By Allyson B. Mullen & Jeffrey N. Gibbs –

All this year, FDA had signaled it intended to finalize the guidance for Laboratory Developed Tests (LDTs). On Friday November 18, 2016, FDA abandoned the effort, stating that it will not provide the requisite 60-day notice to Congress to finalize the Draft Guidances for LDTs (see here and here).  FDA issued the draft guidances in late July 2014, and since then the draft guidances have received a mix of praise and criticism, as we have discussed in our earlier blog posts (here, here, and here).

FDA’s announcement is unsurprising in the wake of the unexpected election results. While this announcement is framing the current status of the draft guidances as delayed, given the current political landscape, these draft guidances are dead for all intents and purposes. Republican members of Congress have been among some of the harshest critics of FDA’s proposal to expand regulatory oversight of LDTs. FDA did say it would “continue to work with stakeholders, our new administration, and Congress to get our approach right.” FDA also said, “We plan to outline our view of an appropriate risk-based approach in the near future.” Nevertheless, with a Republican President committed to less regulation and Republican majorities in both the House and Senate, we believe FDA’s efforts to issue far-reaching LDT guidance is moribund for many years.

With that in mind, what does that mean for laboratories currently running LDTs? If sweeping guidance is off the table, it still does not mean FDA will ignore labs. We don’t have a crystal ball, but we do have a few ideas (i.e., pure speculation).

First, it is unlikely that FDA will view its core mission of ensuring that only “accurate, reliable, and clinically valid” tests are available to customers as changed even with a new administration. Nor do we expect some of FDA’s major concerns with LDTs to abate. Therefore, we expect FDA will take enforcement action against tests that it believes are providing “inaccurate or false test results.” A few ways that we could see this manifest are:

• Stepped Up Enforcement of the 2013 Final RUO/IUO Guidance. Since FDA finalized its Guidance Document regarding Research Use and Investigational Use devices in October 2013, there has been virtually no public enforcement action. This lack of activity came as a surprise to many, including us. After release of the draft LDT guidances less than a year later, it appeared that FDA was focusing on an even broader initiative: LDT regulation. Now that the LDT efforts are done (at least in their current incarnation), FDA may turn its attention back to the marketing of RUOs and IUOs used in LDTs.

• Expansion of Tests that Do Not Meet the Definition of an LDT (e.g., direct-to-consumer (DTC) tests). As many of you are well aware, FDA says it will not exercise enforcement discretion over DTC LDTs. What, exactly, is DTC remains undefined. We had thought that a test ordered by a physician was not DTC, since there was a physician intermediary. FDA disagrees. It is not enough that a physician order the test. FDA has looked at other factors, such as the degree of physician independence. FDA has not, however, publicly articulated these criteria for determining DTC status. Thus, many laboratories struggle to understand how much and what kind of physician interaction is necessary to make a test non-DTC. Now that FDA’s attempt to broadly regulate all LDTs has ended for now, FDA may well attempt to narrow exempt LDTs by expanding the scope of LDTs deemed DTC.  

• Collection Devices. FDA has also historically attempted to regulate (i.e., stop availability of) certain LDTs by preventing the distribution of the collection device necessary to obtain a patient sample for testing. FDA has claimed that the collection device is adulterated and/or misbranded for failure to have clearance or approval for sample collection for the LDT’s intended use. Numerous LDTs use general purpose patient sample collection devices. FDA could try to assert greater oversight of the lab test process by requiring premarket clearance or approval for collection devices for specific intended uses. 

• Public Announcement of “Safety” Concerns. FDA could take another approach and tell consumers and physicians that there are perceived “safety” risks with a particular test or group of tests. In fact, almost a year ago FDA issued a guidance regarding “Public of Emerging Postmarket Medical Device Signals” (see our blog post here). We criticized the draft post for failing to consider industry input before FDA makes an announcement because it could, in part, stop the use of a clinically valid and scientifically sound product. We saw FDA take such action recently with respect Ovarian Cancer Screening Tests. In September, FDA issued a safety communication stating that individuals should not use such tests. FDA did not cite a single confirmed instance of harm from any of these tests – all of the harm cited was theoretical. If FDA chooses to regulate LDTs in this way, we could see an increase in the number of “safety” communications. As a practical matter, this kind of notice and the resulting publicity can kill a test, even though the company never got a chance to address FDA’s concerns before publication.

• Narrowing LDTs. FDA has rarely, in recent years, challenged laboratory tests as not qualifying as LDTs. FDA, though, has done so in the past, and could do so in the future. Given the elastic definition of an LDT, it would not be hard to imagine FDA saying that certain tests don’t qualify as LDTs.

Thus, while many in the lab community have been praising the announcement from FDA, in our view, this fight may not be over. It may now shift from a battle over sweeping guidelines to case-by-case challenges using ill-defined criteria.

As our readers know, a tremendous amount of resources from both FDA and industry was dedicated to the LDT regulatory efforts of the last two years (and before that). For example, the Diagnostic Test Working Group (DTWG), an independent group consisting of representatives from diagnostic manufacturers and clinical laboratories was created to develop alternatives to FDA draft guidances. Congress worked on legislative alternatives to the draft guidances, and the administrative agencies related to LDTs created an interagency task force, which included FDA, CMS, CDC, and NIH, to work on revising the draft guidances. FDA spent countless hours revising its draft guidances, and industry spent countless hours commenting and then lobbying.

While some of the discussions were unproductive, reflecting polarized views, we hesitate to say that these efforts were all wasted because certainly some good ideas have come out of the process. FDA has learned much about the scope, nature, and importance of LDTs, and industry has learned about FDA’s perspective. This may, however, also mean that FDA now has greater knowledge of how to expand enforcement actions to regulate LDTs. Only time will tell. We will certainly be keeping a close eye on how FDA proceeds from an enforcement standpoint and will keep you all updated.

Finally, FDA first announced its authority to regulate LDTs over 24 years ago. Even if the path to broad LDT regulation is blocked for now, FDA may continue to bide its time. In 2021, LDTs will still be around, and so will FDA. The story may not be over.

By Kurt R. Karst –      

Over the years, we’ve witnessed, learned of, and have even been part of several Orange Book “firsts.” There’s the first listing of patent information covering an old antibiotic drug product (here); the Orange Book note addressing a leap year new chemical entity NDA approval (here); the launch of an electronic Orange Book on October 31, 1997, and then the more recent launch of the Orange Book Express app on November 9, 2015 (here); the first (and apparently the last) listing of a tentatively approved ANDA in the Orange Book (ANDA 071611 for Cyclobenzaprine HCl Tablets, 10 mg [FLEXERIL]; added with Cumulative Supplement No. 2 in 1988); the first patents listed in the Orange Book with a “Patent Delist Request Flag” – U.S. Patent Nos. 6,248,735 and 6,316,443 (on April 18, 2008) – identifying that the NDA holder has withdrawn the patent and submitted a request for removal of the patent information from the Orange Book; and then there’s that crazy guy who summited Mt. Kilimanjaro in Tanzania, Africa with the Orange Book (here). 

For all that we’ve seen, however, we never witnessed FDA unilaterally change a patent use code. . . . until now. And the timing of this first is interesting.  It was just last month that FDA issued final regulations implementing portions of the 2003 Medicare Modernization Act.  A major focus of the rule, which goes into effect on December 5, 2016, is patent use codes.  (And, oh, by the way, the new regulations will result in other new Orange Book firsts as FDA is required to make several changes to the Orange Book, including identifying patents for which a dispute has been submitted by an interested party.)

Within the past week or two, the “Newly Added Patents” search function on FDA’s Electronic Orange Book website showed the following entries buried within a larger list of new patent information:

At first blush, there doesn't seem to be anything out of place here. What’s new?  Well, it’s the U-1276 patent use code listing for U.S. Patent No. 8,536,130 (“the ‘130 patent”) covering Depomed, Inc.’s (“Depomed’s”) NUCYNTA ER (tapentadol) Extended-release Tablets that’s “new” . . . . but only “new” insofar as it’s “new again.”

NUCYNTA ER is approved under NDA 200533 for the management of: (1) pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate; and (2) neuropathic pain associated with diabetic peripheral neuropathy in adults severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. In January 2016, Depomed submitted a Citizen Petition (Docket No. FDA-2016-P-0383) to FDA requesting that the Agency stay final approval of any ANDAs referencing NUCYNTA ER that don’t contain either a Paragraph III or Paragraph IV certification to the ‘130 patent and that instead contain a section viii statement seeking to omit from labeling information reflected by the patent use code.

The ‘130 patent was initially listed in the Orange Book with a U-1276 patent use code, which is defined in an addendum to the Orange Book as “MANAGEMENT OF NEUROPATHIC PAIN ASSOCIATED WITH DIABETIC PERIPHERAL NEUROPATHY.” After Depomed acquired NUCYNTA ER from Johnson & Johnson, Depomed “became aware that the ‘130 patent claims were actually much broader than what was reflected in the use code then on file in the Orange Book.”  As such, in Septemebr 2015, Depomed requested that FDA change the patent use code for the ‘130 patent to “MANAGEMENT OF PAIN SEVERE ENOUGH TO REQUIRE DAILY, AROUND -THE-CLOCK, LONG-TERM OPIOID TREATMENT, INCLUDING NEUROPATHIC PAIN ASSOCIATED WITH DIABETIC PERIPHERAL NEUROPATHY.”  Consistent with FDA’s ministerial role in Orange Book patent matters, the Agency acquiesced and assigned the narrative the number U-1739.  With the patent use code change, “a section viii statement is no longer appropriate, as any carve out will require the removal of both labeled indications for Nucynta ER®, and anything less will overlap the new use code and infringe the patent,” according to Depomed.  “Therefore, ANDA applicants with section viii statements must amend their applications to address the new use code as required by FDA regulations.”

In April 2016, FDA denied Depomed’s Citizen Petition, saying that the U-1739 patent use code is “uninterpretable.” FDA also threatened to unilaterally change the use code for the ‘130 patent from U-1739 back to U-1276. 

FDA denies your Petition at this juncture because the information that you have placed before the Agency makes your patent use code for ‘130 patent uninterpretable . . . . FDA . . . requests that Depomed submit a new patent declaration form (Form FDA 3542) for the ‘130 patent, consistent with this response, within 15 calendar days from the date of this response.  If Depomed fails to submit an interpretable use code on the requested Form FDA 3542 within this timeframe, FDA will revert to the last interpretable patent use code submitted for the ‘130 patent, which is the use code submitted before Depomed’s September 2015 revisions.

Apparently Depomed never responded to FDA, and earlier this month FDA carried through with its threat to revert back to the U-1276 patent use code.

What effect the change in patent use code might have in the long-run remains to be seen. In September 2016, Depomed prevailed in district court patent infringement litigation against three ANDA applicants (see Depomed, Inc. v. Actavis Inc., et al., Case No. 2:13-cv-4507 (D. N.J.)), potentially delaying ANDA approval until late 2025. In an Order issued in that case, the court enjoined the ANDA applicants from launching their generic Tapentadol HCL drug products.  One ANDA applicant has already appealed the ruling to the U.S. Court of Appeals for the Federal Circuit.

One potential short-term effect of the patent use code change, however, might be to moot a counterclaim filed by ANDA applicant Actavis Inc. (“Actavis”). That counterclaim was initially filed by Actavis in a separate patent infringement action (Case No. 15-cv-6797 (D. N.J.)) pursuant to FDC Act §505(j)(5)(C)(ii)(I) seeking “an Order requiring Depomed to immediately request the FDA to correct the Orange Book use code for the ‘130 patent from U-1739 to U-1276.”

By Riëtte van Laack –

As previously reported, on May 27, 2016, FDA published the final rules regarding nutrition labeling and serving sizes.  The amended regulations came into effect on July 26, 2016 and the compliance date is July 26, 2018 for all manufacturers, except for manufacturers with less than 10 million in annual food sales (for whom the compliance date is July 26, 2019). FSIS has yet to publish the proposed amendments to its nutritional labeling regulations similar to FDA’s amendments.  (FSIS’s proposed rule, which had been under OMB review since July, just cleared review on November 15, 2016.)  In the interim, FSIS announced that it will allow meat and poultry labels to use the new FDA format until such time as FSIS finalizes its own nutrition labeling and serving size regulations.

Meat and poultry companies that wish to use the new FDA format for meat and poultry products cannot do so generically, i.e., without prior review by FSIS. They must submit a sketch label to FSIS. However, to avoid an adverse effect on the FSIS label review backlog, FSIS will review only one label per corporation. Subsequent similar labels of that corporation that use the new FDA format can be generically approved.  FSIS believes that this procedure will help ensure that the labels will be in compliance with FDA’s regulations.

Although FSIS’s amended nutrition labeling regulations likely will be similar to FDA’s, there is no guarantee that they will be identical. Thus, companies that decide to use the new FDA format may need to change the format again when FSIS issues its final regulations.

Comments to FSIS regarding this announcement may be submitted any time.

By Kurt R. Karst –

Last week, FDA filed a Notice of Appeal with the U.S. Court of Appeals for the District of Columbia Circuit appealing a September 9, 2016 Final Judgment and Order from DC District Court Judge Rudolph Contreras concerning Ferring Pharmaceuticals Inc.’s (“Ferring’s”) eligibility for 5-year New Chemical Entity (“NCE”) exclusivity for PREPOPIK (sodium picosulfate, magnesium oxide, and citric acid) for Oral Solution, which FDA approved under NDA 202535 on July 16, 2012 (and granted a period of 3-year exclusivity that expired in July 2015).  Although Judge Contreras remanded the action to FDA for further proceedings consistent with his September 2016 Memorandum Opinion, FDA decided instead to seek review by the DC Circuit. 

By way of background (and as summarized by Judge Contreras in his March 2016 Memorandum Opinion), “prior to 2014, the FDA interpreted the five-year exclusivity provision to provide that only drug products containing no previously approved drug substances were eligible for exclusivity.  Once eligible, however, the FDA interpreted the bar clause to bar all ANDAs and 505(b)(2) applications referencing that drug product or any later-approved products containing the product’s drug substances, in order to preserve the innovator’s exclusivity to the greatest extent possible.” [(Emphasis in original)]  FDA’s new interpretation, which the Agency has applied only to Fixed-Dose Combination (“FDC”) drug products approved after October 2014, is discussed in a final guidance document issued that same month.  In short, FDA’s reinterpretation of the statutory NCE exclusivity provisions allows for an award of NCE exclusivity for a newly approved FDC drug product containing an NCE and a previously approved drug. 

As we previously reported, Judge Contreras granted Ferring’s Motion for Reconsideration of the DC District Court’s March 15, 2016 ruling that FDA’s pre-October 10, 2014 interpretation of the FDC Act’s 5-year NCE exclusivity provisions as applied to a newly approved FDC drug product containing an NCE and a previously approved drug – and specifically, to Ferring’s PREPOPIK – was not arbitrary and capricious. According to Judge Contreras:

In its motion for reconsideration . . . Ferring now provides three examples that lead the Court to doubt the factual basis for its [March 2016] conclusion. In each instance, a drug substance that had never been previously approved was included as part of a fixed-combination drug product (a fixed-combination drug product that did not receive five-year exclusivity because it contained other, previously approved drug substances).  And, in each case, a single-entity version of the drug substance was later approved, but did not receive the benefit of a five-year exclusivity period, because the drug substance had been previously approved as part of the fixed-combination product. . . .

These newly highlighted examples now show that, even if the FDA’s prior interpretation is reasonable under Chevron Step Two from a conceptual standpoint, that interpretation produces circumstances that fail to treat “similar cases in a similar manner.” [(Internal citations omitted)]

Briefing in the appeal gets underway in December with procedural and dispositive motions due on December 9 and December 27, 2016, respectively (from both FDA and Ferring).

Meanwhile, the sponsor of one NDA cited by Judge Contreras as one of the “newly highlighted examples” has petitioned FDA in light of the DC District Court’s September 2016 decision. Specifically, Gilead Sciences, Inc. (“Gilead”), the sponsor of NDA 203100 for STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets (approved on August 27, 2012), submitted a Citizen Petition (Docket No. FDA-2016-P-3312) to FDA in October 2016 requesting that:

In light of the recent district court’s decision in Ferring v. Burwell, . . . FDA promptly award five-year NCE exclusivity to Stribild, . . . and extend such exclusivity under FDA’s “umbrella policy” to later-approved Gilead products containing the new active moieties, specifically Tybost® and Vitekta®.  Additionally, because all of these drug products should have been protected against the receipt of an [ANDA] before August 27, 2016, Gilead requests that FDA withdraw its January 2016 receipt of the Mylan ANDA 208982 referencing Tybost, as well as any other ANDA filed before August 27, 2016 that references a drug containing elvitegravir or cobicistat.

Of course, Gilead is the company primarily responsible for FDA issuing guidance in October 2014 reinterpreting the FDC Act’s NCE exclusivity provisions with respect to FDC drug products. In January 2013, Gilead petitioned FDA (Docket No. FDA-2013-P-0058) to change the Agency’s interpretation.  As noted above, and as discussed in FDA's petition response to Gilead (see here), FDA did change the Agency's interpretation, but only prospectively.

After Gilead submitted its Citizen Petition to FDA, several other interested parties submitted petitions to the Agency (see our previous posts here and here), including a Citizen Petition (Docket No. FDA-2014-P-0737) from Pfizer Inc. (“Pfizer”) with respect to DUAVEE (conjugated estrogens/bazedoxifene) Tablets (NDA 022247; approved on October 3, 2013).  

In another new Citizen Petition (Docket No. FDA-2016-P-3082) submitted to FDA in early October 2016, Pfizer, like Gilead after it, requests that FDA recognize 5-year NCE exclusivity for bazedoxifene, the new active moiety in DUAVEE, as a result of the DC District Court’s decision in Ferring v. Burwell. “DUAVEE is similarly situated to Ferring’s drug PREPOPIK, as an FDC drug product containing both an NCE and previously-approved drug substance to which FDA applied its historical interpretation of the FDCA to grant 3-year exclusivity,” says Pfizer.  “Pfizer therefore seeks FDA’s reconsideration of its decision not to grant 5-year exclusivity to bazedoxifene, in light of the September 9, 2016 decision in Ferring v. Burwell, holding FDA’s prior interpretation of the FDCA’s exclusivity provisions arbitrary and capricious.”  Unlike PREPOPIK and STRIBILD (including elvitegravir or cobicistat), FDA has not yet received (i.e., filed) any ANDAs for generic versions of DUAVEE.

By Riëtte van Laack –

As we blogged previously, there have been activities both by FDA and the FTC foreboding a bleak future for homeopathic products. Both FDA and the FTC questioned the policies and standards applicable to homeopathic products. The FTC threatened to hold homeopathic products to the standard of modern science, i.e., substantiation by clinical studies, not by homeopathic proofing. The threat has become real.

On November, 15, 2016, the FTC issued an enforcement policy for homeopathic products. Essentially, the FTC has decided to hold homeopathic over-the-counter (OTC) products to the same standard as any other OTC products bearing a health-related claim, i.e., the products’ claims must be supported by modern scientific (not homeopathic) evidence. The Policy Statement applies only to OTC products intended for self-limiting disease conditions amenable to self diagnosis of symptoms and treatment. It does not apply to the practice of medicine and it also does not apply to prescription homeopathic products.

The FTC does not outright prohibit claims for homeopathic products that are not supported by scientific evidence. The Commission asserts that an effective disclaimer (e.g., a disclaimer clarifying that the product claims are based on theories of homeopathy not accepted by most modern medicine) that accompanies the efficacy claim may correct the misleading nature of the claim. At the same time, however, the FTC recognizes that there is an “inherent contradiction in asserting that a product is effective and also disclosing that there is no scientific evidence” for the claim and questions whether any disclaimer can be sufficient to prevent consumer deception. The FTC advises that companies develop evidence that their disclaimer is effective.

The FTC claims that the approach outlined in its Policy Statement is consistent with the First Amendment, and “neither limits consumer access to OTC homeopathic products nor conflicts with the FDA’s regulatory scheme.” However, the question remains whether an alternative but truthful disclaimer informing consumers of the facts pertaining to homeopathy, a practice that is recognized by inclusion in the Federal Food, Drug, and Cosmetic Act (FDC Act), would survive an FTC challenge based on First Amendment grounds. Maybe homeopathics are not dead yet?

For anyone interested in comments the FTC received and the Agency’s responses, the FTC staff has prepared a report discussing the comments and on the workshop, titled "Staff Report on the Homeopathic Medicine & Advertising Workshop."

It remains to be seen what if anything FDA will do regarding prescription homeopathic drug products and if the FTC’s new policy and potential resulting enforcements actions will be challenged.

By Alan M. Kirschenbaum & David C. Gibbons – 

In separate actions implementing the Medicaid Drug Rebate Program (“MDRP”), CMS has delayed for three years the expansion of the MDRP to U.S. Territories, and issued a draft revised National Drug Rebate Agreement.

Delay in Expansion to U.S. Territories

Today CMS released an interim final rule with comment period that delays for three years the expansion of the MDRP to Puerto Rico and the U.S. Territories (collectively, “Territories”).  This expansion will not only require manufacturers to pay rebates to Territories, but also to include sales to customers located in the Territories in their calculations of average manufacturer price (“AMP”) and best price.  In the Final Rule, the expansion was accomplished by amending the definitions of  “states” and “United States” to include the Territories.  The initial effective date for these amendments was April 1, 2017.  CMS has delayed the effective date until April 1, 2020, in recognition of the complexity of the transition for both the Territories and manufacturers. 

Revised Medicaid Rebate Agreement

CMS is proposing to make substantive revisions to the standard National Drug Rebate Agreement for the first time since the MDRP began and the original agreement was issued in 1991. A draft revised agreement, published in the Federal Register last Wednesday, November 9, would bring the Agreement into alignment with Affordable Care Act amendments to the Medicaid rebate statute and CMS’ implementing final rule issued on February 1, 2016 (“Final Rule”).  (We have summarized the Final Rule here.)  The revised Agreement also contains additional changes incorporating CMS policies adopted over the years.  Comments on the draft revised Agreement are due by February 7, 2017.

Changes consistent with Affordable Care Act amendments and Final Rule: The great majority of revisions align the definitions in the Agreement with the definitions in the Final Rule, codified at 42 C.F.R. §§ 447.502-505.  Definitions of AMP, best price, covered outpatient drug, and many others have been revised to simply refer to the regulatory definitions.  Most of these definitional changes reflect amendments to the statute made by the Affordable Care Act — but not all do.  For example, the definition of “best price”, which is defined in the current Rebate Agreement as the manufacturer’s “lowest price … to any purchaser in the United States,” now is revised consistent with the narrower regulatory definition:  the “lowest price available from the manufacturer … to any wholesaler, retailer, provider, health maintenance organization, nonprofit entity, or governmental entity” in the U.S., with certain exclusions.  This definition tracks the statutory definition of best price, which did not change with the Affordable Care Act. See 42 U.S.C. § 1396r-8(c)(1)(C).

Other Revisions: Some of the proposed revisions to the Agreement do not relate to Affordable Care Act amendments, but instead incorporate CMS policy as it has evolved under the MDRP.  For example: 

• The Agreement would now be explicit that a manufacturer must report all of its covered outpatient drugs to CMS, and may not pick and choose which ones to report (Section II(c)).
• Manufacturers “should” ensure that their NDCs are electronically listed with FDA (Section II(c)). In practice, CMS no longer permits drugs to be added to the MDRP unless they are electronically listed with FDA.
• Manufacturers must obtain and maintain access to CMS’ Medicaid Drug Data Reporting (“DDR”) system (Section II(i)).
• A foreign manufacturer must identify a point of contact in the U.S. to communicate with states regarding rebate invoices (Section II(a)).
• Reasonable assumptions must not only be retained in writing, as under the current Agreement, but must be made available to HHS on request (Section II(k)).
• Manufacturers excluded from federal programs will automatically be terminated from the MDRP (Section VII(c)).

To avoid the current situation where the Agreement has become outdated as the statute and regulations have been amended, the draft Agreement provides that it is “subject to any changes in the Medicaid statute or regulations that affect the rebate program.” (Section VIII(a))

We observe that there is some doubt whether this draft Agreement – and, more importantly, the substantial changes to the MDRP enacted in the Affordable Care Act and implemented in the Final Rule – will survive the Trump Administration. President-Elect Trump vowed to seek a full repeal of the Affordable Care Act “on day one” of his presidency, and the Republican-controlled Congress has previously supported a complete repeal, the House having voted in favor of it over 60 times.  However, Mr. Trump suggested in an interview with the Wall Street Journal on Friday that he may not seek a full repeal, in recognition that repealing certain provisions such as the ban on denying coverage based on pre-existing conditions would be unpopular.  A full repeal would also cause 22 million enrollees in exchange plans to lose coverage.  If Mr. Trump and the Congress do not seek a full repeal, it is possible that the MDRP amendments might be spared, since a repeal of those changes, most notably an increase in the base rebate, would be costly to the government.  Moreover, both Mr. Trump and Congressional Republicans have indicated that they favor some actions to restrain drug prices.  Nevertheless, the possibility that the changes to the MDRP made by the Affordable Care Act will be repealed cannot be precluded.  (Note that the expansion of the MDRP to the Territories, discussed above, was not mandated by the Affordable Care Act, and therefore neither the expansion nor the delayed effective date would be affected by a repeal of that law.)

By Jennifer D. Newberger –

Though we are certain it was not only our blog post on the draft Medical Device Reporting ("MDR") guidance that persuaded FDA not to adopt some of the positions it proposed in its Draft Guidance, Medical Device Reporting for Manufacturers (July 2013), we were pleased to see that some of the issues we considered to be most egregious in the draft are absent from the final guidance, issued on November 8, 2016.

One such example pertains to the issue of duplicate reporting between contract manufacturers and specification developers. In the draft guidance, FDA stated,

For devices manufactured under contract, both the firm that actually manufactured the device (“Firm A”) and the firm that initiated the specifications and distributed the device (“Firm B”) are considered a “manufacturer” based on the definition of that term in 21 CFR 803.3. Under 21 CFR 803.3, both the firm that manufactures the device and the firm that initiates the specifications for the device are manufacturers who are required to report. Under 21 CFR 803.10(c), a manufacturer is required to submit reports. Thus, both Firms A and B are responsible for filing reports on MDR reportable events involving their device.

The final guidance takes a position directly in contrast to that above, stating:

The MDR regulation at 21 CFR 803.3 defines a “manufacturer” to include a firm that initiates specifications for devices that are manufactured by a second party for subsequent distribution by the person initiating the specifications. A contract manufacturer who does not distribute or market the devices it manufactures for a specifications developer would not have an MDR reporting obligation under 21 CFR 803.50 and would not require an exemption. However, if the contract manufacturer (Firm A) distributes or markets the devices that it manufactures for the specifications developer (Firm B), then both would have an MDR reporting obligation.

Final Guidance, at 14 (emphasis added).

We should note at the outset that we are pleased with the outcome of this position, as it means that contract manufacturers and specifications developers can continue doing what has been done for year—describe their reporting obligations via contract. While the outcome is a positive one, we do remain puzzled by how FDA reached its conclusion. The bolded language is not only inconsistent with the position put forth by FDA in the draft guidance, but it appears to be inconsistent with the literal language of the regulation, as well as the position FDA has taken in Warning Letters issued prior to the draft guidance. As we noted in our blog post on the draft guidance, in 2011, FDA issued a Warning Letter to Laboratorios B. Braun (LBB), stating that LBB, as a contract manufacturer, had failed to comply with the MDR requirements, even though LBB had a contract with B. Braun Medical US (BBMUS) stating that BBMUS was responsible for reporting. The letter does not specify whether LBB or BBMUS distributed the product in question; FDA’s conclusion was based solely on the fact that LBB “is a contract manufacturer and is required to have established procedures addressing the evaluation of complaints and filing of MDRs.”

Given FDA’s prior positions regarding the reporting obligations of contract manufacturers, and the notable absence of an exemption from the reporting requirements for an entity that contract manufactures, but does not distribute the device, the basis for FDA’s conclusion that such facilities are not required to report is unclear. Nevertheless, as noted, the language in the final guidance represents a good outcome for industry: contract manufacturers do not need to report, and do not need to seek an exemption to avoid doing so.

Next up, the two year presumption. The MDR regulation presumes that once a malfunction has caused or contributed to a death or serious injury, the malfunction is “likely” to do so again if the malfunction were to recur. In its 1997 guidance, FDA stated that the “presumption will continue until the malfunction has caused or contributed to no further deaths or serious injuries for two years, or the manufacturer can show, through valid data, that the likelihood of another death or serious injury as a result of the malfunction is remote.” The draft guidance did away with this two year presumption, and instead proposed that companies submit requests for exemptions from further reporting of the malfunction. The two year presumption has been reintroduced—with some caveats—in the final, which states: “FDA recommends that you submit a notification to FDA with a summary of the data and the rationale for your decision to cease reporting at the end of two years.” Final Guidance, at 13. Such notification has never before been “recommended,” and is not part of the regulations. We would expect that companies will not follow this recommendation moving forward, but will instead continue to operate as they did under the 1997 guidance, and will stop reporting a malfunction when the malfunction has caused or contributed to no further deaths or serious injuries for two years.

FDA also walked back on its position about devices that alarm prior to a malfunction, thereby allowing a clinician to intervene before the occurrence of an adverse event. In the draft guidance, FDA stated that “[i]f the device malfunctions but an alarm alerts the user to intervene before there is any harm to the patient, the event should be reported as a malfunction because of the potential to cause or contribute to a death or serious injury if the malfunction recurred and either the alarm did not work or there was no one to respond.” We found this example to be one of the most egregious in the draft guidance. It has been modified in the final to remove any mention of alarms, and instead merely repeats the regulatory standard to report the event if the malfunction is likely to cause or contribute to a death or serious injury if the malfunction recurred. Final Guidance, at 34. We hope that this modification means FDA agrees that an alarm sounding with no one to respond does not constitute a device malfunction.

One good thing thrown into the final guidance is the relationship between user error and the obligation to report user error as an MDR. Both the draft and the final guidances state that user error could “reflect problems with device labeling, the user interface, or other aspects of device design,” and should therefore “be reported in the same way as other adverse events which are caused or contributed to by the device.” A question that companies often grapple with is whether user error should be considered a “malfunction” such that they are required to assess whether a recurrence of that user error would be likely to cause or contribute to death or serious injury, and therefore report the error. The final guidance includes one sentence that was not in the draft, and that seems to answer this question: “If you determine that an event is solely the result of user error with no other performance issue, and there has been no device-related death or serious injury, you are not required to submit an MDR report, but you should retain the supporting information in your complaint files.” This implies that user error that results in a malfunction is not, on its own, likely to require MDR reporting, which is good news for device manufacturers.

Overall, the final guidance is an improvement over the draft. To the extent there are still some areas in which FDA seems to be recommending more reporting than prior policy or guidance (e.g., two year presumption), manufacturers—and FDA—must keep in mind that guidance documents are not the law, and a manufacturer’s failure to follow the suggestions put forth in the final guidance do not equate to a failure to properly file MDR reports, or otherwise comply with the regulation.

By Ricardo Carvajal –

FDA recently announced the issuance of the 7th edition of the Agency's Questions and Answers Regarding Food Facility Registration.  The latest edition includes nearly 60 new Q&As on a variety of registration-related topics, including:

• Biennial registration renewal – A facility’s registration must be renewed in the last quarter of every even-numbered year.  The new Q&As address scenarios such as a facility’s obligation to renew even when an initial registration has been submitted during any of the first three quarters of a biennial renewal year.
• Unique Facility Identifiers (UFIs) – Although these won’t be required as part of a registration until October 1, 2020, a number of new Q&As address verification and selection of UFIs.  Currently, a DUNS number is FDA’s preferred UFI, but FDA might deem other UFIs acceptable before the requirement takes effect.
• Food product categories and activity types – A registration must include information on food product categories and the types of activity handled by the facility.  The guidance now makes clear that a facility such as a warehouse that frequently changes food product categories “may select all of the food product categories that are normally part of [its] operations.”  The guidance also provides definitions of the different activity types (e.g., “refrigerated human food warehouse/holding facility”).
• Cancelation of registration – Among other things, the guidance explains the circumstances under which FDA will cancel a registration, and the agency’s process for informing the registrant.
• Waiver requests – As of January 4, 2020, registration-related submissions will have to be in electronic format unless FDA grants a waiver.  New Q&As explain the process for obtaining a waiver.

Comments on the guidance are due by February 6, 2017.

Hyman, Phelps & McNamara, P.C. ("HP&M") has once again been ranked as a “Tier 1” law firm in the area of “FDA Law” (both nationally and in Washington, D.C.) by the folks over at U.S. News & World Report, who teamed up with Best Lawyers for the 2017 “Best Law Firms” rankings.  More than 13,000 law firms are ranked in 74 practice areas nationally and in 122 practice areas on the metropolitan lists.  “[R]ankings are based on a rigorous evaluation process that includes the collection of client and lawyer evaluations, peer review from leading attorneys in their field, and review of additional information provided by law firms as part of the formal submission process,” according to U.S. News.  The 2017 list of America’s Best Law Firms can be searched here, or viewed here.  HP&M is noted on page 61 (national ranking) and on page 107 (Washington, D.C. ranking).

By Kurt R. Karst, John R. Fleder & Robert A. Dormer –

The current FDA system to announce hotly contested generic drug approval decisions is broken.  As we see it, FDA’s “system” pleases no one and does not appear to be legally mandated.  Moreover, whatever advantage FDA may think the Agency is getting from hiding the ball from the world on the timing and substance of these decisions is more than overcome by the criticism the Agency has received from judges.  In a new paper, titled “How FDA Announces Drug Approval Decisions: A Broken FDA ‘System’ That Must BE Fixed,” we examine two cases in particular – Hi-Tech Pharmacal Co., Inc., v. United States Food and Drug Administration, No. 08-01495 (JDB) (here) and AstraZeneca Pharmaceuticals LP v. Burwell, No. 16-cv-1336 (RDM) (here) – where FDA’s system to announce ANDA approval decisions has drawn fire from the judge presiding over the case.

FDA’s approval system for handling certain high profile ANDA approval decisions must be fixed. As we note in the paper, there certainly appears to be ample authority conferred on FDA to make changes without the need for additional legislation to be enacted. But if legislation is needed, then we call on FDA to spearhead a legislative fix. Congressional oversight committees may be a sound vehicle to compel FDA to focus on this problem. Perhaps the Department of Health and Human Services may be able to force FDA to change its ways. FDA needs to involve interested stakeholders in this process. We also urge FDA to communicate with the courts to try to get judicial input.

By Jennifer M. Thomas – 

Last week, FDA rolled out a new online reporting program, titled “Reporting Allegations of Regulatory Misconduct,” with little fanfare. No blog post in FDA Voice, no press conference, and even the (longwinded) name of the program seems calculated to send the message “nothing to see here, folks.” Which, of course, made us take a closer look.

1. What is it?

An online tool for reporting allegations of regulatory misconduct against medical device companies. Allegations may be submitted using a simple form, which provides anonymity for the submitter if he or she chooses, or by email or regular mail. According to the program’s homepage, FDA envisions that the types of allegations will include (1) off-label marketing, (2) marketing without the requisite approval/clearance, (3) QSR violations, (4) falsifying records, (5) failure to register and list, (6) failure to submit required reports, or (7) knowingly deceiving FDA. Although the program appears similar in some ways to CDER’s “Bad Ad” Program, the scope is much broader.

2. Is it really “new”?

Not according to FDA. Consistent with the circumstances of its launch, the homepage for FDA’s new reporting tool practically begs readers to view it as a non-event. The homepage indicates that FDA has received these types of reports in the past, and that the online tool is simply a new way of receiving the same information. That said, to our knowledge there has never before been a formal mechanism to capture and track allegations like these.

3. How will FDA use the reports?

This remains to be seen. The homepage mentions only administrative actions in response to allegations submitted through the program, with a Warning Letter or recall request being the harshest administrative measures described (others include conducting inspections, contacting the company for further information, or simply “monitoring the allegation”). Nowhere is there mention of possible referral to the Office of Chief Counsel or Office of Criminal Investigations for review of more egregious alleged misconduct, although several of the categories of misconduct FDA cites as examples are of a kind often referred to the Department of Justice for civil or criminal action. The homepage states that “FDA will not share [the submitter’s] identity or contact information with anyone outside the FDA” unless required by law, but makes no such promise with regard to information obtained from the submitter. Therefore, presumably, FDA is free to share information gleaned through the online reports with other government agencies.

4. Will these reports actually be useful to FDA?

We are trying to see the bright side for FDA, but on balance we think the answer to this question is “no.”

The most likely candidates to use the easy, anonymous, online tool are competitors. This may be an attractive alternative to a trade complaint, with the added benefit that FDA is obligated to follow-up on the allegations. Some companies may simply seek to disrupt a competitor’s business by initiating an FDA investigation. The overall quality and reliability of information FDA receives from competitors probably will be low.

While it is possible that employee whistleblowers will also use this tool, those with significant and well-documented allegations have the potentially much more lucrative option of reporting regulatory misconduct though a qui tam False Claims Act suit. Reporting through this new tool in advance of filing such a suit could have implications for the whistleblower’s ability to recover as a qui tam relator.

It also is highly unlikely that FDA will be able to handle the number of reports that come in through the online reporting tool. As with medical device adverse event reports, the Agency will be forced to prioritize a very few reports, only to then be taken to task for failing to identify or act on serious violations reported to the Agency. See, e.g., GAO Letter Report, Medical Device Reporting: Improvements Needed in FDA’s System for Monitoring Problems with Approved Devices, GAO/HEHS-97-21 (Jan. 29, 1997) (here); GAO Highlights, Shortcomings in FDA’s Premarket Review, Postmarket Surveillance, and Inspections of Device Manufacturing Establishments, GAO-09-370T (June 18, 2009) (here).

5. If this type of report isn’t really new, why does the new online reporting tool matter to industry?

Despite its unassuming appearance, in our view the new reporting tool could present significant additional risks to industry.

First of all, allegations of regulatory misconduct, even if baseless, can disrupt a business as the Agency takes steps to investigate those allegations by conducting inspections, demanding a response from the company, etc. Whereas previously CDRH was under no affirmative obligation to respond to a complainant who, for example, submitted an unreliable or inadequately documented complaint to the Agency, CDRH now has committed to “follow-up communication” and a tracking system. This will allow submitters to demand a response, and will likely necessitate more, and more burdensome, investigative steps by CDRH.

Furthermore, these reports of allegations will be consolidated in a single repository, ripe for requests from the public or other government agencies. Although the reporting tool’s homepage states that records will not be released pursuant to FOIA until an investigation is complete, other government agencies – State Attorneys General, and U.S. Attorneys’ Offices, for example – may request pertinent documents from FDA even during the pendency of an investigation. Relators’ counsel in qui tam cases may also request to see records of an ongoing investigation.

Finally, the fact that allegations are not made public until after an investigation is closed does not necessarily protect companies from bad press tied to baseless accusations. For instance, FDA may close an investigation upon concluding that the allegation does not warrant expenditure of CDRH resources, but without reaching an actual conclusion. The reported allegation would then potentially be subject to disclosure under FOIA, and the company forced to defend itself against that allegation in the court of public opinion.

5. What can companies do about it?

There is no guaranteed way to avoid becoming the subject of an allegation of regulatory misconduct, whether submitted through this new online tool or otherwise. That said, device companies can significantly reduce their risk by having in place a system for internal reporting and a mechanism for fully and efficiently addressing internal reports submitted by employees. Companies should also be sure to respond quickly and completely to any request by CDRH for a response to allegations submitted through the new portal.

6. What do we call it?

Well, we certainly can’t call it “Reporting Allegations of Regulatory Misconduct” – too unwieldy. We welcome your suggestions, but in the meantime – riffing on CDER’s “Bad Ads” – we will be calling it CDRH’s “Bad Acts” Program.

By James E. Valentine & Karla L. Palmer – 

There are a number of lists that are central to FDA’s regulatory framework for the regulation of pharmacy compounding under sections 503A and 503B of the Federal Food, Drug, and Cosmetics Act (FD&C Act). In recent posts, we’ve discussed additions to one such list: the list of drugs that may not be compounded under 503A and 503B (see posts here and here).

FDA’s Pharmacy Compounding Advisory Committee (PCAC) is meeting to consider substances nominated for inclusion on two other lists:

1. Bulk Drug Substances That Can Be Used By Compounders under Section 503A (also known as the “503A Bulks List”)
2. Drug Products That Present Demonstrable Difficulties for Compounding (also known as the “Difficult to Compound List”)

We thought this post would be a good opportunity to discuss what exactly the PCAC is considering when it advises the Agency on whether or not to include a drug on either of these lists.

Substances Nominated for Inclusion on the 503A Bulks List

One of the conditions that must be met for a compounded drug product to qualify for the exemptions in section 503A is that a licensed pharmacist or licensed physician compounds the drug product using bulk substances that meet one of the following criteria:  

1. comply with the standards of an applicable United States Pharmacopoeia [(USP)] or National Formulary [(NF)] monograph, if a monograph exists, and the USP chapter on pharmacy compounding;
2. if such a monograph does not exist, are drug substances that are components of drugs approved by [FDA]; or
3. if such a monograph does not exist and the drug substance is not a component of [an approved drug], that appear on a list developed by [FDA] through regulations issued by [FDA] under subsection (c) [of section 503A (the 503A Bulks List)]

See FD&C Act § 503A(b)(1)(A)(i)).  (FDA defines bulk drug substances as “any substance that is represented for use in a drug and that, when used in the manufacturing, processing, or packaging of a drug, becomes an active ingredient or a finished dosage form of the drug, but the term does not include intermediates used in the synthesis of such substances” (21 C.F.R. 207.3(a)(4)).

Before developing the 503A Bulks List, FDA must convene and consult an advisory committee on compound unless it determines that the issuance of such regulation before consultation with an advisory committee is necessary to protect the public health (see FD&C Act § 503A(c)(1)).  FDA is doing just that at the November 3^rd PCAC meeting.  The full nomination process is discussed in FDA’s Interim Policy that was published in June.

As discussed at the February 2015 PCAC meeting, in the July 2014 Federal Register notice (79 Fed. Reg. 37,747, 37,748) soliciting (re)nominations for the section 503A Bulks List, FDA proposed the following criteria to evaluate the nominated substances: 

1. the physical and chemical characterization of the substance;
2. any safety issues raised by the use of the substance in compounded drug products;
3. historical use of the substance in compounded drug products, including information about the medical condition(s) the substance has been used to treat and any references in peer-reviewed medical literature; and
4. the available evidence of effectiveness or lack of effectiveness of a drug product compounded with the substance, if any such evidence exists.

In evaluating candidates for the 503A Bulks List, FDA is using a balancing test. No single one of these criteria is dispositive; rather, the agency is considering each criterion in the context of the others and balancing them, on a substance-by-substance basis, in deciding whether a particular substance is appropriate for inclusion on the list.

Today, FDA is presenting to the PCAC results of its review of some of the nominated substances to obtain the Committee’s advice on whether to include the substances on the list. Specifically, the substances being discussed at this meeting are:

Whether to Include Products or Categories of Drug Products on the Difficult to Compound List

Both sections 503A and 503B also prohibit compounding of drugs that are on FDA’s Difficult to Compound List. One of the conditions for the exemptions under section 503A is that the compounded drug product is not a drug product that “presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product” (see FD&C Act § 503A(b)(3)).

Similarly, one of the conditions for the exemptions under section 503B is that the compounded drug product “is not identified (directly or as part of a category of drugs) on a list published by the Secretary . . . of drugs or categories of drugs that present demonstrable difficulties for compounding that are reasonably likely to lead to an adverse effect on the safety or effectiveness of the drug or category of drugs, taking into account the risks and benefits to patients,” or “is compounded in accordance with all applicable conditions identified…as conditions that are necessary to prevent the drug or category of drugs from presenting [such] demonstrable difficulties” (see FD&C Act § 503B(a)(6)).

FDA solicited nominations for the Difficult to Compound List in its December 2013 Federal Register notice (78 Fed. Reg. 72,840). For today’s PCAC meeting, FDA considered a drug product that was nominated for the list, and is proposing the following to the advisory committee:

If you are interested in tuning in to see how the PCAC considers products nominated for these two lists, the public comments concerning the same, and the Committee deliberations (and vote), you can find the webcast information here.

That will be among several food policy topics discussed this Friday at a Food and Drug Law Journal Symposium titled Law and Food Systems: Institutional Pathways Toward a New Paradigm?  Proposals for a single food agency have bubbled up over the years, and the impending election makes now a good time to reconsider the issue.  Hyman, Phelps & McNamara, P.C.'s Ricardo Carvajal will participate in a panel discussion of factors weighing for and against such a restructuring, and keynote speakers will discuss a blueprint for a national food system.  Other topics that will be addressed during the symposium include the relative influence and efficacy of public and private food safety regulation, the role of federal agencies in food justice, the intersection of food and environmental regulation, and a reconsideration biotechnology regulation.  The symposium will be held at Georgetown University Law Center.  Additional information and registration is available here.

Technology continues to change the landscape of healthcare and companies are seeking new and innovative ways to leverage advances in other fields to improve quality of care and the diagnosis and treatment of disease. In doing so, they are required to navigate an increasingly complex and ever changing set of legal and regulatory requirements.

This webinar, presented by Dechert LLP, Hyman, Phelps & McNamara, PC, and InFuture LLC, brings together a cross-disciplinary group to discuss issues facing companies in the digital health section today, including those relating to fundraising and financing, IT/IP, data privacy, the U.S. Food and Drug Administration and the Health Insurance Portability and Accountability Act.

When

Tuesday, November 8, 2016
12:00 p.m. – 1:00 p.m. EST

Where

This presentation will be simulcast via Webex as a webinar. Please click here to register. (A recording of the webinar will be available to all registrants after the live event.)

Speakers

Tony Chan
Partner
Dechert LLP
Washington, D.C.

Jeffrey Gibbs
Director
Hyman, Phelps & McNamara P.C.
Washington, D.C.

Violetta Kokolus
Special Counsel
Dechert LLP
New York

Gregory Reid
President and CEO
InFuture LLC
Boston

Shannon Rushing
Associate
Dechert LLP
Philadelphia

By Ricardo Carvajal –

FDA issued a draft guidance document that addresses disclosures required to be provided by a supplier when certain hazards in food have not been controlled.  A disclosure requirement is included in four of the FSMA rules, namely the preventive controls rule for human food, the preventive controls rule for animal food, the produce safety rule, and the foreign supplier verification program (FSVP) rule.   Because of rolling compliance dates for the rules, the disclosure requirement is not yet in effect for many suppliers.

With respect to the specificity of the disclosure required under the human and animal food preventive controls rules and the FSVP rule, FDA would consider acceptable a general disclosure for biological hazards (e.g., “microbial pathogens” as opposed to “Salmonella”), but not for chemical or physical hazards.  Those hazards would need to be disclosed in more specific terms (e.g., “mycotoxins” for that type of chemical hazard, and “stones” for that type of physical hazard).  As to the method of disclosure, the rules require that the disclosure be made in documents that accompany the food, “in accordance with the practice of the trade.”  According to the draft guidance, FDA would consider acceptable providing the disclosure in documents such as “labels, labeling, bill of lading, shipment-specific certificates of analysis, and other documents or papers associated with the shipment that a food safety manager for the customer is likely to read.”  Methods of disclosure that are unlikely to pass muster include references to websites, as well as documents such as “contractual agreements, letters of guarantee, specifications, or terms and conditions” because those types of documents usually aren’t shipment-specific, and might not be seen by a customer’s food safety manager.

FDA’s recommendations with respect to the disclosure required under the produce safety rule parallel the recommendations summarized above, but are silent with respect to disclosure of chemical and physical hazards because that rule does not require their control.

Comments on the draft guidance are due by May 1, 2017.