Instead, its regulations governing label changes state the new warnings should be added “as soon as there is reasonable evidence of a causal association [of a risk] with a drug; a causal relationship need not have been definitely established.” 21 C.F.R. §201.57(c)(6)(i). That’s for drugs approved after mid-2001.

This falls below the science-based regulatory standards that govern what must be included in product labeling. See 21 C.F.R. § 201.57(c)(6) (requiring reasonable evidence of a causal association); id. § 201.57(c)(7) (requiring sufficient basis to believe there is a causal association). The FDA had also not required any of the defendants to add a pancreatic cancer warning, or required the inclusion of a warning in newly approved incretin-based therapies.

First approved in 1983, it’s been a Pregnancy Category D drug since 1988, meaning, according to FDA regulations, that: there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. 21 C.F.R. §201.57(c)(9)(i)(A)(4). Not only that, since 2003, this drug has carried a black box “teratogenicity” warning, as well as other quite explicit, and all-caps, language to the same effect.

By Kurt R. Karst – In a 2-1 panel decision handed down by the U.S. Court of Appeals for the Federal Circuit earlier this week, the Court affirmed a September 2010 Judgment on the Pleadings by the U.S District Court for the Southern District of New York in favor of the ANDA sponsors (Defendants-Appellees) concerning U.S. Patent No. 5,569,652 (“the ‘652 patent”), which is listed in the Orange Book for the contraceptive drug YASMIN (drospirenone 3 mg/ethinyl estradiol 0.03 mg) Tablets (NDA No. 021098) as a method-of-use patent. Based on Federal Circuit precedent (i.e., Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348 (Fed. Cir. 2003) and Allergan Inc. v. Alcon Labs., 324 F.3d 1322 (Fed. Cir. 2003), which have been used to support the proposition that a method-of-use patent infringement claim against an ANDA sponsor cannot stand where that use is not approved by FDA), and FDA’s labeling regulations at 21 C.F.R. § 201.57(c) (stating in part that “[i]ndications or uses must not be implied or suggested in other sections of the labeling if not included in this section”), among other things, the New York District Court determined that the ‘652 patent does not claim an FDA-approved use for YASMIN because the patented use does not appear in the “Indications and Usage” section of the YASMIN labeling, but rather in the “Clinical Pharmacology” section of the labeling. As we previously reported, the case is important enough that PhRMA filed an amicus brief in support of Plaintiffs-Appellants.

ugs for use in animal feeds that are subject to 21 C.F.R. Part 558, including veterinary feed directive drugs. legally marketed unapproved new animal drugs for minor species that are indexed in accordance with Section 572 of the Federal Food, Drug, and Cosmetic Act (FDCA); (2) the labeling of heritable intentional genomic alterations in animals; or (3) to promotional labeling or advertising.Proposed Section 201.403 – DefinitionsThe proposed rule lists several terms that would have the same definition as those already in the FDCA or elsewhere in regulation.Under the proposed rule, prescription new animal drugs would be required to provide a labeling component that includes “full prescribing information.” The proposed rule would define the term as “all information necessary for the safe and effective use of a Rx new animal drug.” The FDA states that it would base the definition on the requirements for full prescribing information for prescription human drugs and biologics established in 21 C.F.R. § 201.57(c).Similarly, all approved or conditionally approved OTC new animal drugs would be required to provide a labeling component that includes “full product information.” The proposed definition of the term is “all information necessary for the safe and effective use of an OTC new animal drug.” However, the proposed rule would also establish content and format requirements for labels of OTC animal drugs that do not provide full product information, for example, for an approved OTC drug with a small label that the FDA determines lacks sufficient space to comply with the requirement.The proposed rule contains several other proposed definitions for terms used in the general requirements proposed regulations. A few examples of the proposed defined terms include “environmental warning,” “target animal,” “residue warning statement,” and “field study.”Proposed Section 201.404 – General requirementsThe proposed rule would require the labeling for animal drugs to conform to an application approved or

exclusivity will attach.Priority Review VouchersSponsors weighing the pros and cons of marketing a rare pediatric disease drug and/or biologic should keep in mind that marketing a rare pediatric drug and/or biologic automatically grants the sponsor a priority review voucher, which could have significant monetary value for the sponsor due to the transferrable nature of the voucher.FOOTNOTESGuidance – Pediatric Drug Development: Regulatory Considerations — Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act, U.S. Food & Drug Administration (May 17, 2023).Guidance – Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations, U.S. Food & Drug Administration (May 17, 2023).See Guidance – How to Comply with the Pediatric Research Equity Act, U.S. Food & Drug Administration (September 2005).88 Fed. Reg. 31766.See 21 CFR 201.23, 201.57(c)(7)(ii)(a). FDA defines “pediatric population” as the age group from birth to younger than seventeen years of age. See21 CFR 201.57(c)(9)(iv)(A); Regulatory Considerations Guidance at FN 1.See Unofficial Guidance – Understanding Unapproved Use of Approved Drugs “Off Label”, U.S. Food & Drug Administration (Feb. 5, 2018).See Status Report – The Pediatric Exclusivity Provision, U.S. Food & Drug Administration (Jan. 2001); FDAMA Public Law 105-115, 111 Stat. 2296 (Nov. 21, 1997).21 U.S.C. 355a(b),(c).See Status Report – The Pediatric Exclusivity Provision at FN 8.See Status Report – BPCA and PREA, U.S. Food & Drug Administration (July 2016).See 21 U.S.C. 355a(b),(c). Regulatory Considerations Guidance at p. 24.21 U.S.C. 355c(a)(1).21 U.S.C. 355c(a)(2)(A).21 U.S.C. 355c(a)(3)-(4), (k). 21 U.S.C. 355c(a)(3)(A).See Guidance – Rare Pediatric Priority Review Vouchers, U.S. Food & Drug Administration at p. 18 (July 2019).See id. At p. 19;Pediatric Drug Development: Challenges and Opportunities, National

A unilateral label change requires reasonable evidence of a causal link between the newly acquired information and the adverse reaction at issue. 21 CFR §201.57(c)(6)(i). Under this standard, the plaintiff had to sufficiently plead that Merck had newly acquired information (i.e., information received after the FDA’s approval of Gardasil) related to the plaintiff’s alleged injuries that justified a label change.Here, the plaintiff failed to meet her burden.

The court found the claims preempted, even though plaintiffs theorized 6,000 adverse event reports relating to diabetes from Pfizer to the FDA constituted “newly acquired information” which would enable the manufacturer to change the label under the FDA’s Changes Being Effected (CBE) regulations. In order to qualify as "newly acquired information," the information must demonstrate "reasonable evidence of a causal association with a drug" 21 C.F.R. § 201.57. But the fact that a user of a drug has suffered an adverse event, standing alone, does not mean that the drug caused that event.

As explained in the Biosimilar Labeling Guidance, labeling should not include a description of or data from clinical studies conducted to support a demonstration of biosimilarity or interchangeability because such studies would typically not be expected to facilitate an understanding of product safety and effectiveness.Interchangeable biosimilar labeling should meet the content and format requirements of the physician labeling rule (PLR) as described in 21 CFR 201.56(d) and 201.57, as well as the final pregnancy and lactation labeling rule (PLLR) as described in 21 CFR 201.57(c)(9)(i)-(iii). Interchangeable biosimilar labeling should also follow the Biosimilar Labeling Guidance for revising biosimilar product labeling and submitting initial and revised labeling.

ce prescription drug to treat a substance use disorder.Counsel the patient on treatment goals, expectations, benefits, and risks.Obtain the consent of the patient to a targeted urine test. Note, however, that urine tests are not required for patients experiencing a medical emergency, pain management associated with cancer, or palliative or hospice care.Include the brand name or generic name, quantity and initial dose of the controlled substance containing an opioid being prescribed.Ensure the patient understands the prescriber and the patient treatment responsibilities, and the prescribing policies of the practice.Ensure the patient understands that a controlled substance has potential to be abused, the associated risks of addiction and overdose, increased risk factors of addiction, the dangers of taking a controlled substance containing an opioid with benzodiazepines, alcohol or other central nervous system depressants, and other information deemed appropriate by the prescriber under 21 C.F.R. 201.57(c)(18).Discuss the efficacy, risks, and benefits of other treatment options, if applicable.The Guidance also provides important considerations applicable when entering an Opioid Treatment Agreement, including, but not limited to, the following:Ensuring that the patient understands what to do in the event of an overdose (and consideration of a co-prescription of naloxone);Ensuring that the patient understands the dangers and risks of sharing medication, and how to safely store and dispose of medication;Engaging in follow-up discussions with the patient to ensure adherence to the treatment plan; andActions to take in the event that a patient does not follow the Opioid Treatment Agreement[View source.]