Attorney East Hampton

By Karla L. Palmer –
The FDA just released Draft Guidance affecting the implementation of the Drug Quality and Security Act’s (DQSA) November 27, 2017 “serialization” requirements for finished dosage form pharmaceutical prescription drug products (as defined by the DQSA). Among addressing other issues, the newly released Draft Guidance states that FDA will extend the manufacturer serialization and product verification deadlines for a year – to now take effect November 27, 2018.
Recall that the Title II of the DQSA, the Drug Supply Chain Security Act (DSCSA) requires in FDCA Section 582(b)(2) that manufacturers “affix or imprint a product identifier” to each package and homogenous case of a product “intended to be introduced into commerce” beginning not later than November 27, 2017, and to verify that identifier in accordance with statutory requirements set forth in Section 582(b)(4). Drugs not including the product identifier after that date would have been deemed “misbranded” pursuant to the terms of the statute, and manufacturers who did not verify products would have been subject to enforcement action. See Draft Guidance at 5.    
Recall that the DSCSA also requires FDA to issue guidance defining “grandfathering” and how to obtain a “waiver, exception and exemption” of the so-called “serialization” requirement – by 2015. See FDCA Section 582 (a)(3), (a)(5). Notwithstanding the statutory deadline, FDA did not issue the guidance, leaving manufacturers to wonder in the years and months leading to the looming November 27, 2017 deadline what “grandfathering” was supposed to mean, whether it would apply to their drug products in the distribution chain or not yet in the distribution chain, and exactly what FDA would deem that distribution chain to be. FDA addresses the “grandfathering” conundrum on the last page of the Draft Guidance (page 8), stating it intends to issue additional guidance “that will outline FDA’s current thinking on the “grandfathering product” provision. (We will eagerly blog on that guidance when FDA releases it.)
In addition, manufacturers questioned whether they would otherwise be able to apply for a “waiver” of,   “exemption,” or ”exception” to the serialization requirement (because, for example, of a manufacturer has a small production or orphan drug, limited distribution channel, an inability to meet the requirement because of economic constraints, or an inability to meet the requirement because of a pending drug product approval near the November 2017 deadline). However, FDA remains silent in the Draft Guidance concerning whether or when it will issue much needed (and statutorily required) guidance on when and how to obtain waivers, exceptions, or exemptions of DSCSA serialization requirements for certain products.
FDA notes that it received comments from manufacturers and other trading partners expressing concerns with industry-wide readiness for implementation of the serialization requirement. It issued the Draft Guidance to minimize potential market disruptions in the United States.  
Importantly, FDA’s Draft Guidance does further define what “introduced in a transaction into commerce” means. This language has caused consternation among manufacturers given the lurking serialization deadline because manufacturers have struggled to understand exactly “when” a product “enters commerce” and thus when a product must serialized (i.e., when manufactured? when delivered to a warehouse? what if the manufacturer owns the warehouse?) Industry also was confused by the statute’s use of the word “intended to be introduced in a transaction into commerce” in the statute’s “Product Identifier” provision in FDCA Section 582(b)(2)(A).   Seemingly ignoring the preface “intended,” FDA now clarifies that it considers “a product to be ‘introduced in a transaction in commerce’ when the manufacturer first engages in a transaction involving the product.” The DSCSA defines “transaction” as the “transfer of product between persons in which a change of ownership occurs.” (Section 581 (24) (note exceptions)). Thus, in simpler terms, it now seems clear that a product must be serialized if a change of ownership from the manufacturer of the “product” occurs after November 27, 2018.
Most importantly, for those manufacturers that have engaged in the serialization process and have product identifiers on their products that are introduced in a transaction in commerce after November 27, 2017, your efforts are not lost on FDA. FDA expects both “manufacturers and downstream trading partners to use it in verification” as required under the DSCSA. See Draft Guidance at 5. (Lines 165-67)
Effect on Downstream Trading Partners (i.e., Wholesalers, Repackagers, Dispensers)
FDA’s Draft Guidance also addresses the trickle down effect of the additional year until enforcement on other participants in the drug distribution chain. Prior to the release of the Draft Guidance, repackagers would be required to engage in transactions with only those products bearing a product identifier by November 27, 2018. Wholesalers and dispensers had parallel requirements, effective November 27, 2019 and November 27, 2020, respectively. In addition, repackagers, wholesalers and dispensers would be required to verify product, including product identifiers at the package level (in certain circumstances) along this same timeline.   FDA states at page 6 of the Draft that it will not take enforcement action for these downstream partners for accepting ownership of unserialized product between November 27, 2017 and November 26, 2018. Draft Guidance at 6.
Repackagers and Product Identifiers: No Extension of Serialization Requirement
FDA’s requirement beginning on November 27, 2018, that repackagers “affix or imprint a product identifier on each packager or homogeneous case of product intended to be introduced into commence” still remains on target. Thus, beginning on November 27, 2018, wholesalers and dispensers that purchase from repackagers should ensure that the products they purchase have product identifiers. Id.       
Verification requirements for Repackagers, Wholesalers, and Dispensers
The Draft Guidance states that FDA recognizes that products introduced in a transaction in interstate commerce between November 27, 2017 and November 26, 2018, without an identifier will not be capable of verification at the package level via a product identifier. Therefore, FDA will not take action against repackagers, wholesalers, and dispensers that do not use a product identifier to verify product at the package level until November 27, 2018, November 27, 2019, and November 27, 2020, respectively. Draft Guidance at 7. Notwithstanding, they still must validate applicable transaction history and transaction information for product in their possession to determine whether it is suspect product, and the Guidance “does not extend the deadline for this requirement.” And, if the product does in fact contain an identifier, it must be used to verify the product.
Saleable Returns Intended for Further Distribution
With respect to saleable returns of product by a repackager or distributor intended for further distribution, the Draft Guidance states that they may receive a return of a product that does not include an identifier if the returned product was introduced in a transaction into commerce by a manufacturer before November 27, 2018. Draft Guidance at 7.
Documentation of the “Date of Introduction in a Transaction into Commerce”
FDA also offers guidance for trading partners to determine whether the product at issue introduced by a manufacturer into commerce without a product identifier between November 27, 2017 and November 26, 2018 is covered by the compliance policy outlined in the Draft Guidance. In other words, how do trading partners ensure that a product was in fact introduced in a transaction in commerce before November 27, 2018 (and thus does not require serialization and verification)?
FDA states that trading partners should make a determination (presumably after November 27, 2018) based on whether: (1) At least one of the transaction information documents (the transaction history) for the product describes an initial transaction date from the manufacturer as one that occurs between November 27, 2017 and November 26, 2018; or (2) there is other documentary evidence created by a trading partner “in the ordinary course of business” that contains a product description matching the product at issue that does not contain a product identifier. This type of documentation should contain a date from which it can be determined that the product was introduced in a transaction into commerce by the manufacturer between November 27, 2017 and November 26, 2018. Examples include “bills of lading, commercial invoices, and shipping invoices.”

By Ricardo Carvajal –
Earlier this week, USDA/AMS posted “Proposed Rule Questions Under Consideration” on its web page dedicated to the establishment of a National Bioengineered Food Disclosure Standard.  The posting asks for comment on 30 questions relating to different aspects of what such a standard might entail.  Most of the questions will doubtless be of great interest to industry and consumer advocates, and can be expected to generate a significant volume of comments.  For example, AMS asks for input on allowable terminology; types of modifications that should be exempt from disclosure; what the threshold for disclosure should be; how disclosures should be made for bulk, vending machine, and online purchases; how AMS should define very small or small packages for purposes of special provisions on disclosure; how AMS should define which retail food establishments are “similar” to restaurants; and what types of records should be required for compliance purposes.
AMS’s latest move is also interesting from a procedural standpoint.  At least some of the questions in the web posting may have originally been included in an Advanced Notice of Proposed Rulemaking (ANPRM) that was submitted to OMB/OIRA for regulatory review on January 18, 2017 – only to be withdrawn less than a week later, a few days after the presidential inauguration.   At that point, the rulemaking was already running behind the schedule that had been forecast in the unified agenda, which called for the ANPRM to be issued in November 2016.  Given that a proposed rule was forecast to be issued in November 2017, the recent web posting appears to be an effort to obtain the type of input that would otherwise have been obtained through the ANPRM – but without the associated delay.  Indeed, the posting states that “USDA will use this input in drafting a proposed rule.”  Because the web posting asks that comments be submitted to the agency via email, it’s not clear how or when those comments will be made accessible to the public.  In any case, an email notification of the posting states that “feedback related to the questions should be submitted to GMOlabeling@ams.usda.gov by July 17, 2017.”

By Etan J. Yeshua –
Last month we reported that FDA decided to delay the compliance date for restaurant menu labeling from May 5, 2017 to May 7, 2018 while it reconsiders certain aspects of the final menu labeling rule. The Agency requested comments from industry and other stakeholder about how the rule should be revised to reduce the regulatory burden on restaurants and other covered establishments: FDA said that only comments submitted within 60 days (by July 3, 2017) would be considered. Now, FDA is adding 30 days to the comment period.
The extension comes in response to a request from the National Restaurant Association (NRA). About halfway into the original comment period, NRA told FDA that it would be “nearly impossible” to prepare and submit its comments without an additional 60-day extension. Yesterday, with the deadline right around the corner, FDA stated in a letter to NRA that the Agency will extend the comment period by 30 days. Although it isn’t the full 60-day extension that NRA requested, restaurants and other interested parties will now have (by our count) until August 2, 2017 to submit comments. An official announcement of the extension (in the Federal Register) is forthcoming. FDA’s decision does not change the May 7, 2018 compliance date.

By Kurt R. Karst –      
The second iteration of the Generic Drug User Fee Amendments (“GDUFA II), which is contained in Title III of the FDA Reauthorization Act of 2017 (“FDARA”) (S. 934 and H.R. 2430) currently pending in Congress, will, if enacted, significantly change the current user fee system and structure that have been in place the past five fiscal years under GDUFA I.  Not only will FDA collect a greater amount of user fee funding each year ($493.6 million annually adjusted for inflation), but one fee type will be eliminated (i.e., the Prior Approval Supplement fee), while others fees would be modified (e.g., a new Finished Dosage Form (“FDF”) facility fee for Contract Manufacturing Organizations (“CMO”)).  GDUFA II will also introduce a new fee type – the ANDA Holder Program Fee – that will account for 35% of annual fee funding.  The annual ANDA Holder Program Fee, along with the annual CMO FDF facility fee, are proposed as “small business considerations,” according to FDA.
Under the GDUFA II fee structure, the ANDA Holder Program Fee is set up as follows: a firm and its affiliates will pay one program fee each fiscal year commensurate with the number of approved ANDAs (both active and discontinued ANDAs) that the firm and its affiliates collectively own. The program fee to be paid each year depends on the number of ANDAs owned.  Firms will not pay a per-ANDA fee.  Instead, the program fee will be split into three tiers that represent different positions held by the firms and their affiliates within the market.  Specifically, FDARA would amend the FDC Act to add Section  § 744B(b)(2)(E) to state:

(i) Thirty-five percent shall be derived from fees under subsection (a)(5) (relating to generic drug applicant program fees). For purposes of this subparagraph, if a person has affiliates, a single program fee shall be assessed with respect to that person, including its affiliates, and may be paid by that person or any one of its affiliates.  The Secretary shall determine the fees as follows:
(I) If a person (including its affiliates) owns at least one but not more than 5 approved [ANDAs] on the due date for the fee under this subsection, the person (including its affiliates) shall be assessed a small business generic drug applicant program fee equal to one-tenth of the large size operation generic drug applicant program fee.
(II) If a person (including its affiliates) owns at least 6 but not more than 19 approved [ANDAs] on the due date for the fee under this subsection, the person (including its affiliates) shall be assessed a medium size operation generic drug applicant program fee equal to two-fifths of the large size operation generic drug applicant program fee.
(III) If a person (including its affiliates) owns 20 or more approved [ANDAs] on the due date for the fee under this subsection, the person (including its affiliates) shall be assessed a large size operation generic drug applicant program fee.
(ii) For purposes of this subparagraph, an [ANDA] shall be deemed not to be approved if the applicant has submitted a written request for withdrawal of approval of such [ANDA] by April 1 of the previous fiscal year.

The statute (FDC Act 744B(g)(5)) would also be amended to include certain penalties for failure to pay the new ANDA Holder Program Fee:

(A) IN GENERAL.—A person who fails to pay a fee as required under subsection (a)(5) by the date that is 20 calendar days after the due date, as specified in subparagraph (D) of such subsection, shall be subject to the following:
(i) The Secretary shall place the person on a publicly available arrears list.
(ii) Any abbreviated new drug application submitted by the generic drug applicant or an affiliate of such applicant shall not be received, within the meaning of section 505(j)(5)(A).
(iii) All drugs marketed pursuant to any abbreviated new drug application held by such applicant or an affiliate of such applicant shall be deemed misbranded under section 502(aa).
(B) APPLICATION OF PENALTIES.—The penalties under subparagraph (A) shall apply until the fee required under subsection (a)(5) is paid.

We don’t yet know exactly how much the annual ANDA Holder Program Fee will be for Fiscal Year 2018, but at 35% of the overall GDUFA user fee funding, we assume it could be a decent amount of cash for some companies to lay out. And for some companies with a small number of ANDAs, they’ll be laying out cash for drug products that they don’t currently market, because their ANDAs are in stasis, as identified in the Discontinued Drug Product List section of the Orange Book. 
FDA is currently collecting information from ANDA sponsors – see here and here – in an effort to set the fee.  In the meantime, our friends over at the Lachman Consultants Blog recently provided a “back of the envelope”  calculation based on the total fees FDA will collect under the ANDA Holder Program Fee initiative.  They estimate that companies in the small tier will pay $130,780; companies in the medium tier will pay $523,120; and that companies in the large tier will pay $1,307,800.
A new venture might offer some user fee relief and a solution to companies that have discontinued ANDAs for drug products not currently marketed. A company called ANDA Repository, LLC (info@andarepository.com) is offering what we can only characterize as “ANDA arbitrage.”  Imagine, if you will, a parking lot.  The owner of a car that is not being used on a daily basis needs a parking space for that car.  In exchange for that parking space (and an annual fee) the car’s owner transfers title of the automobile to the parking lot owner.  The old owner of the car can, with appropriate notice, take back ownership when he decides that he wants to use the automobile again.  Provided the parking lot owner has enough cars, this can be a beneficial venture for all of the parties involved. 
In the imagery above, the automobile owner is an ANDA sponsor, and the parking lot owner is ANDA Repository, LLC. If ANDA Repository, LLC is able to obtain title to 20 or more ANDAs, then the company will be identified as a “large size operation” and will pay a full generic drug applicant program fee regardless of how may additional ANDAs are owned. In exchange for its services, ANDA Repository, LLC will charge an ANDA sponsor an annual fee, which would be significantly less than the ANDA Holder Program Fee such ANDA sponsor would otherwise pay as a small or medium size operation.   Not a bad idea!

By Sara W. Koblitz –
As a prelude to FDA’s Hatch-Waxman Act public meeting next month, FDA announced today an updated a Manual of Policy and Procedures (MAPP) for review of generic drug applications and a public list of off-patent and off-exclusivity NDA products without ANDA competition. 
Effective June 27, 2017, MAPP 5240.3 Rev. 3, Review Order of Original ANDAs, Amendments, and Supplements, updates FDA’s system of priority for review of generic drug applications at all stages of review.  While FDA’s ranking system of types of submissions that will have review priority for OGD has not changed, the MAPP adds as a top review priority generic products for which there are no blocking patents (carved-out patents are not considered blocking) or exclusivities and fewer than three approved ANDAs for the RLDs.  This is a change from the previous MAPP, which only prioritized the review of “first generic products” for which there are no blocking patents or exclusivities for the RLD.  According to FDA’s press release, the policy revision is “based on data that indicate that consumers see significant price reductions when there are multiple FDA-approved generics available.”
To encourage more competition, FDA also published today a List of Off-Patent, Off-Exclusivity Drugs without an Approved Generic.  This list basically serves as a “hit list” for generic manufacturers.  FDA announced in its press release that, in accordance with the revised MAPP, it intends to expedite review of any generic drug application on this list.  Part I of the list identifies products for which FDA could immediately accept an ANDA without prior discussion with FDA, while Part II identifies drug products that may raise legal, regulatory, or scientific issues that should be addressed with FDA prior to ANDA submission (these could be drugs for which a 505(b)(2) is more appropriate or drugs with complex bioequivalence profiles).  Products are identified based on the Orange Book-listed active ingredient, and the list does not differentiate between strength or dosage forms of the same active ingredient.
The list was compiled based on Orange Book Data files accessed May 30, 2017 and will be updated approximately every six months.  NDAs approved in the last year were omitted. 
Both of these efforts combined are part of Commissioner Gottlieb’s Drug Competition Action Plan, designed to address competition and pricing in the generic drug market.  It’s clear that this endeavor is a priority for Commissioner Gottlieb, so we expect more on this initiative soon.

By Kurt R. Karst –
In a new report issued earlier this week, titled “Generic Drug User Fees: Application Review Times Declined, but FDA Should Develop a Plan for Administering Its Unobligated User Fees,” the U.S. Government Accountability Office (“GAO”) examines several aspects of FDA’s implementation of the first iteration of the Generic Drug User Fee Amendments (“GDUFA”). Responding to an inquiry from the U.S. Senate Committee on Health, Education, Labor, and Pensions, the GAO: (1) examines how user fees supported FDA’s generic drug program; (2) describes FDA’s improvements to the generic drug application review process; and (3) analyzes changes in generic drug application review times.  In an appendix to the report, GAO also includes a discussion of the various regulatory science initiatives funded under GDUFA and identified in the GDUFA I Commitment Letter.
Overall, the GAO found that GDUFA user fee funding has been used well to improve FDA’s generic drug program. “FDA has used its user fee funding to enhance OGD’s ability to increase hiring, and undertake numerous activities to improve and speed-up the review of generic drug applications,” says the GAO.  These improvements are apparent in decreased first cycle ANDA and Prior Approval Supplement (“PAS”) review times:

With respect to ANDA review times, the average time for FDA to complete the first review cycle decreased from 26 months for ANDAs submitted in fiscal year 2013 to about 14 months for those submitted in fiscal year 2015. . . . However, as of December 31, 2016, 929 ANDAs (34 percent) submitted since the start of the generic drug user fee program in fiscal year 2013 were still pending review.  As these applications are reviewed, the average review time . . . for each fiscal year will increase since all of the applications that remained to be acted on are at least 15 months old.  As of December 31, 2016, FDA had also acted on 89 percent of all ANDAs submitted in fiscal year 2015 within 15 months of receipt, exceeding its GDUFA goal of acting on 60 percent of ANDAs received in fiscal year 2015 within 15 months. . . .
For PASs, the average time for FDA to complete the first review cycle also declined from 12 months in fiscal year 2013 to 4.5 months in fiscal year 2015.

Despite the decrease in original ANDA and PAS first cycle review times, where the rubber meets the road is in approvals. As Office of Generic Drugs Director Kathleen “Cook” Uhl noted earlier this year only 9% of ANDAs in the Fiscal Year 2015 application cohort were approved (or tentatively approved) during a first cycle review, while 71% were the subject of a Complete Response Letter.  The anemic approval figure improved to 42% (and 56% for Complete Response Letters) on a second cycle review. 
The GAO’s biggest criticism of FDA’s implementation of GDUFA concerns the Agency’s lack of a plan for dealing with user fee carryover. “FDA has accumulated a large unobligated user fee carryover balance, which it uses as an operating reserve,” says the GAO. “At the beginning of fiscal year 2017, FDA had a carryover of approximately $174 million.”  That figure is way down from the staggering $278 million carryover FDA had amassed by the end of Fiscal Year 2014.  Nevertheless, it’s “an amount nearly as great as the annual, inflation-adjusted user fee collection amount of $299 million” established under GDUFA I, notes the GAO. 

Despite the large carryover amounts, FDA has not developed a planning document on how it will administer its carryover—one that includes a fully documented analysis of program costs and risks to ensure that its carryover reflects expected operational needs and probable contingencies. Although FDA uses an internal management report to show GDUFA collection amounts, obligations, and end-of-year carryover amounts, the agency was unable to produce evidence describing whether the carryover of $174 million at the beginning of fiscal year 2017 (or carryover amounts in other years) was within a targeted goal, and it does not have targets for future years in general.

To deal with this lingering issue, and to “ensure efficient use of generic drug user fees, facilitate oversight and transparency, and plan for risks,” the GAO recommends that FDA Commissioner Gottlieb “develop a plan for administering user fee carryover that includes analyses of program costs and risks and reflects actual operational needs and contingencies.”

By Mark I. Schwartz –
Earlier this year, we blogged about FDA’s Field Alert Report (or FARs) reporting requirements under 505(k) of the Federal Food, Drug, and Cosmetic Act. The requirements have been in effect since 1985, when the agency promulgated the regulatory provision at 21 CFR 314.81(b)(i).
At the time of our blog on the issue, among other things, we referenced FDA’s Compliance Program Guidance Manual 7356.021, which provides instructions to FDA personnel for conducting activities to evaluate industry compliance with FDA’s field alert reporting requirements. We also referenced Form 3331, which is the form manufacturers are expected to use to submit their FARS.
What we did not mention is that in May of 2013, FDA had launched a voluntary pilot program to modernize the FAR submission and review process by allowing firms to submit FARs electronically using an XML-enabled PDF form. XML stands for “Extensible Markup Language”, and it is a meta-language which allows users to define their own customized markup languages, particularly to display documents on the Internet. The XML-enabled form is known as FDA Form 3331a, and it eliminates the need to fax or scan the form to the firm’s local FDA field office.
This pilot project ended on June 15th, 2017, and the agency has stated that the following objectives for the pilot project were achieved:

Allowing simultaneous reporting to FDA’s Office of Regulatory Affairs (ORA) and CDER; and

Determining the feasibility of transitioning from a simple PDF to a functional PDF.

FDA concluded that the use of the automated form “…improved the speed and efficiency of reporting on product quality issues related to the manufacture of drug products approved under a new drug application (NDA) or abbreviated new drug application (ANDA) by FDA.”
With the data that FDA gathered from FARs submissions over the four year period of the pilot project, as well as from explicit feedback from pilot project participants, the agency has created a new version of the automated Form 3331a. Some of the changes to the form that was used in the pilot project are as follows:

Fields have been rearranged;

Most of the fields are now expandable;

The lot number and expiration date fields have been combined;

The dosage form and strength/package size data are now in separate fields;

The problem and reporting firm sections now have separate fields for individual address components;

The reporting firm is now asked to provide a DUNS (Data Universal Numbering System) or FEI (Facility Establishment Identifier) number;

The new version of the form can be used to submit FARs for NDA or ANDA products that fall under the jurisdiction of CDER or CBER;

Signatures are not required.

FDA also mentioned that the agency is working on meeting the technical requirements for receiving FARs as part of the electronic Common Technical Document (eCTD) through the Electronic Submissions Gateway, and that this process will be described in a future guidance document.

By Riëtte van Laack –
As readers of this blog know, in May 2016, FDA issued a final rule amending the nutrition labeling regulations for food and dietary supplements. Major amendments include a new requirement to declare “added sugar,” the setting of a daily value for added sugars (but not for total sugars), and a new definition of dietary fiber (see our previous post here).
FDA has received at least two Citizen Petitions requesting a stay of the rule and reconsideration (or withdrawal) of the definition of dietary fiber. Last week, the Agency announced that it will extend the compliance date to provide companies with guidance regarding the final rule (see our previous post here).
FDA’s proposal to require added sugars may be the most controversial issue and generated many comments. However, besides comments to a draft guidance addressing added sugars and comments and questions in other contexts, no party had so far formally objected to the new requirement to declare added sugars. That changed on June 20, 2017, when the Natural Products Association (NPA) submitted a Citizen Petition asking FDA for a stay and reconsideration of the final rule. NPA’s Petition focuses on the rule’s requirements for added sugar but also addresses the dietary fiber definition.
The Petition identifies seven grounds for a stay and reconsideration, five of which focus on the requirement to declare added sugars. Grounds include FDA’s alleged failure to comply with rulemaking procedures of the Administrative Procedures Act and the new administration’s regulatory agenda and directives. Petitioner also asserts that the final rule requiring declaration of added sugars raises First Amendment concerns because it imposes unjustified and unduly burdensome disclosure requirements on companies. NPA also finds fault with FDA’s analyses and conclusions based on consumer and eye tracking studies.
With respect to the dietary fiber definition, Petitioner alleges that all non-digestible carbohydrates have a physiological effect by virtue of being non-digestible and thereby “promoting an osmotic and bulk laxative physiological effect.” In somewhat caustic terms, Petitioner challenges FDA to show that a non-digestible carbohydrate does not have such a beneficial effect.
Thus far, FDA has not given any indication that it will reconsider the final rule. We will be monitoring new developments.

By Sara W. Koblitz – 
On June 21st, FDA announced an all-day public meeting dedicated to the Hatch-Waxman Amendments that will take place on July 18, 2017. The meeting, titled “The Hatch-Waxman Amendments: Ensuring a Balance Between Innovation and Access,” is part of Commissioner Gottlieb’s Drug Competition Action Plan, which he indicated was forthcoming during a May 2017 House Appropriations Committee hearing.  The meeting is intended to further explore the juxtaposition of innovation in drug development and access to lower cost alternatives to innovator drugs. In an FDA Voice blog post, Commissioner Gottlieb explains that FDA is looking at how regulatory rules might be “gamed” or misused to reduce competition, keeping prices high for consumers. FDA is also bringing in the anticompetitive experts at the FTC to help out.
FDA posed several questions for stakeholder input:

How have exclusivity periods, patents and patent listing procedures, innovator drug product labeling, post-approval changes to innovator products, and other regulatory processes (such as the citizen petition process) impacted the balance of innovation and access set forth in the Hatch Waxman Amendments?

Given that many ANDAs are never marketed or subject to substantial delays after approval, what marketplace dynamics dis-incentivize the marketing of approved generics? What can FDA do to help approved generics come to market?

Why are there so many drugs that have lost patent and exclusivity protection but have no generic competition? Are there areas where Hatch-Waxman Amendment incentives are insufficient to develop a generic?

How should FDA use its authority to waive shared REMS systems to avoid delay or should it develop other administrative tools to do so?

What should FDA do to promote access to testing samples?

What other elements of drug product development, regulation, and marketing have the potential to disrupt the Hatch-Waxman Amendments’ balance between innovation and generic availability, and how should the Agency address them?

Written comments are due by September 18, 2017. Registration for the public meeting, as well as requests to make oral presentations, is due to FDA by July 3, 2017. We’re sure we’ll see you all at what promises to be an exciting meeting!

By Kurt R. Karst –
Although both the U.S. House of Representatives and U.S. Senate are still in the midst of considering legislation – the FDA Reauthorization Act of 2017 (“FDARA”) (H.R. 2430 and S. 934) – to, among other things, reauthorize an alphabet soup of user fee programs, including the second iteration of the Generic Drug User Fee Amendments (“GDUFA II”), and as the Congressional Budget Office analyzes the cost of FDARA (see here), FDA has apparently decided that it’s pretty certain that GDUFA will ultimately be enacted into law. Earlier this week, FDA issued a draft guidance document, titled “ANDAs: Pre-Submission Facility Correspondence Associated with Priority Submissions,” that is intended to implement a new Pre-Submission Facility Correspondence (“PFC”) process for certain ANDA sponsors. 
As part of GDUFA II, FDA and the generic drug industry hammered out a Commitment Letter under which FDA agreed to review and act on certain “priority ANDAs” (including original ANDAs, ANDA amendments, and ANDA Prior Approval Supplements) within timeframes shorter than those established for “standard ANDAs.” For example, while FDA agreed to review and act on 90% of standard original ANDAs within 10 months of the date of ANDA submission, 90% of priority original ANDAs will be reviewed and acted on “within 8 months of the date of ANDA submission, if the applicant submits a Pre-Submission Facility Correspondence 2 months prior to the date of ANDA submission and the Pre-Submission Facility Correspondence is found to be complete and accurate and remains unchanged.” If, however, “the applicant does not submit a Pre-Submission Facility Correspondence 2 months prior to the date of ANDA submission or facility information Changes or is found to be incomplete or inaccurate,” then FDA will review and act on 90% of priority original ANDAs within 10 months of the date of ANDA submission.  Whether a particular ANDA submission qualifies for “priority” status will depend on the sponsor meeting the criteria laid out in FDA’s “Prioritization MAPP” (i.e., Manual of Policies and 35 Procedures (MAPP) 5240.3, Rev. 2, “Prioritization of the Review of Original ANDAs, Amendments, and Supplements”).
As described above, the PFC process is the linchpin to obtaining an 8-month priority review goal date. And as we approach the beginning of Fiscal Year 2018 when GDUFA II is expected to go into effect, FDA wants to make the PFC process as clear as possible now so that ANDA sponsors can begin putting together the necessary paperwork to submit requests in anticipation of the GDUFA II goals becoming reality.  To that end, the draft guidance “establishes FDA’s expectations for the content, timing, and assessment of the PFC,” and, specifically defines:

The content and format of the information that should be submitted in the PFC to enable FDA’s assessment of facilities listed in the PFC.
PFC timeframes and their intersection with the subsequent ANDA submissions.
The possible outcomes of the Agency’s assessment of the PFC.
When and how the PFC submitter is notified by the Agency about the status of the PFC.

The draft guidance lays out a detailed set of instructions for ANDA sponsors to follow when making a PFC submission. And knowing FDA’s (the Office of Generic Drug’s) penchant for kicking out or refusing submissions that don’t meet even the smallest detail, ANDA sponsors would be wise to ensure that every “i” is dotted and every “t” is crossed in a PFC submission.
Timing is also a critical component of the new PFC process, because PFCs have a short expiry date. The GDUFA II Commitment Letter provides that a PFC should be submitted to FDA two months ahead of the planned ANDA submission date in order for an application to be eligible to receive the shorter 8-month goal date.  According to FDA:

[I]f the time elapsed between submission of the PFC and submission of the planned ANDA is too long, it is less likely that facility information will remain unchanged, as defined by the GDUFA II Commitment Letter. Thus, FDA’s PFC facility assessment may become out-of-date and need to be repeated after the planned ANDA is submitted, eliminating the benefit of the PFC submission to both FDA and the applicant.  Therefore, this guidance establishes a window of time between 2 and 3 months after PFC submission during which applicants should submit their planned ANDA. 

This is referred to in the draft guidance as the “ANDA Submission Window.” For example, if a PFC is submitted to FDA on December 1st, then the planned ANDA should be submitted to FDA between February 1st and March 1st.  Similarly, if the PFC is submitted to FDA on December 31st, then the planned ANDA should be submitted to FDA between February 28th (in a non-leap year) and March 31st.