WEBVTT
00:00:01.229 --> 00:00:19.960
Bringing a novel Therapeutic to market is an art Hear VAs stat thought leaders as they draw on their specialized expertise to offer insight on timely, relevant topics that impact clinical development, the regulatory landscape, and patient access to these novel therapies.
00:00:21.160 --> 00:00:29.160
Hello and welcome to the Art podcast, Advancing Revolutionary Therapies, a podcast series presented by the Centers for Excellence at Vata.
00:00:29.609 --> 00:00:32.920
My name is Kevin Hennigan, Director of North American Regulatory Affairs.
00:00:33.280 --> 00:00:39.280
Today I will be presenting an overview of the emergency use authorization program available through the US fda.
00:00:39.590 --> 00:00:57.439
This episode is part of season three of the ART podcast, where we will be discussing various topics pertaining to navigating the US regulatory environment, and I encourage you to continue to listen to subsequent episodes as we have explore a variety of topics and issues associated with interacting with the US fda.
00:00:58.049 --> 00:00:59.399
So what are EUAs?
00:00:59.640 --> 00:01:20.760
Emergency use authorizations or EUAs are a mechanism that allows the US FDA to facilitate the availability of medical countermeasures for chemical, biological, radiological, and nuclear agents or CBRN agents, including emerging infectious disease threats such as COVID 19 and pandemic influenza during times of national emergency.
00:01:21.189 --> 00:01:30.799
Products that receive EUA may be legally marketed and sold in the United States for the duration of the emergency or until authorization is revoked by fda.
00:01:31.209 --> 00:01:32.760
So when can these be issued?
00:01:33.260 --> 00:01:53.920
FDA may only issue EUAs when there has been a determination of an emergency involving C B R N agents by the US Secretary of Homeland Security, the Secretary of Defense, or the Secretary of Health and Human Services, and that circumstances exist justifying the emergency use of drugs, biologics, and or medical devices.
00:01:54.019 --> 00:01:59.519
For FDA to issue an EUA under these circumstances for primary criteria must be met.
00:01:59.939 --> 00:02:04.599
One, the threat agent must be capable of causing a serious or life-threatening illness.
00:02:04.939 --> 00:02:11.199
Two, there must be enough evidence of effectiveness to conclude that the product may be effective for its proposed.
00:02:11.200 --> 00:02:15.680
Use a lower threshold than the effectiveness standard required for full approval.
00:02:15.719 --> 00:02:16.280
Three.
00:02:16.349 --> 00:02:26.520
A risk benefit analysis must conclude that the known and potential benefits of the product outweigh the known and potential risks, including consideration of the risks posed by the threat agent.
00:02:26.900 --> 00:02:32.120
And four, there must be no adequate approved and available alternative to the candidate product.
00:02:32.580 --> 00:02:36.479
The standards for adequate and available are usually interpreted quite broadly.
00:02:36.740 --> 00:02:43.400
For example, a product may be considered unavailable if there aren't enough existing doses to meet the emergency need.
00:02:43.710 --> 00:02:49.919
A product may be inadequate if it has contraindications for particular subgroups that are at risk in the emergency.
00:02:49.990 --> 00:02:52.319
What is the application process for an eua?
00:02:52.759 --> 00:03:04.280
Well, prior to submitting an EUA application, FDA encourages sponsors to engage the agency in pre eua interactions to discuss the potential suitability of the product for EUA consideration.
00:03:04.520 --> 00:03:08.560
While this is not an absolute requirement, these meetings are vitally important.
00:03:08.759 --> 00:03:10.759
Emergency situations evolve rapidly.
00:03:11.090 --> 00:03:26.400
So discussions with the agency to help to keep you on the right track with respect to data requirements, trial designs, and even application format, ensuring a more expeditious FDA review and increasing the probability of success when a full EUA is submitted.
00:03:26.740 --> 00:03:38.240
Pre EUA meetings follow the same request process and timelines as other FDA meetings such as pre I N D or pre NDA meetings and are considered type B meetings with respect to PAD Purdue.
00:03:38.439 --> 00:03:43.360
For classifications, though they are usually treated separately from other submissions on file with fda.
00:03:44.240 --> 00:03:54.050
When a sponsor believes they have collected all of the data necessary to fulfill the EUA requirements, they can proceed with submitting their request for drug and biologic submissions.
00:03:54.050 --> 00:04:02.930
Submitting the application electronically in common technical document format or CTD format may help accelerate the FDA's review of the application.
00:04:03.180 --> 00:04:12.330
However, in an acknowledgement of the emergency conditions, FDA can also accept other formats, even paper submissions for EUA applications.
00:04:12.860 --> 00:04:15.610
So let's talk a moment now about the data requirements.
00:04:15.830 --> 00:04:23.129
The data required to support an EUA must be sufficient to fulfill the four primary criteria I mentioned a few minutes ago.
00:04:23.338 --> 00:04:30.050
In practice this often means a lower data threshold than is typically required for a full NDA or vla.
00:04:30.199 --> 00:04:41.610
This might include regulatory flexibility, for example, with respect to completion of full process validation or a significantly shorter duration of safety follow up at the time of UA application.
00:04:41.870 --> 00:04:53.370
The data threshold can and does vary from one public health emergency to another and even through the life cycle of a given public health emergency based on understandings of real and perceived risks.
00:04:53.790 --> 00:05:04.689
The COVID 19 pandemic is certainly an example of this, where we saw the drug hydroxychloroquine receive an EUA early in the pandemic on the basis of small preliminary clinical studies.
00:05:05.120 --> 00:05:10.889
Subsequent studies did not validate those early efficacy results and FDA revoked the eua.
00:05:11.040 --> 00:05:25.449
I think it is safe to say that at this point in the pandemic and I am recording this podcast in September of 2022, an EUA application would not be accepted by the agency without considerably more data than were provided for hydroxychloroquine.
00:05:25.819 --> 00:05:33.850
So while the detailed data requirements may vary, FDA does recommend that the following elements be included in any EUA application.
00:05:34.230 --> 00:05:46.050
One, a description of the product and its approval status that is whether the product is unapproved or approved, but for a different use than the eua two, Available safety and effectiveness data.
00:05:46.370 --> 00:05:46.930
Three.
00:05:47.160 --> 00:05:53.329
A discussion of the risks and benefits including a discussion of the risks of the threat agents that spurred the emergency.
00:05:53.639 --> 00:05:56.689
Four, chemistry, manufacturing and control information.
00:05:57.389 --> 00:06:03.199
Five, The quantity of available product and the production capabilities of the manufacturing site.
00:06:03.420 --> 00:06:06.920
And finally, proposed labeling information and fact sheets.
00:06:07.278 --> 00:06:09.040
According to FDA guidance.
00:06:09.110 --> 00:06:18.600
Sponsors with right of reference may refer to data previously submitted to FDA in a marketing application I n D or master file as part of their eua application.
00:06:18.730 --> 00:06:28.160
However, in our recent experience, FDA has objected to cross-referencing INDs and prefers that the data be submitted directly in the EUA application.
00:06:28.389 --> 00:06:38.759
This is particularly important if the cross reference data is not an E C T D format as evaluating non C T D data will significantly slow down the FDA's review.
00:06:39.230 --> 00:06:49.439
That said, cross references to master files and approved marketing applications do still appear to be fully acceptable to FDA again as long as they are in CTD format.
00:06:50.250 --> 00:06:56.160
So if you are successful in obtaining an EUA for your product, how can that be converted into full approvals?
00:06:56.610 --> 00:07:03.560
So I'll start by saying that in general, UAS remain in effect for the duration of the emergency that precipitated their issuance.
00:07:03.709 --> 00:07:12.560
When the emergency declaration is lifted, the EUAs are no longer in effect and the product can no longer be marketed or commercially distributed within the United States.
00:07:13.089 --> 00:07:24.560
In addition, FDA will continually monitor the state of emergency as it evolves and may revoke EUAs if the risk benefit profile changes or if conditions of the eua are not met.
00:07:25.189 --> 00:07:28.439
EUAs cannot be directly converted into full approvals.
00:07:28.910 --> 00:07:35.319
Sponsors must submit a full marketing application appropriate to the product type just as they would under normal conditions.
00:07:35.870 --> 00:07:42.519
Formally issuance of an EUA does not alter the data requirements necessary to support full product approval.
00:07:42.779 --> 00:07:49.600
But in a practical sense, I do not think it would be fair to say that an EUA had no influence on the full marketing application.
00:07:49.639 --> 00:07:59.639
Those impacts may be positive such as a larger sample size available for the safety database or negative such as a more challenging environment for conducting controlled clinical trials.
00:08:00.089 --> 00:08:09.199
So it is important to plan ahead and discuss the post eua clinical development plan with FDA during pre eua meetings and interactions.
00:08:09.709 --> 00:08:16.279
I will close there for today, but of course there are many more nuances and details that are important to the success of an EUA application.
00:08:17.360 --> 00:08:26.279
Verta has extensive experience in this field and can help you develop a detailed strategic plan tailored to your product that will increase your probability of success.
00:08:26.569 --> 00:08:34.360
If you have specific questions about your program, please reach out through the links available on the ris.website and we will be happy to assist now.
00:08:34.360 --> 00:08:40.159
Keep listening to the art podcast series as we explore more nuances of the US regulatory environment.
00:08:40.409 --> 00:08:42.558
We will be back and talking to you again soon.
00:08:42.559 --> 00:08:43.440
Thank you for listening.
00:08:44.000 --> 00:08:45.360
Don't miss an episode.
00:08:46.039 --> 00:08:49.759
Subscribe to Art Podcasts on your favorite podcast player today.
00:00:01.229 --> 00:00:19.960
Bringing a novel Therapeutic to market is an art Hear VAs stat thought leaders as they draw on their specialized expertise to offer insight on timely, relevant topics that impact clinical development, the regulatory landscape, and patient access to these novel therapies.
00:00:21.160 --> 00:00:29.160
Hello and welcome to the Art podcast, Advancing Revolutionary Therapies, a podcast series presented by the Centers for Excellence at Vata.
00:00:29.609 --> 00:00:32.920
My name is Kevin Hennigan, Director of North American Regulatory Affairs.
00:00:33.280 --> 00:00:39.280
Today I will be presenting an overview of the emergency use authorization program available through the US fda.
00:00:39.590 --> 00:00:57.439
This episode is part of season three of the ART podcast, where we will be discussing various topics pertaining to navigating the US regulatory environment, and I encourage you to continue to listen to subsequent episodes as we have explore a variety of topics and issues associated with interacting with the US fda.
00:00:58.049 --> 00:00:59.399
So what are EUAs?
00:00:59.640 --> 00:01:20.760
Emergency use authorizations or EUAs are a mechanism that allows the US FDA to facilitate the availability of medical countermeasures for chemical, biological, radiological, and nuclear agents or CBRN agents, including emerging infectious disease threats such as COVID 19 and pandemic influenza during times of national emergency.
00:01:21.189 --> 00:01:30.799
Products that receive EUA may be legally marketed and sold in the United States for the duration of the emergency or until authorization is revoked by fda.
00:01:31.209 --> 00:01:32.760
So when can these be issued?
00:01:33.260 --> 00:01:53.920
FDA may only issue EUAs when there has been a determination of an emergency involving C B R N agents by the US Secretary of Homeland Security, the Secretary of Defense, or the Secretary of Health and Human Services, and that circumstances exist justifying the emergency use of drugs, biologics, and or medical devices.
00:01:54.019 --> 00:01:59.519
For FDA to issue an EUA under these circumstances for primary criteria must be met.
00:01:59.939 --> 00:02:04.599
One, the threat agent must be capable of causing a serious or life-threatening illness.
00:02:04.939 --> 00:02:11.199
Two, there must be enough evidence of effectiveness to conclude that the product may be effective for its proposed.
00:02:11.200 --> 00:02:15.680
Use a lower threshold than the effectiveness standard required for full approval.
00:02:15.719 --> 00:02:16.280
Three.
00:02:16.349 --> 00:02:26.520
A risk benefit analysis must conclude that the known and potential benefits of the product outweigh the known and potential risks, including consideration of the risks posed by the threat agent.
00:02:26.900 --> 00:02:32.120
And four, there must be no adequate approved and available alternative to the candidate product.
00:02:32.580 --> 00:02:36.479
The standards for adequate and available are usually interpreted quite broadly.
00:02:36.740 --> 00:02:43.400
For example, a product may be considered unavailable if there aren't enough existing doses to meet the emergency need.
00:02:43.710 --> 00:02:49.919
A product may be inadequate if it has contraindications for particular subgroups that are at risk in the emergency.
00:02:49.990 --> 00:02:52.319
What is the application process for an eua?
00:02:52.759 --> 00:03:04.280
Well, prior to submitting an EUA application, FDA encourages sponsors to engage the agency in pre eua interactions to discuss the potential suitability of the product for EUA consideration.
00:03:04.520 --> 00:03:08.560
While this is not an absolute requirement, these meetings are vitally important.
00:03:08.759 --> 00:03:10.759
Emergency situations evolve rapidly.
00:03:11.090 --> 00:03:26.400
So discussions with the agency to help to keep you on the right track with respect to data requirements, trial designs, and even application format, ensuring a more expeditious FDA review and increasing the probability of success when a full EUA is submitted.
00:03:26.740 --> 00:03:38.240
Pre EUA meetings follow the same request process and timelines as other FDA meetings such as pre I N D or pre NDA meetings and are considered type B meetings with respect to PAD Purdue.
00:03:38.439 --> 00:03:43.360
For classifications, though they are usually treated separately from other submissions on file with fda.
00:03:44.240 --> 00:03:54.050
When a sponsor believes they have collected all of the data necessary to fulfill the EUA requirements, they can proceed with submitting their request for drug and biologic submissions.
00:03:54.050 --> 00:04:02.930
Submitting the application electronically in common technical document format or CTD format may help accelerate the FDA's review of the application.
00:04:03.180 --> 00:04:12.330
However, in an acknowledgement of the emergency conditions, FDA can also accept other formats, even paper submissions for EUA applications.
00:04:12.860 --> 00:04:15.610
So let's talk a moment now about the data requirements.
00:04:15.830 --> 00:04:23.129
The data required to support an EUA must be sufficient to fulfill the four primary criteria I mentioned a few minutes ago.
00:04:23.338 --> 00:04:30.050
In practice this often means a lower data threshold than is typically required for a full NDA or vla.
00:04:30.199 --> 00:04:41.610
This might include regulatory flexibility, for example, with respect to completion of full process validation or a significantly shorter duration of safety follow up at the time of UA application.
00:04:41.870 --> 00:04:53.370
The data threshold can and does vary from one public health emergency to another and even through the life cycle of a given public health emergency based on understandings of real and perceived risks.
00:04:53.790 --> 00:05:04.689
The COVID 19 pandemic is certainly an example of this, where we saw the drug hydroxychloroquine receive an EUA early in the pandemic on the basis of small preliminary clinical studies.
00:05:05.120 --> 00:05:10.889
Subsequent studies did not validate those early efficacy results and FDA revoked the eua.
00:05:11.040 --> 00:05:25.449
I think it is safe to say that at this point in the pandemic and I am recording this podcast in September of 2022, an EUA application would not be accepted by the agency without considerably more data than were provided for hydroxychloroquine.
00:05:25.819 --> 00:05:33.850
So while the detailed data requirements may vary, FDA does recommend that the following elements be included in any EUA application.
00:05:34.230 --> 00:05:46.050
One, a description of the product and its approval status that is whether the product is unapproved or approved, but for a different use than the eua two, Available safety and effectiveness data.
00:05:46.370 --> 00:05:46.930
Three.
00:05:47.160 --> 00:05:53.329
A discussion of the risks and benefits including a discussion of the risks of the threat agents that spurred the emergency.
00:05:53.639 --> 00:05:56.689
Four, chemistry, manufacturing and control information.
00:05:57.389 --> 00:06:03.199
Five, The quantity of available product and the production capabilities of the manufacturing site.
00:06:03.420 --> 00:06:06.920
And finally, proposed labeling information and fact sheets.
00:06:07.278 --> 00:06:09.040
According to FDA guidance.
00:06:09.110 --> 00:06:18.600
Sponsors with right of reference may refer to data previously submitted to FDA in a marketing application I n D or master file as part of their eua application.
00:06:18.730 --> 00:06:28.160
However, in our recent experience, FDA has objected to cross-referencing INDs and prefers that the data be submitted directly in the EUA application.
00:06:28.389 --> 00:06:38.759
This is particularly important if the cross reference data is not an E C T D format as evaluating non C T D data will significantly slow down the FDA's review.
00:06:39.230 --> 00:06:49.439
That said, cross references to master files and approved marketing applications do still appear to be fully acceptable to FDA again as long as they are in CTD format.
00:06:50.250 --> 00:06:56.160
So if you are successful in obtaining an EUA for your product, how can that be converted into full approvals?
00:06:56.610 --> 00:07:03.560
So I'll start by saying that in general, UAS remain in effect for the duration of the emergency that precipitated their issuance.
00:07:03.709 --> 00:07:12.560
When the emergency declaration is lifted, the EUAs are no longer in effect and the product can no longer be marketed or commercially distributed within the United States.
00:07:13.089 --> 00:07:24.560
In addition, FDA will continually monitor the state of emergency as it evolves and may revoke EUAs if the risk benefit profile changes or if conditions of the eua are not met.
00:07:25.189 --> 00:07:28.439
EUAs cannot be directly converted into full approvals.
00:07:28.910 --> 00:07:35.319
Sponsors must submit a full marketing application appropriate to the product type just as they would under normal conditions.
00:07:35.870 --> 00:07:42.519
Formally issuance of an EUA does not alter the data requirements necessary to support full product approval.
00:07:42.779 --> 00:07:49.600
But in a practical sense, I do not think it would be fair to say that an EUA had no influence on the full marketing application.
00:07:49.639 --> 00:07:59.639
Those impacts may be positive such as a larger sample size available for the safety database or negative such as a more challenging environment for conducting controlled clinical trials.
00:08:00.089 --> 00:08:09.199
So it is important to plan ahead and discuss the post eua clinical development plan with FDA during pre eua meetings and interactions.
00:08:09.709 --> 00:08:16.279
I will close there for today, but of course there are many more nuances and details that are important to the success of an EUA application.
00:08:17.360 --> 00:08:26.279
Verta has extensive experience in this field and can help you develop a detailed strategic plan tailored to your product that will increase your probability of success.
00:08:26.569 --> 00:08:34.360
If you have specific questions about your program, please reach out through the links available on the ris.website and we will be happy to assist now.
00:08:34.360 --> 00:08:40.159
Keep listening to the art podcast series as we explore more nuances of the US regulatory environment.
00:08:40.409 --> 00:08:42.558
We will be back and talking to you again soon.
00:08:42.559 --> 00:08:43.440
Thank you for listening.
00:08:44.000 --> 00:08:45.360
Don't miss an episode.
00:08:46.039 --> 00:08:49.759
Subscribe to Art Podcasts on your favorite podcast player today.
