| When submitting a NEW CLINICAL PROTOCOL as part of an IND application, consider the following: | 1 For Phase 1 trials:
- Early developmental protocols should specify in DETAIL ALL THE ELEMENTS of the study that are CRITICAL TO SAFETY.
2 For Phase 2-3 trials:
- All the above-described expectations for ADEQUATE SAFETY ELEMENTS also apply to Phase 2-3 trials;
- Detailed protocols describing EFFICACY & SAFETY be submitted. OBJECTIVES & PURPOSES of a trial should be clearly stated, including description of the observations and measurements to be made to fulfill the objectives of the trial
- Clinical trial protocols should include a clear description of TRIAL DESIGN and PATIENT SELECTION criteria as well as description of CLINICAL PROCEDURES. laboratory tests, and all measures to be taken to MONITOR the effects of the drug |
| STUDY ENROLLMENT CRITERIA should be written with consideration of the following: | (1) BACKGROUND RISKS associated with the disease or condition studied
(2) PREVIOUS KNOWLEDGE OF TOXICITIES of the investigational drug observed in animal studies or with human experience
(3) WARNINGS AND PRECAUTIONS described in the product’s label (when approved products are investigated for other than approved uses)
BPW |
| Chemistry, Manufacturing, and Control Information
(STATE CONTENTS) | 1 Drug Substance
2 Drug Product
3 Environmental Assessment
4 Pharmacology Toxicology Information
- Pharmacology and Drug Disposition
- Toxicology
DDEP |
| Summary of Previous Human Experience with the Investigational Drug
(STATE CONTENTS) | 1 IF NO PREVIOUS HUMAN EXPERIENCE EXISTS, should be stated in this section of the IND application.
2 IF AN INVESTIGATIONAL DRUG HAS BEEN INVESTIGATED OR MARKETED PREVIOUSLY, detailed information about such experience that is relevant to the safety of the proposed investigation or to the investigation’s rationale should be included in this section.
3 If the product has been marketed outside of the United States, all countries where the product has been marketed or withdrawn from any of those markets (and why) should be listed. |
| Additional Information
(STATE CONTENTS) | - information on special topics may be needed
- include: DRUG DEPENDENCE and ABUSE POTENTIAL, RADIATION ABSORPTION calculations for RADIOACTIVE DRUGS, PLANS FOR PEDIATRIC STUDIES,
- IF NO ADDITIONAL INFO IS RELEVANT, this section is NOT APPLICABLE |
| IND Purpose | 1 If the product has been marketed outside of the United States, ALL COUNTRIES WHERE THE PRODUCT HAS BEEN MARKETED OR WITHDRAWN FROM ANY OF THOSE MARKETS (AND WHY) SHOULD BE LISTED.
2 To COLLECT SAFETY AND EFFECTIVENESS INFORMATION in support of marketing applications for biologic and drug products
3 To ensure that SUBJECTS WILL NOT FACE UNDUE RISK of harm |
| IND Principles
The amount of information on a particular drug that must be submitted in an IND | 1 the novelty of the drug
2 the known or suspected risks
3 the developmental phase of the drug |
| IND Principles
The Content outlines the information needed for a commercially sponsored IND for a new molecular entity. | 1 A SPONSOR-INVESTIGATOR who uses, as a research tool, an investigational new drug that is ALREADY SUBJECT TO A MANUFACTURER'S IND or marketing application should FOLLOW THE SAME GENERAL FORMAT.
2 a SPONSOR-INVESTIGATOR who uses an investigational drug NOT SUBJECT TO A MANUFACTURER'S IND or marketing application is ordinarily required to SUBMIT ALL TECHNICAL INFORMATION SUPPORTING THE IND, unless such information may be referenced from the scientific literature. |
| FDA has an opportunity to review the IND application for safety to assure that research subjects will not be subjected to unreasonable risk | IND review |
| 5 REVIEW to be check: | I. MEDICAL REVIEW
II. CHEMICAL REVIEW
III. PHARMACOLOGY/TOXICOLOGY REVIEW
IV. STATISTICAL ANALYSIS
V. SAFETY REVIEW |
| Under Federal regulations, proposed phase I studies are evaluated almost exclusively for safety reasons.
-Since the late 1980’s FDA reviewers have been instructed to provide drug sponsors with greater freedom during phase I
In evaluating phase II and III investigation, FDA reviewers also must ensure that these studies are of sufficient scientific quality to be capable of yielding data that can support marketing approval | Medical Review |
| - They ADDRESS ISSUES RELATED TO DRUG IDENTITY, MANUFACTURING CONTROL & ANALYSIS
- The DRUG SPONSOR SHOULD STATE whether it believes the chemistry of either the drug substances or the drug product presents any signals of potential human risk
- The reviewing chemist evaluated the manufacturing and processing procedures
- If so, these signals should be discussed, with steps proposed to monitor for such risks. Sponsors should describe any chemistry and manufacturing differences between the drug product proposed for clinical use and the drug product use in the animal toxicology trials | II. Chemistry review |
| This team is STAFFED BY PHARMACOLOGIST & TOXICOLOGIST
In this section of the application should contain, if known:
- A DESCRIPTION OF THE PHARMACOLOGIC EFFECTS & MECHANISM OF ACTION OF THE DRUG in animal
- Information on the ABSORPTION, DISTRIBUTION, METABOLISM & EXCRETION of the drug.
The regulations do not further describe the presentation of these data, in contrast to the more detailed description of how to submit toxicology data.
A SUMMARY REPORT, without individual animal record, or individual study results, usually suffices.
An integrated SUMMARY of the TOXICOLOGY EFFECTS of the drug in animals and in-vitro the particular studies needed depend on the nature of the drug and the phase of human investigation.
When species specificity, immunogenicity, or other consideration appear to make many or all toxicological models irrelevant, sponsors are encouraged to contact the agency to discuss toxicology testing | III. Pharmacology / Toxicology review |
| The purpose of these evaluations is to give the medical officers a
better idea of the POWER OF THE FINDINGS to be extrapolated to the LARGER PATIENT POPULATION in the country. | IV. Statistical analysis |
| Following review of an initial IND application submission, Center for Drug Evaluation and Research (CDER) has 30-calendar-days in which to decide if a clinical hold is necessary
Generally, the Drug Review Division does not contact the sponsor if no concerns arise with drug safety and the proposed clinical trials.
The sponsor is notified about the deficiencies through a Clinical hold.
A clinical hold is issued by the FDA to the sponsor to delay a proposed clinical investigation or to suspend a clinical investigation. | V. Safety review |
| __ % of the drugs that enter clinical testing are ultimately
approved. | 10% |
| Drug Classification System
All new drugs filed with the FDA are given a classification that characterizes its chemical type and the expected therapeutic gain. | Type 1 – new molecular entity
Type 2 – new salt
Type 3 – new formulation
Type 4 – new combination
Type 5 – already marketed drug product – marketed by other firm
Type 6 – already marketed drug product by the same firm |
| To respond to concerns that there is a need for a FASTER APPROVAL PROCESS for drugs to treat desperately ill patients > > the FDA issued SPECIAL REGULATIONS describing procedures for EXPEDITING the approval of these types of products.
PROVIDE FOR THE REVIEW AND APPROVAL of a new drug AT AN EARLIER STAGE in the clinical testing program | Expedited Development of Drugs for Life-Threatening Illnesses |
| The major features of the EXPEDITED DEVELOPMENT PROGRAM includes: | 1 EARLY CONSULTATION with the FDA both at the pre-IND stage and at the end of Phase 1 should result in agreement on attesting plan than can allow for the approval of a product after the completion of Phase II testing.
2 RISK BENEFIT ANALYSIS
3 Phase IV STUDIES WILL BE EMPLOYED TO LEARN ADDITIONAL INFORMATION ABOUT THE RISKS, BENEFITS AND OPTIMAL USE OF THE DRUG. These will be post marketing studies and might include investigation of different doses or patient populations.
4 FOCUSED FDA REGULATORY RESEARCH (e.g. development of manufacturing standards and
assays for vaccine or biotechnology products)
5 ACTIVE MONITORING OF CONDUCT AND EVALUATION OF CLINICAL TRIALS
6 Safeguard for patient safety will all still apply a key to expediting the process is earlier and MORE FREQUENT CONSULTATION with the FDA to each early agreement on the design of studies needed for the approval of new drug. |
