IND/NDA [INSERT APPLICATION NUMBER(S)]

[INSERT SPONSOR NAME]

[ATTN: CONTACT NAME]

[ADDRESS]

Dear [INSERT CONTACT NAME]:

Reference is made to your Proposed Pediatric Study Request submitted on [INSERT DATE], for [INSERT DRUG NAME] to IND [APPLICATION NUMBER(S)].

To obtain needed pediatric information on [INSERT DRUG NAME], 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 following studies:

Type of studies:

Multiple-dose pharmacokinetic, safety and activity study(ies) of [INSERT DRUG NAME] in combination with other antiretroviral agents in HIV-infected pediatric patients.

Multiple-dose pharmacokinetic and safety study(ies) of [INSERT DRUG NAME] in HIV-exposed neonates (born to HIV-infected mothers).

The objective of these studies will be to determine the pharmacokinetic and safety profile of [INSERT DRUG NAME] across the age range studied, identify an appropriate dose for use in HIV-infected pediatric patients and exposed neonates, and evaluate the activity of this dose (or doses) in treatment and/or prophylaxis. Studies that do not define the therapeutic dose in pediatric patients in all studied age groups will be considered as non-responsive to this Written Request.

[Not all drugs will be appropriate for study in all age groups, especially HIV-exposed neonates, and this information may not be requested in all Written Request letters.]

Indication to be studied:

Treatment of HIV infection in pediatric patients and/or prophylaxis of HIV infection in exposed neonates

Age group in which studies will be performed:

HIV-infected pediatric patients from 1 month to adolescence [or age range not covered in labeling] and HIV-exposed neonates (born to HIV-infected mothers).

Drug Information

Dosage form: [INSERT ADULT SOLID DOSAGE FORM, IE TABLETS, CAPSULES ETC] and age appropriate-formulation. USE THE FOLLOWING PARAGRAPH IF A NEW DOSAGE FORM FOR THE ACTIVE INGREDIENT WILL NEED TO BE DEVELOPED: The studies described above should use an age-appropriate formulation of DRUG NAME. The relative bioavailability of this formulation should be determined and compared with the marketed formulation of DRUG NAME. Full study reports of any relative bioavailability studies should be submitted to the Agency. If an age-appropriate formulation cannot be developed, complete documentation of your attempts and a detailed explanation of why the attempts were unsuccessful should be submitted. Under these circumstances other formulations can be used, if they are standardized, palatable, and shown in adults to be of acceptable relative bioavailability (compared with the marketed product).

Route of administration: oral

Regimen: to be determined by development program

Drug specific safety concerns:

Based on available toxicity information with your product, please provide specific safety parameters that your pediatric program will address.

Safety of [INSERT DRUG NAME] must be studied in an adequate number of pediatric patients or neonates to characterize adverse events across the age range. [The number of pediatric patients to be studied may be different for different products based on the known safety profile of the drug in adults. This number may range from 50-100 for drugs with no identified serious adult toxicity to > 100 for drugs with significant associated adverse events in adults.]

Statistical information, including power of study and statistical assessments:

Descriptive analyses of multiple-dose pharmacokinetic, safety and activity data in HIV-infected pediatric patients and descriptive analyses of multiple-dose pharmacokinetic and safety data in HIV-exposed neonates (born to HIV-infected mothers). A minimum number of pediatric patients (as stated below) should complete the pharmacokinetic study(ies) conducted to characterize pharmacokinetics for dose selection. Final selection of sample size for each age group should take into account all potential sources of variability. As study data are evaluated, the sample size should be increased as necessary for characterization of pharmacokinetics across the intended age range.

Studies must include an adequate number of patients to characterize pharmacokinetics and select a therapeutic dose for the age ranges studied, taking into account inter-subject and intra-subject variability. The number of patients should be generally well distributed across the age range studied.

Study Endpoints:

Pharmacokinetics

Parameters such as Cmax, Cmin, Tmax, t1/2, AUC and apparent oral clearance.

Safety and tolerability

HIV-infected pediatric patients should be followed for safety for a minimum of six months at the recommended dose. HIV-exposed neonates (born to HIV-infected mothers) should have safety assessments, on or off treatment (as appropriate), for a minimum of six months after start of therapy. In addition, please also submit plans for long-term safety monitoring in HIV-exposed neonates and HIV-infected pediatric patients who have received [INSERT DRUG NAME].

Activity

Assessment of changes in plasma HIV RNA levels and in CD4 cell counts.

Resistance

Collect and submit information regarding the resistance profile (genotypic and phenotypic) of clinical isolates at baseline and during treatment from pediatric patients receiving [INSERT DRUG NAME], particularly from those who experience loss of virologic response.

Labeling that may result from the study(ies):

Information regarding dosing, safety and activity in HIV-infected pediatric population and information regarding dosing and safety in HIV-exposed neonates (born to HIV-infected mothers).

Format of reports to be submitted:

Full study reports not previously submitted to the Agency addressing the issues outlined in this request with full analysis, assessment, and interpretation. 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 or as a supplement to your 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.

If you have any questions, contact [insert project manager name and title], at 301-827-2335.

 

Sincerely yours,