lake (he phase of (he investigation outlined in section 10 of the "Notice 
of Claimed Investigational exemption 'for a New Drug." (In crucial 
situations, phase 3 investigators may be added and this form supple- 
mented by rapid communication methods, and the signed l-'orm FD- 
1573 shall be obtained promptly thereafter.) 
10. An outline of any phase or phases of the planned investigations 
and a description of the institutional review committee, as follows: 
a. Clinical pharmacology. This is ordinarily divided into two phases: 
Phase I starts when the new drug is first introduced into man - only 
animal and In vitro data are available - with the purpose of determining 
human toxicity, metabolism, absorption, elimination, and other phar- 
macological action, preferred route of administration, and safe dosage 
range; phase 2 covers the initial trials on a limited number of patients 
for specific disease control or prophylaxis purposes. A general outline 
of these phases shall be submitted, identifying the investigator or invest- 
igators, the hospitals or research facilities where the clinical pharma- 
cology will be undertaken, any expert committees or panels to be 
utilized, the maximum number of subjects to be involved, and the esti- 
mated duration of these early phases of investigation. Modification of 
the experimental design on the basis of experience gained need be 
reported only in the progress reports on these early phases, or in the 
development of the plan for the clinical trial, phase 3. The first two 
phases may overlap and, when indicated, may require additional animal 
data before these phases can be completed or phase can be undertaken. 
Such animal tests shall be designed to take into account the expected 
duration of administration of the drug to human beings, the age groups 
and physical status, as for example, infants, pregnant women, pre- 
menopausal women, of those human beings to whom the drug may be 
administered, unless this has already been done in the original animal 
studies. If a drug is a radioactive drug, the clinical pharmacology phase 
must include studies which will obtain sufficient data for dosimetry 
calculations. These studies should evaluate the excretion, whole body 
retention, and organ distribution of the radioactive material. 
b. Clinical trial. This phase 3 provides the assessment of the drug’s 
safety and effectiveness and optimum dosage schedules in the diagnosis, 
treatment, or prophylaxis of groups of subjects involving a given disease 
or condition. A reasonable protocol is developed on the basis of the 
facts accumulated in the earlier phases, including completed and sub- 
mitted animal studies. This phase is conducted by separate groups fol- 
lowing the same protocol (with reasonable variations and alternatives 
permitted by the plan) to produce well-controlled clinical data. For this 
phase, the following data shall be submitted: 
i. The names and addresses of the investigators. (Additional investi- 
gators may be added.) 
ii. The specific nature of the investigations to be conducted, to- 
gether with information or case report forms to show the scope and 
detail of the planned clinical observations and the clinical laboratory 
tests to be made and reported. 
iii. The approximate number of subjects (a reasonable range of 
subjects is permissible and additions may be made), and criteria pro- 
posed for subject selection by age, sex, and condition. 
iv. The estimated duration of the clinical trial and the intervals, 
not exceeding 1 year, at which progress reports showing the results of 
the Investigations will be submitted to the Food and Drug Administra- 
tion. 
c. Institutional review board (IRB). The sponsor must give assur- 
ance that an IRB that complies with the requirements set forth in Part 
56 of this chapter will be responsible for the initial and continuing 
Attachment III - Page 2 
review and approval of (he proposed clinical study. The sponsor must 
also provide assurance that (he investigators will report to the IRB all 
changes in the research activity and all unanticipated problems involv- 
ing risks to human subjects or others, and that the investigators will not 
make any changes in the research without IRB approval, except where 
necessary to eliminate apparent immediate hazard to the human sub- 
jects. FDA will regard the signing of the Form FDA-1571 as providing 
the necessary assurances above. 
(The notice of claimed investigational exemption may be limited 
to any one or more phases, provided the outline of the additional 
phase or phases is submitted before such additional phases begin. A 
limitation on an exemption docs not preclude continuing a subject 
on the drug from phase 2 to phase 3 without interruption while the 
plan for phase 3 is being developed.) 
Ordinarily, a plan for clinical trial will not be regarded as reasonable 
unless, among other things, it provides for more than one independent 
competent investigator to maintain adequate case histories of an ade- 
quate number of subjects, designed to record observations and permit 
evaluation of any and all discernible effects attributable to the drug in 
each individual treated, and comparable records on any individuals 
employed as controls. These records shall be individual records for each 
subject maintained to include adequate information pertaining to each, 
including age, sex, conditions treated, dosage, frequency of administra- 
tion of the drug, results of all relevant clinical observations and labora- 
tory examinations made, adequate information concerning any other 
treatment given and a full statement of any adverse effects and useful 
results observed, together with an opinion as to whether such effects 
or results are attributable to the drug under investigation. 
11. A statement that the sponsor will notify the Food and Drug 
Administration if the investigation is discontinued, and the reason 
therefor. 
12. A statement that the sponsor will notify each investigator if 
a new-drug application is approved, or if the investigation is discon- 
tinued. 
13. If the drug is to be sold, a full explanation why sale is required 
and should not be regarded as the commercialization of a new drug for 
which an application is not approved. 
14. A statement that the sponsor assures (hat clinical studies in 
humans will not be initiated prior to 30 days after the date of receipt 
of the notice by the Food and Drug Administration and that he will 
continue to withhold or to restrict clinical studies if requested to do so 
by the Food and Drug Administration prior to the expiration of such 
30 days. If such request is made, the sponsor will be provided specific 
information as to the deficiencies and will be afforded a conference on 
request. The 30-day delay may be waived by the Food and Drug 
Administration upon a showing of good reason for such waiver; and 
for investigations subject to institutional review committee approval 
as described in item 10c above, and additional statement assuring that 
the investigation will not be initiated prior to approval of the study by 
such committee. 
15. When requested by the agency, an environmental impact 
analysis report pursuant to §25.1 of this chapter. 
16. A statement that all nonclinical laboratory studies have been, 
or will be, conducted in compliance with the good laboratory practice 
regulations set forth in Part 5R of this chapter, or, if such studies have 
not been conducted in compliance with such regulations, a statement 
that describes In detail all differences between the practices used in 
conducting the study and those required in the regulations. 
Very truly yours, 
SPONSOR 
PER 
INDICATE AUTHORITY 
(This notice may be amended or supplemented from time to time on the basis of the experience gained with the new drug. I’rogress reports may be bsed 
to update the notice.) 
ALL NOTICES AND CORRESPONDENCE SHOULD BE SUBMITTEO IN TRIPLICATE. 
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