As we wait for FDA’s Fall 2022 Unified Agenda, a look at what regulations are likely ahead for next year
Life Sciences
| By BY LAURA DIANGELO, MPH
In advance of the anticipated publication of the Fall 2022 Unified Agenda – the government’s list of all regulations under active development – AgencyIQ looks at FDA’s progress so far on its Spring 2022 agenda and what it’s already announced is in progress for 2023.
The Unified Agenda and its timing.
- The Unified Agenda: Twice a year, the White House releases a Unified Agenda that outlines the “actions administrative agencies plan to issue in the near and long term.” Practically, this means that twice a year the government’s various departments and agencies issue lists of regulations (both proposed and final versions) that they are working on with anticipated dates of release. These dates are largely aspirational and non-binding, and departments and agencies can issue rules that are not listed on the Unified Agenda if needed.
- While the Unified Agenda is released semi-annually, with a “Spring” and “Fall” version, the publishing schedule is not necessarily tied to the seasons. For example, the current Unified Agenda is the Spring 2022 version, which was issued in August 2022, while the Fall 2021 Unified Agenda was published in January 2022, while the Fall 2020 agenda was published in March 2021.
- Regulated industries are currently awaiting the next Unified Agenda, the Fall 2022 agenda. The final call for agencies to submit data and information to the Office of Information and Regulatory Affairs at the White House’s Office of Management and Budget for the Fall 2022 agenda was September 30, 2022 (i.e., the last day of the federal fiscal year). As noted above, it would not be unprecedented for the publication of the Fall agenda to take place in the first quarter of the new year.
In anticipation of the Fall 2022 agenda, AgencyIQ looked through the Spring 2022 agenda.
- That agenda lists 76 actions planned by the FDA, including 51 proposed rules and 25 final rules, including subjects from definitions of “healthy” food to policies on institutional review board (IRB) requirements. Excluding regulations specifically addressing food, tobacco or veterinary medical products, the agenda includes 41 policies, and 27 proposed and 15 final rules.
- Some big ticket items have been achieved since the initial publication of the last Unified Agenda, including, notably, the FDA proposed rule on allowing over-the-counter (OTC) drugs to be approved with additional conditions for nonprescription use (ACNU). The agency also issued its long-awaited final OTC hearing aids regulation, as well policies on reporting under Investigational New Drug (IND) applications and institutional review board (IRB) regulations.
- Other expected rules are still outstanding, including a proposed rule on the biologics regulations – outstanding since 2019 – to “clarify existing requirements and procedures related to Biologic License Applications and to promote the goals associated with FDA’s implementation of the abbreviated licensure pathway created by the Biologics Price Competition and Innovation Act.” In addition, a series of regulations about drug compounding are still on the schedule. A new final rule on co-packaged and fixed-combination products in OTC drugs – following a proposed rule in 2015 – is also on the schedule for 2023.
- What’s on deck for publication in 2023 (and the rest of 2022), according to FDA-TRACK, the “agency-wide performance management system that monitors FDA Centers and Offices through key performance measures and projects,” according to the system’s homepage. (AgencyIQ has taken out regulations having to do with food, tobacco and veterinary products.)
| Regulation Title | Summary | Target Date |
| Postmarketing Safety Reporting Requirements, Pharmacovigilance Plans, and Pharmacovigilance Quality Systems for Human Drug and Biological Products | The proposed rule would modernize FDA’s regulations on postmarketing safety reporting and pharmacovigilance for human drug and biological products, including blood and blood components, by capturing important new safety-related information, improving the quality and utility of submitted reports, and supporting enhanced alignment with internationally harmonized reporting guidelines. Among other things, the proposed rule would require the submission of certain nonclinical and clinical data to FDA in a periodic safety report, rather than the annual report. The proposed rule also would require application holders for drug products and certain biological products to establish and maintain a pharmacovigilance quality system that reflects the application holder’s unique needs and that may support a more streamlined, flexible approach to satisfying certain postmarketing safety reporting requirements. | 11/1/2023 |
| Revisions to Regulation for Receiving an Abbreviated New Drug Application | FDA is taking this action to revise 21 CFR 314.101 Filing an NDA and Receiving an ANDA in order to ensure the submission of high-quality, sufficiently complete abbreviated new drug applications (ANDAs) for technical assessment and approval. FDA’s regulations at 21 CFR 314.101(b), (d), and (e) set forth general criteria for the receipt or refusal of an ANDA for assessment. Specifically, 21 CFR 314.101(d)(3) states that in determining whether to receive or refuse to receive (RTR) an ANDA, FDA considers the nature of the deficiency (i.e., whether the deficiency is major or minor) and the number of deficiencies that have been identified during the filing review. The current regulations, while providing examples of deficiencies for which FDA will or may RTR an ANDA, do not specify whether the deficiencies are major or minor, nor do the regulations establish the number of deficiencies that will result in an RTR determination. In the absence of these specifics, FDA has issued a series of guidance documents over the last several years identifying more specific examples of what we have considered to be major or minor deficiencies. To improve the clarity and predictability of the ANDA assessment process and facilitate the submission of sufficiently complete applications, we intend to define what we consider to be major and minor deficiencies, provide examples of such deficiencies, and establish the number of deficiencies that will cause FDA to RTR an ANDA (e.g., one major deficiency or 10 or more minor deficiencies) consistent with current agency practices. We will also establish a timeframe in which an applicant may respond to an information request from FDA to resolve minor deficiencies and ensure receipt of the ANDA consistent with current agency practices. For example, we have permitted ANDAs for which we have identified a few minor deficiencies a limited period of time to address those minor deficiencies. | 8/1/2023 |
| Requirements for Determining Donor Eligibility and Donation Suitability of Blood and Blood Components Intended for Transfusion or for Further Manufacturing Use | FDA is proposing to revise certain regulations applicable to establishments that collect blood or blood components, including blood or blood components intended solely for autologous use. The proposed rule would revise and permit limited exceptions to certain donor eligibility and donation suitability requirements. The proposed rule would provide more flexibility to accommodate advancing technology, while continuing to help ensure the safety of the nation’s blood supply and donor health. | 7/1/2023 |
| Abbreviated New Animal Drug Applications | The Generic Animal Drug and Patent Restoration Act (GADPTRA) authorized abbreviated applications for the approval of a new animal drug. This rulemaking is intended to establish the procedural requirements for the submission and approval of generic new animal drug applications. | 7/1/2023 |
| General and Plastic Surgery Devices: Restricted Sale, Distribution, and Use of Sunlamp Products | This rule will apply device restrictions to sunlamp products. Sunlamp products include ultraviolet (UV) lamps and UV tanning beds and booths. The incidence of skin cancer, including melanoma, has been increasing, and a large number of skin cancer cases are attributable to the use of sunlamp products. The devices may cause about 400,000 cases of skin cancer per year, and 6,000 of which are melanoma. Beginning use of sunlamp products at young ages, as well as frequently using sunlamp products, both increases the risk of developing skin cancers and other illnesses, and sustaining other injuries. Even infrequent use, particularly at younger ages, can significantly increase these risks. | 6/1/2023 |
| Direct-to-Consumer Prescription Drug Advertisements: Presentation of the Major Statement in a Clear, Conspicuous, Neutral Manner in Advertisements in Television and Radio Format | The Food and Drug Administration (FDA) is amending its regulations concerning direct-to-consumer (DTC) advertisements of prescription drugs. Prescription drug advertisements presented through media such as TV and radio must disclose the product’s major side effects and contraindications in what is sometimes called the major statement. The rule would revise the regulation to reflect the statutory requirement that in DTC advertisements for human drugs in television or radio format, the major statement relating to side effects and contraindications of an advertised prescription drug must be presented in a clear, conspicuous, and neutral manner. This rule also establishes standards for determining whether the major statement in these advertisements is presented in the manner required. | 5/1/2023 |
| Medical Devices; Immunology and Microbiology Devices; Classification of Human Leukocyte, Neutrophil and Platelet Antigen or Antibody Tests | FDA intends to issue a proposed rule to classify Human Leukocyte Antigen (HLA), Human Platelet Antigen (HPA), and Human Neutrophil Antigen (HNA) devices into class II (special controls). FDA is also proposing to identify special controls for HLA, HPA, and HNA devices that are necessary to provide a reasonable assurance of safety and effectiveness. The proposed rule would include the recommendations of the Blood Products Advisory Committee regarding the classification of these devices. | 4/1/2023 |
| Fixed-Combination and Co-Packaged Drugs: Applications for Approval and Combinations of Active Ingredients Under Consideration for Inclusion in an Over-the-Counter Monograph | The final rule amends FDA regulations on fixed-combination prescription and over-the-counter (OTC) drugs. Current regulations require, among other things, that the sponsor of a fixed-combination drug demonstrate that each of the components makes a contribution to the drug’s claimed effects. The final rule harmonizes the combination drug requirements into a single set of regulations for both prescription and OTC combination drugs and codifies existing policy on what kinds of studies are needed to show that the combination drug requirements are met. The final rule also applies these regulations to combinations of biological drug products and to drug-biological product combinations; clarifies application of FDA’s requirements regarding fixed combinations to certain natural source drugs and certain synthetic drugs; establishes circumstances under which the Agency might waive the combination requirements for a particular drug or biological product; and addresses the issue of co-packaging. | 3/1/2023 |
| Current Good Manufacturing Practice for Outsourcing Facilities | This rule would set forth the minimum current good manufacturing practice (cGMP) requirements for human drug products compounded by an outsourcing facility. | 3/1/2023 |
| Permanent Listing of Color Additive Lakes | The Food and Drug Administration (FDA) is proposing to streamline and clarify the regulations for color additive lakes (water-insoluble pigments prepared by chemically reacting water-soluble dyes with water-insoluble substances). This proposed rule, if finalized would consolidate current regulatory provisions and would permanently list certain color additive lakes as suitable and safe for use in foods, drugs, and cosmetics. The proposed rule, if finalized, also would prescribe conditions for the preparation and labeling of these lakes. | 3/1/2023 |
| Amendments to the List of Bulk Drug Substances That Can Be Used To Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act | FDA has issued a regulation creating a list of bulk drug substances (active pharmaceutical ingredients) that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act), although they are neither the subject of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph nor components of FDA-approved drugs (the 503A Bulks List). FDA has proposed to amend the 503A Bulks List by placing five additional bulk drug substances on the list. FDA has also identified 26 bulk drug substances that FDA has considered and proposed not to include on the 503A Bulks List. Additional substances nominated by the public for inclusion on this list are currently under consideration and will be the subject of a future rulemaking. | 3/1/2023 |
| Biologics Regulation Modernization | FDA’s biologics regulations will be updated to clarify existing requirements and procedures related to Biologic License Applications and to promote the goals associated with FDA’s implementation of the abbreviated licensure pathway created by the Biologics Price Competition and Innovation Act of 2009. | 3/1/2023 |
| Clinical Holds in Medical Device Investigations | The proposed rule would create procedures for suspending, i.e., imposing a hold (a “clinical hold”) on, a clinical investigation of a medical device. The proposed rule would implement section 520(g)(8) of the Federal Food, Drug, and Cosmetic Act authorizing clinical holds for device investigations. | 3/1/2023 |
| Amending Regulations That Require Multiple Copies Submissions | This proposed rule would amend FDA’s regulations to remove requirements for submission of multiple copies and replace them with the requirement for a single submission, electronic format. This action is being undertaken to revise regulations that required paper submission in duplicate, triplicate, etc. | 3/1/2023 |
| Amendment of Procedural Requirements for Color Additive Petitions | The Food and Drug Administration (FDA) is proposing to amend procedural requirements for color additive petitions (CAPs). This action, if finalized, would modernize the procedural requirements related to the data requirements, submission procedures, review process, and regulatory timeframes for CAPs. FDA is proposing to revise the regulations to provide additional transparency, streamline current procedures, ease regulatory burden, and modernize the regulations. The proposed rule, if finalized, would improve regulatory efficiencies by implementing petition data requirements that are specific to the requested action. | 3/1/2023 |
| Contact Lens Devices; Designation of Special Controls for Daily Wear Contact Lenses | FDA is proposing in this rulemaking to designate special controls for daily wear contact lenses in order to address by regulation our current understanding of the risks to health for these devices, which were originally reclassified from class III (premarket approval) into class II (special controls) in 1994. The proposed special controls will reflect the Agency’s current guidance and review practice for daily wear contact lenses. | 3/1/2023 |
| Amendments to the Final Rule Regarding the List of Bulk Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug and Cosmetic Act | FDA has issued a regulation creating a list of bulk drug substances (active pharmaceutical ingredients) that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act), although they are neither the subject of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph nor components of FDA-approved drug products (the 503A Bulks List). The proposed rule will identify certain bulk drug substances that FDA has considered and is proposing to place on the 503A Bulks List and certain bulk drug substances that FDA has considered and is proposing not to include on the 503A Bulks List. | 3/1/2023 |
| Amendments to Patent Term Restoration | FDA is proposing to amend its Patent Term Restoration regulations to identify the effective date of approval for scheduled drugs, to define when the beginning of the 60-day review period occurs for an application to extend the patent term, to define the term business day, and to explain how approvals after 4:30 p.m. fit in this definition. The proposed amendments will make existing FDA regulations consistent with the statutory amendments. Other proposed changes to the regulations will make them conform with existing practices. | 2/1/2023 |
| Color Additive Certification; Increase in Fees for Certification Services | The Food and Drug Administration (FDA) is proposing to amend the color additive regulation to increase the fees for certification services. The change in fees will allow FDA to maintain an adequate color certification program as required by section 721(e) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 379e(e)). | 2/1/2023 |
| Post Approval Changes to Approved Applications | The proposed rule would update the existing regulations governing supplements and other changes to approved new drug applications (NDAs) abbreviated new drug applications (ANDAs), and biologics license applications (BLAs), as well as regulations regarding certain post-approval reports. | 1/1/2023 |
| Requirements for Foreign and Domestic Establishment Registration and Listing for Human Drugs, Including Drugs That Are Regulated Under a Biologics License Application, and Animal Drugs | FDA is amending its drug establishment registration and drug listing regulations via Direct Final Rule to extend the current exemption from drug establishment registration for certain manufacturers, repackers, relabelers, or salvagers of Type B or Type C medicated feeds to exempt all manufacturers, repackers, relabelers, or salvagers of Type B and C medicated feeds from drug establishment registration. All manufacturers, repackers, relabelers, or salvagers of Type B or Type C medicated feeds are already exempt from the drug listing requirements. | 1/1/2023 |
| Sunlamp Products; Amendment to the Performance Standard | FDA is updating the performance standard for sunlamp products and ultraviolet lamps for use in these products to improve safety, reflect new scientific information, and work towards harmonization with international standards. By harmonizing with the International Electrotechnical Commission, this rule will decrease the regulatory burden on industry and allow the Agency to take advantage of the expertise of the international committees, thereby also saving resources. | 12/1/2022 |
| Biologics License Applications and Master Files | The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) deems any biological product approved in a new drug application (NDA) to be a biologics license application (BLA) on March 23, 2020. Some of the affected NDAs were approved using drug master files (DMFs). A DMF, or other master file, allows an applicant to incorporate proprietary information from another manufacturer into its application by reference to the master file. FDA’s longstanding policy is that BLAs generally may not rely on drug substance, drug substance intermediate, or drug product information contained in master files. The final rule will permit the continued use of DMFs for NDAs subject to the BPCI Act transition. The final rule will codify that a biological product that was originally approved as a new drug application under the FD&C Act can continue to reference a DMF for drug substance, a drug substance intermediate, or a drug product information after the application is deemed to be a license under the PHS Act. The final rule also codifies FDA’s existing practice that a BLA may not otherwise rely on a master file for information concerning a drug substance, a drug substance intermediate, or a drug product except in the investigational phase of the application under an investigational new drug application. The final rule also clarifies that the non-biological constituent part(s) of a combination product regulated under a BLA may rely on any information in a DMF. | 12/1/2022 |
| Radiological Health Regulations; Amendments to Records and Reports for Radiation Emitting Electronic Products; Amendments to Performance Standards for Diagnostic X-ray, Laser, and Ultrasonic Products | The rule will clarify and update FDA radiological health regulations by repealing and amending parts of the general provisions, records and reports requirements, and electronic performance standards for radiation emitting electronic products and medical devices. Current regulations contain radiation protection recommendations, reporting requirements for manufacturers and assemblers of electronic products, and performance standards for certain electronic products. Some of the current regulations apply to electronic products (i.e., not necessarily having a medical application) but not devices (i.e., having a medical application). The revisions will amend and repeal certain radiation protection recommendations, reporting requirements for certain electronic products, and performance standards that have been identified as outdated or duplicative of other means to better protect public health. | 12/1/2022 |
| Revision of Product Jurisdiction Regulations | FDA is amending its regulation on classifying medical products as drugs, devices, biological products, or combination products (products composed of two or more different types of medical products, e.g., a drug and device) and on Center assignment and regulation of combination products, in two respects. First, it would remove a duplicative administrative appeals process for appealing product classification and assignment determinations, streamlining the process for appealing these determinations for product sponsors and FDA staff and making the process more efficient. Second, it would also enhance regulatory clarity and efficiency by removing a provision that might be interpreted inconsistently with new requirements under the 21st Century Cures Act, which addresses when combination products can be marketed under a single application for the complete combination product or under separate applications for each constituent part (e.g., the drug and device) of the combination product. | 12/1/2022 |
| Classification of Wound Dressings Containing Antimicrobials and/or Other Chemicals | FDA is proposing to classify the following three categories of unclassified, preamendments wound dressings that contain antimicrobials, and/or other chemicals currently grouped under product code FRO: Solid wound dressings; wound dressings formulated as a gel, cream, or ointment; and liquid wound washes. | 12/1/2022 |
| Drug Products or Categories of Drug Products That Present Demonstrable Difficulties for Compounding Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act | Compounded drug products must satisfy the conditions of section 503A or section 503B of the FD&C Act to qualify for certain statutory exemptions listed under each section. Both sections 503A and 503B contain conditions that concern whether a compounded drug product is one that the Agency has identified as presenting demonstrable difficulties for compounding. FDA is proposing to establish the criteria by which it will evaluate drug products and categories of drug products for inclusion on the list of drug products and categories of drug products that present demonstrable difficulties for compounding under section 503A and/or under section 503B. Based on the results of its evaluation of nominated categories of drug products to date, as well as consultation with the Pharmacy Compounding Advisory Committee (PCAC), FDA is also proposing to include certain categories of drug products on these lists. | 12/1/2022 |
| Classification of Spinal Spheres For Use in Intervertebral Fusion Procedures | FDA is classifying spinal spheres for use in intervertebral fusion procedures, an unclassified preamendments device, into class III. FDA believes that there is insufficient information to determine that general controls and special controls would provide reasonable assurance of safety and effectiveness for this device. After considering the recommendations of the Orthopedic and Rehabilitation Devices Panel (Panel held December 12, 2013), FDA is publishing this regulation that will protect and promote the public health by classifying spinal spheres for use in intervertebral fusion procedures. | 12/1/2022 |
| Medical Devices; Cardiovascular Devices; Classification of More Than Minimally Manipulated Allograft Heart Valves | FDA is proposing to classify more than minimally manipulated (MMM) allograft heart valves, an unclassified preamendments device (product code OHA) into class III. FDA believes that there is insufficient information to determine that general controls and special controls provide reasonable assurance of safety and effectiveness for this device. FDA is publishing this proposed rule after considering the recommendations of the Circulatory System Devices Panel, regarding the classification of MMM allograft heart valves. These devices are currently reviewed through the 510(k) process. As part of the classification process, we are required to discuss the potential classification before an advisory committee and seek the committee’s recommendation on classification, which took place in October 2014. The proposed rule would provide necessary clarity and transparency regarding the regulatory controls required to ensure that these devices are reasonably safe and effective. The proposed rule would benefit device recipients by reducing the risk of device-related complications and death. | 12/1/2022 |
| Conduct of Analytical and Clinical Pharmacology, Bioavailability and Bioequivalence Studies | FDA is proposing to amend 21 CFR 320, in certain parts, and establish a new 21 CFR 321 to clarify FDA’s study conduct expectations for analytical and clinical pharmacology, bioavailability (BA) and bioequivalence (BE) studies that support marketing applications for human drug and biological products. The proposed rule would specify needed basic study conduct requirements to enable FDA to ensure those studies are conducted appropriately and to verify the reliability of study data from those studies. This regulation would align with FDA’s other good practice regulations, would also be consistent with current industry best practices, and would harmonize the regulations more closely with related international regulatory expectations. | 12/1/2022 |
| Distribution of Compounded Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act | The Food and Drug Administration is proposing rulemaking regarding statutory requirements for certain distributions of compounded human prescription drug products. The proposed rule, if finalized, will include provisions regarding a standard memorandum of understanding (MOU) that describes the responsibilities of a State Board of Pharmacy or other appropriate State agency that chooses to sign the standard MOU in investigating complaints related to drug products compounded in such State and distributed outside such State and in addressing the interstate distribution of inordinate amounts of compounded human drug products. It will also, if finalized, include provisions regarding the statutory 5 percent limit on distribution of compounded human drug products out of the State in which they are compounded in States that do not sign the standard MOU, and may address adverse event reporting, product quality reporting, and communication with State boards of pharmacy. | 12/1/2022 |
| Amendment to Device Registration and Listing Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products | FDA intends to issue a direct final rule and companion proposed rule clarifying registration and listing requirements that apply to human cells, tissues, or cellular or tissue-based products regulated as devices to make clear that the establishments that manufacture such products are required to follow the procedures in 21 CFR part 807. This proposed revision to 21 CFR 807 is for consistency with FDA’s current regulations under 21 CFR part 1271, subpart A. | 12/1/2022 |
| Amendment to Records and Reports Concerning Adverse Drug Experiences on Marketed Prescription Drugs for Human Use Without Approved New Drug Applications | FDA is proposing to amend the Adverse Event Reporting regulations for marketed prescription drug products that are not the subject of an approved new drug or abbreviated new drug application. The proposed amendment will provide clarity to industry regarding when adverse event reports should be submitted to the Agency. | 11/1/2022 |
| Medication Guide; Patient Medication Information | The proposed rule would amend FDA medication guide regulations to require a new form of patient labeling, Patient Medication Information, for submission to and review by FDA for human prescription drug products and certain blood products used, dispensed, or administered on an outpatient basis. The proposed rule would include requirements for Patient Medication Information development and distribution. The proposed rule would require clear and concisely written prescription drug product information presented in a consistent and easily understood format to help patients use their prescription drug products safely and effectively. | 10/1/2022 |
To contact the author of this item, please email Laura DiAngelo.
To contact the editor of this item, please email Alexander Gaffney