Making regulatory submissions to U.S. Food and Drug Administration (FDA), is a highly standardized process.
In 2006, FDA established their own dedicated recipient entity, the Electronic Submissions Gateway (ESG), to serve submitters of different scales.
Quoting FDA, the ESG “is a highly scalable, easily available, high performance and secure exchange point for FDA and its partners
to transact a variety of documents and submissions over industry-standard protocols”.
FDA ESG in operation
At a high level, FDA ESG operates like a post office:
- accepts submissions from all clients, targeted at different FDA centers
- issues the initial acknowledgement (MDN)
- verifies the structure of the submission archive and issues a second ack (ACK2), usually in text or XML form
- routes each submission to the relevant FDA center
- when the center has processed the submission, relays the generated acks (ACK3, ACK4, …) back to the client, usually in PDF form
Correlation of ACKs
ESG uses a special correlation ID (CoreID) on its sequence of acknowledgements, to associate them with the original submissions.
ACK2 contains the mapping details: namely the original message reference (e.g. AS2 Message-ID header value from the client submission),
against the ESG-assigned CoreID.
Subsequent ACKs will only contain the CoreID (as the name of the transmitted file),
and the client is responsible of mapping them back to the original submission trail, based on the mapping delivered in the original ACK2.
Modes of submission
FDA ESG allows two modes of submission:
- WebTrader: a web portal for manual, low-volume submissions
- AS2: a HTTP(S) endpoint implementing AS2 protocol for automated,
Both modes involve secure communications with encryption and digital signatures; however, AS2 is preferred by most organizations because it:
- can be integrated easily into the organization’s overall information pipeline
- allows room for future growth in volume, without relying on manual actions/efforts
- can be extended to support routing to multiple FDA centers,
using a simple configuration of HTTP headers
- binds each submission (and acknowledgement) with a digital receipt
ensuring end-to-end integrity and non-repudiation of receipt (NRR)
- has built-in support for VLF (very large file) submissions, such as AS2 Restart,
useful when making large-sized submissions over potentially unreliable connections
To decide on what solution to choose, following questionnaire may be helpful:
- How many average submissions do you wish to perform, say, per month; now, vs. one/two years into the future?
- How many FDA centers do you wish to communicate with?
- What would be the average and maximum size of a submission archive?
(In some cases such as adverse events reporting, involving multimedia content like video files, your submission may well exceed several gigabytes;
some AS2 gateway applications provide AS2 Restart capabilities to efficiently handle such transfers.)
- Do you have a mechanism to track and correlate the acknowledgements
returned for each submission?
(For example, some AS2 gateway softwares are capable of automatically keeping track of each ACK received for a particular submission,
like a transaction trail.)
FDA has detailed documentation on setting up each submission mechanism:
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