Related to US regulatory intelligence, the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) has released a new guidance agenda (posted below) detailing the new and revised guidance documents scheduled for release this year. Many of the new and revised guidelines slated for release are for generic drugs, and many also address new International Council for Harmonization (ICH) topics. CDER is not bound by this list of topics, nor required to issue every guidance document on this list and can generate others not on the list.
Of the 88 guidelines scheduled for release in 2025, 28 are new and the others are carried over from July 2024.
Many are directed at the generic drug industry. Among these are a new guidance on Abbreviated New Drug Applications (ANDAs) for certain highly purified systemic peptide drugs, the content and format of ANDA submissions, and bioavailability and bioequivalence studies for nasal products.
Also included are new guidelines regarding post-approval requirements and resources for ANDAs, considerations for design differences in comparative analyses for drug-device combination products, new product-specific guidance, and the use of Type V Drug Master Files for model master file submissions.
Many guidelines focus on International Council for Harmonisation (ICH) including a new ICH E21 guidance on including pregnant and breastfeeding individuals in clinical trials; E22 covering general considerations for patient preference studies; ICH M4Q(R2) addressing common technical document (CTD) quality-related questions; ICH M11 on clinical electronic structured harmonized protocols (CeSHaP); ICH M13C regarding bioequivalence for immediate-release solid oral dosage forms; and ICH Q3C(R10) maintaining the guidelines on residual solvents.
New is a guidance covering considerations for container closure systems and device components for biosimilars and interchangeable biosimilars.
Importantly for biostatistics, three new or revised guidelines are planned for using Bayesian methods in clinical trials involving drugs and biologics, the application of informative Bayesian methods in pediatric clinical trials, and the implementation of master protocols for drug and biologics development.
In the clinical and medical area, the Center for Drug and Evaluation Research (CDER) plans to issue new guidance on the development of drugs to treat disseminated coccidioidomycosis. Notably, the agency plans to release a guideline addressing considerations for including older adults in clinical trials. CDER intends to publish a new enforcement policy regarding non-animal-derived thyroid products that are marketed without an approved biologics license application (BLA). Also, the center plans to provide guidance on the information needed to support the adequacy of safety evaluation planning.
Three new and revised guidance documents are planned for clinical pharmacology. These will cover clinical drug interaction studies involving combined oral contraceptives, the evaluation and study design of clinical pharmacogenomic studies, and guidelines for conducting pharmacokinetic studies in patients with impaired hepatic function.
CDER plans to issue new guidance on clinical pharmacogenomics information in drug and biological product labeling.
New guidelines are being developed for minor changes to solid oral dosage forms of certain OTC monograph drugs.
Three upcoming guidelines in the pharmaceutical quality and Chemistry, Manufacturing, and Controls (CMC) area are a new guideline on establishing impurity limits for antibiotics, a revised draft guidance on GMPs for medical gases, and a revised draft guidance on the certification process for designated medical gases. The exact titles are below from the posting.
CDER Guidance Agenda New and Revised Draft Guidances Planned for Publication in Calendar Year 20251 (January 2025) See the Good Guidance Practices (GGPs) regulation on this Web page
(https://www.fda.gov/media/185228/download) or
21 CFR 10.115 for details about the Guidance Agenda.
CATEGORY – Administrative/Procedural
• Civil Monetary Penalties for Failure to Meet Accelerated Post Marketing Requirements
• Exclusivity for First Interchangeable Biosimilar Biological Products
• NDC Creation, Assignment, Listing and Appropriate Use for Human Drugs, Including Biological Products • Priority Review Voucher Programs
• Qualified Infectious Disease Product Designation—Questions and Answers
• Repackaging and Relabeling of Human Drugs: Labeling; Registration and Listing, Safety Reporting, Supply Chain Security, and Good Manufacturing Practice
CATEGORY – Biosimilars
• Biosimilar and Interchangeable Biosimilar Products: Considerations for Container Closure Systems and Device Constituent Parts
• Pediatric Study Plans for Biosimilar Products
• Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (Revision 1)
CATEGORY – Biostatistics
• Use of Bayesian Methodology in Clinical Trials of Drug and Biological Products
CATEGORY – Biostatistics / Clinical / Medical
• Informative Bayesian Methods in Pediatric Clinical Trials
• Master Protocols for Drug and Biological Product Development
CATEGORY – Clinical/Antimicrobial
• Disseminated Coccidioidomycosis: Developing Drugs for Treatment
• Malaria: Developing Drugs for Treatment.
CATEGORY – Clinical/Medical
• Chronic Spontaneous Urticaria: Developing Drugs for Treatment
• Considerations for the Inclusion of Older Adults in Clinical Trials; Draft Guidance for Industry
• Development of Animal-Derived Thyroid Products
• Development of Non-Opioid Analgesics for Chronic Pain
• Drugs With Teratogenic Potential-Recommendations for Pregnancy Planning and Prevention
• Endometriosis-Associated Pain: Establishing Effectiveness and Safety of Drugs for Management
• Enforcement Policy – Animal-Derived Thyroid Products Marketed Without an Approved Biologics License Application
• Erosive Esophagitis: Developing Drugs for Treatment
• Information To Submit and To Support the Adequacy of Safety Evaluation Planning
• Radiation Dosimetry for First-in-Human Studies of Positron Emission Tomography Drugs
• Small Volume Parenteral Drug Products and Pharmacy Bulk Packages for Parenteral Nutrition: Aluminum Content and Labeling Recommendations; Revised Draft
• Symptomatic Nonerosive Gastroesophageal Reflux Disease: Developing Drugs for Treatment
CATEGORY – Clinical Pharmacology
• Clinical Drug Interaction Studies With Combined Oral Contraceptives
• Clinical Pharmacogenomics: Evaluation, Study Design, and Analysis
• Pharmacokinetics in Patients with Impaired Hepatic Function – Study Design, Data Analysis, and Impact on Dosing and Labeling
• Pharmacokinetics in Pregnancy — Study Design, Data Analysis, and Impact on Dosing and Labeling
CATEGORY – Compounding
• Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act; Revised Draft
• Compounded Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act; Revised Draft
• Compounding Under Section 503B of the Federal Food, Drug and Cosmetic Act and Considerations for Related to Drug Shortages
• Nomination of Bulk Drug Substances for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
• Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act; Revised Draft 2
• Prohibition on Wholesaling Under Section 503B of the Federal Food, Drug and Cosmetic Act
• Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors-Guidance for Outsourcing Facilities Under Section 503B of the FD&C Act
CATEGORY – Drug Safety
• Development of a Shared System or Separate REMS; Revised Draft
• REMS Logic Model: A Framework to Link Program Design with Assessment
CATEGORY – Generics • 180-Day Exclusivity: Questions and Answers; Revised Draft
• 30-Month Stay of Approval of an ANDA or 505(b)(2) Application
• ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin
• ANDA Submissions — Content and Format Guidance for Industry
• ANDA Submissions-Refuse-to-Receive for DMF Facilities Deficiencies
• ANDA Submissions-Refuse-to-Receive Standards: Questions and Answers
• Assessing Adhesion with Transdermal Delivery Systems and Topical Patches for ANDAs; Revised Draft
• Assessing the Irritation and Sensitization Potential of Transdermal and Topical Delivery Systems for Abbreviated New Drug Applications; Revised Draft
• Bioavailability and Bioequivalence Studies for Nasal Products
• Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application; Revised Draft
• Certain Post-Approval Requirements and Resources for ANDAs
• Considerations For Other Design Differences Identified in Comparative Analyses for a Drug-Device Combination Product Submitted in an ANDA
• Determining Whether to Submit an ANDA or 505(b)(2) Application
• Forms FDA 3542a and FDA 3542: Questions and Answers • Handling and Retention of BA and BE Testing Samples; Revised Draft
• In Vitro Permeation Tests for Semisolid Topical Products Submitted in ANDAs; Revised Draft
• In Vitro Release Tests for Semisolid Topical Products Submitted in ANDAs; Revised Draft
• Mechanistic Modeling and Simulation Approaches to Assess Local and Systemic Bioavailability and Bioequivalence for Non-Orally Administered Drug Products
• New Clinical Investigation Exclusivity (3-Year Exclusivity) for Drug Products: Questions and Answers
• “Open for Business” Under 744B of the Federal Food, Drug and Cosmetic Act
• Submission of Patent Information for Listing in the Orange Book: Questions and Answers
• Pediatric Exclusivity General Considerations for ANDAs
• Product-Specific Guidances for Generic Drug Development 3
• Use of a Type V Drug Master File for Model Master File Submissions
CATEGORY – ICH
• E20 Adaptive Clinical Trials
• E21 Inclusion of Pregnant and Breastfeeding Individuals in Clinical Trials
• E22 General Considerations for Patient Preference Studies
• M4Q(R2) Addressing Common Technical Document (CTD) Quality-Related Questions
• M11 Clinical Electronic Structured Harmonized Protocol (CeSHarP) Revised Draft Technical Specification
• M13B Bioequivalence for Immediate-Release Solid Oral Dosage Forms; Biowaiver Considerations for Additional Strengths
• M13C Bioequivalence for Immediate-Release Solid Oral Dosage Forms; Advanced Bioequivalence Study Design and Data Analysis Considerations
• Q1/Q5C Targeted Revisions of ICH Stability Guidelines
• Q3C(R10) Maintenance of the Guideline for Residual Solvents
• Q3E Impurity: Assessment and Control of Extractables and Leachables for Pharmaceuticals and Biologics
CATEGORY – Labeling
• Clinical Pharmacogenomics Information in Human Prescription Drug and Biological Product Labeling • Combined Hormonal Contraceptives for Prevention of Pregnancy-Labeling for Health Care Providers and Patients
• Impact of Identifying Group Purchasing Organizations on a Drug Label
CATEGORY– Over-the-Counter Drugs
• Minor Changes to Solid Oral Dosage Forms for Certain Over-the-Counter Monograph Drugs
CATEGORY – Pharmaceutical Quality CGMP • Approaches to Meeting CGMP Requirements for Distributed Manufacturing
• Laboratory Testing of Drugs Held in Interstate Commerce: Compliance with CGMP
• PET Drugs – Current Good Manufacturing Practice (CGMP); Revised Draft
• Responding to Form FDA 483 Observations at the Conclusion of a Drug CGMP
CATEGORY – Pharmaceutical Quality/CMC
• ANDAs: Stability Testing of Drug Substances and Products Q & A
• Container Closure Systems for Drugs, Including Biological Products
• Stability Considerations for Drug Substances and Drug Products in NDAs, ANDAs, and BLAs and Associated Labeling Statements for Drug Products 4
• Stability Recommendations for Additional Manufacturing Facilities in NDAs, ANDAs and BLAs, and Additional Drug Substance Sources in NDAs and ANDAs
• Guidelines for Establishing Impurity Limits for Antibiotics
• Current Good Manufacturing Practice for Medical Gases; Revised Draft • Certification Process for Designated Medical Gases; Revised Draft Note: Agenda items reflect guidances under development as of the date of this posting.