How FDA Entry Point Files Drug SPL and NDC Listing Submissions

From source files to an FDA system record

We turn approved labeling and registration data into a validated Structured Product Labeling XML package, transmit it through FDA Electronic Submissions Gateway NextGen, follow the acknowledgement sequence, and return the filing record. FDA Entry Point handles establishment registration, labeler code, drug listing, and labeling SPL submissions for foreign drug manufacturers. FDA Entry Point SPL services

Our SPL workflow covers establishment registrations and renewals, NDC labeler code requests, and drug product listings. It also carries the applicable labeling content: Prescribing Information, OTC Drug Facts, Medication Guides, and Patient Package Inserts. Each submission uses the FDA document type and XML sections that match the product and filing purpose.

Collect the source record. We receive the current artwork or Prescribing Information text, formulation, NDC and package data, labeler code status, establishment DUNS number, U.S. Agent details, and importer information.
Map the data into SPL/XML. We select the applicable SPL document type and structure the establishment, product, ingredient, package, and labeling fields.
Validate before transmission. We check the XML against FDA validation rules, including identifiers, required sections, controlled terminology, and relationships between the labeler, product, packages, and manufacturing establishments.
Transmit through ESG NextGen. We send the production submission to the applicable FDA center and monitor ACK1, ACK2, and ACK3.
Return and reconcile the record. We provide the submitted XML, gateway identifiers, acknowledgement files, and the applicable establishment or product-record verification.

Drug obligation-to-action record

Regulatory mechanics and windows are based on FDA establishment registration instructions, FDA drug listing instructions, and FDA ESG acknowledgement specifications.
Obligation	FDA system and SPL action	Window or trigger	What the client provides	What we do	Artifact returned
Annual establishment renewal	eDRLS establishment registration or no-change SPL/XML, transmitted through ESG NextGen	October 1 to December 31 each year	Current legal name, physical address, DUNS number, operations, official contact, U.S. Agent, and known U.S. importers	Review the prior record, create the correct annual version, validate it, and transmit it	Submitted XML, ESG Core ID, acknowledgement set, and DECRS record check
Labeler code request or update	NDC labeler code request SPL/XML through eDRLS and ESG NextGen	Before the initial drug listing, or when labeler identity or contact data changes	Labeler legal entity, DUNS number, contact data, business status, and any existing labeler code	Prepare the labeler code SPL, validate identifying data, transmit it, and track the FDA response	Submitted request XML, acknowledgements, and the FDA labeler code response
Initial drug listing and NDC record	Human prescription, human OTC, bulk ingredient, animal drug, or other applicable drug listing SPL/XML	Initial listing after establishment registration and before U.S. commercial distribution	Formulation, dosage form, route, NDC configuration, package sizes, marketing data, establishment DUNS numbers, and current labeling	Build the product and package hierarchy, encode labeling content, attach required artwork, validate, and transmit	Submitted listing XML, SPL identifiers, ACK1 to ACK3, and applicable listing verification
June and December listing update	New version of the existing drug listing SPL, retaining its Set ID	When listing data changes, with required review and updates no later than June or December	Changed formulation, labeling, packages, establishments, marketing status, or NDC data	Create a new document and root ID, increment the version, apply the effective date, validate, and transmit	Updated XML version, gateway acknowledgements, and updated system-record check
Annual no-change certification	Blanket No Changes Certification SPL	October 1 to December 31 for human drug listings not updated during that calendar year	Confirmed inventory of active listings and written confirmation that the listed data remain current	Reconcile active NDCs, prepare the certification SPL, validate it, and transmit it	Certification XML, ESG Core ID, and acknowledgement set
Labeling content update	Updated product-labeling SPL containing Prescribing Information, Drug Facts, Medication Guide, or PPI content	New warning, revised indication, reformulation, new package presentation, or other material labeling change	Final approved text, revised artwork, effective date, affected NDCs, and supporting product data	Update the correct SPL sections and images, preserve the filing lineage, validate, and retransmit	Updated labeling XML, version identifiers, and acknowledgement set

The responsibility split is direct: the manufacturer controls the approved source content and confirms its factual accuracy; we control SPL assembly, technical validation, ESG transmission, acknowledgement follow-up, and the filing handback.

What must be complete before we build the XML

A foreign establishment registration requires the facility-specific DUNS number, not a corporate-headquarters identifier, together with the official contact, business operations, one U.S. Agent, and known U.S. importers. FDA compares importer and establishment information against entry data, so the names and identifiers must match the entities used for U.S. importation. FDA human drug import requirements

A drug listing requires the proposed NDC, proprietary and established names, dosage form, route of administration, active and inactive ingredients, strengths, manufacturing establishments, package configurations, marketing category, and current labeling. Artwork for the outer package and principal display panel is supplied as image files for inclusion in the applicable SPL sections.

Prescription labeling inputs include the current Prescribing Information and any applicable Medication Guide, Patient Package Insert, or Instructions for Use. OTC inputs include the complete Drug Facts content, including active ingredient, purpose, uses, warnings, directions, inactive ingredients, and other information. FDA uses SPL for the electronic content of prescription labeling and FDA-approved patient labeling. FDA SPL labeling codes

What the ESG acknowledgement sequence proves

The audit trail begins with the ESG Core ID, submitted filename, submission timestamp, destination, and status history. These values tie the XML package to a specific gateway transaction rather than relying on a provider-issued registration certificate.

ACK1 confirms upload. ESG NextGen received the submission package.
ACK2 confirms routing. ESG NextGen transmitted the package to the selected FDA center or office.
ACK3 reports the center response. For Office of the Commissioner SPL submissions, an .ack response indicates that validation passed; an XML response contains validation failures that require correction.
ACK4 is not expected for this submission type. FDA’s current production acknowledgement matrix identifies ACK1, ACK2, and ACK3 for Office of the Commissioner SPL submissions.

ACK1 and ACK2 establish receipt and routing, but they do not establish successful SPL validation. We treat the filing as accepted only after the center-level response confirms that the XML passed validation. A failed response remains part of the audit trail, followed by the corrected submission and its new gateway transaction.

Our handback record contains the filed XML, Core ID, status history, and acknowledgement files. We then reconcile the accepted filing against the applicable FDA publication. A successful establishment registration should appear in the Drug Establishments Current Registration Site by the end of the next business day. The NDC Directory is updated daily, although publication depends on the marketing start date and the type of listed product. FDA National Drug Code Directory

How we control SPL versions when information changes

The Set ID preserves the lineage of an existing establishment or product record. For an update, we retain that Set ID, generate a new document ID and root ID, increment the version number, enter the effective date, and change only the applicable registration, listing, or labeling data.

The change determines which SPL lineage moves. A new warning, revised indication, Drug Facts revision, reformulation, or package-label change updates the product listing or labeling SPL. A labeler identity change updates the labeler code record. A facility name, address, DUNS, operation, official-contact, U.S. Agent, or importer change updates the establishment registration SPL.

A reformulation also requires an NDC assessment before we update the XML. Changes to the active ingredient, strength or concentration, dosage form, route of administration, or product name can require a new product-level NDC rather than another version of the existing product record. The SPL is built after that product-identity decision is resolved.

Published SPL price and response commitment

As of 2026, our published SPL price starts at $249 per submission. SPL work is priced separately from U.S. Agent coverage, drug establishment registration, NDC product listing, and drug label review unless a written quote expressly bundles those services. FDA Entry Point pricing

We respond to drug registration, listing, labeling, submission, renewal, and FDA communication inquiries within 24 business hours. This is our response commitment, not a guaranteed FDA processing or acknowledgement time. FDA controls gateway routing, center validation, labeler code assignment, and publication timing. FDA Entry Point drug and pharma service commitments

Illustrative scenario: two OTC package NDCs and one warning change

On October 20, 2026, a foreign OTC manufacturer supplies final Drug Facts artwork for one product sold in two package sizes. Both packages use the same formulation and labeling content. The intake also includes the labeler code, product and package NDC segments, establishment DUNS number, dosage form, route, active and inactive ingredients, marketing data, and principal display panel images.

We open the latest accepted Human OTC Drug Label SPL, retain its Set ID, generate new document identifiers, increment the version, replace the warning text, attach the two current package images, and validate the complete XML. FDA permits multiple product or package NDCs in one listing SPL when they share the same content of labeling.

We transmit one updated SPL through ESG NextGen. At the current published starting price, the submission is $249. We return the submitted XML, ESG Core ID, ACK1, ACK2, and ACK3, then check the NDC Directory after FDA processes the accepted version and the applicable marketing start date permits publication.

Frequently asked questions

Does FDA Entry Point have experience with drug SPL submissions and annual renewals?

Yes. We prepare and submit establishment registration SPLs, labeler code requests, NDC drug listings, Prescribing Information, OTC Drug Facts, Medication Guides, PPIs, annual registration renewals, and listing updates. The service includes XML preparation, validation, ESG transmission, version management, and acknowledgement tracking rather than only forwarding FDA correspondence.

Do ACK1 and ACK2 mean that FDA accepted my SPL?

No. ACK1 confirms that ESG NextGen received the upload, and ACK2 confirms that it was transmitted to the selected FDA center or office. The center-level ACK3 establishes whether the Office of the Commissioner SPL passed validation. We do not close the technical filing record based only on an upload receipt.

Can one drug listing SPL contain more than one NDC?

Yes. One drug listing SPL can include multiple product or package NDCs when they use the same content of labeling. Different formulations or materially different labeling can require separate SPL records. We review the product hierarchy before building the XML so package variations are grouped only where FDA’s listing structure permits it. FDA drug listing requirements

What happens if FDA rejects the SPL XML?

We read the ACK3 validation response, identify the affected identifier, data field, code, relationship, image, or XML structure, correct the source package, and submit a new gateway transaction. Both the failed transaction and corrected submission remain in the audit trail, which makes the sequence reviewable by regulatory affairs, quality assurance, or procurement teams.

Should a manufacturer wait until June or December to submit a new warning?

No. A material labeling change should be reflected in the SPL record promptly. June and December are required listing-review and update points, not waiting periods for known changes. We create a new version of the applicable product-labeling SPL when the final warning or other revised content is ready for submission.

Does an NDC Directory entry mean that FDA approved the drug?

No. An NDC Directory entry shows that listing information was submitted to FDA and met the conditions for publication. Registration, listing, and NDC assignment do not establish FDA approval or confirm that FDA verified the submitted information. Approval status must be evaluated separately through the applicable NDA, ANDA, OTC monograph, or other regulatory pathway.