Description
With FDA's recent successes in meeting the Prescription Drug User Fee Act of 1992 (PDUFA) review action performance goals, and the resulting significant declines in mean and median time from submission of a marketing application to approval for marketing, attention has turned to increasing the efficiency of other components of the drug development process without sacrificing the longstanding safety and efficacy standards Americans expect their drug products to meet. One part of IND regulation of particular interest - under active discussion for more than two years and the subject of various degrees of attention since the McMahon Committee - is the regulation of the initial testing of drugs in humans (i.e., Phase 1 trials).
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
1Including Well-Characterized, Therapeutic, Biotechnology-derived Products; Well-characterized therapeutic products requiring specific validation
Stakeholders
4responsible for justifying omission of studies
Janet Woodcock, M.D. and Kathryn Zoon, Ph.D.
Murray Lumpkin, M.D.
Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining
Regulatory Context
Regulatory Activities
5Regulatory submissions for clinical trials.; General requirements for INDs apply to development programs
Investigational New Drug submissions
IND for treatment use; Regulatory submission required for clinical trials and expanded access.
FDA may place a protocol on clinical hold if design is deficient
Reporting modifications of experimental design that do not affect safety
Document Types
10integrated summary report of toxicology findings based upon the unaudited draft toxicologic reports
IND Process and Review Procedures Manual of Policies and Procedures
experience may be presented in an integrated summary report
Should include biological rationale for subgroups
Reference material available from the Division of Biostatistics, CDRH.
Summary of safety and tolerability
Document containing information on investigational products and reference safety information.; Compilation of clinical and nonclinical data on the investigational product; Document provided to investigators containing clinical and nonclinical data.; investigator site staff should follow the current approved version; Basis of safety assessment and reporting for the clinical trial.; A compilation of clinical and nonclinical data on investigational products.; The IB should provide a description of
Protocols for adaptive trials should include pre-specified criteria
Document indicating analytical results of testing; record relied on to control L. monocytogenes in ingredients; document provided for a food prior to or upon receipt of the food; COA documentation
Protocol design for formal stability studies; Incorporates information to establish re-test period or shelf life; Design and execution of a stability protocol to support formal studies; Design for supporting drug substance or drug product shelf life; Design of the stability study including frequency and conditions; Written protocol for holding time studies; Design of in-use stability study protocols; Reduced Stability Protocol Design discussed in Annex 1; Including intermediate storage condition
Attributes
3attempting to determine early pharmacokinetic properties
exemption from environmental assessment
attempting to determine early pharmacodynamic properties
Technical Details
Substances
2Differences in excipients may affect product stability
Treatment with investigational drug for MDS
Testing Methods
4quantitative high performance liquid chromatography (HPLC) analysis to relate the quantity of those compounds
Used to prove identity of the drug substance
Test performed at release
Required for sterile dosage forms
Processes
2Required for contaminated equipment and media before disposal
systematic presentation of findings
Clinical Concepts
2regulation of the initial testing of drugs in humans
Table of contents section G
Identified Hazards
Hazards
2Indicative of a potential health hazard
possible signals of human risk in animal studies
Standards & References
External Standards
3Prescription Drug User Fee Act review performance goals and timelines.
Standard for inactive ingredient titles and monographs; Anhydrous and dihydrate terms are consistent with USP-NF monograph terminology.
Quality grade for reagents and solvents
Specifications
1Assure identity, strength, quality, and purity
ICH References (2)
Guideline for the Investigator's Brochure
Sponsors are referred to this document for further information on recommended elements
Related CFR Sections (4)
- 21CFR312.32§ 312.32 IND safety reporting.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
- 21CFR312.22§ 312.22 General principles of the IND submission.
(a) FDA's primary objectives in reviewing an IND are, in all phases of the investigation, to assure the safety and rights of subjects, and, in Phase 2 and 3, to help assure that the quality of the scientific evaluation of drugs is adequate to permit an evaluation of the drug's effectiveness and safeRead full regulation →
- 21CFR312.6§ 312.6 Labeling of an investigational new drug.
(a) The immediate package of an investigational new drug intended for human use shall bear a label with the statement “Caution: New Drug—Limited by Federal (or United States) law to investigational use.”Read full regulation →
See Also (8)
- Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers (Status: Final)
- PHS Guideline on Infectious Disease Issues in Xenotransplantation: PHS Guideline (Status: Final)
- Postmarketing Safety Reporting for Human Drug and Biological Products Including Vaccines: Draft Guidance for Industry (Status: Draft)
- Guidance for Industry: Providing Regulatory Submissions to CBER in Electronic Format -- Investigational New Drug Applications (INDs) (PDF) (Status: Final)
- Gingivitis: Development and Evaluation of Drugs for Treatment or Prevention (Status: Draft)
- How to Comply with the Pediatric Research Equity Act (Status: Draft)
- Establishment and Operation of Clinical Trial Data Monitoring Committees: Guidance for Clinical Trial Sponsors (Status: Final)
- Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines: Guidance for Industry (Status: Final)