By Kurt R. Karst –
Thanks to everyone who participated in our “30 for 30” Hatch-Waxman Trivia! Based on the corrrespondence we received since posting the trivia questions earlier this week, FDA Law Blog readers enjoyed the trip down memory lane. . . and were entertained along the way. We know you are chomping at the bit to see the answers, so without further ado, we give you the answers to each of the trivia questions.
Q1: What U.S. Senator is a musician, songwriter and producer, a member of ASCAP, and whose works have been recorded by Gladys Knight, Donny Osmond and Brooks and Dunn, among others?
Q2: When standing at the base of the U.S. Capitol, this dome (pictured below) stands at 93.5 feet above sea level. To whom does this dome belong?
Q3: President Ronald Reagan returned from where before signing into law the Drug Price Competition and Patent Term Restoration Act of 1984 in the Rose Garden on September 24, 1984?
A. New York, New York after addressing the 39th Session of the United Nations General Assembly. President Reagan commented during the signing of Hatch-Waxman: “I just returned from New York -- literally minutes ago -- where I addressed the United Nations. . . .”
Q4: Who has a lower “Bacon Number”: President Ronald Reagan, Sen. Orrin Hatch, or Rep. Henry Waxman?
A. This is, of course, a reference to prolific Hollywood character actor Kevin Bacon and the game wherein movie buffs challenge each other to find the shortest path between an arbitrary actor and Kevin Bacon. President Reagan, Sen. Hatch, and Rep. Waxman have all appeared in movies. According to the Oracle of Bacon, all three are tied with a “Bacon Number” of 2. Here’s the path to Kevin Bacon for each:
Brother Rat (1938)
The Big Picture (1989)
MoveOn: The Movie (2009)
Come Together: A Night for John Lennon's Words and Music (2001)
Orrin G. Hatch
The 60th Primetime Emmy Awards (2008)
Q5: Were rain umbrellas needed in the Rose Garden on September 24, 1984?
A: No. According to the Farmers’ Almanac, the high temperature in Washington, DC that day was 88°F with no precipitation. And, according to President Reagan, it was hot. He commented during the signing ceremony: “I don't know why it is on some of these hot rallies out in the countryside the chairs are black instead of white, and they get very warm when you stand too long.”
Q6: What is the typographical error in the text of FDC Act § 505(j) that was never corrected? (Hint: The affected section was replaced by the 2003 Medicare Modernization Act (“MMA”).)
FDC Act § 505(j)(5)(B)(iv), as enacted states:
If the application contains a certification described in subclause (IV) of paragraph (2)(A)(vii) and is for a drug for which a previous application has been submitted under this subsection continuing such a certification, the application shall be made effective not earlier than one hundred and eighty days after-
(I) the date the Secretary receives notice from the applicant under the previous application of the first commercial marketing of the drug under the previous application, or
(II) the date of a decision of a court. ..holding the patent which is the subject of the certification to be invalid or not infringed,
whichever is earlier. [Emphasis added].
The word “continuing” should have been “containing,” as some courts have recognized. See, e.g., Purepac Pharm. Co. v. Friedman, 162 F.3d 1201, 1203 n.3 (D.C. Cir. 1998); Mova Pharm. Corp. v. Shalala, 140 F.3d 1060, 1064 n.3 (D.C. Cir. 1998).
Q7: What is the significance of January 1, 1982 to the Orange Book?
FDC Act § 505(j)(7)(A)(i)(II) requires FDA to include in “the list” (i.e., the Orange Book) the date of approval and application number of drug products approved after 1981. Information on products approved prior to 1981 may be included in the Orange Book, however, no date of approval is included. Instead, the approval date field in the printed version of the Orange Book is left blank. In the electronic version of the Orange Book, products approved prior to January 1, 1982 contain the phrase “Approved prior to Jan 1, 1982.”
Q8: What is the significant difference between ANDA No. 076933 and ANDA No. 076934? (The answer is neither “1,” nor the drug name.)
A. ANDAs with a number less than or equal to 076933 are pre-MMA applications, and ANDAs with a number equal to or greater than 076934 are post-MMA applications.
Q9: What pharmaceutical industry trade organization executive referred to the pre-Hatch-Waxman hurdles to generic competition of post-1962 drugs as an “iron curtain”?
A: William F. Haddad, President of the Generic Pharmaceutical Industry Association, according to a June 8, 1984 article in The Washington Post, titled “FDA Lets Some Drugs Take Effect Slowly”: “But until the law is changed, the FDA will continue approving drugs according to the old rules -- a system that William F. Haddad, president of the Generic Pharmaceutical Industry Association, and other critics say acts as an ‘iron Curtain’ that makes it difficult to get new generic drugs approved.”
Q10: What almost-U.S. President opposed efforts to pass legislation that would have extended brand-name drug patents without creating a generic drug approval process?
A: Then-Representative Albert Gore, Jr. (D-TN). See The Push to Protect Patents on Drugs; The Drug Industry Nearly Won Last Year, but Then the Political Winds Changed. (Science 1983: Vol. 222 no. 4624 pp. 593-595).
Q11: Donald Hare, R.Ph., who has since retired from FDA, is sometimes referred to as the Father of the Orange Book. To whom does the distinction of Mother of the Orange Book – or at least Mother-in-Law – belong?
A: CAPT Mary Ann Holovac, R.Ph., who oversaw the publication for nearly 25 years, until December 2013.
Q12: As of today, what is the longest, unexpired period of non-patent exclusivity listed in the Orange Book?
A: A period of GAIN exclusivity expiring on August 6, 2024 is listed for NDA No. 206334 for ORBACTIV (oritavancin diphosphate) Lyophilized Powder Injection. This is the latest of the few periods of GAIN exclusivity FDA has granted. The other GAIN Act approvals are NDA Nos. 205435 and 205346 for SIVEXTRO (tedizolid phosphate) (GAIN exclusivity expiring on June 20, 2024), and NDA No. 021883 for DALVANCE (dalbavancin HCl) (GAIN exclusivity expiring on May 23, 2024).
Q13: When were Reference Listed Drug (“RLD”) designations added to the Orange Book?
A: RLD designations (identified by a “+” in the paper version of the Orange Book) first appeared with publication of the 12th Edition (1992).
Q14: When was an electronic Orange Book search function added to FDA’s website?
A: An electronic Orange Book search function was added to FDA’s website on October 31, 1997. Beginning in 1998, current patent listings for approved drug products could be obtained from the electronic Orange Book through a search by active ingredient, proprietary name, application holder, or application number. Since February 2005 (25th Edition), FDA has provided daily electronic Orange Book product updates, and made the volume available in a downloadable PDF format.
Q15: What is the “Blue Book”?
A: Before the Orange Book came into existence, there was a predecessor publication known as the “Blue Book,” which was a list of manufacturers with approved NDAs and ANDAs (or manufacturers who were named as distributors in those applications) for drug products having known or potential bioequivalence problems.
Q16: Prior to FDA’s formal creation of Orange Book patent listing forms (Form FDA 3542a and Form FDA 3542) in 2003, did FDA offer any informal guidance to NDA sponsors on patent listing?
A: Yes. FDA provided a Patent Submission Sample Format to sponsors who requested it.
Q17: Can you identify 10 types of non-patent marketing exclusivities (or non-patent exclusivity extensions) recognized by the FDC Act?
A: (1) 5-year New Chemical Entity Exclusivity; (2) 3-year new clinical investigation exclusivity for an original NDA; (3) 3-year new clinical investigation exclusivity for a supplemental NDA; (4) 10-year window exclusivity; (5) 2-year window exclusivity; (6) 5-year Generating Antibiotic Incentives Now Act exclusivity; (7) 6-month pediatric exclusivity; (8) 5-year enantiomer exclusivity; (9) QI Act antibiotic exclusivity; (10) 180-day generic drug exclusivity; (11) 7-year orphan drug exclusivity
Q18: How long did it take after the December 8, 2003 enactment of the MMA for a member of Congress to propose a revision to the law (and specifically to the 180-day exclusivity forfeiture provisions)?
A: One day. On December 9, 2003, Sen. Hatch suggested changes to the failure-to-market 180-day exclusivity forfeiture provision. See 149 Cong. Rec. S16104 (daily ed. Dec. 9, 2003) (statement of Sen. Orrin Hatch).
Q19: What U.S. law is modeled after the Hatch-Waxman Amendments, and how long has it taken FDA to issue implementing regulations?
A: The Generic Animal Drug and Patent Term Restoration Act of 1988, Pub. Law No. 98-417, 98 Stat. 1585 (1988), which is the Hatch-Waxman equivalent for generic animal drugs. FDA has not yet proposed regulations to implement the law.
Q20: How many times has FDA used its “active pursuit” regulation at 21 C.F.R. § 314.107(c)(3) (“[I]f FDA concludes that the applicant submitting the first application is not actively pursuing approval of its abbreviated application, FDA will make the approval of subsequent [ANDAs] immediately effective if they are otherwise eligible for an immediately effective approval.”) to effectively take away a first applicant’s 180-day exclusivity eligibility?
Q21: What case (and involving what drug) was the first judicial test of the 3-year exclusivity provisions of the Hatch-Waxman Amendments?
A: Zenith Labs., Inc. v. Bowen, Case No. 85-cv-3646 (D.N.J. 1986), which involved the drug Tolazamide.
Q22: Who is Gary P. Jordan?
A: Gary P. Jordan is the the first assistant U.S. attorney who prosecuted a case arising from the so-called “generic drug scandal.”
Q23: Who is Marion J. Finkel?
A: Marion J. Finkel is credited with developing the framework for the so-called “paper NDA,” which is a predecessor to the 505(b)(2) NDA.
Q24: What is the only instance in which a court has ordered FDA to approve an ANDA during another sponsor’s period of 180-day exclusivity?
A: In Watson Laboratories, Inc. v. Sebelius, et al., Case No. 12-1344 (ABJ) (D.D.C. Oct. 22, 2012), which concerned 180-day exclusivity for generic ACTOS (pioglitazone) under the pre-MMA statute, the district court overruled FDA’s determination that Watson was not eligible to share in 180-day exclusivity because the company was not the first (or among the first) to amend its pending ANDA to convert a patent certification to Paragraph IV. Instead, the district court ruled that Watson was entitled to share in another applicant’s 180-day exclusivity period, because FDA’s long-standing interpretation of the FDC Act was contrary to the terms of the statute, and ordered the Agency to approve Watson’s ANDA. FDA appealed the decision to the U.S. Court of Appeals for the District of Columbia Circuit (Docket Nos. 12-5332 & 12-5342), where a motion for vacatur (based on mootness) was ultimately granted.
Q25: What is the only instance in whch FDA was faced with a leap year NCE NDA approval?
A: FDA approved PRISTIQ (desvenlafaxine) Extended-Release Tablets under NDA No. 021992 in a leap year, on February 29, 2008, and granted NCE exclusivity expiring in a non-leap year, on March 1, 2013. FDA added a note to the Orange Book stating: “Applications referencing NDA 021992 Pristiq (Desvenlafaxine Succinate) and challenging the listed patent may be received by the Agency beginning on Feb 29, 2012, four years from the NDA approval date” (see our previous post here).
Q26: FDA’s regulation at 21 C.F.R. § 314.94(a)(12)(viii) states, in relevant part, “an applicant who has submitted a paragraph IV patent certification may not change it to a paragraph III certification if a patent infringement suit has been filed against another paragraph IV applicant unless the agency has determined that no applicant is entitled to 180-day exclusivity or the patent expires before the lawsuit is resolved or expires after the suit is resolved but before the end of the 180-day exclusivity period.” What is the status of this regulation?
A: This regulation has not been enforced by FDA for several years. The regulation was promulgated in the early 1990s at a time when it was unclear to FDA whether a first-filer’s period of 180-day exclusivity could extend beyond the life of the patent(s) on which eligibility to exclusivity was based. At the time, FDA was concerned that a subsequent ANDA Paragraph IV filer would convert its certification in an effort to circumvent a first-filer’s 180-day exclusivity. As such, the above passage from 21 C.F.R. § 314.94(a)(12)(viii) was included to guard against that possibility. Subsequently, FDA and the courts have ruled that 180-day exclusivity cannot extend beyond the expiration of the patent(s) on which such exclusivity is based. As such, the need for this regulation has, as a general matter, been outlived. (The only time such a prohibition might still arise is in the case where an ANDA sponsor submits an ANDA with a Paragraph IV certification during the NCE-1 year, and then, after FDA receives – i.e., files – the ANDA, converts that Paragraph IV certification to a Paragraph III certification. In that case, the conversion would remove the basis for the ANDA submission in the first place. But even in this case, FDA still has not taken action to enforce the general prohibition at 21 C.F.R. § 314.94(a)(12)(viii).)
Q27: Can a single patent use code serve as the basis for a split Paragraph IV certification and “section viii” statement? (This question is a nod to recent controversies involving patent use codes.)
A: Yes. ANDA No. 076565 for Venlafaxine HCl Extended-Release Capsules included such a split certification with respect to the “U-459” (TREATMENT OF DEPRESSION AND GENERALIZED ANXIETY DISORDER) patent use code associated with U.S. Patent No. 6,419,958.
Q28: In what case was the U.S. Patent and Trademark Office’s (“PTO”) longstanding interpretation of 35 U.S.C. § 156(a)(5)(A) concerning Patent Term Extensions (“PTE”) struck down?
A: On May 10, 2010, the U.S. Court of Appeals for the Federal Circuit issued its decision in PhotoCure v. Kappos, 603 F.3d 1372 (Fed. Cir. 2010) (and in a second case, Ortho-McNeil Pharm., Inc. v. Lupin Pharms., Inc., 603 F.3d 1377 (Fed. Cir. 2010)) concerning the proper interpretation of 35 U.S.C. § 156(a)(5)(A), which states that the term of a patent claiming a drug shall be extended from the original expiration date of the patent if, among other things, “the permission for the commercial marketing or use of the product . . . is the first permitted commercial marketing or use of the product under the provision of law under which such regulatory review period occurred.” For several years, the PTO interpreted the term “product” in 35 U.S.C. § 156(a)(5)(A) to mean “active moiety” rather than “active ingredient.” The Federal Circuit’s PhotoCure and Ortho-McNeil decisions say that the an “active ingredient” interpretation of the statute should be applied for PTE purposes.
Q29: What is the connection between the drugs INDOCIN (indomethacin) and CAPOZIDE (captopril and hydrochlorothiazide), U.S. Patent Nos. 3,849,549 (INDOCIN) and 4,217,347 (CAPOZIDE), and Title II of the Hatch-Waxman Amendments?
A: Both drugs and both patents were cited in a March 25, 1985 letter from Reps. Henry Waxman and Robert Kastenmeier (D-WI) to the PTO Commissioner as examples of drug products covered by a patent that the Congressmen did not believe should be granted a PTE because the drugs contain an active ingredient previously approved by FDA.
Q30: What patent concerning what drug led to a change in the PTE statute at 35 U.S.C. § 156 involving the deadline for submitting a PTE application to PTO?
A: U.S. Patent No. 5,196,404 covering ANGIOMAX (bivalirudin) (see our previous post here).