law Firms” rankings.  We’re truly honored!  But the honors don’t stop there.  HP&M was also once again ranked as a “Tier 1” law firm in the area of “FDA Law” (both nationally and in Washington, D.C.).

“The 2021 rankings are based on the highest lawyer and firm participation on record, incorporating 8.3 million evaluations of more than 110,000 individual leading lawyers from more than 22,000 firms. . . .  This year we reviewed 15,587 law firms throughout the United States – across 75 national practice areas – and a total of 2,179 firms received a national law firm ranking,” according to U.S. News.  The “Best Law Firms” rankings are based on a combination of client feedback, information provided on the Law Firm Survey, the Law Firm Leaders Survey, and Best Lawyers peer review.

As we blogged about last week, DEA published its long-anticipated Notice of Proposed Rulemaking (“NPRM”) addressing suspicious orders of controlled substances.  The Proposed Rule is intended to (finally) “clarify” the procedures that DEA registrants must follow for what DEA now deems “orders received under suspicious circumstances” (“ORUCS”).  In particular, DEA sets forth exactly what registrants are supposed to report to DEA’s centralized reporting database if they determine, through the exercise of due diligence, that the order is indeed “suspicious” as defined in 21 C.F.R. § 1301.74(b).  DEA states that the reporting requirement is one of the five “closely related legal obligations contained in the CSA and DEA regulations,” relating to the obligation to identify and report suspicious orders of controlled substances.

DEA elaborates on the five “requirements” as follows: (1) The obligation to maintain effective controls against diversion; (2) to conduct due diligence; (3) to design and operate a system to identify suspicious orders for the registrant; (4) to report suspicious orders (the reporting requirement); and (5) to refuse to distribute controlled substances that are likely to be diverted into illegitimate channels (the shipping requirement).  DEA also notes that Congress’ inclusion of the phrase “may include, but not be limited to” in the definition of “suspicious order” as part of the Preventing Drug Diversion Act (“PDDA”) of 2018 clarified that an order for controlled substances may be “suspicious” for reasons of its size, pattern or frequency, including reasons “related to the customer selling the order.”  While this “clarification” is indeed welcome, it surely was not readily ascertainable from either the PDDA’s, or Section 1301.74(b)’s definition of “suspicious order.”  DEA’s suspicious order regulation itself had left registrants guessing on what exactly to report — and DEA second guessing those reports — for years.

Under the Proposed Rule’s clarified framework for reporting suspicious orders after their identification, registrants have two options: (1) immediately file a suspicious order report (and maintain a record of the same), or (2) conduct due diligence concerning the suspicious circumstances surrounding the ORUSC (and maintain a record of the same).

DEA states that all suspicious order reports must be entered in the DEA’s centralized database within a seven calendar day time period “upon discovering” a suspicious order.  Importantly, the reports must contain certain required information, as follows:

• The DEA registration number of the registrant placing the order
• The date the order was received
• The DEA registration number of the registrant reporting the suspicious order
• The National Drug Code number, unit, dosage strength, and quantity of the controlled substances ordered
• The order form number for Schedule I and II controlled substances
• The unique transaction identification number for the suspicious order, and
• What information and circumstances render the order actually suspicious.

Readers may remember that one year ago, on October 23, 2019, DEA announced the availability of the Suspicious Orders Report System (“SORS”) Online for reporting of suspicious orders, as required by the PDDA.  DEA made this announcement, however, without providing the industry any advance notice or opportunity for comment (likely because DEA was facing a statutory deadline under the PDDA to make this portal available).  Importantly, SORS Online established more than just an online reporting method because DEA also for the first time required registrants to provide a “reason code” in the electronic suspicious order report.  Now — a year later — it appears DEA is trying to put some context around its expectations for documenting the basis for reporting a suspicious order.

Notwithstanding this proposed “new” requirement, which seems extremely costly and burdensome if the registrant does not already have such an electronic data capture and reporting system in place, DEA states that reporting to the DEA centralized database “is estimated to impose no additional burden” on registrants.  Hmmmm.  DEA notes that it believes that it is further “reasonable to estimate virtually all affected registrants have information systems capable of completing, submitting, and retaining electronic suspicious order reports at minimum additional cost.”  However, DEA admits that there are 15,974 practitioners and NTPs that distribute pursuant to the DEA’s “5 percent rule” that would now be required to identify and report suspicious orders.  In our opinion, few of these entities have previously established comprehensive SOM policies and procedures as DEA is now requiring.  Our continued review of the NRPM also raises concerns that DEA significantly underestimates the Rule’s regulatory impact and financial burden. The regulatory impact and financial burden will be addressed in a subsequent blogpost.

DEA adds that it “welcomes any comments” regarding the cost of complying with the reporting requirement, especially for those registrants that may not have access to broadband internet access.  Interestingly, in continuing to address its understanding and belief this is not a significant burden on registrants, DEA also says reporting of this information is a “codification of content expected of current suspicious order reports or content subsequently requested by DEA if not reported in a suspicious order report.”  Again,  hmmmm.  This may also leave numerous registrants (and their counsel) scratching their heads, because DEA (in its regulations, guidance or even less formal communications) never before has articulated any expectation — clear or otherwise — concerning “what” suspicious order information must be reported.  It is our understanding that, contrary to DEA’s claim that this is the type of information DEA requested from registrants in follow-up communications, we know of few, if any, registrants that received follow-up communications from DEA concerning an earlier suspicious order report.  In any event, such DEA follow-up was likely quite rare relevant to the number of reports the Agency received.

The comment period for the proposed rule ends on January 4, 2021, so time is ticking if for those registrants that find some (or all) of the new requirements inappropriate or otherwise unworkable.   And, stay tuned for another post soon on what DEA wants to hear about in industry comments.

On November 5, the Maryland Federal District Court dismissed a Federal False Claims Act qui tam suit alleging that Forest Laboratories knowingly reported inflated best prices under the Medicaid Drug Rebate Program (MDRP), resulting in underpayment of rebates.  United States ex. rel. Sheldon et al. v. Forrest Laboratories, LLC et al. The case, in which the Department of Justice and numerous state attorneys general had declined to intervene, addressed the question whether discounts provided to different customers on a single unit of drug must be added together – or “stacked” – when determining best price.

The relator alleged that Forest provided rebates to both third party payors on one hand and purchasers (pharmacies and GPO members) on the other, so that a single unit of drug could be subject to both types of rebates.  The relator claimed that the statute, regulations, and CMS guidance unambiguously required Forest to add the rebates to different customers together in determining best price, because they all affected the price that Forest “actually realized” on a unit of drug.  The relator relied primarily on statements in the former version of the Medicaid Rebate Agreement and in CMS Manufacturer Releases from the 1990s that best price must be adjusted “if cumulative discounts, rebates, or other arrangements subsequently adjust the prices actually realized.”  Forest countered that best price aggregates only discounts to a single customer.

The Court first found that the language used by CMS to address cumulative discounts has not been clear or consistent, because the best price regulation initially published in 2007, unlike the former Medicaid Rebate Agreement or the Releases, required best price to be adjusted if cumulative discounts adjust prices “available from” – not “realized by” – the manufacturer.  (The 2007 regulatory text remains the same today.)  The Court went on to find that the statute, legislative history, regulations, manufacturer comments on rulemakings, and other sources demonstrate ambiguity, rather than unequivocal guidance on this point.  The court noted that the relator had not pointed to a single example where CMS had explicitly stated that manufacturers must aggregate discounts to different customers along the supply chain on a given unit.  Since Forest’s interpretation was found to be objectively reasonable, the Court decided that Forest’s best price reports could not qualify as objective falsehoods, and furthermore, that Forest could not have acted with the requisite knowing intent since it had not been warned away from its interpretation by CMS.

This lawsuit involved conduct that occurred before February 2016, when CMS amended its MDRP regulations.  The relevant text about cumulative discounts subsequently adjusting the price available from the manufacturer remains identical to the pre-2016 text, but the 2016 preamble did contain a discussion of “stacking” that was not considered by the Court in Forest.  Unfortunately, that discussion did not clear up the ambiguity regarding stacking.  CMS stated that “multiple price concessions to two entities for the same drug transaction” should be considered in best price, but then addressed only an example where a rebate paid to a PBM is designed to adjust prices at the pharmacy level and a discount is also provided to pharmacies.  81 Fed. Reg. 5170, 5253 (Feb. 1, 2016). In that scenario, it is not unreasonable to view the pharmacy as receiving two discounts on the same unit.  However, CMS did not address other situations, such as the one at issue in Forest, where discounts are given to two different customers and the discount to one does not affect the price to the other – e.g., a formulary discount to a third party payor and a discount to a GPO or pharmacy chain.  Therefore, ambiguity persists on the question of stacking.  The Forest case is the most recent in a long line of cases holding that a reasonable interpretation of an ambiguous statute or regulation is not actionable under the FCA.  After Forest, it will be especially difficult for the government or a relator to successfully prosecute an FCA claim alleging inflation of best price due to a failure to stack discounts.

The Priority Review Voucher (“PRV”) program is a powerful incentive to encourage sponsors to develop treatments for conditions that are not ordinarily priorities for industry, such as infectious diseases for which there is no significant market in developed nations (tropical disease) or rare pediatric diseases.  These vouchers can be sold and historically have been worth up to hundreds of millions of dollars.  As we explained back in May, Congress, in the 2016 Cures Act, added medical countermeasures to the list of available PRVs in an effort to incentivize development of FDA-regulated product to assist in the “event of a potential public health emergency.”  The catch is that a medical countermeasure (“MCM”) PRV is available only if the Department of Homeland Security (DHS)—in consultation with Health and Human Services (HHS)—issues a determination that the potential public health emergency is a “material threat” under 42 USC 247d–6b(c)(2).  A “material threat” is defined as a threat “sufficient to affect national security.”  Yet, even as the world is facing the biggest public health emergency it has seen since 1918, and even as products to treat COVID-19 have been declared “security countermeasures,”  DHS has not made such a determination for COVID-19, rendering them ineligible for a material threat MCM PRV.  At least, that’s what we thought until October 2020.

On October 22, 2020, FDA announced the approval heard round the world (or at least the country): Veklury (remdesivir), for use in adult and pediatric patients 12 years of age and older and weighing at least 40 kilograms (about 88 pounds) for the treatment of COVID-19 requiring hospitalization.  Buried at the end of that FDA press release, in a single sentence, FDA noted that the product had been awarded a material threat MCM PRV.  Such an award is . . . interesting.  When we checked in with DHS and HHS in April, they confirmed that COVID-19 had not been designated a material threat, and a Congressional Research Services Report from September 2020 explaining medical countermeasures for COVID-19 made no mention of COVID-19’s designation as a material threat.  Indeed, a search of Federal Register notices shows DHS and HHS’s announcement of a Material Threat Determination for Ebola and Anthrax, which appear in a list of designated material threats in April 2007 (though no Federal Register notice was released for the initial determination for Ebola in September 2006).  EUAs issued in the Federal Register for Ebola and Anthrax also specifically refer to related “material threat determinations.”  No similar announcement or EUA including such specific language was published for COVID-19.  Nor have we been able to locate any other announcements from DHS or HHS, and our follow-up inquiry to the agencies as to the date of the Material Threat Determination has yet to receive a response.  All of this raises the question of whether such a designation was ever formally made.

Though no law expressly requires the publication of a material threat designation, section 319F–2(c)(3)(B) requires HHS to make publicly available its assessment of the ongoing availability of appropriateness of specific countermeasures to address the “specific threats identified” under section 319F–2(c)(2)(A)(ii) – or “material threats.”  Though the provision allows the withholding of some information that may “reveal public health vulnerabilities” or is otherwise confidential under FOIA (like the existence of specific pending applications), such a publicly available assessment should at least provide notice that a Material Threat Designation has been issued.  Historically HHS announces its statutorily-mandated assessments in its annual Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) Strategic Implementation Plan, but a new version of that Plan has not been released since December 2017, precluding its utility for publicizing current material threat determinations.

As mentioned, COVID publicly has been declared a “security countermeasure” in the Federal Register since March 2020, but “material threats” under 319F-2(c)(2)(B) of the PHS Act are expressly distinct from “security countermeasures” under 319F-2(c)(1)(B).  If the “security countermeasure” declaration intended to suffice for a 319F-2(c)(2)(B) Material Threat Determination, HHS and DHS would not have stated back in April that “At this time, a Material Threat Determination (MTD) has not been issued for SARS-CoV-2 (COVID-19).”  Though there are some vague references to “material threat” in almost all of the Federal Register EUA announcements, nothing published since April suggests that HHS issued any formal Material Threat Determination under 319F-2(c).  Indeed, the language in EUAs related to “material threats” has not changed since April.  As such, even if a Material Threat Determination was made after April or May, it certainly wasn’t publicized.

And therein lies the real issue: As FDA explains in guidance, “Section 565A of the FD&C Act was designed to encourage development of new drug and biological MCMs, by offering additional incentives for obtaining FDA approval of certain MCMs.”   (After all, Congress did entitle the provision “Priority review to encourage treatments for agents that present national security threats,” and the statute itself refers to a PRV as an “incentive program” and a “supplement” to “any other provisions . . . that encourage the development of medical countermeasures.”)  But if a “material threat determination” – necessary to obtain that incentive – is not public, how can such a material threat Priority Review Voucher encourage development?  It’s unclear how a reward can serve as motivation when it remains a secret.

And there is no reason to believe that this is a problem that will be limited to COVID treatments, as the statute does not mandate the publication of the Material Threat Determination in the Federal Register; rather, the statute requires only a vague “assessment,” which apparently HHS has not published in three years.  With no way to request a Material Threat Determination and no knowledge of a preexisting Material Threat Determination, small drug development companies—particularly those that focus on rare diseases—have no incentive to even consider whether a drug could be repurposed to treat a material threat or whether exploring development of a material threat could provide any return on investment.

Further, FDA requires sponsors to request a material threat MCM PRV at time of application submission.  This suggests that FDA expects some sort of announcement, such as a published Material Threat Determination, to be public.  Otherwise, how could a sponsor know to request the MCM PRV?    Perhaps FDA informs a sponsor of a Material Threat Determination at a meeting, but, if that were the case, the material threat MCM PRV does not serve as an incentive for other companies to develop treatments, as Congress clearly intended.  Reviewing FDA’s Material Threat MCM PRV Guidance, it is apparent that the Agency expected HHS to publicize “identified material threat agents that may qualify an MCM application for a PRV,” and it even directs sponsors to reach out to HHS for confirmation during development.  If the goal is to broadly encourage development of such therapies, informing sponsors of a material threat determination at the soonest opportunity would seem to be the most efficient approach to achieving that objective

Regardless, now that the world knows that a Material Threat Designation has been made, and because a PRV is not limited to the first treatment for a Material Threat MCM, other sponsors have the opportunity to obtain such a voucher.  As long as an additional treatment is a new active moiety and otherwise eligible for Priority Review – it’s for a “Serious Condition” and demonstrates potential to be a significant improvement in safety or effectiveness – other Material Threat MCM PRVs should be available for COVID-19 treatments.  But those companies who are planning to invest in COVID-19 treatments are likely already doing so, rendering our new-found knowledge of the Material Threat Designation relatively useless for purposes of encouraging innovation.  Perhaps, as we said in May, if DHS and HHS had made an early Material Threat Determination and actually publicized it—whenever it may have been issued—maybe some of the companies that really could have used the incentive to develop a treatment for COVID-19 would have jumped into the game.

Moreover, the Material Threat Designation has potentially created a different issue that companies should think about: dilution of the incentive.  Many companies are investing in COVID-19 therapeutic products.  If all or most of them are eligible for a PRV, the resulting supply of PRVs on the market may be expected to decrease the value of all PRVs—even those unrelated to COVID-19—such as those awarded for the approval of a drug to treat an infectious disease for which there is no significant market in developed nations (tropical disease), or a rare pediatric diseases.  Much of the value of a PRV is that it can be sold as a commodity; an oversupply would inherently decrease its market value.  Without significant market value – especially for small companies that may not have other products in the pipeline to utilize the PRV internally – will a PRV still serve as incentive?

In sum, the government’s approach to the material threat MCM PRV does not seem to further Congressional intent to provide incentives for the development of drugs to treat material threats.  And, to be clear, the problem with the lack of Material Threat Determination publication is bigger than COVID.  Veklury just put a spotlight on the problem, which ultimately is whether an incentive program can really function as an incentive if important information is not public.

The Alcoholic Beverage Labeling Act of 1988 (ABLA) directs the Treasury Department’s Alcohol and Tobacco Tax and Trade Bureau (TTB) to notify Congress if science shows that the required warning statement on alcoholic beverages must be updated.  Specifically, the ABLA provides that TTB “shall promptly report such information to the Congress together with specific recommendations for such amendments to this subchapter as the Secretary determines to be appropriate and in the public interest.”  Currently, the ABLA and TTB’s regulation require the following warning statement:

GOVERNMENT WARNING: (1) According to the Surgeon General, women should not drink alcoholic beverages during pregnancy because of the risk of birth defects. (2) Consumption of alcoholic beverages impairs your ability to drive a car or operate machinery, and may cause health problems.

On October 21, several public health and consumer group advocates filed a Petition with TTB requesting that the warning be updated.  Petitioners assert that there is consensus that alcohol consumption is linked to cancer.  Among other things, they cite statistics from the American Cancer Society indicating that, in 2014, 6.4% of all cancers in women and 4.8% of all cancers in men were linked to alcohol consumption.  They claim that drinking alcohol is the third most important modifiable cancer risk in women and the fourth in men.

In light of this evidence, they request that TTB report to Congress that available scientific information (accrued since 1988) shows that alcohol consumption causes cancer.  Petitioners request that TTB recommend that Congress amend the current health disclosure to state:

GOVERNMENT WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.

In addition, they request that TTB report to Congress the available scientific evidence in support of rotating health disclosures, as opposed to a single static warning. They suggest that the new requirements would require rotating the three different warnings, i.e.,

(1) GOVERNMENT WARNING: According to the Surgeon General, women should not drink alcoholic beverages during pregnancy because of the risk of birth defects.

(2) GOVERNMENT WARNING: Consumption of alcoholic beverages impairs your ability to drive a car or operate machinery and may cause health problems.

(3) GOVERNMENT WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.

Welcome to the latest edition of HP&M’s monthly wrap up of food, beverage and supplement news, including regulations, guidances, events, and whatever else is catching our eye.

Food & Beverage

• Are your cows happy? Check out Karin’s blog post on corporate social responsibility claims.
• Is it a Sugar? Riëtte and Ricardo wrote about FDA’s request for information pertinent to nutrition labeling of sugars that don’t act like traditional sugars.
• Cell-Based Meat and Seafood Labeling: The North American Meat Institute and the Alliance for Meat, Poultry and Seafood Innovation joined forces to back a mandatory labeling requirement for cell-based meat and poultry products. Meanwhile, FDA published a constituent updateand Federal Register notice asking for comment by March 8, 2021 on a number of questions pertaining to labeling of “foods comprised of or containing cultured seafood cells.”  More details can be found in Ricardo’s blog post on the notice.
• Some processes preclude a “100% natural” claim. The National Advertising Review Board recommended that GSK discontinue a “100% natural” claim for a product consisting solely of wheat dextrin because consumers “would likely conclude that the manufacturing exceeded minimal processing” compatible with that claim. The panel held out the possibility that a qualified use of “natural” might be supportable.
• Gluten Free Alcoholic Beverages: TTB has updated its guidance on gluten content statements for wines, distilled spirits, and malt beverages in response to the August 2020 FDA final rule on verifying “gluten-free” labeling claims for fermented or hydrolyzed foods.
• The Incredible, Edible Egg: The HAACP and sanitation SOPs for egg producers final rule was just published in the Federal Register.
• Take Me to the Pilot: The FDA is launching a voluntary pilot program to evaluate alignment of private third-party food safety audit standards with the food safety requirements in Preventive Controls for Human Food and the Produce Safety rules.
• Ingredient safety assessments under fire: A late September 2020 citizen petition asks FDA to enforce the FDC Act requirement regarding the cumulative effect of food substances as part of safety assessment. See Riëtte’s blog post for more details.
• Boring but important: FDA is issuing guidance establishing a U.S. Agent Voluntary Identification System (VIS) for food facility registration, which is intended to be used in conjunction with the food facility registration database to streamline and expedite the U.S. agent verification process.
• Also boring but important: Don’t forget to renew your food establishment registration.

Supplements

• DMAA out. The Supreme Court rejected a request to review a case involving the legality of DMAA (1,3-dimethylamylamine), a once-prevalent ingredient marketed in sports supplements, leaving in place a 2019 ruling by the 11^th Circuit – which you can read about in our blog posting on that ruling.
• Branched chain amino acids? Natural Products Association Petitions FDA on Nutrition Facts and Supplement Facts Labeling Regulations Pertaining to Caloric Values.
• Challenge to DEA’s Clarification of the Farm Bill: Should intermediates containing in excess of 0.3% THC that have been derived from hemp be regulated as controlled substances by DEA? Not if plaintiffs in these lawsuits

Some Things We Are Monitoring:

• 2020-2025 Dietary Guidelines: Expected by year end.
• A hemp case where HIA and RE Botanicals filed a lawsuit against the DEA in the D.D.C., seeking a declaration that the definition of hemp in Section 1639o, includes “intermediate hemp material” (IHM) and “waste hemp material” (WHM) and that the THC in IHM and WHM is not a controlled substance. You can read about that litigation in our colleagues’ blog posting.
• Supreme Court oral arguments on December 1 on the application of the Alien Tort Statute to ethical sourcing claims in Nestlé v. Doe I and Cargill v. Doe I.
• Interesting perspectives on the possible direction of the FTC’s consumer protection mission under a Biden administration, particularly when it comes to consumer redress and civil penalties.

Upcoming Events:

• FDA public meeting on ‘‘CBD and Other Cannabinoids: Sex and Gender Differences in Use and Responses.” November 19, 2020
• FDA public meetings on the proposed rule for “Requirements for Additional Traceability Records for Certain Foods.” November 6, 2020, November 18, 2020, and December 2, 2020.
• The Center for Research on Ingredient Safety at Michigan State University will host a virtual CBD Science Symposium on November 11-12. Ricardo will present a primer on key issues in the regulation of hemp-derived CBD.

Today, more than two years after Congress passed the Preventing Drug Diversion Act of 2018 (PDDA) and after more than a decade of industry requests for regulations addressing the Drug Enforcement Administration’s (DEA) interpretation of suspicious order requirements under 21 C.F.R. § 1301.74(b), DEA has finally spoken, with its proposed rule “to revise its regulations relating to suspicious orders” and “clarify the procedures a registrant must follow” to identify and report suspicious orders.  Suspicious Orders of Controlled Substances, Notice of Proposed Rulemaking, 85 Fed. Reg. 69,282 (Nov. 3, 2020).

DEA’s New Definitions

DEA’s proposed rule establishes three new definitions: (1) “orders received under suspicious circumstances (ORUSC),” (2) “order,” and (3) “due diligence.”  DEA’s existing regulations only define a “suspicious order,” which the PDDA codified in 2018 as including orders, or a “series of orders” of unusual size, pattern or frequency.  DEA’s new definition of an “order received under suspicious circumstances” is essentially a prequel to a suspicious order determination permitting registrants to identify an order as “potentially suspicious.”  The regulatory definition of ORUSC is critical for DEA to establish the two-option order review framework summarized below.

DEA defines the term “order,” to standardize what is a controlled substance order, which definition is far broader than considered before.  DEA proposes the following “order” definition:

[A]ny communication by a person to a registrant proposing or requesting a distribution of a controlled substance, regardless of how it is labeled by the person or the registrant, and regardless of whether the distribution is made by the registrant, except that simple price/availability inquiries, standing alone, do not constitute an order.

(Emphasis added.)

DEA’s definition raises questions when one considers the logistical and financial differences in the way that the regulated industry engages in distribution of controlled substances.  And, speaking of the “regulated” industry, DEA clarifies that proposed suspicious order reporting requirements will apply to practitioners when such distributions are made pursuant to the five percent rule.  The rule also will apply to “all registrants authorized to distribute controlled substances: distributors, manufacturers, importers, pharmacies, hospital/clinics teaching institutions, practitioners, Mid-level Practitioners (MLP), MLP- Ambulance Services, Researchers, Analytical Labs and NTPs,” but not reverse distributors.

The Two-Option Framework for Orders

After years of telling the regulated industry that it would not approve any particular method for identifying and reporting suspicious orders, DEA is now establishing a “two-option framework.”  The NPRM states that, upon receipt of an ORUSC, registrants will have a choice: (1) immediately file a suspicious order report through the DEA centralized database, decline to distribute the order, and maintain a record including any due diligence conducted related to the suspicious order; or, (2) before distributing pursuant to the order, conduct due diligence to investigate each suspicious circumstance surrounding the ORUSC, and maintain a record of its due diligence regarding the ORUSC.  The two options proposed by DEA are consistent with the D.C. Circuit’s 2017 Masters Decision and a recognition that, in the absence of sorely needed guidance from DEA over the past decade, most manufacturers and distributors have adopted some variation of these two options, otherwise known as a “Flag and Terminate,“ or  “Order of Interest” systems.

In regard to the second option, the DEA is establishing a deadline of seven calendar days for the registrant to determine if all of the suspicious circumstances for the held order have been resolved.  If the registrant is able to resolve all suspicious circumstances, then the order is not considered a suspicious order.  The registrant must maintain a record of its due diligence (thus likely leaving registrants’ due diligence subject to DEA scrutiny and second-guessing in the future).

Due Diligence Requirements

DEA defines its expectations for “due diligence” that a registrant must follow — within a seven calendar-day time period — before clearing an order to ship.  The expansive definition of “due diligence” includes: a “reasonable and documented investigation” and “examination of all facts and circumstances.”  And, concerning another “broad” definition, DEA’s new regulation will require the following concerning the system to identify suspicious orders:

In addition, the system shall be designed and operated to identify suspicious orders based on facts and circumstances that may be relevant indicators of diversion in determine whether hat person (or a person submitting an order) is engaged in, or is likely to engage in the diversion of controlled substances.

The failure to conduct sufficient due diligence has been at the heart of a number of civil and criminal settlements, and litigated cases over the years.  It will be interesting to see how these new requirements compare to already well-established industry procedures.  For example, DEA states that, “regarding recordkeeping, the proposed rule would require more than just a ‘check the box’ type of documentation.”  DEA also footnoted “rigid formulas” (using the terms “algorithm,” “blocked,” “flagged,” “held,” “order of interest,” “pended,” or “threshold”) that may not identify suspicious orders.  The new rule instead would require the registrant’s “record” to include:

(1) how the registrant handled such orders;

(2) what information and circumstances rendered the order actually or potentially suspicious;

(3) what steps if any the registrant took to investigate the order;

(4) if the registrant investigated the order, what information it obtained during its investigation;

(5) where the registrant concludes that each suspicious circumstances had been dispelled the specific basis for each such conclusion.

Of course, the significant irony here is that the rulemaking comes more than 15 years since DEA first announced its “Distributor Initiative,” which resulted in hundreds of millions of dollars in civil penalties, administrative suspensions and revocations of registrations, and several criminal charges — all based on DEA’s claims that the industry failed to comply with the requirement to identify and report suspicious orders.  Like the play, the regulated industry has been waiting for guidance from DEA concerning what “is” a suspicious order, other than an order of unusual size, pattern or frequency; and what to do about a suspicious order once detected.  As a result of its waiting, industry has engaged in all sorts of philosophical (and likely quite expensive) interpretations of DEA’s vague order monitoring requirements.  And while waiting, registrants have moved forward developing policies, procedures and elaborate monitoring systems without clear guidance from DEA as to its expectations.  Industry generally relied instead on two DEA “guidance” letters to industry dated in 2006 and 2007, and two cases referenced in the NPRM, Southwood and the fairly recent Masters decision, in developing “systems” to report to the registrant orders of unusual size, frequency and pattern.

More to Come

The NPRM provides additional background and detail as to how DEA arrived at the proposed rule, which will be the subject of further posts in the coming days, including, but not limited to, a post on the content of reports that must be submitted to DEA once an order is deemed suspicious, and a  post on industry comments on the proposed rule.  So, while the wait is over, we are just beginning another act in DEA long-running suspicious order saga.

Identification of and comparison to a Reference Listed Drug (“RLD”) and Reference Standards (“RS”) are the lynchpin of generic drug development and approval.  It’s therefore no surprise that, upon significantly updating the Orange Book in January 2017, FDA dedicated an entire guidance to fundamental definitions and procedures relating to RLDs and RSs.  Now, on the 40th anniversary of the Orange Book, FDA has updated and finalized this guidance, formally titled Referencing Approved Drug Products in ANDA Submissions, as part of its ongoing Drug Competition Action Plan.

Admittedly, very little has changed between the draft and final versions of the guidance Referencing Approved Drug Products in ANDA Submissions.  Subtle changes dominated, including a shift in the language used to discuss ANDAs approved under section 505(j): the draft guidance generally referred to ANDAs as drugs that are “the same” as their RLDs while the new version chose the much more precise word, “duplicates.”  Given that FDA has shifted its interpretation of the PDUFA exception for “same product as another product” from therapeutic equivalence to pharmaceutical equivalence, it could be that the use of “duplicate” rather than “same” was intended to avoid revisiting discussions of whether same drug, in this case, means therapeutic equivalents or pharmaceutical equivalents.  Regardless, this choice of language makes it very clear when FDA is referring to true ANDAs rather than suitability petition ANDAs or pharmaceutical equivalents approved as 505(b)(2) NDAs.

The most notable change in the guidance document is practical.  Previously, sponsors seeking designation of an additional RLD or RS were required to submit a Citizen Petition; a Controlled Correspondence could be used for such a request only when no RLD or RS was designated.  Because, unless a Citizen Petition is subject to Section 505(q) of the FDC Act, FDA responds at a snail’s pace, Citizen Petitions for new RLDs or RSs languished for years.  Now, the final guidance directs all requests for new RLDs and RSs through the Controlled Correspondence pathway, subjecting them to GDUFA response deadlines of 60 days for non-complex questions and 120 days for complex questions.  Theoretically, designation of RLDs and RSs should not be complex, but even if such requests are considered complex, a 120 day response timeline is significantly preferred to no discernable timeframe.  A question remains, however, of how and when FDA will deal with the many outstanding Citizen Petitions requesting a new RLD or RS, particularly because Controlled Correspondence GDUFA goals do not apply when the Controlled Correspondence is related to a pending Citizen Petition; in such a case, the GDUFA timeline starts only after FDA has responded to the Citizen Petition in question.

There are some other small but notable changes in the final version of the guidance.  In the final version, FDA explains that it can move a listed drug product to the Discontinued Section of the Orange Book if the “listed drug is not available for sale.”  Previously, FDA would only move a listed drug to the Discontinued Section after an applicant notifies FDA that it is withdrawing the listed drug from sale or if FDA determines that the listed drug has been withdrawn; the final guidance appears to change the policy so that FDA can merely determine that a product is “not available for sale.”  Whether this means that FDA will move a product of its own volition based on an inability to obtain the product on the open market is yet to be seen, but it certainly seems as though FDA is giving itself more leeway to proactively move products to the Discontinued List.  Similarly, FDA previously had stated that it would select a new RS based, among other elements, on “units sold,” but the final guidance revises this factor to “commercial data,” which, again, provides FDA more flexibility to interpret the term “commercial data” so that it is not bound to select an RS based specifically on “units sold.”

FDA included a few other revisions.  The final guidance also notes that authorized generics can be used as an RS, but suggests that additional documentation may be required; sponsors are directed to contact Office of Generic Drugs for more information.  The guidance suggests that all in vitro testing be performed in the RS, even though not specifically required under FDA regulations.  And, even though the 2017 guidance made clear that only NDAs approved under 505(c) are eligible as RLDs, the final version made it expressly clear that ANDAs cannot serve as RLDs (so please stop asking!).

In sum, the revised guidance isn’t game changing, but the procedural elements should help facilitate the designation of additional RLDs or RSs.  The little changes throughout will likely have minimal effect, but to the extent that they do, they provide FDA more flexibility than the draft version.  Regardless, both versions are certainly helpful for generic manufacturers navigating the generic drug approval system to do what they do best – making copies.

We have a free Election-eve presentation for you to download!  On October 28th, 2020, Hyman, Phelps & McNamara, P.C. Director Jeffrey K. Shapiro presented a webinar, titled “The Potential Life Sciences Implications of the Election.”  Mr. Shapiro explored the role politics plays at FDA and analyzed the potential impact of upcoming U.S. presidential election, with a special focus on the medical device industry.  It was an engaging discussion with lots of questions at the end.  MedMarc has now made the entire webinar available for free download in order to allow a broad audience to access it.  You can access the webinar at either of these places: Landing page or YouTube.

Companies are embracing corporate social responsibility (CSR) more and more; it is a way for companies and brands to incorporate the company’s values into their business model, and engage with customers and employees on a different level. It is not without risk, however, and our readers should be cognizant of the risks when the company’s values make their way to their product labels – whether it’s food, cosmetics, personal care products, or any other product for sale.

What does “sustainable” mean, anyway?

If you were to ask me five years ago what “sustainable” meant, I would have given you some response that likely included the words “environment” and “recyclable”.   Today, a quick Google search shows “sustainable” encompasses the management of environmental, social and financial demands and concerns to ensure responsible, ethical and ongoing success of a company. That is a whole lot wrapped into one word, a great deal of which is the subject of litigation.  It encompasses recycling and biodegradability (see FTC Green Guides, the EPA’s guidance, and more and more state laws), fair trade, animal welfare claims (happy cows, anyone?), ethical sourcing, child and slave labor (on the Supreme Court docket, oral arguments on December 1, 2020), worker’s rights, fair labor practices, and responsible land management, among many other things.  Given the breadth of concepts, and the importance that companies and consumers are placing on these types of claims, what should companies consider when conveying these concepts on their product labels?

The “reasonable consumer”:  While the marketing and advertising departments may focus on millennials or the target demographic du jour, you should keep the “reasonable consumer” front of mind.  The “reasonable consumer” is sometimes the recipient of scorn (the lack of fruit in Froot Loops), but is the standard that governs whether a label claim is misleading.

Location, location, location.  Any self-respecting HGTV binge watcher knows location matters.  Regulatory lawyers know the same thing.  CSR statements on product packaging may increase a company’s risk of litigation, as courts may presume that consumers relied on those statements when pulling products from the store shelves.

Go beyond the label.  Statements on websites may also present some risk, in particular if there are online sales.  Adding disclaimer language with classic “waffle” words, like “should,” “expect,” or “endeavor” may help to keep the CSR statements aspirational.  But do know that courts are likely to review a claim in context with all the other things on a label – as well as things off the label, like advertising and the company websites.

Do your research.  This cannot be emphasized enough. Understand how that “reasonable consumer” will interpret the claims on your label and your website. Be familiar with the CSR statements on the company websites, public filings, and other public statements.  Know what words are defined in regulations, and more importantly, what words are not defined.  Know what terms have been the subject of litigation. Know everything about any third party “seals of approval” and what they may – or may not – cover.

Do even more research.  Talk to your supply chain experts.  Know where your ingredients come from.  Find out where the fish are caught, where the cows are raised, where the mica and cobalt are mined.  Know where the ingredients are produced, and whether the risk of labor abuse is high. You want to know more about your product and your claims than anyone else.

As we previously reported, FDA was petitioned to exempt allulose, a monosaccharide, from being included as a carbohydrate, sugar, and added sugar in the Nutrition Facts box, as well as recognize that the number of calories for this monosaccharide is less than the 4 calories per gram used for traditional sugars.  In response, FDA issued a draft guidance, which was finalized on  Oct. 16.  The final guidance informs manufacturers that the Agency plans to exercise enforcement discretion regarding the requirement to include allulose in the amount of total sugars and added sugars, and for the use of 0.4 calories per gram of allulose when calculating calories for purposes of nutrition labeling.  However, allulose must be included in the amount of total carbohydrates.

On the same day, FDA announced that it would be issuing a request for information regarding the nutrition labeling of “sugars” (i.e., mono- and di-saccharides) that are metabolized differently than “traditional sugars,” and thus do not provide the same amount of calories per gram (traditional sugars provide 4 cal/g), do not cause an increase in blood glucose and insulin upon consumption, and are not associated with tooth decay.  FDA has received requests from industry to treat these “non-traditional” sugars, such as allulose, D-tagatose and isomaltulose differently from “traditional sugars” for purposes of nutrition labeling.  As mentioned above, FDA has decided to exercise enforcement discretion for allulose, and a petition to do the same for D-tagatose is pending.

FDA asks for information about several topics, including:

1. General information about sugars that are metabolized differently than traditional sugars.
2. Should the non-traditional sugars be included in total sugars and added sugars for purposes of nutrition labeling and, if yes, how should the amount be corrected for the difference in metabolic effects?
3. Should FDA adjust the % Daily Value for “added sugars,” using the caloric value of the non-traditional sugar?
4. Should FDA allow inclusion of the non-traditional sugars in the Nutrition Facts box similar to sugar alcohols?

The answers to these questions could carry significant implications for nutrition labeling of foods that contain non-traditional sugars, and thereby affect the formulation of such foods.

Comments may be submitted until Dec. 18, 2020.

The medtech industry has significantly changed during the Trump administration’s last four years. FDA processes are streamlined, the medical device excise tax repealed, and the Senate is in the process of confirming a third Supreme Court nominee. The industry also rapidly responded to the unprecedented COVID-19 health crisis.

What changes are on the horizon for the medtech industry after the November 3rd election, whether with another Trump administration or a Biden administration?  On Wednesday, October 28th, 2020, from 2:00 – 3:00 p.m. ET, Hyman, Phelps & McNamara, P.C. Director Jeffrey K. Shapiro will present at a webinar, titled “The Potential Life Sciences Implications of the Election.”  Mr. Shapiro will cover the upcoming U.S. presidential election and its possible ramifications for the medical device industry.

You can register for this free webinar here.

Genetics and genomics are becoming crucial to clinical care. As the “precision medicine” revolution spreads, cancer treatment, rare disease diagnosis, and cardiac care increasingly utilize genomics. Unfortunately, law and policy lag behind science, and the law governing genomics remains unclear – which means the time is ripe for analysis and thoughtful recommendations.

On Wednesday, December 2, top experts from Harvard Medical School, Columbia University, Vanderbilt University, the University of Minnesota, and other leading genomics and regulatory institutions will convene online to tackle these issues. Hyman, Phelps & McNamara PC is co-hosting this conference on “LawSeq^SM: Facing the Legal Barriers to Genomic Research & Precision Medicine.” Join us to discuss pressing legal and policy issues in genomic research and clinical care; FDA regulation of genomic devices, software, and algorithms; and uses of genomic data. Speakers include Gail Javitt, JD, MPH, from Hyman Phelps; Mark Barnes, JD, LLM, from Ropes & Gray; Alberto Gutierrez, PhD, and Elizabeth Mansfield, PhD, both formerly at FDA; Wendy Chung, MD, PhD, from Columbia University; Barbara Bierer, MD, from Harvard Medical School; and Ellen Wright Clayton, MD, JD, from Vanderbilt University. An agenda and more information is available here. This free conference will offer general CLE credits for New York, California, Illinois, and Minnesota.

Register now to attend. The event is presented by the Consortium on Law and Values in Health, Environment & the Life Sciences at the University of Minnesota in collaboration with Ropes & Gray, LLP, Hyman, Phelps & McNamara PC, and Vanderbilt University Medical Center. This conference grows out of an NIH-funded grant on “LawSeq^SM: Building a Sound Legal Foundation for Translating Genomics into Clinical Application” based at the University of Minnesota and Vanderbilt University Medical Center, in collaboration with a Working Group of national experts. For more information on “LawSeq^SM,” visit here.