Sample Written Request For Division of Oncology Drug Products
This is a sample Written Request outlining the pediatric studies for oncology
drugs the Agency believes will provide a meaningful public health benefit to pediatric populations.
An actual Written Request may differ
from this sample depending upon the nature of the specific drug product, what is
already known about it, and any other indications for which it is used. If you
wish to receive a formal Written Request for pediatric studies under section
505A of the Federal Food, Drug, and Cosmetic Act for a particular oncologic
agent, please submit a proposed pediatric study request to the Division of
Oncology Drug Products. The proposed pediatric study request should incorporate
the kind of information indicated in this sample and include descriptions of any
other studies necessary to provide a meaningful health benefit to pediatric
populations. Please refer to the outline in the "Guidance for Industry -
Pediatric Oncology Studies in Response to a Written Request," for additional
information.
IND/NDA APPLICATION NUMBER(S)
WRITTEN REQUEST
SPONSOR
Attention: CONTACT, TITLE
ADDRESS
Dear CONTACT:
Reference is made to your Proposed Pediatric Study Request submitted on INSERT
DATE for DRUG PRODUCT(S) to APPLICATION NUMBER(S).
To obtain needed pediatric information on DRUG, the Food and Drug Administration
(FDA) is hereby making a formal Written Request, pursuant to Section 505A of the
Federal Food, Drug, and Cosmetic Act (the Act), that you submit information from
the trials in pediatric patients described below. These studies investigate the
potential use of DRUG in the treatment of children with cancer.
Background:
[The following may not be appropriate if the sponsor has submitted a detailed
study request or if there exists substantial information about the use of the
drug in children.]
The design of studies in pediatric oncologic drug development is discussed in
detail in the guidance for industry, Pediatric Oncology Studies in Response to a
Written Request. http://www.fda.gov/cder/guidance/3756dft.pdf
Protocols for each of your studies should be submitted to the FDA for review
prior to initiation of the studies. Each submission should review the overall
development plan and justify the study design(s).
COMPLETE AND INCLUDE ALL APPROPRIATE SECTIONS FOR EACH STUDY DESCRIBED.
• Type of study(ies): (e.g., dose-finding and/or pk, phase 1, 2, or 3,
double-blind, randomized, parallel group, safety, etc.)
• Indication(s) to be studied (i.e., objective and population of each study):
• Age group in which study(ies) will be performed: INDICATE SPECIFIC AGE RANGE
AND DISTRIBUTION WHEN APPROPRIATE.
• Study endpoints
The Phase 1 study should have maximum tolerated dose (MTD) or biologically
effective dose (BED) as a primary endpoint.
The Phase 2 studies should have a disease-specific surrogate or clinically
relevant endpoint.
Pharmacokinetics: Relevant pharmacokinetic endpoints may be derived through
approaches such as optimal sparse sampling in all patients with rich sampling in
a sub-group. Such data should then be appropriately analyzed using methods such
as nonlinear mixed effects modeling.
Data from the Phase 1 and Phase 2 studies should be combined to develop
pharmacokinetic and pharmacodynamic (PK-PD) models to explore exposure-response
relationships for measures of safety and effectiveness.
The Phase 3 studies should use clinically meaningful endpoints.
• Drug information
• dosage form
• route of administration
• regimen
Dose-response should be characterized over an adequate range of doses/dosing
regimens, in an adequate number of target patients. A priori knowledge about the
drug response rates, if available, should be fully utilized to rationally select
the clinical trial design. We recommend consultation with the Agency regarding
the choice of the doses/dosing regimens.
• drug-drug interactions if appropriate
• Use an age-appropriate formulation in the study(ies) described above.
If the
studies you conduct in response to this Written Request demonstrate this drug
will benefit children, then an age-appropriate dosage form must be made
available for children. This requirement can be fulfilled by developing and
testing a new dosage form for which you will seek approval for commercial
marketing. If you demonstrate that reasonable attempts to develop a commercially
marketable formulation have failed, you must develop and test an age appropriate
formulation that can be compounded by a licensed pharmacist, in a licensed
pharmacy, from commercially available ingredients.
Development of a commercially-marketable formulation is preferable. Any new
commercially marketable formulation you develop for use in children must meet
agency standards for marketing approval.
If you cannot develop a commercially marketable age-appropriate formulation, you
must provide the Agency with documentation of your attempts to develop such a
formulation and the reasons such attempts failed. If we agree that you have
valid reasons for not developing a commercially marketable, age-appropriate
formulation, then you must submit instructions for compounding an
age-appropriate formulation from commercially available ingredients that are
acceptable to the Agency. If you conduct the requested studies using a
compounded formulation, the following information must be provided and will
appear in the product label upon approval: active ingredients, diluents,
suspending and sweetening agents; detailed step-by-step compounding
instructions; packaging and storage requirements; and formulation stability
information.
Bioavailability of any formulation used in the studies should be characterized,
and as needed, a relative bioavailability study comparing the approved drug to
the age appropriate formulation may be conducted in adults.
• Drug specific safety concerns: e.g., acute toxicity and/or long-term events
such as growth or development, secondary malignancies
• Statistical information, including power of study and statistical assessments:
• Labeling that may result from the study(ies):
Appropriate sections of the label may be changed to incorporate the findings of the studies.
• Format of reports to be submitted:
Full study reports (including data sets and individual data listings) not previously submitted to the Agency addressing the issues outlined in this request with full analysis, assessment, and interpretation. Even if the study fails, we need full study reports with data to support study conclusion. In addition, the reports are to include information on the representation of pediatric patients of ethnic and racial minorities. All pediatric patients enrolled in the study(ies) should be categorized using one of the following designations for race: American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or other Pacific Islander or White. For ethnicity one of the following designations should be used: Hispanic/Latino or Not Hispanic/Latino. INCLUDE OTHER INFORMATION AS APPROPRIATE.
• Timeframe for submitting reports of the study(ies):
Reports of the above studies must be submitted to the Agency on or before INSERT DATE. Please keep in mind that pediatric exclusivity attaches only to existing patent protection or exclusivity that has not expired at the time you submit your reports of the studies in response to this Written Request.
• Response to Written Request: As per the Best Pharmaceuticals for Children Act,
section 4(A), within 180 days of receipt of this Written Request you must notify
the Agency as to your intention to act on the Written Request. If you agree to
the request then you must indicate when the pediatric studies will be initiated.
Please submit protocols for the above studies to an investigational new drug
application (IND) and clearly mark your submission “PEDIATRIC PROTOCOL SUBMITTED
FOR PEDIATRIC EXCLUSIVITY STUDY” in large font, bolded type at the beginning of
the cover letter of the submission. Please notify us as soon as possible if you
wish to enter into a written agreement by submitting a proposed written
agreement. Clearly mark your submission “PROPOSED WRITTEN AGREEMENT FOR
PEDIATRIC STUDIES” in large font, bolded type at the beginning of the cover
letter of the submission.
Reports of the studies should be submitted as a new drug application (NDA) or as
a supplement to an approved NDA with the proposed labeling changes you believe
would be warranted based on the data derived from these studies. When submitting
the reports, please clearly mark your submission "SUBMISSION OF PEDIATRIC STUDY
REPORTS – PEDIATRIC EXCLUSIVITY DETERMINATION REQUESTED" in large font, bolded
type at the beginning of the cover letter of the submission and include a copy
of this letter. Please also send a copy of the cover letter of your submission,
via fax (301-594-0183) or messenger to the Director, Office of Generic Drugs,
HFD-600, Metro Park North II, 7500 Standish Place, Rockville, MD 20855-2773.
In accordance with section 9 of the Best Pharmaceuticals for Children Act,
Dissemination of Pediatric Information, if a pediatric supplement is submitted
in response to a Written Request and filed by FDA, FDA will make public a
summary of the medical and clinical pharmacology reviews of pediatric studies
conducted. This disclosure, which will occur within 180 days of supplement
submission, will apply to all supplements submitted in response to a Written
Request and filed by FDA, regardless of the following circumstances:
1. the type of response to the Written Request (complete or partial);
2. the status of the supplement (withdrawn after the supplement has been filed
or pending);
3. the action taken (i.e. approval, approvable, not approvable); or
4. the exclusivity determination (i.e. granted or denied).
FDA will post the medical and clinical pharmacology review summaries on the FDA
website at http://www.fda.gov/cder/pediatric/Summaryreview.htm and publish in
the Federal Register a notification of availability.
If you wish to discuss any amendments to this Written Request, please submit
proposed changes and the reasons for the proposed changes to your application.
Submissions of proposed changes to this request should be clearly marked
“PROPOSED CHANGES IN WRITTEN REQUEST FOR PEDIATRIC STUDIES” in large font,
bolded type at the beginning of the cover letter of the submission. You will be
notified in writing if any changes to this Written Request are agreed upon by
the Agency.
We hope you will fulfill this pediatric study request. We look forward to
working with you on this matter in order to develop additional pediatric
information that may produce health benefits in the pediatric population.
As a reminder, you are responsible for compliance with section 113 of the Food
and Drug Administration Modernization Act of 1997 and section 15 of the Best
Pharmaceuticals for Children Act of 2002 by registering certain clinical trials
in the Clinical Trials Data Bank (http://clinicaltrials.gov/) http://prsinfo.clinicaltrials.gov/). If your drug is for the treatment of a serious or life-threatening disease
or condition and you are conducting trials to test its effectiveness, then you
must register the trials. Although not required, we encourage you to register
trials for non-serious diseases. For additional information on registering your
clinical trials, including the required and optional data elements, refer to the
Protocol Registration System (PRS) Information Site (http://prsinfo.clinicaltrials.gov)
and FDA's Guidances for Industry entitled "Information Program on Clinical
Trials for Serious or Life-Threatening Diseases and Conditions" (March 2002;
revised draft January 2004).
If you have any questions, call NAME, Project Manager, at PHONE NUMBER.
Sincerely,
{See appended electronic signature page}
OFFICE DIRECTORS SIGNATURE BLOCK