FDA QUESTIONS AND ANSWERSWithin the draft guidance, FDA also provides answers to some likely questions. Among these answers are the following:A drug must be reported even if no quantity of that drug was manufactured, prepared, propagated, compounded, or processed for commercial distribution during the previous year. In essence, the quantity in the report will be zero;In determining the total amount of drug to report, registrants must not subtract amounts that have been returned or recalled; andA report must still be submitted by a registrant even if they manufactured, prepared, propagated, compounded, or processed an applicable drug during only part of the calendar year.FDA recognized the potential reporting burden for applicants that also have to submit distribution data under the applicant’s annual report requirement pursuant to 21 C.F.R. § 314.81(b)(2)(ii)(a) as well as in the new 510(j)(3) report. While both reports still need to be submitted, in an attempt to streamline the process, FDA indicated applicants do not need to regenerate the distribution data in the annual report submitted under 21 C.F.R. § 314.81(b)(2)(ii)(a) provided the following criteria is met:A timely and complete 510(j)(3) report is submitted;Information concerning the amount of listed drug product (organized by NDC number) that was distributed for foreign use during the reporting period is added to the 510(j)3) report; andThe applicant’s annual report provides: 1) the NDC number(s) and strength(s) of drug product it included in the 510(j)(3) report and 2) the submission date for the 510(j)(3) report.If the aforementioned criteria are met, FDA will not take regulatory action against an applicant for not submitting the distribution data in the exact format prescribed in 21 C.F.R. § 314.81(b)(2)(ii)(a).

The information in the follow-up and final FAR is used by FDA to assess the risk to public health and the adequacy of the firm’s response.Aseptic process simulation failures for a distributed drug product require a FAR when the failure indicates a potential problem related to sterility assurance that requires an investigation, including an assessment on the impact of distributed drug product that has been produced since the last successful media fill.Even if the root cause of a problem related to a distributed drug product is identified and corrected within three working days, the applicant must still submit a FAR if the problem had originally met the criteria under 21 CFR 314.81(b)(1).The undertaking of a recall does not absolve the applicant of the responsibility to perform a FAR, if the issue with the drug product which led to the recall meets the criteria for a FAR under 21 CFR 314.81(b)(1).FARs associated with multiple NDAs/ANDAs need to be submitted on separate Forms (Form FDA 3331a), one for each NDA/ANDA.Ultimate responsibility for submitting the FAR rests with the NDA/ANDA holder, even if certain steps in the manufacturing, holding, packaging, labeling or distribution of the drug product in question are contracted out to other parties.Failing to submit a required FAR within the three working day timeframe is not only a violation of 21 CFR 314.81(b)(1), but also a violation of section 505(k) of the Federal Food, Drug and Cosmetic Act (FDCA) as well as section 301(e) FDCA.We will keep you posted on any interesting comments posted to the docket for this draft guidance, as well as the publication of any revised or final guidance documents by the agency.

3287 Fed. Reg. at 38324; 21 C.F.R. §§ 201.67(d), 201.130(a)(2) (proposed).3387 Fed. Reg. at 38322; 21 C.F.R. § 314.81(b)(3)(v) (proposed).3487 Fed. Reg. at 38322; 21 C.F.R. § 314.81(b)(3)(v) (proposed).

OPDP continues to focus its enforcement efforts on high-risk drug or biological products, such as opioids or products under a Risk Evaluation and Mitigation Strategy (REMS). 2021 was no different with letters directed towards marketing of at least one opioid product also subject to a REMS, a product used in a vulnerable pediatric patient population that may cause serious adverse reactions, and a product associated with serious and potentially life-threatening risks.Three of the letters cited companies for failing to submit the promotional materials to OPDP under cover of Form FDA-2253 at the time of initial dissemination as required by 21 CFR 314.81(b)(3)(i).2While we do not think this will be the sole reason for a Warning or Untitled Letter, OPDP will certainly include it in a letter that cites other regulatory issues.Two of the letters discussed direct-to-consumer videos, signifying the agency’s monitoring and scrutiny of advertisements directed at consumers, an audience considered more vulnerable compared to healthcare providers.

The report provides the results of the FTC’s preliminary data analysis on the short-term effects of authorized generics on competition during 180-day exclusivity. The authorized generics final rule, which goes into effect in six months, amends FDA’s regulations at 21 C.F.R. § 314.3(b) to add the following definition of an “authorized generic drug” that is substantially identical to that in FDC Act § 505(t):Authorized generic drug means a listed drug, as defined in this section, that has been approved under section 505(c) of the act and is marketed, sold, or distributed directly or indirectly to retail class of trade with labeling, packaging (other than repackaging as the listed drug in blister packs, unit doses, or similar packaging for use in institutions), product code, labeler code, trade name, or trademark that differs from that of the listed drug.The final rule also amends FDA’s postmarketing reporting requirements to add 21 C.F.R. § 314.81(b)(2)(ii)(b) to require NDA holders to include in their annual reports information detailing: (1) the date each authorized generic entered the market; (2) the date each authorized generic ceased being distributed; and (3) the corresponding brand name drug. FDA considers each dosage form and/or strength to be a different authorized generic drug that should be separately listed in an annual report.

package insert, which states, “[b]ecause 51% of patients discontinued treatment prematurely due to adverse reaction, lack of efficacy, or other reasons, these results should be interpreted with caution.” This information was not included on the company’s website, and FDA asserted that the omission undermined the ability of the reader to understand and evaluate the study results presented, thereby creating a misleading impression about the drug’s efficacy.FDA issued a close-out letter on August 9, 2023, which represents a prompt resolution to this misstep for the company.The second untitled letterof 2023, issued on August 11, 2023, took issue with promotional material posted on social media regarding an oral contraceptive. OPDP asserted that the post had multiple infirmities, including making misrepresentations regarding the drug’s efficacy and its risks. OPDP also pointed out that the material was not submitted to FDA at the time of initial dissemination or publication as required by 21 CFR 314.81(b)(3)(i). With respect to efficacy, the social media post claimed the ability to “[o]ffer your patients estrogen-free birth control with periods on a schedule.” According to OPDP, this claim is misleading because it overstates the drug’s efficacy by claiming patients will have predictable menstrual bleeding that is “on a schedule” when this has not been demonstrated.With respect to risks, FDA asserts that while the post presents claims and representations about the benefits of the drug, it fails to communicate any risk information. According to FDA, failing to include any risk information creates a misleading impression about the drug’s expected benefits and safety.As corrective actions, FDA requested that the company submit a written response to the untitled letter within 15 working days from the date of receipt:addressing the concerns described in the letter;listing all other promotional communications (with the 2253 submission date) for the drug that contain representations such as those de

mmendations for biosimilar and interchangeable biosimilar product labeling in this draft guidance pertain only to the prescribing information, except for certain recommendations pertaining to FDA-approved patient labeling (e.g., Patient Information, Medication Guide, Instructions for Use). This draft guidance provides an overview of FDA’s recommendations for labeling for biosimilar and interchangeable biosimilar products. When finalized, this draft guidance will revise and replace the guidance for industry entitled “Labeling for Biosimilar Products.”On September 15, 2023, FDA issued draft guidance entitled, Annual Status Report Information and Other Submissions for Postmarketing Requirements and Commitments: Using Forms FDA 3988 and FDA 3989. This guidance is intended for applicants that are required to report annually on the status of postmarketing studies and clinical trials for human drug and biological products under section 506B of the FD&C Act and its implementing regulations at 21 CFR 314.81(b)(2)(vii) and 601.70. FDA explains in the guidance that this document is intended for applicants that are required by statute or regulation, or that have agreed in writing, to conduct postmarketing studies or clinical trials concerning a product’s clinical safety, clinical efficacy, clinical pharmacology, and nonclinical toxicology as postmarketing requirements (PMRs) or postmarketing commitments (PMCs).On September 15, 2023, FDA issued draft guidance entitled, Fostering Medical Device Improvement: FDA Activities and Engagement with the Voluntary Improvement Program. FDA issued this guidance to describe its policy regarding FDA’s participation in the Voluntary Improvement Program (VIP). The VIP is a voluntary program facilitated through the Medical Device Innovation Consortium (MDIC) that evaluates the capability and performance of a medical device manufacturer’s practices using third-party appraisals, and is intended to guide improvement to enhance the quality of devices. The VIP builds on the

o each development plan.” FDA cautions that a marketing application comprised of patients predominantly outside of the United States may trigger requirements or requests for additional clinical studies to characterize the safety or efficacy of a drug in relevant patient subpopulations in the United States.***We recommend that companies begin familiarizing themselves now with the new legal requirements related to Diversity Action Plans and how those requirements will impact clinical trial designs and drug development programs—including the possibility of postmarketing studies to obtain data on underrepresented populations.FDA is requesting comments on the draft guidance by October 10, 2023.1See https://www.fda.gov/media/170899/download.2Section 505(z) of the FD&C Act, as added by section 3601 of The Consolidated Appropriations Act, 2023 (enacted December 29, 2022).3See, e.g., section 505(o)(3) and 506 of the FD&C Act (regarding postmarketing requirements); section 506B of the FD&C Act, 21 CFR 314.81, 601.70 (regarding postmarketing commitments).4Draft Postmarketing Approaches Guidance, at 4.5Id. at 5.6See https://www.fda.gov/media/157635/download.

We acknowledge the contributions to this publication from our summer associate Katie L. Hollingsworth.1See Thomas Sullivan, FDA Issues Guidance on Drug Shortage Notifications, POL’Y & MEDICINE (Apr. 22, 2020), https://www.policymed.com/2020/04/fda-issues-guidance-on-drug-shortage-notifications.html.2See 21 C.F.R. § 314.81(b)(3)(iii)(f) (2016); 21 C.F.R. § 600.82(f) (2015).3See 21 U.S.C. § 356-1.4This includes persons that operate establishments that manufacture drug-led, drug-device, or biologic-led, biologic-device products (i.e., single-entity, co-packaged, and cross-labeled combination products, as defined in 21 C.F.R § 3.2(e) (2005)).

16House Draft § 804.17Id.18Id.; see U.S. Food & Drug Admin., Guidance for Industry: Labeling for Human Prescription Drug and Biological Products Approved Under the Accelerated Approval Regulatory Pathway 3 (2019).19House Draft § 804; see 21 C.F.R. § 314.81(b)(2)(vii) (“The status of these postmarketing studies shall be reported annually until FDA notifies the applicant, in writing, that the agency concurs with the applicant's determination that the study commitment has been fulfilled or that the study is either no longer feasible or would no longer provide useful information.”).20House Draft § 804.21Accelerated Approval Integrity Act, H.R. 6963, § 2 (2022) (introduced March 2022 by E&C Chairman Rep. Frank Pallone Jr.).22U.S. Food & Drug Admin., Draft Guidance for Industry: Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials (2022); see also Eva Temkin et al., Client Alert, A Pandemic Silver Lining: FDA’s New Guidance on Using Digital Health Technologies for Clinical Investigations (Feb. 7, 2022), available at https://www.kslaw.com/attachments/000/009/402/original/A_Pandemic_Silver_Lining_-_FDA's_New_Guidance_on_Using_DHTs_for_Clinical_Investigations.pdf?1644263853.