Regulatory Open Forum

Pharma is not my background but I'll do my best to answer this.

Found this in Guidance for Industry Submitting Separate Marketing Applications and Clinical Data for Purposes of Assessing User Fees, Dec 2004

2. Different Routes of Administration
Products to be administered using different routes of administration (see FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (the Orange Book) Appendix C) should be submitted in separate original applications unless the product(s) for use by all routes in a given application are quantitatively and qualitatively identical (drugs) or alike (biological products) in composition (e.g., an injectable liquid dosage form intended for use by the intravenous and intraperitoneal routes).

So my guess is if you demonstrate that the two routes do not present new risks or hinder effectiveness of the drug through bioavailability/bioequivalence studies (animal models, bench testing, modelling?), you should be able to conduct the study under a single IND.


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Vidyalakshmi Jayaraman
Marlborough MA
United States
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Original Message:
Sent: 29-Jan-2018 11:52
From: J. Fox
Subject: Multiple routes of administration

I have a client who wants to conduct clinical studies using their compound in both injectable and oral form for the same indication. The indication is an acute injury that would best be treated with an IV-formulation initially but there is a strong scientific basis to believe continued treatment with the same compound (via oral formulation) post-surgery would improve patient outcomes.

The question is whether these studies could be done under one IND and if there are any additional regulatory issues in using multiple routes of administration in one therapy. Are there any FDA guidance documents on the subject? I have not been able to find any as yet.

Thanks,

Wes

This message was posted by a user wishing to remain anonymous

​Another consideration is the dosage form/formulation - is the oral formulation different from the IV formulation. The CMC of your IND would be significantly impacted if there are two different dosage forms.  But this would be a fairly straightforward question that you can have addressed in your pre-IND meeting with FDA. 

From my actual experience (with CBER though) - we were asked to file an entirely separate IND for the exact same product/formulation and exact same indication simply because we went from the SC/ID routes to the IV route.  Difference from your situation is that for you the two routes are part of the same therapy, for us it was an either or situation for the route of administration.
Original Message:
Sent: 29-Jan-2018 14:50
From: Vidyalakshmi Jayaraman
Subject: Multiple routes of administration

Pharma is not my background but I'll do my best to answer this.

Found this in Guidance for Industry Submitting Separate Marketing Applications and Clinical Data for Purposes of Assessing User Fees, Dec 2004

2. Different Routes of Administration
Products to be administered using different routes of administration (see FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (the Orange Book) Appendix C) should be submitted in separate original applications unless the product(s) for use by all routes in a given application are quantitatively and qualitatively identical (drugs) or alike (biological products) in composition (e.g., an injectable liquid dosage form intended for use by the intravenous and intraperitoneal routes).

So my guess is if you demonstrate that the two routes do not present new risks or hinder effectiveness of the drug through bioavailability/bioequivalence studies (animal models, bench testing, modelling?), you should be able to conduct the study under a single IND.


------------------------------
Vidyalakshmi Jayaraman
Marlborough MA
United States

Original Message:
Sent: 29-Jan-2018 11:52
From: J. Fox
Subject: Multiple routes of administration

I have a client who wants to conduct clinical studies using their compound in both injectable and oral form for the same indication. The indication is an acute injury that would best be treated with an IV-formulation initially but there is a strong scientific basis to believe continued treatment with the same compound (via oral formulation) post-surgery would improve patient outcomes.

The question is whether these studies could be done under one IND and if there are any additional regulatory issues in using multiple routes of administration in one therapy. Are there any FDA guidance documents on the subject? I have not been able to find any as yet.

Thanks,

Wes

Hi Wes 

There are some examples of approved products that used with multiple routes of administration. I would suggest if you visit either the review reports (on FDA) or the Public Assessment Reports (in EU) for these products to get more idea. You can also reverse engineering these review reports by checking the scope of the supporting clinical trials on Clinicaltrials.gov  or the European Clinical Trials Register website. 

Examples may include: 
1- Cafcit: New route of administration was added a year after the original NDA approval 
2-  Vancomycin vials approved in EU as oral and injection. See their PAR
3- A prostaglandin was approved for vaginal and oral use. Can't remember the name on the top of my head 

Regards

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Ahmed Abouelnour RAC
Hamilton ON
Canada
------------------------------

Original Message:
Sent: 29-Jan-2018 11:52
From: J. Fox
Subject: Multiple routes of administration

I have a client who wants to conduct clinical studies using their compound in both injectable and oral form for the same indication. The indication is an acute injury that would best be treated with an IV-formulation initially but there is a strong scientific basis to believe continued treatment with the same compound (via oral formulation) post-surgery would improve patient outcomes.

The question is whether these studies could be done under one IND and if there are any additional regulatory issues in using multiple routes of administration in one therapy. Are there any FDA guidance documents on the subject? I have not been able to find any as yet.

Thanks,

Wes

This message was posted by a user wishing to remain anonymous

​Not an expert of IND filling but ahemd's suggestion is really good.

If this was the case of ANDA, it is not possible to combine different dosage forms in one application. See,

Guidance for Industry:Variations in Drug Products that May Be Included in a Single ANDA.

Original Message:
Sent: 29-Jan-2018 22:34
From: Ahmed Abouelnour
Subject: Multiple routes of administration

Hi Wes

There are some examples of approved products that used with multiple routes of administration. I would suggest if you visit either the review reports (on FDA) or the Public Assessment Reports (in EU) for these products to get more idea. You can also reverse engineering these review reports by checking the scope of the supporting clinical trials on Clinicaltrials.gov  or the European Clinical Trials Register website.

Examples may include:
1- Cafcit: New route of administration was added a year after the original NDA approval
2-  Vancomycin vials approved in EU as oral and injection. See their PAR
3- A prostaglandin was approved for vaginal and oral use. Can't remember the name on the top of my head

Regards

------------------------------
Ahmed Abouelnour RAC
Hamilton ON
Canada

Original Message:
Sent: 29-Jan-2018 11:52
From: J. Fox
Subject: Multiple routes of administration

I have a client who wants to conduct clinical studies using their compound in both injectable and oral form for the same indication. The indication is an acute injury that would best be treated with an IV-formulation initially but there is a strong scientific basis to believe continued treatment with the same compound (via oral formulation) post-surgery would improve patient outcomes.

The question is whether these studies could be done under one IND and if there are any additional regulatory issues in using multiple routes of administration in one therapy. Are there any FDA guidance documents on the subject? I have not been able to find any as yet.

Thanks,

Wes

It is quite unlikely that an oral and intravenous formulation will be either quantitatively or qualitatively similar.  FDA will want separate INDs for the two formulations.  However, you can file one IND and substantively cross-reference from the second IND, except for studies required for the two routes of administration.  For example, there will be oral tox studies in the oral IND and IV tox studies in the IV IND.

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Glen Park
Jersey City NJ
United States
------------------------------

Original Message:
Sent: 29-Jan-2018 11:52
From: J. Fox
Subject: Multiple routes of administration

I have a client who wants to conduct clinical studies using their compound in both injectable and oral form for the same indication. The indication is an acute injury that would best be treated with an IV-formulation initially but there is a strong scientific basis to believe continued treatment with the same compound (via oral formulation) post-surgery would improve patient outcomes.

The question is whether these studies could be done under one IND and if there are any additional regulatory issues in using multiple routes of administration in one therapy. Are there any FDA guidance documents on the subject? I have not been able to find any as yet.

Thanks,

Wes