Q.01

What is structured product labeling at the FDA?

At the FDA, Structured Product Labeling (SPL) is "a document markup standard approved by Health Level Seven (HL7) and adopted by FDA as a mechanism for exchanging product and facility information." In practice, it's the electronic format companies use to send FDA their labeling and their product and facility data, so the agency can process, review and archive it.

Approach: I read FDA's Structured Product Labeling Resources page and the 21 CFR Part 314 drug application regulations. The page gives only that one-line definition; it doesn't set out the document structure or which CFR rules require SPL.

What FDA uses SPL for (FDA SPL Resources):

  • Drug establishment registration, drug listing, and the content of labeling for human drugs.
  • Product reporting by human drug compounding outsourcing facilities under section 503B of the FD&C Act.
  • Registration and listing of animal drug products.
  • Registration and listing of cosmetic facilities and products.
  • Registration and product listing for blood and tissue establishments.
  • Risk Evaluation and Mitigation Strategies (REMS) documents.
  • Electronic lot distribution reports.

Where the regulations require electronic labeling. Part 314 doesn't name SPL in the sections I checked. It does require the content of labeling, meaning the package insert or professional labeling "including all text, tables, and figures," to be submitted in electronic format. The format must be one FDA "can process, review, and archive." This applies to:

  • NDAs, under § 314.50(l) [1]
  • ANDAs, under § 314.94(d)(1) [2]
  • Labeling submitted with postmarketing reports, under § 314.81 [3]

Where the public sees it. FDA's page notes that "FDALabel and DailyMed have the same database but have different search functions and different displays of search results." DailyMed, run by the National Library of Medicine, is the public repository of current SPL labels.

I can look up the current SPL for a specific product in DailyMed next if that would help.

Q.02

What goes into an SPL submission?

An SPL submission is one XML file. It holds the full labeling text, split into coded sections, together with machine-readable product data. For a drug listing, FDA says the SPL must include:

  • the full proposed NDC;
  • the proprietary and non-proprietary names;
  • the dosage form and route of administration;
  • each active ingredient, with its UNII code and strength;
  • each inactive ingredient, with its UNII code;
  • a copy of the current labeling, including a .jpg of the package and label;
  • the name and DUNS number of every establishment involved in manufacturing.

Approach: I read live SPLs held in NLM's DailyMed, 21 CFR Part 314, and FDA's "How to List a Drug" and SPL resource pages. FDA's SPL Implementation Guide and technical-error training would set out the element-by-element rules, but FDA's site returned "not found" for both PDFs, so that detail isn't covered here.

1. Listing content FDA requires (FDA, How to List a Drug)

  • The submitter must "select the appropriate SPL document type for the product." They must also "create a section within the SPL file for each section of content for labeling."
  • One listing SPL "may include multiple national drug codes (NDCs)" when those products share the same labeling content.

2. What a filed SPL looks like. Here are two current DailyMed records.

Prescription example: Amneal's metformin HCl tablets [4]

  • Document data: a set ID (45cc673a-…), version 9, effective date 2012-09-06, labeler Amneal Pharmaceuticals, and document type "HUMAN PRESCRIPTION DRUG LABEL".
  • Product data: 12 NDC product and package codes, plus UNII codes for the ingredients.
  • Labeling text: each section carries a LOINC code, for example 34089-3 Description, 34090-1 Clinical Pharmacology, 34067-9 Indications, 34068-7 Dosage and Administration, and 51945-4 Package label.
  • Product data element block (LOINC 48780-1): names, ingredients, colour ("white to off-white") and imprint codes ("IP175;500").

OTC example: an ibuprofen 200 mg label [5]

  • Document type "HUMAN OTC DRUG LABEL".
  • The Drug Facts panels are each a separately coded section: Active ingredient (55106-9), Purposes (55105-1), Uses (34067-9), Warnings (34071-1), Do not use (50570-1), Directions (34068-7), Inactive ingredients (51727-6) and Questions (53413-1).
  • Each retail pack (Lil' Drug Store, Casey's, Circle K) has its own principal display panel section.

3. The labeling content rule for applications. For an NDA, § 314.50(l)(1)(i) requires "the content of labeling … (commonly referred to as the package insert or professional labeling), including all text, tables, and figures" in electronic format. This comes on top of copies of the formatted label and all labeling under (e)(2)(ii). The submission must follow Part 11, with the exemptions listed there. Under (l)(5), it must be in a form FDA "can process, review, and archive," with transmission and file details left to FDA guidance [1].

4. FDA's supporting files. FDA's SPL Resources page publishes:

  • the SPL schema and stylesheet;
  • the Implementation Guide with Validation Procedures;
  • the LOINC section headings;
  • terminology validation files (dosage forms, marketing categories, DEA schedules, REMS components);
  • UNII files.

From submitted SPLs, FDA also produces the daily NSDE file (FDA NSDE). Its fields are:

  • item code (NDC, NHRIC or ISBT);
  • NDC11;
  • proprietary name;
  • dosage form;
  • marketing category;
  • application number or citation;
  • product type;
  • marketing start and end dates;
  • billing unit;
  • inactivation and reactivation dates.

I can pull the current SPL for a specific product from DailyMed and show its full section and data-element breakdown, if that would help.

Q.03

How do SPL files end up on DailyMed?

Labeling companies write SPL files and send them to the FDA. The FDA passes them to the National Library of Medicine (NLM), and NLM posts them on DailyMed without reviewing the content itself. So a DailyMed label is the most recent version a company has submitted to the FDA, which isn't necessarily the most recent version the FDA has approved.

Approach: I checked the DailyMed labels I hold for a filing trail, then read NLM's DailyMed pages and NLM's tutorial on health data standards. FDA's step-by-step gateway instructions PDF and its Electronic Submissions Gateway page both returned "not found," so I can't give the transmission mechanics in FDA's own words.

The route, step by step

  1. The company builds and sends the SPL. NLM's tutorial puts the chain as "Manufacturer SPL goes to Approval by FDA goes to NLM DailyMed" (NLM tutorial). FDA's "How to List a Drug" page has a "Submit SPL" step. It points to "FDA Direct" and the "Electronic Submissions Gateway Next Generation (ESG NextGen)" as the ways to send it (FDA, How to List a Drug).
  2. FDA passes it to NLM. Once NLM's DailyMed team receives the SPL information from the FDA, it shows it in a searchable format. You can look labels up by NDC, set ID or drug class (NLM tutorial).
  3. NLM publishes it as filed. In NLM's words, "NLM does not review any SPL content prior to publication." DailyMed holds "the most recent submitted labeling to the FDA by companies and currently in use" (About DailyMed).

"Approved" versus "in use." NLM's two pages don't quite match:

  • The tutorial's diagram has an FDA approval step in the middle.
  • DailyMed's own page says the "in use" labeling "may not have been verified by FDA." It also says this labeling can differ from the latest FDA-approved version, and points to Drugs@FDA for that.

The likely reason, which neither page states, is that many SPL types never go through pre-approval review: OTC monograph labels, unapproved drugs and listing updates are examples. Either way, Drugs@FDA is the reference for approved prescription labeling, and DailyMed shows what is actually on the market.

How quickly it shows up. The Amneal metformin label from the last answer shows the lag:

  • Version 9 has an effective date of 2012-09-06 in its XML.
  • It was uploaded to DailyMed on 2012-09-07 [4].

Each new version keeps the same set ID and gets a higher version number. The DailyMed page then shows only the current version.

How it's passed on. DailyMed calls itself "the official provider of FDA drug label information (package inserts)." It offers "daily, weekly or monthly periodic updates or full releases of all drug labels" as zip downloads. In early October 2026 the daily files held about 173 to 291 labels a day. The weekly file for 28 September to 2 October 2026 held 889 labels, and the September 2026 monthly file held 3,734 (DailyMed, SPL resources). Pharmacy databases, EHR vendors and FDALabel pick up labels from these files and DailyMed's web services.

If it would help, I can take one product and match its current DailyMed version against its NDC Directory listing to see whether the two are in step.

Q.04

What software do people use to make SPL?

People make SPL with three kinds of software: FDA's own free tools (FDA Direct, which includes Cosmetics Direct), the free SPL Xforms tool built with Pragmatic Data, LLC, and commercial SPL editors or conversion services. FDA asks for a valid SPL file and does not name a required tool on the drug listing page I read.

Approach: The labeling datasets I can search hold the published SPLs but nothing on authoring software, so I used FDA's own web pages instead. FDA's step-by-step SPL instruction PDFs (the Xforms basic instructions and the drug establishment registration guide) returned "not found," so I couldn't quote them.

1. FDA Direct (FDA's web portal)

  • FDA's "How to List a Drug" page sends human drug listers to "instructions to list a human drug using FDA Direct." It lists FDA Direct, Xforms and ESG NextGen as related resources (FDA, How to List a Drug).
  • For cosmetics, FDA calls Cosmetics Direct "an FDA Structured Product Labeling (SPL) authoring tool and electronic submission portal at https://direct.fda.gov/" (FDA cosmetics announcement, 8 January 2024).
  • FDA's SPL Resources page also lists "CDER Direct" as a resource (FDA SPL Resources).
  • The main advantage is that the file is built and submitted in one place. You don't need a separate gateway account.

2. SPL Xforms (free desktop forms)

  • FDA says: "FDA is collaborating with Pragmatic Data, LLC on software to create SPL files based on XForms technology." The forms are free to download from Pragmatic Data's website (FDA Xforms page). That page was last updated on 27 March 2018.
  • The SPL Resources page also lists a separate "CVM SPL Xforms" for animal drugs.
  • FDA also names SPL Xforms as an authoring tool for MoCRA cosmetic facility registration and product listing. Questions go to SPL@fda.hhs.gov (FDA cosmetics announcement).
  • With Xforms you still have to send the finished file through the Electronic Submissions Gateway (ESG NextGen).

3. Commercial software and outsourcing

  • FDA's SPL Resources page links to an external list called "SPL Software and Conversion Vendors" (FDA SPL Resources). I didn't open that list, so I can't name the vendors on it.
  • Companies with many labels, or with Rx labeling that changes often, typically buy SPL editing software or pay a vendor to convert Word labeling into SPL. They then submit through ESG NextGen.

How to choose in practice

  • FDA Direct: suits low volumes of drug listings, registrations or cosmetics. It is free and both builds and submits the file.
  • Xforms: free and runs offline, but it is an older tool and you need ESG access to submit.
  • Vendor tools or services: suit high volumes or complex content of labeling, such as PLR-format package inserts with tables and figures.

Whichever route you use, the file has to pass FDA's SPL validation against the Implementation Guide described in the previous answer.

I can try to retrieve FDA's linked vendor list or the FDA Direct drug listing guide next if that would help.

Q.05