FDA Final Rule regarding Title XI of MMA of 2003 (Hatch-Waxman Regulations)

On October 6, 2016, FDA published a final rule implementing portions of Title XI of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). The final rule which goes into effect on December 05, 2016 implements a number of important provisions including:

·      Submission of patent information by NDA holders, such as use codes;

·      Notice to patent owners of patent certifications made by 505(b)(2) NDA and ANDA applicants;

·      The availability of 30-month stays of approval on 505(b)(2) NDAs and ANDAs;

·      Submission of amendments and supplements to 505(b)(2) NDAs and ANDAs

The 79-page final rule is vast and interesting to read, however it is not possible to digest all the information at one go. Therefore this summary covers mainly the procedural changes that happened because of this rule and how generic company should adopt/change their practice in Hatch-Waxman space according to this rule. These changes are categorized into simply old rule and new rule. New changes/amendments are in bold.

Old Rule	New Rule
PATENT CERTIFICATION NOTICE
(a) Notice of certification
The applicant shall send the notice of P-IV certification by registered or certified mail, return receipt requested.	The applicant must send the notice of P-IV certification by registered or certified mail, return receipt requested or by a designated delivery service. An applicant may send notice by an alternative method only if FDA has agreed in advance that the method will produce an acceptable form of documentation.
The name and address of the application NDA holder or its attorney, agent, or authorized official may be obtained from orange book staff.	The name and address of the application NDA holder or its attorney, agent, or authorized official may be obtained by sending a written or electronic communication to orange book staff or to the Orange Book Staff as the email address listed on the Agency’s Web site at http://www.fda.gov.
(b) Sending the notice
The applicant shall send notice when it receives from FDA an “acknowledgement letter” stating that ANDA is sufficiently complete for substantive review	The applicant must send notice on or after the date it receives a “paragraph IV acknowledgment letter” from FDA, but not later than 20 days after the date of the “postmark” on the paragraph IV acknowledgment letter. Notice is invalid if it is sent before the applicant’s receipt of a paragraph IV acknowledgment letter, or before the first working day after the day the patent is published in the list.
At the same time, the applicant shall amend its abbreviated new drug application to include a statement certifying that the notice has been provided to each person identified under paragraph (a) of this section and that the notice met the content requirements under paragraph (c) of this section.	The applicant must submit to FDA an amendment to its ANDA that includes a statement certifying that the notice has been provided to each person identified and that the notice met the content requirements of this section. A copy of the notice itself need not be submitted to the Agency.
(c) Content of a notice
In the notice, the applicant shall cite section 505(j)(2)(B)(ii) of the act and shall include, but not be limited to, the following information:	In the notice, the applicant must cite section 505(j)(2)(B)(iv) of the Federal Food, Drug, and Cosmetic Act and the notice must include, but is not limited to, the following information:
A statement that FDA has received an abbreviated new drug application submitted by the applicant containing any required bioavailability or bioequivalence data or information.	A statement that FDA has received an ANDA submitted by the applicant containing any required bioavailability or bioequivalence data or information.
	A statement that the applicant has received the “paragraph IV acknowledgment letter” for the ANDA.
	If the applicant alleges that the patent will not be infringed and the applicant seeks to preserve the option to later file a civil action for declaratory judgment in accordance with section 505(j)(5)(C) of the Federal Food, Drug, and Cosmetic Act, then the notice must be accompanied by an offer of confidential access to the ANDA for the sole and limited purpose of evaluating possible infringement of the patent that is the subject of the paragraph IV certification.
(d) Amendment to an application	(d) Amendment or supplement to an application
If abbreviated application is amended to include the certification described in § 314.94(a)(12)(i)(A)(4), the applicant shall send the notice at the same time that the amendment to abbreviated application is submitted to FDA.	If, after receipt of a paragraph IV acknowledgment letter or acknowledgment letter, an applicant submits an amendment or supplement to its ANDA that includes a paragraph IV certification the applicant must send the notice at the same time regardless of whether the applicant has already given notice with respect to another such certification contained in the ANDA or in an amendment or supplement to the ANDA.
	An applicant that submits an amendment or supplement to seek approval of a different strength must provide notice of any paragraph IV certification in accordance this section, as applicable.
(e) Documentation of timely sending & notice receipt
The applicant shall amend its abbreviated application to document receipt of the notice required under paragraph (a) of this section by each person provided the notice. The applicant shall include a copy of the return receipt or other similar evidence of the date the notification was received. FDA will accept, as adequate documentation of the date of receipt a return receipt or a letter acknowledging receipt by the person provided the notice.	The applicant must amend its ANDA to provide documentation of the date of receipt of the notice required under paragraph (a) of this section by each person provided the notice. The amendment must be submitted to FDA within 30 days after the last date on which notice was received by a person described in this section. The applicant’s amendment also must contain documentation that its notice was sent on a date that complies with the timeframe, and a dated printout of orange book that includes the patent that is the subject of the P-IV certification. FDA will accept, as adequate documentation of the date the notice was sent, a copy of the registered mail receipt, certified mail receipt, or receipt from a designated delivery service. FDA will accept as adequate documentation of the date of receipt a return receipt, signature proof of delivery by a designated delivery service, or a letter acknowledging receipt by the person provided the notice.
(g) Designated delivery services.
	(1) For purposes of this section, the term “designated delivery service” is any delivery service provided by a trade or business that the Agency determines: (i) Is available to the general public throughout US; (ii) Records electronically to its database, kept in the regular course of its business, or marks on the cover in which any item referred to in this section is to be delivered, the date on which such item was given to such trade or business for delivery; and (iii) Provides overnight or 2-day delivery service throughout the United States. (2) FDA may periodically issue guidance regarding designated delivery services.
AMENDMENTS TO AN UNAPPROVED ANDA
	Different listed drug: An applicant may not amend an ANDA to seek approval of a drug referring to a listed drug that is different from the reference listed drug identified in the ANDA. A change of the reference listed drug must be submitted in a new ANDA.
	Patent certification requirements: Appropriate patent certification or statement or a recertification for a previously submitted P-IV certification required if approval is sought for any of the following types of amendments:- - To add new indication - To add a new strength                                                                - To change the physical form or crystalline structure             - - To make other than minor changes If the amendment to the ANDA does not contain a patent certification or statement, the applicant must verify that the proposed change described in the amendment is not one of the types of amendments mentioned above.
SUPPLEMENTS AND OTHER CHANGES TO AN APPROVED ANDA
	Different listed drug: An applicant may not supplement an ANDA to seek approval of a drug referring to a listed drug that is different from the current reference listed drug identified in the ANDA. A change of the reference listed drug must be submitted in a new ANDA.
FILING AN NDA AND RECEIVING AN ANDA
Receipt of an abbreviated new drug application means that FDA has made a threshold determination that the abbreviated application is sufficiently complete to permit a substantive review.	Receipt of an ANDA means that FDA has made a threshold determination that the abbreviated application is substantially complete.
	If FDA determines, upon evaluation, that an ANDA was substantially complete as of the date it was submitted to FDA, FDA will consider the ANDA to have been received as of the date of submission.
If FDA considers the abbreviated new drug application not to have been received, FDA will notify the applicant ordinarily by telephone. The applicant may then: (i) Withdraw the abbreviated new drug application or (ii) Amend the abbreviated new drug application to correct the deficiencies or (iii) Take no action, in which case FDA will refuse to receive the abbreviated new drug application.	If FDA considers ANDA not to have been received, FDA will notify the applicant of the refuse-to-receive decision. The applicant may then: (i) Withdraw the ANDA or (ii) Correct the deficiencies and resubmit the ANDA; or (iii) Take no action, in which case FDA may consider the ANDA withdrawn after 1 year.
DATE OF APPROVAL OF A 505(b)(2) APPLICATION OR ANDA
Approval of an application or abbreviated application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for the application or abbreviated application.	A 505(b)(2) application or ANDA for a drug product is approved on the date FDA issues an approval letter under § 314.105 for 505(b)(2) application or ANDA.
Effect of patent(s) on the listed drug: If approval of an abbreviated new drug application submitted under section 505(j) of the act or of a 505(b)(2) application is granted, that approval will become effective in accordance with the following:	Effect of patent(s) on the listed drug: The first possible date on which the 505(b)(2) application or ANDA can be approved will be calculated for each patent, and may be approved on the last applicable date. Timing of approval based on patent certification or statement: If none of the reasons for refusing to approve the 505(b)(2) application or ANDA applies then 505(b)(2) application or ANDA may be approved immediately in cases of P-I, P-II, P-IV with no suit filed and statement under section viii.
Disposition of patent litigation: (1) Approval upon expiration of 30-month period or 7½ years from date of listed drug Approval may be made effective 30 months after the date of the receipt of the notice of certification by the patent owner or by the exclusive licensee (or their representative(s)) unless the court has extended or reduced the period. (2) District court decision If before the expiration of the 30-month period, district court issues a final order that the patent is invalid, unenforceable, or not infringed  approval may be made effective on the date the court enters judgment (3) Appeal of district court judgment If before the expiration of the 30-month period, the district court issues a final order or judgment that the patent has been infringed approval may be made effective on the date the court determines that the patent will expire or otherwise orders (4) Grant of preliminary injunction by Federal district court If before the expiration of the 30-month period, or 71/2 ½ years where applicable, the district court grants a preliminary injunction prohibiting the applicant from engaging in the commercial manufacture or sale of the drug product until the court decides the issues of patent validity and infringement, and if the court later decides that: the patent is invalid, unenforceable, or not infringed, approval may be made effective on the date the court enters a final order or judgment that the patent is invalid, unenforceable, or not infringed.	Disposition of patent litigation: (1) Approval upon expiration of 30-month period or 7½ years from date of listed drug approval505(b)(2) application or ANDA may be approved 30 months after the later of the date of the receipt of the notice of certification by the any owner of the listed patent or by the NDA holder (or their representative(s)) unless the court has extended or reduced the period. (2) District court decision If before the expiration of the 30-month period, district court decides that the patent is invalid, unenforceable, or not infringed  (including any substantive determination that there is no cause of action for patent infringement or invalidity), the 505(b)(2) application or ANDA may be approved on a) The date on which the court enters judgment reflecting the decision; or b) The date of a settlement order or consent decree signed and entered by the court (3) Appeal of district court judgment if the judgment of the district court is appealed, the 505(b)(2) application or ANDA may be approved on: a) The date on which the mandate is issued by the court of appeals entering judgment that the patent is invalid, unenforceable, or not infringed b) The date of a settlement order or consent decree signed and entered by the court of appeals (4) Grant of preliminary injunction by Federal district court If before the expiration of the 30-month period, or 71/2 ½ years where applicable, the district court grants a preliminary injunction until the court decides the issues of patent validity and infringement, and if the court later decides that: (i) The patent is invalid, unenforceable, or not infringed, the 505(b)(2) application or ANDA may be approved as provided in this section. (ii) The patent is infringed, the 505(b)(2) application or ANDA may be approved as provided in this section (5) Written consent to approval by patent owner ANDA may be approved any time on or after the date of the consent, approval may be granted on or after that date. (6) Court order terminating 30-month or 7½-year period If the court enters an order requiring the 30-month or 7½-year period to be terminated, the 505(b)(2) application or ANDA may be approved in accordance with the court’s order. (7) Court order of dismissal without a finding of infringement If before the expiration of the 30-month period, or 7½ years where applicable, the court(s) enter(s) an order of dismissal, with or without prejudice, without a finding of infringement the 505(b)(2) application or ANDA may be approved on or after the date of the order.
Timing of approval of subsequent ANDA: Approval of the subsequent abbreviated new drug application will be made effective no sooner than 180 days from whichever of the following dates is earlier: (i) The date the applicant submitting the first application first commences commercial marketing of its drug product; OR (ii) The date of a decision of the court holding the relevant patent invalid, unenforceable, or not infringed.	Timing of approval of subsequent ANDA: The ANDA of a subsequent applicant will not be approved during the period when any first applicant is eligible for 180-day exclusivity or during the 180-day exclusivity period of a first applicant. A first applicant must submit correspondence to its ANDA notifying FDA within 30 days of the date of its first commercial marketing of its drug product or the reference listed drug. If an applicant does not notify FDA before this date, the date of first commercial marketing will be deemed to be the date of the drug product’s approval.
Notification of court actions or written consent to approval The applicant shall submit a copy of the entry of the order or judgment to the Office within 10 working days of a final judgment.	Notification of court actions or written consent to approval The ANDA applicant must submit: 1) A copy of any judgment by the court or settlement order or consent decree signed and entered by the court 2) Written notification of whether or not any action by the court described in this section has been appealed within the time permitted for an appeal; 3) A copy of any order entered by the court terminating the 30-month or 7½-year period 4) A copy of any written consent to approval by the patent owner or exclusive patent licensee 5) A copy of any court order that a 505(b)(2) application or ANDA may be approved no earlier than the date specified All information required by above paragraph must be sent within 14 days of the date of entry by the court, the date of appeal or expiration of the time for appeal, or the date of written consent to approval.
Notification of filing of legal action The abbreviated new drug applicant or the 505(b)(2) applicant shall notify FDA immediately of the filing of any legal action filed within 45 days of receipt of notice	Notification of filing of legal action The 505(b)(2) or ANDA applicant must notify FDA in writing within 14 days of the filing of any legal action filed within 45 days of receipt of the notice of P-IV certification.