Sample Written Request for Oncology Drugs

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