Attorney East Hampton

By Kurt R. Karst —

If your 2020 FDA BINGO card included the end to FDA’s Unapproved Drugs Initiative, then, BINGO!  Late last Friday, the Department of Health and Human Services—but not FDA—announced a forthcoming Federal Register Notice withdrawing both the 2006 (Docket No. FDA-2003-D-0030) and 2011 (Docket No. FDA-2011-D-0633) versions of FDA’s guidance document/Compliance Policy Guide (“CPG”), titled “Marketed Unapproved Drugs – Compliance Policy Guide Sec. 440.100, Marketed New Drugs Without Approved NDAs or ANDAs.”

According to the Notice and a Frequently Asked Questions document, “although [the CPGs] originated with the laudable goal of generating more clinical data about unapproved drugs, [they] are linked to prescription drug price increases and shortages.”  That alleged link comes from the results of a 2017 study published in the Journal of Managed Care and Specialty Pharmacy (“JMCP”), titled “The FDA Unapproved Drugs Initiative: An Observational Study of the Consequences for Drug Prices and Shortages in the United States.”  Another, more recent 2020 analysis also alleged prices increases as a result of FDA’s Unapproved Drugs Initiative.

It seems like it was just yesterday that we announced FDA’s September 2011 decision to ramp up enforcement on marketed unapproved drugs with the Agency’s revision to the 2006 Marketed Unapproved Drugs CPG, which is part of the Agency’s broader Unapproved Drugs Initiative.  And now it appears that it is on its way to the ash heap history.  (Though folks should keep in mind that someone’s trash is another’s treasure.  After all, the new administration may decide to reverse course.)

By way of background (and only some background, as the Marketed Unapproved Drugs CPG is rooted in the entirety of FDA law history), for a drug to be legally marketed in the United States, generally it must be approved by FDA as safe and effective for its intended use or comply with an FDA Over-the-Counter (“OTC”) drug monograph.  However, as a result of various changes to the law over the last 100+ years, certain drug products are marketed without approval.  FDA permits, subject to the Agency’s “enforcement discretion,” the marketing of certain unapproved drugs that are neither approved by FDA nor marketed under an OTC drug monograph.  They are, with some exceptions, considered “illegally marketed drug products,” but FDA, for myriad reasons, has generally not opted to take enforcement action against them.

The 2011 Marketed Unapproved Drugs CPG clarified FDA’s approach to prioritizing enforcement actions and exercising enforcement discretion with respect to marketed unapproved drug products.  For products marketed on or prior to September 19, 2011, FDA applied a historical risk-based enforcement approach.  FDA’s risk-based enforcement approach placed higher priority on actions involving unapproved drugs in the following categories:

• Drugs with potential safety risks;
• Drugs that lack evidence of effectiveness;
• Health fraud drugs;
• Drugs that present direct challenges to the new drug approval and OTC drug monograph systems;
• Unapproved new drugs that violate the FDC Act in other ways; and
• Drugs that are reformulated to evade an FDA enforcement action.

Unapproved drugs introduced to the market after September 19, 2011, have been subject to immediate enforcement action.  FDA stated in the 2011 Unapproved Drugs CPG that:

The enforcement priorities and potential exercise of enforcement discretion discussed in [the Unapproved Drugs CPG] apply only to unapproved drug products that are being commercially used or sold as of September 19, 2011.  All unapproved drugs introduced onto the market after that date are subject to immediate enforcement action at any time, without prior notice and without regard to the enforcement priorities set forth below.  In light of the notice provided by this guidance, we believe it is inappropriate to exercise enforcement discretion with respect to unapproved drugs that a company (including a manufacturer or distributor) begins marketing after September 19, 2011. [(Emphasis added)]

Although FDA states in the Unapproved Drugs CPG that “any product that is being marketed illegally is subject to FDA enforcement action at any time,” there is a general exception to this policy for marketed unapproved drugs subject to an ongoing proceeding under the Drug Efficacy Study Implementation (“DESI”) program.  There are very few pending DESI proceedings under the DESI program, which started nearly 50 years ago.  FDA explains this exception in the Unapproved Drugs CPG as follows:

Some unapproved marketed products are undergoing DESI reviews in which a final determination regarding efficacy has not yet been made.  In addition to the products specifically reviewed by the NAS/NRC (i.e., those products approved for safety only between 1938 and 1962), this group includes unapproved products identical, related, or similar [(“IRS”)] to those products specifically reviewed (see 21 CFR 310.6).  In virtually all these proceedings, FDA has made an initial determination that the products lack substantial evidence of effectiveness, and the manufacturers have requested a hearing on that finding.  It is the Agency’s longstanding policy that products subject to an ongoing DESI proceeding may remain on the market during the pendency of the proceeding.  See, e.g., Upjohn Co. v. Finch, 303 F. Supp. 241, 256-61 (W.D. Mich. 1969). [(Emphasis added)]

In addition, some companies market drug products without approval under the premise that they are so-called “grandfathered” drugs, and, therefore, are not “new drugs” subject to the FDC Act’s approval requirements.  To qualify for exemption from the statutory “new drug” definition, a drug product must have been subject to the Federal Food and Drugs Act of 1906 prior to the enactment of the FDC Act on June 25, 1938, and at such time its labeling must have contained the same representations concerning the conditions of its use.  See FDC Act § 201(p)(1).  Thus, for FDA to determine that a drug product is not a new drug under the grandfather exemption, the following two questions must be answered affirmatively:

1. Was the drug product marketed between January 1, 1907 (the effective date of the 1906 Federal Food and Drugs Act) and June 25, 1938?; and
2. Is the drug product at issue the same drug product that was marketed between January 1, 1907 and June 25, 1938, and does its labeling describe the same conditions of use?

Further, a drug product is not a “new drug” if: (1) its composition is such that the drug product is Generally Recognized As Safe and Effective (“GRASE”) by qualified experts under the conditions of use for which it is labeled; and (2) it has been used “to a material extent or for a material time under such conditions.”  See Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609, 631 (1973); Premo Pharmaceutical Labs., Inc. v. United States, 629 F.2d 795, 801 (2d Cir. 1980).

Both of these grandfathered drug exemptions have been construed narrowly by courts and FDA.  The burden of proof falls on the party seeking grandfathered status to prove the drug qualifies for such status, and that showing may be difficult to make.  In a 2010 district court decision, the court explained:

Unless the evidence produced by plaintiffs establishes that there have been no changes whatsoever in the formulation, dosage form, potency, route of administration, indication for use, or intended patient population for their 20 mg/ml morphine sulfate oral solution since 1938, plaintiffs’ drug does not qualify for the 1938 grandfather clause exemption. . . .  Plaintiffs admit that they have only been marketing their drug for the past five years and have failed to produce any pre-1938 labeling for their drug.  Thus, it is impossible for plaintiffs to demonstrate that their drug’s “labeling contained the same representations concerning the conditions of its use” in 1938 that it presently contains.

Cody Laboratories, Inc. v. Sebelius, No. 10-DC-00147-ABJ, 2010 WL 3119279 at *13 (D. Wyo. filed July 26, 2010).  Further, FDA has stated, “the Agency believes it is not likely that any currently marketed prescription drug product is grandfathered or is otherwise not a new drug.  However, the Agency recognizes that it is at least theoretically possible.”  Unapproved Drugs CPG at 12 (italics in original).

According to the forthcoming Federal Register Notice, the concern with FDA’s Unapproved Drugs Initiative stems from a passage in the 2011 Marketed Unapproved Drugs CPG concerning so-called “de facto market exclusivity.”

The September 2011 Marketed Unapproved Drugs CPG states that when a company obtains approval of a drug previously marketed without approval, other similar drug products on the market without approval become “[d]rugs that present direct challenges to the new drug approval and OTC drug monograph systems.”  Thus, they become a target for FDA enforcement action.  But that enforcement action is not immediate (or certain).  Here’s how FDA explains the situation in the 2011 Marketed Unapproved Drugs CPG:

When a company obtains approval to market a product that other companies are marketing without approval, FDA normally intends to allow a grace period of roughly 1 year from the date of approval of the product before it will initiate enforcement action (e.g., seizure or injunction) against marketed unapproved products of the same type.  However, the grace period provided is expected to vary from this baseline based upon the following factors: (1) the effects on the public health of proceeding immediately to remove the illegal products from the market (including whether the product is medically necessary and, if so, the ability of the holder of the approved application to meet the needs of patients taking the drug); (2) whether the effort to obtain approval was publicly disclosed; (3) the difficulty associated with conducting any required studies, preparing and submitting applications, and obtaining approval of an application; (4) the burden on affected parties of removing the products from the market; (5) the Agency’s available enforcement resources; and (6) any other special circumstances relevant to the particular case under consideration.  To assist in an orderly transition to the approved product(s), in implementing a grace period, FDA may identify interim dates by which firms should first cease manufacturing unapproved forms of the drug product, and later cease distributing the unapproved product.

The length of any grace period and the nature of any enforcement action taken by FDA will be decided on a case-by-case basis.  Companies should be aware that a Warning Letter may not be sent before initiation of enforcement action and should not expect any grace period that is granted to protect them from the need to leave the market for some period of time while obtaining approval.  Companies marketing unapproved new drugs should also recognize that, while FDA normally intends to allow a grace period of roughly 1 year from the date of approval of an unapproved product before it will initiate enforcement action (e.g., seizure or injunction) against others who are marketing that unapproved product, it is possible that a substantially shorter grace period would be provided, depending on the individual facts and circumstances.

The shorter the grace period, the more likely it is that the first company to obtain an approval will have a period of de facto market exclusivity before other products obtain approval.  For example, if FDA provides a 1-year grace period before it takes action to remove unapproved competitors from the market, and it takes 2 years for a second application to be approved, the first approved product could have 1 year of market exclusivity before the onset of competition.  If FDA provides for a shorter grace period, the period of effective exclusivity could be longer.  FDA hopes that this period of market exclusivity will provide an incentive to firms to be the first to obtain approval to market a previously unapproved drug.  [(Emphasis added)]

Latching on to this last paragraph, the HHS Notice states:

Through a guidance document issued in 2006 and later revised in 2011, and without conducting notice-and-comment rulemaking, FDA launched a program called the Unapproved Drugs Initiative (UDI).  The UDI sprang from a laudable objective, namely to reduce the number of unapproved drugs on the market.  To achieve this end, FDA provided in its 2011 UDI Guidance that “the first company to obtain an approval [of a previously unapproved drug] will have a period of de facto market exclusivity before other products obtain approval.”  The agency “hope[d] that this period of market exclusivity will provide an incentive to firms to be the first to obtain approval to market a previously unapproved drug.”  Ultimately, manufacturers of older drugs previously thought to be exempt from the FDA approval requirement obtained market exclusivity for those products after FDA took unapproved versions off the market.  An unintended consequence of the “period of de facto market exclusivity” provided by the UDI allowed manufacturers an opportunity to raise prices in an environment largely insulated from market competition.

This proffered basis for ending the Unapproved Drugs Initiative seems to this blogger like a bunch of malarkey.

Here are the results and conclusions from the 2017 JMCP article:

RESULTS: Between 2006 and 2015, 34 previously unapproved prescription drugs were addressed by the UDI.  Nearly 90% of those with a drug product that received FDA approval were supported by literature reviews or bioequivalence studies, not new clinical trial evidence.  Among the 26 drugs with available pricing data, average wholesale price during the 2 years before and after voluntary approval or UDI action increased by a median of 37% (interquartile range [IQR] = 23%-204%; P < 0.001).  The number of drugs in shortage increased from 17 (50.0%) to 25 (73.5%) during the 2 years before and after, respectively (P = 0.046).  The median shortage duration in the 2 years before and after voluntary approval or UDI action increased from 31 days (IQR = 0-339) to 217 days (IQR = 0-406; P = 0.053).

CONCLUSIONS: The UDI was associated with higher drug prices and more frequent drug shortages when compared with the period before UDI action, while the approval process for these drugs did not necessarily require new clinical evidence to establish safety or efficacy.

Buried in the article is a short discussion of “de facto exclusivity” as one of the “several possibilities that may account for why the UDI was associated with increased drug prices and shortages” (emphasis added).  And even then, the study authors suggest alternative ways to address the issue:

Our findings suggest several ways to mitigate the unintended consequences of the FDA’s regulation of unapproved drugs through the UDI.  First, the FDA views a short grace period as a way to incentivize manufacturers to be the first to obtain approval of a previously unapproved drug, since it may establish a period of de facto exclusivity for the first manufacturer.  However, grace periods should only be granted when the manufacturer guarantees supply and sets a fair price.  Grace periods should also be made longer to allow time for additional manufacturers to obtain approval.

While FDA’s forthcoming Federal Register Notice states that “[n]othing in this Notice otherwise limits FDA’s authority to take action against manufacturers of unapproved drugs that meet the statutory definition of a ‘new drug’ (such as, for example, an unapproved drug that claims to mitigate, treat, or cure COVID-19) or violate the FD&C Act in other ways,” one has to wonder whether there will now be a return to the Wild West of marketed unapproved drugs instead of companies deciding to seek FDA approval.  Curiously, FDA has been silent on the HHS announcement.

By Karin F.R. Moore —

A new administration always brings with it the excitement of new political appointees, briefing books and never-ending speculation about forthcoming changes in the direction of various agencies.  It also brings the opportunity for meetings with incoming government officials for an airing of the grievances.  While Festivus will soon be upon the rest of us (we will save the Feats of Strength for another blogpost), we are referring to the First Amendment: the right of all persons to “petition the government for redress of grievances.”

Companies oftentimes meet with the government entities alone, or under the auspices of a trade association.  But similar-minded competitors collaborating on lobbying, advocacy, comments and other types of “petitioning” as part of a formal or ad hoc coalition is also common.  Regardless of the form the group takes, if two or more competitors are in a room together with or without government officials, all involved should be aware of the antitrust laws.

The law provides a limited exemption from antitrust liability for certain actions by individuals or groups that are intended to influence government decision-making, called the “Noerr-Pennington doctrine.” The purpose of the Noerr-Pennington doctrine is to protect the fundamental right to petition the government, including filing litigation in the courts.  It also seeks to support the flow of information to the government.  Noerr-Pennington immunity developed from two cases in the 1960s: Eastern Railroad Conference v. Noerr Motor Freight, 365 U.S. 127 (1961) and United Mine Workers of America v. Pennington, 381 U.S. 657 (1965).  But like most immunities from the antitrust laws, Noerr-Pennington is narrowly construed and has its limits—parties can’t just point to some potential future political impact of their actions to benefit from Noerr-Pennington immunity.  You can read more about the applicability and limits of the Noerr Pennington doctrine in Federal Trade Commission, Enforcement Perspectives on the Noerr-Pennington Doctrine: An FTC Staff Report (2006).

The bottom line here is any sharing or discussion among competitors regarding pricing, output, business strategies and likely responses to government action can be a minefield unless you carefully establish procedures to prevent the improper use of the information.  Before speaking with competitors, consider a few key antitrust guidelines:

DOs

• Set the ground rules for any competitor meeting, and clearly define the purpose of the meeting. There are many legitimate and laudable purposes for competitors to work together. Identify them and limit discussion accordingly.
• Involve antitrust counsel at the outset to identify potential competition concerns and develop procedures to mitigate risk. Have in-house or outside counsel for at least one party attend industry meetings to ensure that meetings stay appropriately focused and to document what transpires.
• Ensure that all petitioning efforts are focused on obtaining government relief, and not on how individual firms will behave in the market, either independent of such government actions or in response to them. Prospective government petitioning is generally protected activity but agreeing on how to react to existing laws and regulations is not.

DON’Ts

• Avoid exchanging competitively sensitive information. Information exchanges can be pro-competitive and lawful if done correctly. Among other things, data should generally be anonymized, collected by a third party and aggregated.
• Do not have discussions among the competitors about how they will price or compete among each other AFTER they achieve the requested relief from the government.
• Do not use the process of working together as an industry to seek relief from the government as an opportunity to have discussions or enter into agreements that could harm competition that are unrelated, or merely tangentially related, to the requested relief.

When in doubt, talk to your in-house counsel, or give us a call.

By Faraz Siddiqui & Jeffrey N. Wasserstein —

On Monday, the Office of Inspector General (OIG) at the U.S. Department of Health and Human Services (HHS) issued a Special Fraud Alert highlighting “some of the inherent fraud and abuse risks” associated with in-person speaker programs, a widely used channel to educate physicians and other health care professionals (“HCPs”) that prescribe the products of pharmaceutical drug and medical device manufacturers. According to the OIG, drug and device companies reported paying nearly $2 billion to HCPs for speaker-related services in the past three years.  While most companies have switched to virtual programs due to the COVID pandemic, OIG seems to be taking advantage of the pause in the action to fire what is likely the opening salvo in their renewed focus on speaker programs.

The alert noted OIG’s “significant concerns” that company-sponsored speaker programs that remunerate external HCPs to speak on the company’s drug or device product on behalf of the company may violate the anti-kickback statute (AKS). A party violates that AKS if it makes an offer, payment, solicitation, or receipt of any remuneration (defined as the transfer of anything of value) purposefully to induce or reward referrals of items or services payable by a Federal health care program such as Medicare and Medicaid. See Social Security Act 1128B(b)(1)-(2), 42 U.S.C. § 1320a-7b(b)(1)-(2). The alert warned that all parties involved in speaker programs may be subject to increased scrutiny, including any “drug or device company that organizes or pays remuneration associated with the program, any HCP who is paid to speak, and any HCP attendees who receive remuneration,” such as free food and drink.

The OIG expressed skepticism whether such programs have any educational value, referring to its large number of investigations where speaker programs were purportedly organized with the intent to induce HCPs to prescribe or order (or recommend the prescription or ordering of) the companies’ products paid for by Federal health care programs. The OIG provided examples of practices that were part of violative speaker programs: tying sales targets to HCP speaker recruitment or remuneration; holding programs at non-conducive venues or events; providing expensive meals; and repeat attendance by HCPs at substantially similar trainings, or attendance by the HCP friends or families. According to the OIG, these examples “strongly suggest that one purpose of the remuneration to the HCP speaker and attendees is to induce or reward referrals.” The OIG noted that “[t]he availability of [educational and training] information through means that do not involve remuneration to HCPs further suggests that at least one purpose of remuneration associated with speaker programs is often to induce or reward referrals.”

The alert acknowledged that companies may engage in “meaningful HCP training and education” programs, and a remunerative arrangement may be lawful, depending on the particular facts and circumstances and the intent of the parties. Nevertheless, it presented a non-exhaustive list of “suspect characteristics” that may indicate whether a speaker program arrangement could violate the AKS. Many of the suspect characteristics mirrored the OIG’s examples of violative behavior (no substantive information presented; expensive meal; non-conducive venue for an education event; repeat attendees or attendance by HCP family or friends). Some additional “suspect characteristics” mentioned were the following:

• The company’s sales or marketing business units influence the selection of speakers or the company selects HCP speakers or attendees based on past or expected revenue that the speakers or attendees have or will generate by prescribing or ordering the company’s product(s) (e.g., a return on investment analysis is considered in identifying participants);
• The company sponsors a large number of programs on the same or substantially the same topic or product, especially in situations involving no recent substantive change in relevant information;
• There has been a significant period of time with no new medical or scientific information nor a new FDA-approved or cleared indication for the product;
• Alcohol is available or a meal exceeding modest value is provided to the attendees of the program (the concern is heightened when the alcohol is free);
• The company pays HCP speakers more than fair market value for the speaking service or pays compensation that takes into account the volume or value of past business generated or potential future business generated by the HCPs.

Some of OIG’s “suspect characteristics” remind us of the Corporate Integrity Agreement (CIA) the OIG asked Novartis to sign as part of the parties’ settlement agreement in July 2020. Under that CIA, the OIG put unusually strict restrictions on the company’s speaker programs, including prohibitions on holding any speaker events at restaurants and on serving or allowing the sale of alcohol. The CIA also limited the speaker program budget to $100,000 per product or indication (no more than $10,000 per speaker per drug or indication) and only permitted the company to hold such events within eighteen months of approval of such product or indication.

The OIG does not have express authority from Congress or the HHS Secretary to establish regulations or other policy defining acts prohibited by the Medicare and Medicaid fraud and abuse statutes. Nevertheless, the OIG has historically used Special Fraud Alerts to put providers on notice of what it viewed with skepticism, and what it considered to be suspicious and potentially indicative of an anti-kickback statute violation. These alerts are rare—there were only five such alerts issued in the last twenty years. They lay out the OIG’s rationale on expanding the interpretation of prohibited acts under the Medicare and Medicaid fraud and abuse laws and often suggest the general direction in which the Agency intends to shift its enforcement and litigation strategies. Taken together with OIG’s recent actions, and specifically in light of the Novartis CIA, which required all External Speaker Programs to be “conducted in a virtual format meaning that the External Speakers shall be remote and shall not be in the same location as any audience member,” the OIG may be getting ready to set up the stage to increasingly scrutinize speaker programs for illegal kickbacks and erode the landscape of external speaker program in the industry.

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.”

By Larry K. Houck —

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.

By Karla L. Palmer & John A. Gilbert —

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.

By Alan M. Kirschenbaum —

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.

By Sara W. Koblitz & David B. Clissold —

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.

By Riëtte van Laack —

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.