Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

For a novel therapeutic that will go directly into pediatrics in its IND(US)/CTA(EU)-opening studies due to the nature of the disease and therapy, when is the iPSP/PIP submitted or is there a waiver process? Does it quality for rare disease exemption? Insights appreciated on this, as to how this is handled specific to diseases occurring only in pediatric patients, in particular in cases of persistent therapy where FIH healthy volunteers or adults are not possible populations.

Yes, an iPSP/PIP should be submitted. The development strategy for an indication that cannot be studied in healthy volunteers or adults should be discussed at a PreIND meeting. I am not sure what you mean about rare disease exemption since a rare disease exemption  in this context applies to whether you are required to do pediatric studies. If there is an orphan product designation, you are not required to submit a iPSP but a PIP is still required.

------------------------------
Glen Park PharmD
Vice President, Regulatory Affairs and Quality Assurance
New York NY
United States
------------------------------

Original Message:
Sent: 17-May-2022 16:39
From: Anonymous Member
Subject: Pediatric only disease iPSP/PIP

This message was posted by a user wishing to remain anonymous

For a novel therapeutic that will go directly into pediatrics in its IND(US)/CTA(EU)-opening studies due to the nature of the disease and therapy, when is the iPSP/PIP submitted or is there a waiver process? Does it quality for rare disease exemption? Insights appreciated on this, as to how this is handled specific to diseases occurring only in pediatric patients, in particular in cases of persistent therapy where FIH healthy volunteers or adults are not possible populations.

Since you indicated its a rare disease, you should get an Orphan designation and therefore exempt from IPSP but not the EU PIP. Once you get preliminary pk/pd, safety results from your P1 FIH study, you should try to populate as many sections as possible in the PIP template for EU and make an initial PIP submission to the EU authorities (if the disease is applicable to all pediatric ages then you need to outline your development for all the applicable ages i.e. Adolescents, 5-12, below 12 etc....deferrals and waivers for certain age groups possible but need rationale). Its unlikely a one time deal, they will come back with comments/suggestions etc and then you submit it again until an agreement is reached.

Good luck!

------------------------------
GRSAOnline
------------------------------

Original Message:
Sent: 17-May-2022 16:39
From: Anonymous Member
Subject: Pediatric only disease iPSP/PIP

This message was posted by a user wishing to remain anonymous

For a novel therapeutic that will go directly into pediatrics in its IND(US)/CTA(EU)-opening studies due to the nature of the disease and therapy, when is the iPSP/PIP submitted or is there a waiver process? Does it quality for rare disease exemption? Insights appreciated on this, as to how this is handled specific to diseases occurring only in pediatric patients, in particular in cases of persistent therapy where FIH healthy volunteers or adults are not possible populations.

Per section 505B(a)(2) of the Pediatric Research Equity Act, applicants are required to submit a pediatric assessment that contains data to support the safety and efficacy in pediatric subjects. You should consult with the FDA at the Pre-IND but no later than EOP1 meetings specially if your drug product is intended for life-threatening disease or severely debilitating illnesses.  Applicants are encouraged to submit and discuss pediatric plans no later than EOP2 meeting for other drugs.  Please refer to  Guidance for Industry "How to Comply with the Pediatric Research Equity Act" (2005). 

Copied from the Pediatric Study Plans Guidance :  "The sponsor must submit an iPSP for any new application or supplement that is subject to PREA, regardless of whether the FDA has previously granted waivers or deferrals under PREA for the same drug.  Additionally, for drugs that are being developed specifically for use in pediatric populations, the sponsor should submit an iPSP." 

If you are planning to request a partial waiver you'll need to provide a justification in your iPSP with a summary of supporting data from all available sources for the specific pediatric age group for which the waiver will be sought.

------------------------------
Juliane Carvalho RAC, MSc
Lead Regulatory Health Project Manager
United States
**My comments are an informal communication and represent my own best judgement. These comments do not bind or obligate the U.S. Food and Drug Administration**
------------------------------

Original Message:
Sent: 17-May-2022 16:39
From: Anonymous Member
Subject: Pediatric only disease iPSP/PIP

This message was posted by a user wishing to remain anonymous

For a novel therapeutic that will go directly into pediatrics in its IND(US)/CTA(EU)-opening studies due to the nature of the disease and therapy, when is the iPSP/PIP submitted or is there a waiver process? Does it quality for rare disease exemption? Insights appreciated on this, as to how this is handled specific to diseases occurring only in pediatric patients, in particular in cases of persistent therapy where FIH healthy volunteers or adults are not possible populations.

We have an interesting situation where we have an orphan drug (exempt) being developed for use in pediatric populations (where the guidance says sponsor should submit an iPSP). I was wondering which trumps which, especially since our FDA meeting minutes always came back with boilerplate language about PREA requirements. Quick check with the RPM confirmed that we are exempt from iPSP. 
As stated by others, PIP is required. I also agree with others - when in doubt check with FDA either with RPM for a quick question or via a meeting to get a lot more substantive feedback. Good luck!

------------------------------
Anna Sedello, PhD, RAC
Director of Regulatory Affairs
Palo Alto CA
United States
------------------------------

Original Message:
Sent: 19-May-2022 10:55
From: Juliane Carvalho
Subject: Pediatric only disease iPSP/PIP

Per section 505B(a)(2) of the Pediatric Research Equity Act, applicants are required to submit a pediatric assessment that contains data to support the safety and efficacy in pediatric subjects. You should consult with the FDA at the Pre-IND but no later than EOP1 meetings specially if your drug product is intended for life-threatening disease or severely debilitating illnesses.  Applicants are encouraged to submit and discuss pediatric plans no later than EOP2 meeting for other drugs.  Please refer to  Guidance for Industry "How to Comply with the Pediatric Research Equity Act" (2005).

Copied from the Pediatric Study Plans Guidance :  "The sponsor must submit an iPSP for any new application or supplement that is subject to PREA, regardless of whether the FDA has previously granted waivers or deferrals under PREA for the same drug.  Additionally, for drugs that are being developed specifically for use in pediatric populations, the sponsor should submit an iPSP."

If you are planning to request a partial waiver you'll need to provide a justification in your iPSP with a summary of supporting data from all available sources for the specific pediatric age group for which the waiver will be sought.

------------------------------
Juliane Carvalho RAC, MSc
Lead Regulatory Health Project Manager
United States
**My comments are an informal communication and represent my own best judgement. These comments do not bind or obligate the U.S. Food and Drug Administration**

Original Message:
Sent: 17-May-2022 16:39
From: Anonymous Member
Subject: Pediatric only disease iPSP/PIP

This message was posted by a user wishing to remain anonymous

For a novel therapeutic that will go directly into pediatrics in its IND(US)/CTA(EU)-opening studies due to the nature of the disease and therapy, when is the iPSP/PIP submitted or is there a waiver process? Does it quality for rare disease exemption? Insights appreciated on this, as to how this is handled specific to diseases occurring only in pediatric patients, in particular in cases of persistent therapy where FIH healthy volunteers or adults are not possible populations.

I agree with Anna that is a good idea to check with the RPM and/or the review team via formal meeting. If you have a drug product for which orphan designation has been granted you may be exempt. However, certain indications (I believe pediatric oncology products) are not exempt from PREA (see section 505B(k)(2) and will be required to conduct the targeted pediatric studies as required per 505B(a)(1)(B), unless a waiver or deferral is granted and these are typically requested via iPSP (pediatric assessment).

------------------------------
Juliane Carvalho RAC, MSc
Lead Regulatory Health Project Manager
United States
**My comments are an informal communication and represent my own best judgement. These comments do not bind or obligate the U.S. Food and Drug Administration**
------------------------------

Original Message:
Sent: 20-May-2022 08:01
From: Anna Sedello, PhD, RAC
Subject: Pediatric only disease iPSP/PIP

We have an interesting situation where we have an orphan drug (exempt) being developed for use in pediatric populations (where the guidance says sponsor should submit an iPSP). I was wondering which trumps which, especially since our FDA meeting minutes always came back with boilerplate language about PREA requirements. Quick check with the RPM confirmed that we are exempt from iPSP.
As stated by others, PIP is required. I also agree with others - when in doubt check with FDA either with RPM for a quick question or via a meeting to get a lot more substantive feedback. Good luck!

------------------------------
Anna Sedello, PhD, RAC
Director of Regulatory Affairs
Palo Alto CA
United States

Original Message:
Sent: 19-May-2022 10:55
From: Juliane Carvalho
Subject: Pediatric only disease iPSP/PIP

Per section 505B(a)(2) of the Pediatric Research Equity Act, applicants are required to submit a pediatric assessment that contains data to support the safety and efficacy in pediatric subjects. You should consult with the FDA at the Pre-IND but no later than EOP1 meetings specially if your drug product is intended for life-threatening disease or severely debilitating illnesses.  Applicants are encouraged to submit and discuss pediatric plans no later than EOP2 meeting for other drugs.  Please refer to  Guidance for Industry "How to Comply with the Pediatric Research Equity Act" (2005).

Copied from the Pediatric Study Plans Guidance :  "The sponsor must submit an iPSP for any new application or supplement that is subject to PREA, regardless of whether the FDA has previously granted waivers or deferrals under PREA for the same drug.  Additionally, for drugs that are being developed specifically for use in pediatric populations, the sponsor should submit an iPSP."

If you are planning to request a partial waiver you'll need to provide a justification in your iPSP with a summary of supporting data from all available sources for the specific pediatric age group for which the waiver will be sought.

------------------------------
Juliane Carvalho RAC, MSc
Lead Regulatory Health Project Manager
United States
**My comments are an informal communication and represent my own best judgement. These comments do not bind or obligate the U.S. Food and Drug Administration**

Original Message:
Sent: 17-May-2022 16:39
From: Anonymous Member
Subject: Pediatric only disease iPSP/PIP

This message was posted by a user wishing to remain anonymous

For a novel therapeutic that will go directly into pediatrics in its IND(US)/CTA(EU)-opening studies due to the nature of the disease and therapy, when is the iPSP/PIP submitted or is there a waiver process? Does it quality for rare disease exemption? Insights appreciated on this, as to how this is handled specific to diseases occurring only in pediatric patients, in particular in cases of persistent therapy where FIH healthy volunteers or adults are not possible populations.

This message was posted by a user wishing to remain anonymous

This depends on a number of other factors. For the EU there is no rare disease exemption so a PIP will be required, it is best to start discussions with the EMA as soon as possible, it may be that you could also request scientific advise. It would be recommended to have an agreed PIP before starting your trial, particularly for rare disease with limited patient population to ensure the study conducted will meet the regulators requirements.
For the US, if you have ODD then you may not need a iPSP, however this may not be the case if the product is for oncology. Again early discussions with the FDA would be recommended.
Original Message:
Sent: 17-May-2022 16:39
From: Anonymous Member
Subject: Pediatric only disease iPSP/PIP

This message was posted by a user wishing to remain anonymous

For a novel therapeutic that will go directly into pediatrics in its IND(US)/CTA(EU)-opening studies due to the nature of the disease and therapy, when is the iPSP/PIP submitted or is there a waiver process? Does it quality for rare disease exemption? Insights appreciated on this, as to how this is handled specific to diseases occurring only in pediatric patients, in particular in cases of persistent therapy where FIH healthy volunteers or adults are not possible populations.

This message was posted by a user wishing to remain anonymous

"It would be recommended to have an agreed PIP before starting your trial...." If you meant FIH phase 1 study, then your response is 100% incorrect!
Agreed PIP before submitting MAA or registration trial.....is more accurate.

"it is best to start discussions with the EMA as soon as possible.." Again if you meant before FIH study-100% incorrect

Since its a novel therapeutic, you need basic safety/pk/pd data (as previously mentioned in the above response) from a FIH phase1 study (in this case First in Pediatric study) before one starts preparing PIP.........clearly and rationally mentioned in the EU and FDA guidances as well....


Original Message:
Sent: 19-May-2022 03:15
From: Anonymous Member
Subject: Pediatric only disease iPSP/PIP

This message was posted by a user wishing to remain anonymous

This depends on a number of other factors. For the EU there is no rare disease exemption so a PIP will be required, it is best to start discussions with the EMA as soon as possible, it may be that you could also request scientific advise. It would be recommended to have an agreed PIP before starting your trial, particularly for rare disease with limited patient population to ensure the study conducted will meet the regulators requirements.
For the US, if you have ODD then you may not need a iPSP, however this may not be the case if the product is for oncology. Again early discussions with the FDA would be recommended.
Original Message:
Sent: 17-May-2022 16:39
From: Anonymous Member
Subject: Pediatric only disease iPSP/PIP

This message was posted by a user wishing to remain anonymous

For a novel therapeutic that will go directly into pediatrics in its IND(US)/CTA(EU)-opening studies due to the nature of the disease and therapy, when is the iPSP/PIP submitted or is there a waiver process? Does it quality for rare disease exemption? Insights appreciated on this, as to how this is handled specific to diseases occurring only in pediatric patients, in particular in cases of persistent therapy where FIH healthy volunteers or adults are not possible populations.