Guidance on submitting pediatric development plans and pediatric studies: Foreign-approved plans

On this page

• Format and content
• Situations where the foreign decision may not apply
• Verifying a foreign-approved PDP
• Amending a foreign-approved PDP

Format and content

Both the US Food and Drug Administration (US FDA) and European Medicines Agency (EMA) require detailed plans for pediatric drug development programs to be submitted during the adult drug development program. The US FDA requires an initial pediatric study plan (iPSP) and the EMA requires a pediatric investigation plan (EU-PIP).

Both agencies will have typically reached agreements with the sponsor on these plans by the time a sponsor files a submission with Health Canada for the same drug.

Sponsors who wish to participate in the pilot may submit any of the following documents:

• an approved EU-PIP
• an agreed iPSP pending the US FDA's final decision on deferral and/or waiver requests
• an agreed iPSP following final decisions by the US FDA on granting or denying deferral and/or waiver requests at the time of marketing application

Sponsors should include the most recently approved/agreed version of the plan. Sponsors who have both an iPSP and EU-PIP may select which plan to submit to participate in the pilot.

Health Canada will accept the submitted plan as the pediatric development plan (PDP).

Sponsors who submit an agreed iPSP for which the final US FDA decision on deferral and/or waiver requests is pending should contact Health Canada about how to submit the final decision. If Health Canada's review has been completed before the US FDA or EMA make their final decision, sponsors should consult the section Amending a foreign-approved PDP. This section provides information on how to submit the update.

Products with more than 1 indication may have more than 1 iPSP and/or EU-PIP. For these products, sponsors may choose plans from both the US FDA and EMA for the PDP, as appropriate. For example, sponsors may choose a US FDA plan for indication A and an EMA plan for indication B.

Information on how pediatric plans will be reviewed is provided in the section Verifying a foreign-approved PDP.

Canadian addendum

Sponsors may choose to complete a supplementary annex (Canadian addendum) if they have additional information that may help to clarify aspects of their foreign plan. This addendum may include details such as:

• communications between sponsors and foreign regulators, outside of confidential business information as defined in the Food and Drugs Act (act) that clarify the rationale for any aspects of the plan that may not be clear to Health Canada without this context
• special considerations to factors that are specific to the Canadian population (for example, genetic or extrinsic factors)
• information that reflects the authorized indication(s) in Canada for drugs where the Canadian-authorized indication varies from that of the US FDA and/or EMA
• relevant differences in the authorized and marketed therapies for the condition in Canada, compared to the therapies authorized and marketed in the jurisdiction for which the plan was developed
• other information that the sponsor believes is relevant to the Canadian context

Information should be submitted as a single Canadian addendum document.

Situations where the foreign decision may not apply

In some cases, the foreign decision may not align with Health Canada's pediatric study submission policy. These include the EMA class waiver and the US FDA orphan drug exemption.

EMA class waiver

Health Canada will not be following the same process as the EMA class waiver. Sponsors who do not have a PIP or an iPSP should follow the procedure outlined in the following section:

• Rationale for not conducting studies based on an adult-related condition that rarely or never occurs in children or is on the EMA class waiver

US FDA orphan drug exemption

The US FDA exempts drugs classified as orphan drugs from iPSP requirements. Health Canada will not be using the US FDA orphan drug exemption.

Sponsors taking part in the pilot who do not have an iPSP because their product has orphan status in the US will be asked to either:

• submit an approved EU-PIP, if they have one, or
• follow the procedure for submitting a C-PDP to outline ongoing or proposed studies and/or
• provide a rationale for not studying the drug in all or part of the pediatric population

Verifying a foreign-approved PDP

Health Canada will accept iPSPs agreed to by the US FDA or PIPs approved by the EMA as the PDP for the pilot. The guidance for pediatric plan content is aligned between the 3 regulators.

Verification of a foreign-approved pediatric plan will consist of confirming that the iPSP or PIP is complete and is in line with Canadian PDP (C-PDP) recommended content. During the verification, Health Canada may seek clarification on parts of the plans. Once Health Canada verifies that the foreign-approved plan meets the C-PDP content recommendations, then it will become identified as the PDP without changes to the plan.

The verification period for iPSPs and EU-PIPs begins after Health Canada issues the screening acceptance letter for the submission. We will verify the information in the foreign pediatric plans at the same time we review the rest of the submission.

Verification will be done according to the performance standards of the submission for which the pediatric plan is included. For example, if a sponsor is including pediatric plan(s) with an NDS associated with a 300-day review timeline, verification of those plans will occur within the timelines established for the submission. The verification of the foreign-approved PDP will not affect the review of the submission, including timelines.

Health Canada will advise the sponsor if the foreign pediatric plan(s) does not meet the C-PDP content recommendations. The sponsor may choose to withdraw from the pilot, or submit a C-PDP in place of the foreign plan. Withdrawal from the pilot will not affect the review decision for the associated NDS or SNDS.

Health Canada will provide the outcome of the foreign pediatric plan verification when we issue our final review decision. This will be done in a letter, which will be sent out at the time of the notice of compliance (NOC). The letter will identify the timeframe within which the completed pediatric study reports should be submitted to Health Canada.

We request that all studies within the PDP be submitted within 6 months of the final study completion, unless otherwise agreed to by the sponsor and Health Canada.

If:

• the review decision on the submission is negative, no decision will be made on the foreign pediatric plan
• a drug authorized for sale in Canada is cancelled pre- or post-market, completion of the studies identified in the PDP for that drug will not be expected

Health Canada's adoption of an iPSP or EU-PIP as the Canadian PDP does not:

• indicate future concurrence with a decision by the US FDA or EMA to approve the pediatric indication, formulation or labelling change
  • We will conduct an independent review based on the Canadian context and regulatory framework.
• constitute approval of the clinical trials described in the PDP
  • Sponsors must seek approvals for clinical trials from the jurisdictions where the trials take place.

For Canadian clinical trials, sponsors should communicate with the relevant Office of Clinical Trials and follow the guidelines set out in:

• Guidance document for clinical trial sponsors: Clinical trial applications

Amending a foreign-approved PDP

Health Canada requests that sponsors inform us of all amendments once the US FDA or EMA approves them. If an iPSP or EU-PIP is amended with the foreign regulator, the approved amendment may be submitted to Health Canada in the same format in which it has been submitted to the US FDA or EMA.

Amendments should be filed through the Common Electronic Submissions Gateway (CESG) under the regulatory activity Pediatric Drug Plan – Amendments (PDPAM) in the electronic common technical document (eCTD) format as follows:

Document type	eCTD module	eCTD document leaf title
Foreign amended/approved PDP(s)	1.2.7 International information	Annotated FDA iPSP Non-annotated FDA iPSP or Annotated EMA PIP Non-annotated EMA PIP

Any supporting quality, nonclinical or clinical studies should be:

• submitted in their respective eCTD modules and
• organized in accordance with the current electronic specifications in the following guidance document:
  • Preparation of drug regulatory activities in Electronic Common Technical Document (eCTD) format

For more information on how to file submissions electronically, refer to:

• Filing submissions electronically

Amendments will be subject to a 10-calendar day processing period, a 15-calendar day screening period and a 90-calendar day verification service standard.