This webinar is hosted by The Knowledge Group.

On March 22nd at 12 p.m. ET, Dean Fanelli and Jamaica Szeliga, along with Timothy Shea of Sterne, Kessler, Goldstein & Fox P.L.L.C., will present a live webcast on Biosimilar Litigation and Your BPCIA Compliance: Key Strategies In Light of AbbVie v. Boehringer.

The previous year saw an increase in biosimilar filings in the U.S., including the recent suit filed by AbbVie in the U.S. District Court for the District of Delaware against Boehringer Ingelheim regarding Boehringer Ingelheim’s adalimumab product, Cyltezo®, a proposed biosimilar to AbbVie’s Humira®. The complaint alleges infringement of 8 patents in the initial phase of litigation, as Boehringer Ingelheim was able to cap the scope of litigation by complying with the procedures of the Biologics Price Competition and Innovation Act of 2009 (BPCIA). This case reflects the benefits of complying with the BPCIA’s patent dispute resolution procedure, also known as patent dance.

In this LIVE webcast, a panel of distinguished professionals and thought leaders will discuss the latest legal and regulatory updates that are continuously changing the biosimilar landscape. They will review the on-goings of the AbbVie v. Boehringer Ingelheim litigation and give insights on the benefits and risks of engaging in the BPCIA’s patent dance. Speakers will also provide considerations in adopting appropriate litigation strategies.

Key issues that will be covered in this course are:

  • Biosimilar Litigation Landscape Post Sandoz v. Amgen
  • Complying with BPCIA: AbbVie v. Boehringer Ingelheim
  • The Benefits and Risks of Patent Dance
  • Recent Legal and Regulatory Updates
  • Strategic Considerations for Biosimilar Litigation
  • Significant Trends and Legal Updates

For more information and to register for the webinar, click here.

Seyfarth Shaw Offers Hatch-Waxman And Biosimilars Litigation: 2017 Year-in-Review

Today’s rapid scientific and technological advances demand not only a thorough understanding of the complex technology, but also a meticulous application of intellectual property law to protect the technology.

Seyfarth’s Intellectual Property and Hatch-Waxman Litigation practitioners are pleased to announce the release of Hatch-Waxman And Biosimilars Litigation: 2017 Year-in-Review which provides a brief overview of the Hatch-Waxman Act, a summary of the recently released FDA Draft Guidance, a general timeline of Hatch-Waxman and Biosimilars litigation and summaries of some of the related decisions issued by the U.S. Supreme Court and Court of Appeals for the Federal Circuit in the year 2017.

How to Get Your Desktop Guide:

To request the Hatch-Waxman And Biosimilars Litigation: 2017 Year-in-Review as a pdf or hard copy, please click the button below:

 

 

For updates and insight on Hatch-Waxman related issues, we invite you to subscribe to our BioLoquitur Blog.

Continue Reading Now Available! Seyfarth Shaw’s Hatch-Waxman and Biosimilars Litigation: 2017 Year-in-Review

As a special feature of our blog, we include special guest postings by experts, clients, and other professionals—please enjoy this blog entry which includes guest author Rolf J. Haag.[1]

It has been impossible to miss the surreal volatility in Bitcoin’s per unit price—having gone from $1,000 in January 2017 to almost $20,000 (~$750B mkt. cap) toward the end of last year and retracting to under $8,000 (~$500B mkt. cap) in February 2018. Whether these G-LOC-inducing price undulations are reflective of a radical paradigm shift in the mode of financial transactions, history’s greatest pyramid scheme, or some mix thereof, remains to be seen. Continue Reading Will Blockchain Revolutionize Bio/Pharma R&D, Tech Transfer, and IP?

In late December the FDA issued a new guidance, entitled “Best Practices for Communication Between IND Sponsors and FDA During Drug Development.” The purpose of the guidance is to “describe best practices and procedures for timely, transparent, and effective communications between investigational new drug application (IND) sponsors and FDA at critical junctures in drug development.” The hope is the guidance facilitates an earlier availability of safe, effective and high-quality drugs to the American public, including biosimilars.

The IND phase of drug development is the time during which human trials of investigational drugs are conducted. From the FDA’s perspective, the IND phase spans the time from the first IND-related submission (including a pre-IND or Biosimilar Initial Advisory (BIA) meeting request or an original IND) to the submission of a marketing application. The FDA engages in thousands of communication with drug sponsors during the IND phase. As such, the FDA’s guidance encourages efficient, consistent, clear and concise communications.

The new guidance particularly lays out and describes the following: the FDA’s philosophy regarding timely communications with IND sponsors as a core activity; the scope of appropriate interactions between review teams and IND sponsors; the types of advice that are appropriate for IND sponsors to seek from FDA; the expectations for the timing of FDA responses to IND sponsor inquiries; the best practices and communication methods to facilitate interactions with the FDA; and the expectations for appropriate methods of communication with the FDA.

At bottom, the FDA engages in thousands of communications with IND sponsors each year. Given the sheer volume of communications the FDA must review and respond to, facilitating a consistent, complete and concise communication protocol will assist the FDA in reviewing and providing timely and cogent feedback to the sponsors where appropriate. This, in turn, should result in greater efficiency during the drug development process to the benefit of the American public.

The Federal Circuit on Wednesday reversed Court precedent and long held belief that inter partes review (“IPR”) institution decisions were categorically non-reviewable. The Court, sitting en banc, held that the issue of whether a petitioner is time-barred from filing an IPR petition  under 35 U.S.C. § 315(b) is in fact reviewable.[i]

This case arose when the patent owner alleged that an IPR petition was time barred based on the petitioner being privy with parties sued over the patent more than a year before the petition was filed. The IPR was instituted and a final written decision was published.

Congress granted the Director of the USPTO, subject to certain requirements, the sole discretion in whether to institute an IPR.  It is the extent of that discretion that the Court clarified on Wednesday. The Court honed in on two sections of the AIA—§§ 314 and 315. Section 314(a) authorizes the Director to institute an IPR if there is a “reasonable likelihood” that the petitioner will prevail with respect to at least one claim challenged in the petition. Section 315(b) on the other hand is a statutory time bar provision that limits a petitioner’s ability to successfully pursue an IPR proceeding if the “petitioner, real party in interest, or privy of the petitioner” was served with a complaint alleging infringement of the patent more than one year before the IPR petition was filed. The question answered by the court was whether § 314(d), which deems the Director’s decision to institute an IPR “under this section” final an nonappelable, extends to the time bar set out in § 315(b). According to the court, § 314(d) does not extend to § 315(b), but it is unclear if other determinations may soon be reviewable.

In concluding that the time bar determination is appealable, the Court highlighted the “fundamentally different” analysis of § 314 and § 315. On one hand, § 314(a) relates to a substantive analysis of the merits—a “preliminary patentability determination.” On the other hand, § 315(b) is a “condition precedent to the Director’s authority to act.” In other words, § 315(b) is precondition that if met grants the Director the authority to make a determination under § 314(a). According to the Court, the lack of a clear indication that Congress intended to bar appeals related to § 315(b) gave way to “the strong presumption in favor of judicial review of agency actions.”

This decision, although limited to time bar appeals, opens the door for other challenges to the Director’s “sole discretion.” Based on the Court’s heavy reliance on the language of § 314 being directed to preliminary patentability determinations, it is possible that the Court may be amenable to further appeals that do not relate directly to the “patentability merits of the claims.” Other AIA threshold requirements that may be challenged include the requirement that petitioner name all interested parties in the case and the AIA estoppel provisions.


[i] The case is Wi-Fi One LLC v. Broadcom Corp., Nos. 15-1944, 15-1945, and 15-1946 (Fed. Cir. Decided January 8, 2018).

It was a busy year for patent litigation across the broad, including the U.S. Patent and Trademark Office Patent Trial and Appeals Board (PTAB), U.S. District Courts (USDC), Court of Appeals for the Federal Circuit (CAFC), and the Supreme Court of the United States (SCOTUS). A quick look at the number of patent litigation cases filed over the years, particularly the last five years, show that while there has been a decrease in the number of cases filed with the USDC, the filings with the PTAB and CAFC saw a significant increase.

Total Number of Patent Litigation Cases 2008 to 2017

USDC patent case counts include cases addressing the infringement, validity, or enforceability of a U.S. patent that are pending in a U.S. district court or the Court of Federal Claims. This encompasses cases flagged with Nature of Suit (“NOS”) 830 in the PACER system as well as other cases that are known to meet the above criteria. Transferred, consolidated, coordinated, or bifurcated actions may contribute to the number of cases counted.

PTAB cases include applications to the PTAB for inter partes reviews and post-grant reviews pursuant to 35 U.S.C. § 6(a)(4), as reported in the PTAB’s Patent Review Processing System (“PRPS”). The term does not include proceedings conducted pursuant to 35 U.S.C. § 6(a)(1)-(3) such as appeals of adverse decisions of examiners, appeals of reexaminations, or derivation proceedings. Data obtained from Docket Navigator analytics.

SCOTUS was called upon to make important decisions ranging from patent venue laws, patent exhaustion to a U.S. manufacturer’s liability for exporting components later incorporated into an infringing product, including amendments during inter partes review. The year started with predictions as to whether the Supreme Court will consider the issue of whether IPR violates the U.S. Constitution by extinguishing private property rights through a non-Article III forum without a jury, in Oil States Energy Services LLC v. Greene’s Energy Group, LLC, and ended with predictions regarding the outcome of the oral arguments heard by the Court in November. Although faced with the issue before, the fact that Supreme Court decided to hear the issue now is not surprising given the increasing number of IPRs being filed with the PTAB and a slow decrease in the number of IPR petitions being instituted (coupled with increase in the number of IPR petitions being denied).

Institution Rates from FY13 to FY18 (Source: PTAB)

The number of post-grant proceedings filed in the technologies related to Electrical/Computer & Mechanical are much higher than those filed in the Bio/Pharma and Chemical technology areas. However, the rate at which the petitions are instituted is similar in each of the technology areas.

Institution Rates by Technology 09/16/2012 to 11/30/2017(Source: PTAB)

Also, the post- and pre-institution settlement rates have remained the same for the last two years, which are noticeably lower as compared to two years prior to that and significantly lower (at least for post-settlements) compared to five years ago. Although it may be tempting to associate this decrease in settlements to the predictions of Oil States’ challenge for the constitutionality of IPR proceedings, it would not be appropriate to do so given that the issue has been discussed previously.

Pre-Institution Settlements (Source: PTAB)

Post-Institution Settlements (Source: PTAB)

The Supreme Court’s decision in Oil States could have a major impact on the patent world, and is clearly the center of attention as the new year begins. Certainly, the decision in TC Heartland has proved to be a game-changer in patent filings. According to a recently published report by Fried, Frank, Harris, Shriver & Jacobson LLP, a substantial difference was noticed in the patent infringement filings from May 2017 to September 2017 when compared to the same period in 2016 in at least two of the top ten District Courts. The patent filings in the Eastern District of Texas, which is considered a plaintiff-friendly jurisdiction, decreased from 39.61% in 2016 to 15.04% in 2017; while the district of Delaware saw a rise in the filings, which is not surprising given most companies are either based out of, or majorly operate, in Delaware.

Top 10 District Courts: Pre- and Post-TC Heartland

It is not unusual that a decision, even by the Supreme Court, sometimes tends to pose more questions than it answers. The decision in Life Technologies Corp v. Promega Corp. is certainly amongst the top in 2017, wherein the Supreme Court had to address the issue of a U.S. manufacturer’s liability for exporting components later incorporated into an infringing product. While addressing a specific dispute pertaining to diagnostic kits between the parties, the Court raised many questions without providing any guidance as to the answers for those questions. The court held that the term “substantial portion” in Section 271(f)(1) has a quantitative, not a qualitative, meaning. More specifically, the court held that the phrase “substantial portion” in the statute does not cover the supply of a single component of a multicomponent invention. One of the obvious questions this decision raises is what if the invention is a two-component invention?” Would the supply of a single component of a two components invention still be outside the scope of the statute? Given the continuing growth in international commerce, it is fair to predict that the Courts might have to address this issue sooner than later.

This year was also marked by the Supreme Court deciding on its first case related to Biologics Price Competition and Innovation Act (“BPCIA”). The Court was called upon to review an issue regarding the notice requirements of BPCIA. Although, the Court provided clear guidance that biosimilar applicants may provide 180-day notice of commercial marketing prior to the FDA’s approval of the application, it left some questions for the CAFC to decide. The Court held that the Federal law does not provide for an injunction requiring a biosimilar applicant to start the patent dance by providing its application and manufacturing information to the reference product’s sponsor under 42 U.S.C. § 262(l)(2)(A) and remanded the case to CAFC for further proceedings. In December, the CAFC held that BPCIA preempts any state law remedies for failure to comply with § 262(l)(2)(A) and concluded that applying state law would create a conflict with the careful balance struck by Congress in establishing the BPCIA.

The CAFC also had its share (65% of its docket) of intellectual property law cases, including 29% resulting from appeals from the District Court decisions and 33% resulting from appeals from the PTAB.

Appeals Filed, by Category for FY 2017 (Source: CAFC)

A review of filings over the last 10 years reveals that the number of appeals filed with the Federal Circuit resulting from the PTAB have risen significantly in the last 4 years.

Appeals Filed, by Category for FY 2006 to FY 2017 (Source: CAFC)

This increase in the appeals resulting from PTAB is consistent with the number of petitions for post-grant proceedings filed with the PTAB. It will be interesting to see how the trend, particularly in inter-partes review filings, will change once the Supreme Court issues its final written decision.

On December 7, 2017, the FDA announced three new policy documents geared toward advancing and properly overseeing innovative new digital health tools. The documents mark an acute recognition by the FDA that as consumers and health care providers increasingly use digital technologies as health tools to acquire information, the FDA’s policies must continue to encourage the development of such technologies.

Of the three new guidance documents, two are drafts and one is final. The guidances address the provisions of the 21st Century Cures Act and clarify where the FDA has a role in the promotion of digital health care.

The first guidance is titled “Clinical and Patient Decision Support Software” and addresses clinical decision support software (CDS). CDS technology assists health care providers in making decisions as to the course of treatment for a patient’s disease or condition. The FDA seeks to encourage software developers to create and expand CDS functionality in treating old and new diseases. The guidance identifies which types of CDS do not qualify as a “medical device” and thus do not require FDA regulation, namely, CDS that permits the health care provider to independently review the basis of the recommendation for treatment.

The second guidance addresses the FDA’s interpretation of other types of software that are similarly no longer considered medical devices, titled “Changes to Existing Medical Software Policies Resulting from Section 3060 of the 21st Century Cures Act.” In particular, this guidance sets out that digital health technologies such as mobile apps that are used by consumers to log, record, track, evaluate and make decisions on a healthy lifestyle, like dietary logs, meal planners, or activity trackers, fall outside the scope of FDA regulations.

Lastly, the FDA issued a final guidance, “Software as a Medical Device: Clinical Evaluation,” expanding the draft issued in October 2016. The guidance establishes and harmonizes global principles for evaluating the safety, efficacy and performance of Software as a Medical Device, based upon the overall risk of the product.

The three guidances issued last week seek to continue to clarify the FDA’s role and oversight in digital health technologies. As the ever-changing field of digital health technology expands, so too will the FDA’s efforts to encourage innovators to create and expand such technology.

The ability to facilitate the regeneration of parts of the human body is “no longer the stuff of science fiction” according to FDA Commissioner Scott Gottlieb.[i] According to Commissioner Gottlieb, the cell based therapies and their use in regenerative medicine is one of the most promising fields of science already producing “improbable advances.” At the current early stages of development, deceptive claims from unscrupulous actors risks “jeopardizing the legitimacy and advancement of the entire field.” In order to curb such deception while simultaneously providing a clear and efficient path for product developers, the FDA has recently published a suite of four new guidance documents related to their regenerative medicine policy framework.

These four guidance documents represent a broad policy framework by the FDA building upon the framework put into effect in 2005. In its never ending battle to ensure the safety and efficacy of medical products while simultaneously supporting innovation, the FDA’s new approach will undoubtedly entail additional requirements on those innovators in the regenerative medicine field. It is important to review the guidance documents to ensure compliance with the FDA, but also to take advantage of the various opportunities for approval for those medicines and products that meet certain criteria. For this purpose, below is a brief summary of what the guidance documents include.

As guidance documents, the information provided does not create legally enforceable responsibilities, but rather they provide a glimpse into how the FDA is currently thinking and how the FDA will likely apply the existing laws and regulations that govern regenerative medicine products. Two of the documents are final guidance documents now in effect with the remaining two documents in draft form allowing the public to provide their comments.

Final guidance documents

The first guidance document titled “Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception”[ii] provides clarity on when cell and tissue-based products would be excepted from the current regulations if they are removed from and implanted into the same individual during the same surgical procedure and remain in their original form.

The second guidance document titled “Regulatory Considerations for Human, Cell, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use”[iii] clarifies how the FDA interprets the regulatory definitions for “minimal manipulation” and “homologous use.” This guidance is particularly helpful in that these concepts establish the legal threshold for when a particular product is subject to the FDA’s premarket approval requirements. In light of the how this new interpretation will effect manufacturers, healthcare providers, the FDA plans to exercise ‘enforcement discretion’ to those products that do not pose a potential significant safety concern for 36 months.

Draft guidance documents

The first draft guidance document titled “Evaluation of Devices Used with Regenerative Medicine Advanced Therapies”[iv] attempts to clarify how the FDA will evaluate devices referred to as “regenerative medicine advanced therapies” or “RMATs” in accordance with the regenerative medicine provisions in the 21st Century Cures Act. These devices include medical devices used in the recovery, isolation, or delivery of RMATs. It is the goal of the FDA to simplify and streamline the application of the regulatory requirements of RMATs.

The second draft guidance document titled “Expedited Programs for Regenerative Medicine Therapies for Serious Conditions”[v] describes, unsurprisingly, various expedited programs to sponsors of RMATs. In addition, the guidance also describes the new RMAT designation process to be used.

The two draft guidance documents were posted to the Federal Register on November 17, 2017, with a comment period ending February 15, 2018. There is ample time for interested parties to assist the FDA in finalizing the draft guidance documents by submitting a comment by the February 15, 2018, deadline.

These guidance documents may provide new opportunities or new requirements for those operating in the field of regenerative medicines. They should be reviewed to ensure compliance with existing laws and regulations while also looking to take advantage of the programs to accelerate FDA approval.


[i] “Statement from FDA Commissioner Scott Gottlieb, M.D. on FDA’s comprehensive new policy approach to facilitating the development of innovative regenerative medicine products to improve human health” posted November 16, 2017, available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm585342.htm; see also, “FDA announces comprehensive regenerative medicine policy framework” posted November 16, 2017, available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm585345.htm.

[ii]  Available at https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/UCM419926.pdf.

[iii] Available at https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM585403.pdf.

[iv] Available at https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM585417.pdf.

[v] Available at https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM585414.pdf.

This article provides a summary of the draft guidance[1] released by the FDA to assist applicants in determining which one of the abbreviated approval pathways under the Federal Food, Drug and Cosmetic Act (FD&C Act) is appropriate for the submission of a marketing application to the FDA. The draft guidance was released on October 13, 2017, for which comments are due by December 12, 2017.

The guidance expanded on the different pathways for obtaining approval of new drug applications (NDAs) and abbreviated new drug applications (ANDAs), which became available with the passage of the Hatch-Waxman Amendments. In addition, the guidance discussed the regulatory and scientific considerations for determining whether to file an ANDA or a 505(b)(2) Application.

Abbreviated Approval Pathways:

1. Stand-Alone NDA Application:

  • Submitted under section 505(b)(1) and approved under section 505(c) of the FD&C Act and contains “full reports of investigations of safety and effectiveness that were conducted by or for the applicant or for which the applicant has a right of reference or use.”

The guidance did not discuss stand-alone NDAs. It focused on those applications that can be submitted as ANDAs under section 505(j) of the FD&C Act, petitioned ANDAs under 505(j)(2)(c) of the FD&C Act, or NDAs pursuant to section 505(b)(2) of the FD&C Act.

2. 505(b)(2) Application:

  • Submitted under § 505(b)(1) and approved under § 505(c) of the FD&C Act, and contains “full reports of investigations of safety and effectiveness, where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use.”
  • May rely on the FDA’s safety and/or efficacy findings for a listed drug only to the extent that the proposed product of the 505(b)(2) application shares characteristics in common with the listed drug.
    • NOTE: A drug product in a 505(b)(2) application will not necessarily be treated as bioequivalent or therapeutically equivalent to the listed drug(s) relied upon. The applicant is expected to establish a bridge (e.g., by using comparative bioavailability data) between the proposed drug product and each listed drug that the applicant seeks to rely upon to demonstrate that reliance on the listed drug is scientifically justified.
  • Must include sufficient data to support the differences, to the extent that the listed drug and the proposed § 505(b)(2) drug differ.

3. ANDAs

  • Submitted and approved under section 505(j) of the FD&C Act.
  • Must establish that the proposed generic product (1) is the same as the reference listed drug (RLD) with respect to the active ingredient(s), dosage form, route of administration, strength, previously approved conditions of use, and labeling (with permissible differences), and (2) is bioequivalent to the RLD.
  • May not be submitted if studies are necessary to establish the safety and effectiveness of the proposed product because it relies on FDA’s finding of safety and effectiveness for an RLD.

4. Petitioned ANDAs:

  • Submitted and approved under § 505(j) of the FD&C Act.
  • A type of ANDA for a drug product that differs from the RLD in its dosage form, route of administration, strength, or active ingredient (in a product with more than one active ingredient), and for which, in response to a petition under § 505(j)(2)(c) of the FD&C Act, the FDA has determined that safety and efficacy studies are not necessary for the proposed drug product.

Regulatory Considerations for ANDAs and 505(b)(2) Applications:

1. Duplicates:

  • The FDA generally will refuse a 505(b)(2) application for a drug that is a duplicate of a listed drug and eligible for approval under § 505(j) of the FD&C Act.
    • However, if FDA approves a duplicate product after a § 505(b)(2) application is submitted, but before the § 505(b)(2) application is approved, the 505(b)(2) application would remain eligible for approval.

2. Petitioned ANDAs:

  • An applicant may submit a petition under § 505(j)(2)(c) of the FD&C Act (a suitability petition) to FDA requesting permission to submit an ANDA for a generic drug product that differs from an RLD in its route of administration, dosage form, or strength or that has one different active ingredient in a fixed-combination drug product.
  • A suitability petition will generally be approved unless (1) the FDA determines that the safety and effectiveness of the proposed change from the RLD cannot be adequately evaluated without data from investigations that exceed what may be required for an ANDA, or (2) the petition is for a drug product for which a pharmaceutical equivalent has been approved in an NDA.

3. Bundling:

  • An applicant may seek approval for multiple drug products containing thesame active ingredient(s) when some of these products would qualify for approval under the section 505(j) pathway and some would qualify for approval under the 505(b)(2) pathway.
  • FDA has permitted an applicant to submit a single “bundled” 505(b)(2) application forall such multiple drug products.

Scientific Considerations for ANDAs and § 505(b)(2) Applications:

1. Limited Confirmatory Studies:

  • If the safety or effectiveness of a proposed drug product must be established by investigations, then an ANDA application is not appropriate.
  • However, data from limited confirmatory testing to show that the characteristics that make the proposed drug product different from the listed drug do not alter its safety and effectiveness may be submitted in an ANDA.

2. Active Ingredient Sameness Evaluation:

  • “If the active ingredient in an applicant’s proposed drug product cannot be demonstrated to be the same as the active ingredient in the RLD by using the information and data that may be submitted in connection with an ANDA, the drug product should not be submitted for approval in an ANDA.”
  • In situations where current limitations of scientific understanding and technology may preclude approval of an ANDA with the data permitted for submission in an ANDA, FDA may be able to receive, review and approve ANDAs as the scientific understanding and technology evolve.

3. Intentional Differences Between the Proposed Drug Product and an RLD:

Differences in Formulation:

  • An ANDA must include information regarding the identity and quantity of all active and inactive ingredients of the proposed drug product and a characterization of any permitted differences between the formulations of the proposed drug product and the RLD, along with a justification demonstrating that the safety and effectiveness of the proposed drug product is not adversely affected by these differences. If the proposed drug product contains changes to its formulation that are not permissible in an ANDA, the applicant should consider submitting a 505(b)(2) application.

Differences in Bioequivalence and/or Bioavailability Differences:

  • An ANDA must contain information to show that the proposed drug product is bioequivalent to the RLD, such as (i) the rate and extent of absorption of the proposed drug do not show a significant difference from that of the RLD when administered at the same molar dose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses.
    • NOTE: “[(w]here there is an intentional difference in rate (e.g., in certain extended-release dosage forms), certain pharmaceutical equivalents or alternatives may be considered bioequivalent if there is no significant difference in the extent to which the active ingredient or moiety from each product becomes available at the site of drug action.”
  • An application for a proposed drug product where the rate and/or extent of absorption exceed, or are otherwise different from, the 505(j) standards for bioequivalence may be submitted under the 505(b)(2) pathway and may require studies to show the safety and efficacy of the proposed product at the different rate and/or extent of delivery.  However, the FDA generally will not accept a 505(b)(2) application for a drug product where the only difference from a listed drug is that (1) the extent to, or (2) the rate at, which its active ingredient is absorbed or otherwise made available at the site of action isless than that of the RLD.

Differences in Conditions of Use:

  • A § 505(j) application must include a statement that the conditions of use prescribed, recommended, or suggested in the labeling for the proposed drug product have been previously approved for the RLD. The application cannot be approved as an ANDA if the proposed drug product has added a new indication. However, the FDA will not refuse to approve an ANDA whose proposed labeling excludes conditions of use approved for the RLD because of patents or exclusivity.

4. Other Differences:

  • Drug products that differ considerably from the RLD are generally not candidates for the § 505(j) pathway. In assessing whether differences between a proposed generic drug product and the RLD would necessitate additional data or information to establish the safety or efficacy of the proposed drug product, FDA will examine the individual differences between the products and the combined effects of those differences.

 


[1] https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM579751.pdf

In an unprecedented move by the U.S. Patent and Trademark Office (USPTO), the Patent Trials and Appeals Board (PTAB) has permitted the filing of amicus briefs on whether the Saint Regis Mohawk Tribe (“Tribe”) should be permitted to terminate the inter partes review of Allergan’s patents contested in IPR2016-00127, IPR2016-01128, IPR2016-01129, IPR2016-01130, IPR2016-01131, and IPR2016-01132. Allergan assigned the patents challenged in these IPRs to the Tribe, while retaining an exclusive license in exchange for ongoing payments. As a sovereign entity, the Tribe seeks to terminate the IPR challenges of these patents, a move which the PTAB had ruled in 2016 shielded the University of Florida Research Foundation as a sovereign entity from IPRs. See Covidien LP v University of Florida Research Foundation Inc., IPR2016-01274, Paper 21 (PTAB Jan. 25, 2016). Amicus briefs of no more than 15 pages are due to be filed by December 1, 2017, and the Petitioners and Tribe are each authorized to file a single response to any amicus brief by December 15, 2017.

This maneuvering has caught the attention of many, including members of Congress and the district court specifically addressing the validity of these patents. In response to a bipartisan committee investigating the Allergan-Tribe deal, Senator McCaskill has already drafted a bill to block tribal claims of sovereign immunity, which could otherwise preclude USPTO review of patents assigned to tribes. Court of Appeals for the Federal Circuit Judge William Bryson, sitting by “designation” in the Eastern District Court of Texas, expressed concerned that Allergan sought to “rent” sovereign immunity from the Tribe. On the other hand, heralded as an innovative defense, patent attorneys now seek such a defense to patent challenges before the USPTO. The Saint Regis Mohawk Tribe has reportedly already taken ownership of patents from SRC Labs and is in discussion with another technology company.

Interestingly, the district court under Judge Bryson recently found four of the six patents invalid, a decision which will likely be appealed to the CAFC. However, the PTAB nevertheless will need to answer, inter alia, the question of  whether the Tribe’s right as a sovereign immunity will shield the Allergan patents from IPRs. Due to additional parties joining as Petitioner and the complicated issues surrounding this challenge, the PTAB has extended a deadline to render its final decision in the IPR from December 8, 2016, to April 6, 2018.