21 Cfr 316

21 CFR 316.10, 316.12, 316.14

[Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2006]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR316.10]

[Page 175-176]

TITLE 21--FOOD AND DRUGS

CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES (CONTINUED)

PART 316_ORPHAN DRUGS--Table of Contents

Subpart B_Written Recommendations for Investigations of Orphan Drugs

Sec. 316.10 Content and format of a request for written recommendations.

(a) A sponsor's request for written recommendations from FDA
concerning the nonclinical and clinical investigations necessary for
approval of a marketing application shall be submitted in the form and
contain the information required in this section. FDA may require the
sponsor to submit information in addition to that specified in paragraph
(b) of this section if FDA determines that the sponsor's initial request
does not contain adequate information on which to base recommendations.
(b) A sponsor shall submit two copies of a completed, dated, and
signed request for written recommendations that contains the following:
(1) The sponsor's name and address.
(2) A statement that the sponsor is requesting written
recommendations on orphan-drug development under section 525 of the act.
(3) The name of the sponsor's primary contact person and/or resident
agent, and the person's title, address, and telephone number.
(4) The generic name and trade name, if any, of the drug and a list
of the drug product's components or description of the drug product's
formulation, and chemical and physical properties.
(5) The proposed dosage form and route of administration.
(6) A description of the disease or condition for which the drug is
proposed to be investigated and the proposed indication or indications
for use for such disease or condition.
(7) Current regulatory and marketing status and history of the drug
product, including:
(i) Whether the product is the subject of an IND or a marketing
application (if the product is the subject of an IND or a marketing
application, the IND or marketing application numbers should be stated
and the investigational or approved indication or indications for use
specified);
(ii) Known marketing experience or investigational status outside
the United States;

[[Page 176]]

(iii) So far as is known or can be determined, all indications
previously or currently under investigation anywhere;
(iv) All adverse regulatory actions taken by the United States or
foreign authorities.
(8) The basis for concluding that the drug is for a disease or
condition that is rare in the United States, including the following:
(i) The size and other known demographic characteristics of the
patient population affected and the source of this information.
(ii) For drugs intended for diseases or conditions affecting 200,000
or more people in the United States, or for a vaccine, diagnostic drug,
or preventive drug that would be given to 200,000 or more persons per
year, a summary of the sponsor's basis for believing that the disease or
condition described in paragraph (b)(6) of this section occurs so
infrequently that there is no reasonable expectation that the costs of
drug development and marketing will be recovered in future sales of the
drug in the United States. The estimated costs and sales data should be
submitted as provided for in Sec. 316.21(c).
(9) A summary and analysis of available data on the pharmacologic
effects of the drug.
(10) A summary and analysis of available nonclinical and clinical
data pertinent to the drug and the disease to be studied including
copies of pertinent published reports. When a drug proposed for orphan
drug designation is intended to treat a life-threatening or severely
debilitating illness, especially where no satisfactory alternative
therapy exists, the sponsor may wish voluntarily to provide this
information. A sponsor of such a drug may be entitled to expeditious
development, evaluation, and marketing under 21 CFR part 312, subpart E.
(11) An explanation of how the data summarized and analyzed under
paragraphs (b)(9) and (b)(10) of this section support the rationale for
use of the drug in the rare disease or condition.
(12) A definition of the population from which subjects will be
identified for clinical trials, if known.
(13) A detailed outline of any protocols under which the drug has
been or is being studied for the rare disease or condition and a summary
and analysis of any available data from such studies.
(14) The sponsor's proposal as to the scope of nonclinical and
clinical investigations needed to establish the safety and effectiveness
of the drug.
(15) Detailed protocols for each proposed United States or foreign
clinical investigation, if available.
(16) Specific questions to be addressed by FDA in its
recommendations for nonclinical laboratory studies and clinical
investigations.

[57 FR 62085, Dec. 29, 1992; 58 FR 6167, Jan. 26, 1993]

*****************************************************************

Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2006]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR316.12]

[Page 176]

TITLE 21--FOOD AND DRUGS

CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES (CONTINUED)

PART 316_ORPHAN DRUGS--Table of Contents

Subpart B_Written Recommendations for Investigations of Orphan Drugs

Sec. 316.12 Providing written recommendations.

(a) FDA will provide the sponsor with written recommendations
concerning the nonclinical laboratory studies and clinical
investigations necessary for approval of a marketing application if none
of the reasons described in Sec. 316.14 for refusing to do so applies.
(b) When a sponsor seeks written recommendations at a stage of drug
development at which advice on any clinical investigations, or on
particular investigations would be premature, FDA's response may be
limited to written recommendations concerning only nonclinical
laboratory studies, or only certain of the clinical studies (e.g., Phase
1 studies as described in Sec. 312.21 of this chapter). Prior to
providing written recommendations for the clinical investigations
required to achieve marketing approval, FDA may require that the results
of the nonclinical laboratory studies or completed early clinical
studies be submitted to FDA for agency review.

**************************************************************

[Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2006]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR316.14]

[Page 176-177]

TITLE 21--FOOD AND DRUGS

CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES (CONTINUED)

PART 316_ORPHAN DRUGS--Table of Contents

Subpart B_Written Recommendations for Investigations of Orphan Drugs

Sec. 316.14 Refusal to provide written recommendations.

(a) FDA may refuse to provide written recommendations concerning the
nonclinical laboratory studies and clinical investigations necessary for
approval of a marketing application for any of the following reasons:
(1) The information required to be submitted by Sec. 316.10(b) has
not been submitted, or the information submitted is incomplete.

[[Page 177]]

(2) There is insufficient information about:
(i) The drug to identify the active moiety and its physical and
chemical properties, if these characteristics can be determined; or
(ii) The disease or condition to determine that the disease or
condition is rare in the United States; or
(iii) The reasons for believing that the drug may be useful for
treating the rare disease or condition with that drug; or
(iv) The regulatory and marketing history of the drug to determine
the scope and type of investigations that have already been conducted on
the drug for the rare disease or condition; or
(v) The plan of study for establishing the safety and effectiveness
of the drug for treatment of the rare disease or condition.
(3) The specific questions for which the sponsor seeks the advice of
the agency are unclear or are not sufficiently specific.
(4) On the basis of the information submitted and on other
information available to the agency, FDA determines that the disease or
condition for which the drug is intended is not rare in the United
States.
(5) On the basis of the information submitted and on other
information available to the agency, FDA determines that there is an
inadequate basis for permitting investigational use of the drug under
part 312 of this chapter for the rare disease or condition.
(6) The request for information contains an untrue statement of
material fact.
(b) A refusal to provide written recommendations will be in writing
and will include a statement of the reason for FDA's refusal. Where
practicable, FDA will describe the information or material it requires
or the conditions the sponsor must meet for FDA to provide
recommendations.
(c) Within 90 days after the date of a letter from FDA requesting
additional information or material or setting forth the conditions that
the sponsor is asked to meet, the sponsor shall either:
(1) Provide the information or material or amend the request for
written recommendations to meet the conditions sought by FDA; or
(2) Withdraw the request for written recommendations. FDA will
consider a sponsor's failure to respond within 90 days to an FDA letter
requesting information or material or setting forth conditions to be met
to be a withdrawal of the request for written recommendations.