Regulatory Open Forum

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hello Gregory

You pose an interesting question!

I think it is important to keep in mind that the final objective is to demonstrate, with a reasonable amount of data, that your product is safe and effective. If you believe that a higher limit on "one impurity" is still acceptable based on a sound analysis of benefit-risk in the context of the state of the art, then there is nothing "pushy" about it.

Personally, I don't think FDA will give you a yes/no answer, but I leave that to other experts on this forum. 

I believe it is important to make sure you are not seen by the FDA as someone trying to "push the boundary" just for the sake of convenience. 

Best regards

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hello Gregory

You pose an interesting question!

I think it is important to keep in mind that the final objective is to demonstrate, with a reasonable amount of data, that your product is safe and effective. If you believe that a higher limit on "one impurity" is still acceptable based on a sound analysis of benefit-risk in the context of the state of the art, then there is nothing "pushy" about it.

Personally, I don't think FDA will give you a yes/no answer, but I leave that to other experts on this forum. 

I believe it is important to make sure you are not seen by the FDA as someone trying to "push the boundary" just for the sake of convenience. 

Best regards

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

I am not going to say anything new here, but just to add that I have taken it as a point of pride in my discussions with regulatory agencies to push the boundaries of how regulations and guidance are interpreted by the industry. Many times, we in the industry do not really understand what authorities are thinking or how they would react to novel approaches to establishing evidence of product quality. My rule is that if it passes the "red face" test, it is a fair question/proposal. I have had "sensible" (to me) proposals soundly rejected and have never felt that posing that proposal had a negative effect on overall interactions. I am often surprised when FDA makes suggestions themselves that I thought were out of bounds. 

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!

I think asking questions that may be seen as pushing the boundaries is absolutely within your right. The key is to ask in a way that is not pushy, and to provide a sound rationale for why you believe your methodology/analysis is the correct path to follow. If you do this, I do not believe you will be seen negatively by the health authorities and may actually create a rapport that could prove beneficial as you continue working with that reviewer and/or department.  

Hi, I am preparing a CMC meeting package for a clinical phase drug. I got pushed by management to ask pushing questions. The idea is that we have nothing to lose if FDA does not agree with us. One of the examples is to ask for one higher-than-the-ICH limit for one impurity based on real thin data. In case got lucky, no need to spend on additional experiments. Another example is to ask if it is acceptable to make one bridging batch to double the tablet counts per bottle while retaining the validity of the primary batches including the process and expiry. If FDA does not agree, we just fall back to the original package. 

In the past, my mentor carried such an air around her that people did not dare to ask that kind of question. Now that I am on my own and look weak...the floodgate opens. My question is what is the downside of asking FDA pushy questions? What do we have to lose if FDA does not agree with us?

Thanks!