Paragraph IV certification

For each patent that claims the listed drug, or a use of it for which the applicant seeks approval, and for which information is required to be filed, the applicant certifies one of four things (21 U.S.C. 355(j)(2)(A)(vii)). Approval is made effective on the last applicable date determined by applying the rules to each certification¹.

Where a method of use patent does not claim a use for which the applicant seeks approval, the applicant instead provides a statement to that effect (clause (viii))¹. FDA describes a paragraph IV certification as an opinion that the patent is invalid, unenforceable, or will not be infringed by the generic product, made about a patent submitted by the brand sponsor and listed in the Orange Book². For an application described in section 505(b)(2), the same certification appears in section 505(b)(2)(A)(iv)¹.

A brand application must include the patent number and expiration date of each patent for which a claim of infringement could reasonably be asserted against an unlicensed maker, and that claims the drug (as a drug substance or drug product patent) or claims a method of using the drug for which approval is sought or granted (21 U.S.C. 355(b)(1)(A)(viii))¹. FDA lists this information with the approved product in the Orange Book^2,5. A generic applicant certifies against those listed patents².

• Commitment. An applicant that makes a paragraph IV certification must include in the application a statement that it will give notice¹.
• Timing. If the certification is in the application, the statute requires notice not later than 20 days after the postmark on FDA's notice that the application has been filed. If it is in an amendment or supplement, notice is due when the amendment or supplement is submitted¹. Under FDA's rule, the notice is sent on or after the date the applicant receives FDA's paragraph IV acknowledgment letter, but not later than 20 days after the postmark on that letter, and a notice sent before receipt of the letter is invalid³.
• Recipients. Each owner of the patent (or its designated representative) and the holder of the approved brand application for the drug^1,3. Notice goes by registered or certified mail, return receipt requested, or by a designated delivery service³.
• Contents. The notice must state that an application containing bioavailability or bioequivalence data has been submitted to obtain approval to commercially manufacture, use or sell the drug before the patent expires, and include a detailed statement of the factual and legal basis of the opinion that the patent is invalid or will not be infringed¹. If the applicant alleges non-infringement and wants to preserve the option of a declaratory judgment action, the notice must be accompanied by an offer of confidential access to the application³.
• Submission is an act of infringement. It is an act of infringement to submit an application under section 505(j) for a drug claimed in a patent or the use of which is claimed in a patent. In that case the court orders the effective date of any approval to be not earlier than the expiration of the infringed patent (35 U.S.C. 271(e)(2)(A) and (e)(4)(A))⁴. For how such cases proceed, see Patent litigation.

1. Suit within 45 daysAs to a paragraph IV certification, approval is made effective immediately unless, before 45 days after the notice is received, an action for infringement is brought on the patent that is the subject of the certification, and for which information was submitted to FDA before the application was submitted¹.
2. 30-month periodIf such an action is brought in time, approval is made effective at the end of the 30-month period beginning on the date the notice is received, or a shorter or longer period the court orders because a party failed to reasonably cooperate in expediting the action¹. FDA describes this as a postponement of approval that generally lasts 30 months unless the patent expires or is judged invalid or not infringed before then².
3. Court decision before the period endsIf the district court decides before the period ends that the patent is invalid or not infringed, approval is made effective on the date the court enters judgment, or on the date of a settlement order or consent decree stating that the patent is invalid or not infringed¹. If the district court decides that the patent is infringed, approval is made effective on the date specified in the court's order under 35 U.S.C. 271(e)(4)(A) if the judgment is not appealed or is affirmed, or, if it is appealed, on the date the court of appeals decides that the patent is invalid or not infringed¹.
4. No suit in 45 daysIf no suit is brought within the 45 days, the applicant may bring a declaratory judgment action, but only if the statutory conditions are met, and an action for a declaration of non-infringement is available only where the notice was accompanied by an offer of confidential access to the application¹.

• New chemical entities. For a drug approved after September 24, 1984 whose active moiety had not been approved in any other application under subsection (b), no section 505(j) application may be submitted before five years from approval, except that one containing a paragraph IV certification may be submitted after four years. If infringement suit is commenced during the one-year period beginning 48 months after approval, the 30-month period is extended by the time required for seven and one-half years to elapse from approval (21 U.S.C. 355(j)(5)(F)(ii))¹.
• Counterclaim. If the patent owner or brand holder sues, the applicant may counterclaim for an order requiring the holder to correct or delete patent information on the ground that the patent claims neither the approved drug nor an approved method of using it (21 U.S.C. 355(j)(5)(C)(ii)(I))¹.

Subject to forfeiture, an application with a paragraph IV certification, for a drug for which a first applicant has submitted such an application, is made effective 180 days after the date of first commercial marketing of the drug (including the commercial marketing of the listed drug) by any first applicant (21 U.S.C. 355(j)(5)(B)(iv))¹. FDA lists this as Patent Challenge exclusivity, for ANDAs only⁵.

• First applicant. An applicant that, on the first day on which a substantially complete application containing a paragraph IV certification is submitted for a drug, submits a substantially complete application that contains and lawfully maintains such a certification¹. FDA says the first company or companies to do so are generally eligible for 180 days².
• Forfeiture. The statute lists the events that forfeit the period, including failure to market the drug by the statutory deadline, withdrawal of the application, amendment or withdrawal of the certification for all qualifying patents, failure to obtain tentative approval within 30 months after the application is filed, unless the failure is caused by a change in or review of the approval requirements, an agreement with another applicant, the brand holder or a patent owner that a final decision finds violates the antitrust laws, and expiration of all the qualifying patents (21 U.S.C. 355(j)(5)(D))¹.
• Orange Book entry. If FDA determines an ANDA is eligible, the Orange Book posts a Patent Challenge (PC) code in the exclusivity data for the approved ANDA upon any first applicant's commercial marketing, showing when the 180 days will expire. If FDA defers its decision, no PC code is entered².

See also Patent cliff.

FDA publishes a list of drug products for which a substantially complete application with a paragraph IV certification has been submitted. The list is shown for how the information is organized, and says nothing about any applicant or patent.

The page describes the list, which records for each drug product the date of the first substantially complete application with a paragraph IV certification and FDA's 180-day decision status. FDA says it makes regulatory decisions on the data in the applications and not on the information in the list2.