Regulatory Open Forum

Dear All,
In your experience what is the best time to hold this meeting for an initial IND. I have seen it happen prior to start of GLP toxicology studies ie once there is animal efficacy data, good idea of manufacturing process/specifications/analytical methods. The rest is proposed.

Also, what is the equivalent of a preIND meeting in Europe?
-------------------------------------------
Madhu

Dear Madu,
There does not appear to be a specific timetable but yes certain tox and manufacturing data  needs to be available prior to starting in the first in human clinical trial. 

For the meetings, a helpful guidance document is:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM153222.pdf
There is also a regulation  for the pre-IND meeting, which is a Type B meeting (scheduled 60 days after a formal request is sent to the FDA), 21 CFR 312.82 which states, "Prior to the submission of the initial IND, the sponsor may request a meeting with FDA-reviewing officials. The primary purpose of this meeting is to review and reach agreement on the design of animal studies needed to initiate human testing. The meeting may also provide an opportunity for discussing the scope and design of phase 1 testing, plans for studying the drug product in pediatric populations, and the best approach for presentation and formatting of data in the IND".

For EU, it would appear that the equivalent would be a meeting for Scientific Advice with the Scientific Advice Working Party (SAWP): this is a great guidance Q&A: http://www.emea.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004089.pdf

HealthCanada (Canadian FDA) has a pre-CTA meeting procedure and specific meeting package process: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/cta_pre_application-eng.php

Good luck, hope these help!
Danielle
-------------------------------------------
Danielle Littee
Boston MA
United States
-------------------------------------------






Original Message:
Sent: 07-04-2012 18:30
From: Madhu Singh
Subject: Timing of preIND/CTA meeting

Dear All,
In your experience what is the best time to hold this meeting for an initial IND. I have seen it happen prior to start of GLP toxicology studies ie once there is animal efficacy data, good idea of manufacturing process/specifications/analytical methods. The rest is proposed.

Also, what is the equivalent of a preIND meeting in Europe?
-------------------------------------------
Madhu

-------------------------------------------
Gary Kikuchi RAC
Regulatory Strategy Consultant
Morris Plains NJ
United States
-------------------------------------------

Dear Madu and Danielle,

My experience with pre-INDs has been similar, however a pre-IND is a terrific opportunity to get feedback on a clinical synopsis as well. It is also a great time to get feedback on the design of the GLP toxicology studies; and hopefully there is sufficient information regarding CMC to get FDA to provide feedback on manufacturing and lot release information.

My experience with EMA SAWP is that this procedure tends to be more equivalent to FDA end-of-phase 2; especially since EMA is not involved in CTA submissions in Europe.

Thanks,

Gary Kikuchi PhD RAC
Regulatory Strategy Consultant
973-714-2319
gary.kikuchi@gmail.com




Original Message:
Sent: 07-04-2012 22:54
From: Danielle Littee
Subject: Timing of preIND/CTA meeting

Dear Madu,
There does not appear to be a specific timetable but yes certain tox and manufacturing data  needs to be available prior to starting in the first in human clinical trial. 

For the meetings, a helpful guidance document is:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM153222.pdf
There is also a regulation  for the pre-IND meeting, which is a Type B meeting (scheduled 60 days after a formal request is sent to the FDA), 21 CFR 312.82 which states, "Prior to the submission of the initial IND, the sponsor may request a meeting with FDA-reviewing officials. The primary purpose of this meeting is to review and reach agreement on the design of animal studies needed to initiate human testing. The meeting may also provide an opportunity for discussing the scope and design of phase 1 testing, plans for studying the drug product in pediatric populations, and the best approach for presentation and formatting of data in the IND".

For EU, it would appear that the equivalent would be a meeting for Scientific Advice with the Scientific Advice Working Party (SAWP): this is a great guidance Q&A: http://www.emea.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004089.pdf

HealthCanada (Canadian FDA) has a pre-CTA meeting procedure and specific meeting package process: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/cta_pre_application-eng.php

Good luck, hope these help!
Danielle
-------------------------------------------
Danielle Littee
Boston MA
United States
-------------------------------------------






Original Message:
Sent: 07-04-2012 18:30
From: Madhu Singh
Subject: Timing of preIND/CTA meeting

Dear All,
In your experience what is the best time to hold this meeting for an initial IND. I have seen it happen prior to start of GLP toxicology studies ie once there is animal efficacy data, good idea of manufacturing process/specifications/analytical methods. The rest is proposed.

Also, what is the equivalent of a preIND meeting in Europe?
-------------------------------------------
Madhu

Dear Madu,

The comments already provided are very good.  I would like to add that generally the timing for conducting a pre-IND meeting should be at least 6 months to 1 year prior to time of IND submission.  You will want to get FDA's response to your proposed tox program as well as your Phase-1 clinical design.  In your briefing packet you will include a clinical precis which outlines your Phase-1 study.  The questions you raise should be formed more in the way of declarative sentences rather than open-ended questions.  You want to propose to FDA what your program will be and see if they concur.  An example would be "ABC Pharma will conduct a 28-day acute toxicity study in rats and dogs .... Does FDA concur?"  By proposing your studies and questions in this manner allows you to negotiate with FDA during the meeting and come to agreement on what needs to be done.

I hope this helps.

-------------------------------------------
Michael Tomasovich
Director Business Development
Regulatory Affairs Associates
Inkster MI
United States
-------------------------------------------






Original Message:
Sent: 07-05-2012 09:49
From: Gary Kikuchi
Subject: Timing of preIND/CTA meeting



-------------------------------------------
Gary Kikuchi RAC
Regulatory Strategy Consultant
Morris Plains NJ
United States
-------------------------------------------

Dear Madu and Danielle,

My experience with pre-INDs has been similar, however a pre-IND is a terrific opportunity to get feedback on a clinical synopsis as well. It is also a great time to get feedback on the design of the GLP toxicology studies; and hopefully there is sufficient information regarding CMC to get FDA to provide feedback on manufacturing and lot release information.

My experience with EMA SAWP is that this procedure tends to be more equivalent to FDA end-of-phase 2; especially since EMA is not involved in CTA submissions in Europe.

Thanks,

Gary Kikuchi PhD RAC
Regulatory Strategy Consultant
973-714-2319
gary.kikuchi@gmail.com




Original Message:
Sent: 07-04-2012 22:54
From: Danielle Littee
Subject: Timing of preIND/CTA meeting

Dear Madu,
There does not appear to be a specific timetable but yes certain tox and manufacturing data  needs to be available prior to starting in the first in human clinical trial. 

For the meetings, a helpful guidance document is:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM153222.pdf
There is also a regulation  for the pre-IND meeting, which is a Type B meeting (scheduled 60 days after a formal request is sent to the FDA), 21 CFR 312.82 which states, "Prior to the submission of the initial IND, the sponsor may request a meeting with FDA-reviewing officials. The primary purpose of this meeting is to review and reach agreement on the design of animal studies needed to initiate human testing. The meeting may also provide an opportunity for discussing the scope and design of phase 1 testing, plans for studying the drug product in pediatric populations, and the best approach for presentation and formatting of data in the IND".

For EU, it would appear that the equivalent would be a meeting for Scientific Advice with the Scientific Advice Working Party (SAWP): this is a great guidance Q&A: http://www.emea.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004089.pdf

HealthCanada (Canadian FDA) has a pre-CTA meeting procedure and specific meeting package process: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/cta_pre_application-eng.php

Good luck, hope these help!
Danielle
-------------------------------------------
Danielle Littee
Boston MA
United States
-------------------------------------------






Original Message:
Sent: 07-04-2012 18:30
From: Madhu Singh
Subject: Timing of preIND/CTA meeting

Dear All,
In your experience what is the best time to hold this meeting for an initial IND. I have seen it happen prior to start of GLP toxicology studies ie once there is animal efficacy data, good idea of manufacturing process/specifications/analytical methods. The rest is proposed.

Also, what is the equivalent of a preIND meeting in Europe?
-------------------------------------------
Madhu

Fully agree with the comments.  The pre-IND meeting (and the preceeding briefing package)  is also very important if the dosing in the clinic is going to be with an-conventional route of delivery or dosage form.  For example, if the route of administration is inhalation in to lungs, FDA would want to know how the animal tox studies are planned to be conducted; inhalation tox is very imporatnt to FDA so that the dose proposed in the Phase I study has some correlation with the doses used in the GLP tox program and the organ toxicities are well delineated.  Similalry for novel nano formulations, FDA gets concerned about the bio-disposition of the nanomaterials and may ask a sponsor to study this in an explortaory tox study. 
-------------------------------------------
PRAFULLA AGRAWALA
SANOFI US LLC
KENDALL PARK NJ
United States
-------------------------------------------






Original Message:
Sent: 07-06-2012 11:07
From: Michael Tomasovich
Subject: Timing of preIND/CTA meeting

Dear Madu,

The comments already provided are very good.  I would like to add that generally the timing for conducting a pre-IND meeting should be at least 6 months to 1 year prior to time of IND submission.  You will want to get FDA's response to your proposed tox program as well as your Phase-1 clinical design.  In your briefing packet you will include a clinical precis which outlines your Phase-1 study.  The questions you raise should be formed more in the way of declarative sentences rather than open-ended questions.  You want to propose to FDA what your program will be and see if they concur.  An example would be "ABC Pharma will conduct a 28-day acute toxicity study in rats and dogs .... Does FDA concur?"  By proposing your studies and questions in this manner allows you to negotiate with FDA during the meeting and come to agreement on what needs to be done.

I hope this helps.

-------------------------------------------
Michael Tomasovich
Director Business Development
Regulatory Affairs Associates
Inkster MI
United States
-------------------------------------------






Original Message:
Sent: 07-05-2012 09:49
From: Gary Kikuchi
Subject: Timing of preIND/CTA meeting



-------------------------------------------
Gary Kikuchi RAC
Regulatory Strategy Consultant
Morris Plains NJ
United States
-------------------------------------------

Dear Madu and Danielle,

My experience with pre-INDs has been similar, however a pre-IND is a terrific opportunity to get feedback on a clinical synopsis as well. It is also a great time to get feedback on the design of the GLP toxicology studies; and hopefully there is sufficient information regarding CMC to get FDA to provide feedback on manufacturing and lot release information.

My experience with EMA SAWP is that this procedure tends to be more equivalent to FDA end-of-phase 2; especially since EMA is not involved in CTA submissions in Europe.

Thanks,

Gary Kikuchi PhD RAC
Regulatory Strategy Consultant
973-714-2319
gary.kikuchi@gmail.com




Original Message:
Sent: 07-04-2012 22:54
From: Danielle Littee
Subject: Timing of preIND/CTA meeting

Dear Madu,
There does not appear to be a specific timetable but yes certain tox and manufacturing data  needs to be available prior to starting in the first in human clinical trial. 

For the meetings, a helpful guidance document is:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM153222.pdf
There is also a regulation  for the pre-IND meeting, which is a Type B meeting (scheduled 60 days after a formal request is sent to the FDA), 21 CFR 312.82 which states, "Prior to the submission of the initial IND, the sponsor may request a meeting with FDA-reviewing officials. The primary purpose of this meeting is to review and reach agreement on the design of animal studies needed to initiate human testing. The meeting may also provide an opportunity for discussing the scope and design of phase 1 testing, plans for studying the drug product in pediatric populations, and the best approach for presentation and formatting of data in the IND".

For EU, it would appear that the equivalent would be a meeting for Scientific Advice with the Scientific Advice Working Party (SAWP): this is a great guidance Q&A: http://www.emea.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004089.pdf

HealthCanada (Canadian FDA) has a pre-CTA meeting procedure and specific meeting package process: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/cta_pre_application-eng.php

Good luck, hope these help!
Danielle
-------------------------------------------
Danielle Littee
Boston MA
United States
-------------------------------------------






Original Message:
Sent: 07-04-2012 18:30
From: Madhu Singh
Subject: Timing of preIND/CTA meeting

Dear All,
In your experience what is the best time to hold this meeting for an initial IND. I have seen it happen prior to start of GLP toxicology studies ie once there is animal efficacy data, good idea of manufacturing process/specifications/analytical methods. The rest is proposed.

Also, what is the equivalent of a preIND meeting in Europe?
-------------------------------------------
Madhu

Madhu,

If you are planning a pre-IND meeting, make it as comprehensive as possible and get as many issues and topics on the table.  The advise provided below is sound and discussion of the clinical protocol is key as the GLP tox study(ies) are relevant in identifying toxicities that might be expected in humans based on the relevant animal species (Monkey or rat) depending on the molecule.  If you see anything concerning, cardiovascular, GI, liver function, etc, these are the types of issues that will need to be presented and plans for keeping the study subjects safe identified.  Schedule the pre-IND meeting early enough so the responses matter and you have time to revise the pivotal tox studies if requested and consider any comments to the clinical protocol. 

If you write a comprehensive and clear briefing document once the meeting is "granted" by  FDA and in my experience FDA has requested a t-con rather than face-to-face and on one of my INDs responded to our questions in writing and we cancelled the t-con.  

If you have something really novel, new target, complicated manufacturing process or tox signals that might be concerning, then it is even more important to generate a clear dossier.

My only comment on the EU question is that scientific advise is strictly for scientific advise.  If you need a regulatory question answered the SAWP is not the forum.  I would suggest regional discussion is necessary for example, MHRA or TGA, as scientific advise meetings are not free and if a question is addressed in a guidance or regulation, the meeting will not be granted. 

Hope this adds some additional information,

Dar

-------------------------------------------
Darlene Rosario, BS, RAC, MBA
Oxnard CA
United States
-------------------------------------------






Original Message:
Sent: 07-04-2012 22:54
From: Danielle Littee
Subject: Timing of preIND/CTA meeting

Dear Madu,
There does not appear to be a specific timetable but yes certain tox and manufacturing data  needs to be available prior to starting in the first in human clinical trial. 

For the meetings, a helpful guidance document is:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM153222.pdf
There is also a regulation  for the pre-IND meeting, which is a Type B meeting (scheduled 60 days after a formal request is sent to the FDA), 21 CFR 312.82 which states, "Prior to the submission of the initial IND, the sponsor may request a meeting with FDA-reviewing officials. The primary purpose of this meeting is to review and reach agreement on the design of animal studies needed to initiate human testing. The meeting may also provide an opportunity for discussing the scope and design of phase 1 testing, plans for studying the drug product in pediatric populations, and the best approach for presentation and formatting of data in the IND".

For EU, it would appear that the equivalent would be a meeting for Scientific Advice with the Scientific Advice Working Party (SAWP): this is a great guidance Q&A: http://www.emea.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004089.pdf

HealthCanada (Canadian FDA) has a pre-CTA meeting procedure and specific meeting package process: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/cta_pre_application-eng.php

Good luck, hope these help!
Danielle
-------------------------------------------
Danielle Littee
Boston MA
United States
-------------------------------------------






Original Message:
Sent: 07-04-2012 18:30
From: Madhu Singh
Subject: Timing of preIND/CTA meeting

Dear All,
In your experience what is the best time to hold this meeting for an initial IND. I have seen it happen prior to start of GLP toxicology studies ie once there is animal efficacy data, good idea of manufacturing process/specifications/analytical methods. The rest is proposed.

Also, what is the equivalent of a preIND meeting in Europe?
-------------------------------------------
Madhu

Thank you for your valuable advice. Can you please point me to the guidance or weblink for such meetings in UK, Germany and Netherland?





Original Message:
Sent: 07-05-2012 11:21
From: Darlene Rosario
Subject: Timing of preIND/CTA meeting

Madhu,

If you are planning a pre-IND meeting, make it as comprehensive as possible and get as many issues and topics on the table.  The advise provided below is sound and discussion of the clinical protocol is key as the GLP tox study(ies) are relevant in identifying toxicities that might be expected in humans based on the relevant animal species (Monkey or rat) depending on the molecule.  If you see anything concerning, cardiovascular, GI, liver function, etc, these are the types of issues that will need to be presented and plans for keeping the study subjects safe identified.  Schedule the pre-IND meeting early enough so the responses matter and you have time to revise the pivotal tox studies if requested and consider any comments to the clinical protocol. 

If you write a comprehensive and clear briefing document once the meeting is "granted" by  FDA and in my experience FDA has requested a t-con rather than face-to-face and on one of my INDs responded to our questions in writing and we cancelled the t-con.  

If you have something really novel, new target, complicated manufacturing process or tox signals that might be concerning, then it is even more important to generate a clear dossier.

My only comment on the EU question is that scientific advise is strictly for scientific advise.  If you need a regulatory question answered the SAWP is not the forum.  I would suggest regional discussion is necessary for example, MHRA or TGA, as scientific advise meetings are not free and if a question is addressed in a guidance or regulation, the meeting will not be granted. 

Hope this adds some additional information,

Dar

-------------------------------------------
Darlene Rosario, BS, RAC, MBA
Oxnard CA
United States
-------------------------------------------






Original Message:
Sent: 07-04-2012 22:54
From: Danielle Littee
Subject: Timing of preIND/CTA meeting

Dear Madu,
There does not appear to be a specific timetable but yes certain tox and manufacturing data  needs to be available prior to starting in the first in human clinical trial. 

For the meetings, a helpful guidance document is:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM153222.pdf
There is also a regulation  for the pre-IND meeting, which is a Type B meeting (scheduled 60 days after a formal request is sent to the FDA), 21 CFR 312.82 which states, "Prior to the submission of the initial IND, the sponsor may request a meeting with FDA-reviewing officials. The primary purpose of this meeting is to review and reach agreement on the design of animal studies needed to initiate human testing. The meeting may also provide an opportunity for discussing the scope and design of phase 1 testing, plans for studying the drug product in pediatric populations, and the best approach for presentation and formatting of data in the IND".

For EU, it would appear that the equivalent would be a meeting for Scientific Advice with the Scientific Advice Working Party (SAWP): this is a great guidance Q&A: http://www.emea.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004089.pdf

HealthCanada (Canadian FDA) has a pre-CTA meeting procedure and specific meeting package process: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/cta_pre_application-eng.php

Good luck, hope these help!
Danielle
-------------------------------------------
Danielle Littee
Boston MA
United States
-------------------------------------------






Original Message:
Sent: 07-04-2012 18:30
From: Madhu Singh
Subject: Timing of preIND/CTA meeting

Dear All,
In your experience what is the best time to hold this meeting for an initial IND. I have seen it happen prior to start of GLP toxicology studies ie once there is animal efficacy data, good idea of manufacturing process/specifications/analytical methods. The rest is proposed.

Also, what is the equivalent of a preIND meeting in Europe?
-------------------------------------------
Madhu