Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hello,

We are currently using a tablet formulation in our IND and plan to include a study cohort with a capsule formulation. This means that the Drug Substance section remains the same, but now we will have 2 drug product sections - one for tablet which was previously approved and a new capsule formulation.

Technically, once an IND is open, amendments can be implemented immediately, given that it is approved by the Ethics board (for e.g. if IND was approved with Phase 1 protocol, a Phase 2 protocol may be submitted and patients dosed as long as Ethics approval is received). However, in such an instance as described above, where the amendment is as big as a whole new DP formulation, should you typically wait for 30 days for FDA to comment; or should you proceed with the new formulation; or should you ASK the FDA to comment?

Thank you.
Regards,
Anon

​Hi, Anon -

It sounds like you have a good grasp on what is permissible by the regulations, and you are instead asking what is strategically the best approach.  In general, if there are no concerns about bioavailability or release timing, stability, etc., I would file and wait the 30 days.  If you have a good relationship with your regulatory project manager, I recommend sending them a brief heads-up at the time of the submission and touching base with them again at the end of the 30 days as a professional courtesy.  If there are concerns about the differences between the tablet and capsule, it is absolutely a good idea to ask FDA to comment on the protocol, etc., or perhaps request a meeting (depending on the level of concern).  You never want to blindside the FDA, so even if you are confident there are no differences, I recommend sending your regulatory project manager a brief update at the time of submission.

Best regards,

Cathy

------------------------------
Catherine Anderson PhD, RAC
Associate Director - Regulatory CMC
Hillsborough NC
United States
------------------------------

Original Message:
Sent: 16-Aug-2019 18:50
From: Anonymous Member
Subject: New formulation and IND amendment

This message was posted by a user wishing to remain anonymous

Hello,

We are currently using a tablet formulation in our IND and plan to include a study cohort with a capsule formulation. This means that the Drug Substance section remains the same, but now we will have 2 drug product sections - one for tablet which was previously approved and a new capsule formulation.

Technically, once an IND is open, amendments can be implemented immediately, given that it is approved by the Ethics board (for e.g. if IND was approved with Phase 1 protocol, a Phase 2 protocol may be submitted and patients dosed as long as Ethics approval is received). However, in such an instance as described above, where the amendment is as big as a whole new DP formulation, should you typically wait for 30 days for FDA to comment; or should you proceed with the new formulation; or should you ASK the FDA to comment?

Thank you.
Regards,
Anon

There is no need to wait 30 days for FDA to comment to the IND amendment no matter how large. It is not unusual to try new formulations during development. I would typically notify the PM at FDA in advance as a heads up but would not build any delay in starting the study into the timelines.

------------------------------
Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
Jersey City NJ
United States
------------------------------

Original Message:
Sent: 16-Aug-2019 18:50
From: Anonymous Member
Subject: New formulation and IND amendment

This message was posted by a user wishing to remain anonymous

Hello,

We are currently using a tablet formulation in our IND and plan to include a study cohort with a capsule formulation. This means that the Drug Substance section remains the same, but now we will have 2 drug product sections - one for tablet which was previously approved and a new capsule formulation.

Technically, once an IND is open, amendments can be implemented immediately, given that it is approved by the Ethics board (for e.g. if IND was approved with Phase 1 protocol, a Phase 2 protocol may be submitted and patients dosed as long as Ethics approval is received). However, in such an instance as described above, where the amendment is as big as a whole new DP formulation, should you typically wait for 30 days for FDA to comment; or should you proceed with the new formulation; or should you ASK the FDA to comment?

Thank you.
Regards,
Anon

I thought a new dosage form would require a new IND. I was involved in a situation where we had a tablet IND open and wanted to introduce an oral suspension dosage form (same drug substance and same indication) but had to file a separate IND for the new dosage form. You may want to check with your FDA Project Manager before adding the capsule to the tablet IND.

------------------------------
Tom
Senior Director, Regulatory Affairs CMC
Chicago
------------------------------

Original Message:
Sent: 16-Aug-2019 18:50
From: Anonymous Member
Subject: New formulation and IND amendment

This message was posted by a user wishing to remain anonymous

Hello,

We are currently using a tablet formulation in our IND and plan to include a study cohort with a capsule formulation. This means that the Drug Substance section remains the same, but now we will have 2 drug product sections - one for tablet which was previously approved and a new capsule formulation.

Technically, once an IND is open, amendments can be implemented immediately, given that it is approved by the Ethics board (for e.g. if IND was approved with Phase 1 protocol, a Phase 2 protocol may be submitted and patients dosed as long as Ethics approval is received). However, in such an instance as described above, where the amendment is as big as a whole new DP formulation, should you typically wait for 30 days for FDA to comment; or should you proceed with the new formulation; or should you ASK the FDA to comment?

Thank you.
Regards,
Anon

First, I don't disagree at all with the advice to speak to the PM. Whether a new IND is required for a new dosage form generally depends on the development program and the intention for the new form. If, for example, you are developing a new formulation and want to test that new formulation to see if it improves bioavailability and could eventually replace the current formulation you wouldn't need a new IND and it would be wasteful as far as the resources needed for a whole new IND.  This would be the case if you are considering switching between a tablet and capsule, for example.

If, however, you are introducing a new dosage form such as a liquid dosage form or a parenteral dosage form it would make sense to have a new IND since it could impact other IND sections such as toxicology.

With respect to the original question posed Anonymous, they are incorporating the capsule formulation into a study as a new cohort of a study using the tablet. It would be quite inefficient from a IND management and review to have two INDs for one study.

------------------------------
Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
Jersey City NJ
United States
------------------------------

Original Message:
Sent: 20-Aug-2019 12:49
From: Tom Stothoff
Subject: New formulation and IND amendment

I thought a new dosage form would require a new IND. I was involved in a situation where we had a tablet IND open and wanted to introduce an oral suspension dosage form (same drug substance and same indication) but had to file a separate IND for the new dosage form. You may want to check with your FDA Project Manager before adding the capsule to the tablet IND.

------------------------------
Tom
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 16-Aug-2019 18:50
From: Anonymous Member
Subject: New formulation and IND amendment

This message was posted by a user wishing to remain anonymous

Hello,

We are currently using a tablet formulation in our IND and plan to include a study cohort with a capsule formulation. This means that the Drug Substance section remains the same, but now we will have 2 drug product sections - one for tablet which was previously approved and a new capsule formulation.

Technically, once an IND is open, amendments can be implemented immediately, given that it is approved by the Ethics board (for e.g. if IND was approved with Phase 1 protocol, a Phase 2 protocol may be submitted and patients dosed as long as Ethics approval is received). However, in such an instance as described above, where the amendment is as big as a whole new DP formulation, should you typically wait for 30 days for FDA to comment; or should you proceed with the new formulation; or should you ASK the FDA to comment?

Thank you.
Regards,
Anon

Just to add to Glen's points, I, too, would agree you should speak directly with your PM before deciding anything.  This likely will save a lot of questions, headaches, and ultimately work for all parties.  As has been noted, many changes can simply be done by opening a new cohort within the project as opposed to trying to open a completely new project. 

But to Tom's point about needing to open a new IND for a change from tablet to oral suspension, I would also argue that this change makes a lot of sense from a public health perspective.  Think about it - the reason for prescribing a suspension is usually to prescribe the product to some vulnerable population like children, the elderly or even people with significant additional co-morbidities (think cancer patients) who can't swallow the pill effectively.  I could see FDA requesting a new IND for this to ensure that they themselves have done the necessary due diligence on the study and to also ensure that the IRB reviewing the study are in agreement that you have factored all these points into the study to run it as safely and reasonably as possible.​

------------------------------
Victor Mencarelli
Director Regulatory Affairs
United States
------------------------------

Original Message:
Sent: 20-Aug-2019 14:11
From: Glen Park
Subject: New formulation and IND amendment

First, I don't disagree at all with the advice to speak to the PM. Whether a new IND is required for a new dosage form generally depends on the development program and the intention for the new form. If, for example, you are developing a new formulation and want to test that new formulation to see if it improves bioavailability and could eventually replace the current formulation you wouldn't need a new IND and it would be wasteful as far as the resources needed for a whole new IND.  This would be the case if you are considering switching between a tablet and capsule, for example.

If, however, you are introducing a new dosage form such as a liquid dosage form or a parenteral dosage form it would make sense to have a new IND since it could impact other IND sections such as toxicology.

With respect to the original question posed Anonymous, they are incorporating the capsule formulation into a study as a new cohort of a study using the tablet. It would be quite inefficient from a IND management and review to have two INDs for one study.

------------------------------
Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
Jersey City NJ
United States

Original Message:
Sent: 20-Aug-2019 12:49
From: Tom Stothoff
Subject: New formulation and IND amendment

I thought a new dosage form would require a new IND. I was involved in a situation where we had a tablet IND open and wanted to introduce an oral suspension dosage form (same drug substance and same indication) but had to file a separate IND for the new dosage form. You may want to check with your FDA Project Manager before adding the capsule to the tablet IND.

------------------------------
Tom
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 16-Aug-2019 18:50
From: Anonymous Member
Subject: New formulation and IND amendment

This message was posted by a user wishing to remain anonymous

Hello,

We are currently using a tablet formulation in our IND and plan to include a study cohort with a capsule formulation. This means that the Drug Substance section remains the same, but now we will have 2 drug product sections - one for tablet which was previously approved and a new capsule formulation.

Technically, once an IND is open, amendments can be implemented immediately, given that it is approved by the Ethics board (for e.g. if IND was approved with Phase 1 protocol, a Phase 2 protocol may be submitted and patients dosed as long as Ethics approval is received). However, in such an instance as described above, where the amendment is as big as a whole new DP formulation, should you typically wait for 30 days for FDA to comment; or should you proceed with the new formulation; or should you ASK the FDA to comment?

Thank you.
Regards,
Anon