Structured Product Labeling (SPL) is the format FDA uses to receive and publish drug labeling and listing information. Every prescribing information document, patient labeling document, and carton or container label submitted in SPL ends up in FDA's systems and on DailyMed, where pharmacies, healthcare systems, and drug databases pick it up.
That reach is the point of SPL. It's also the risk. A text error in an SPL file doesn't stay on one printed label. It travels to every system that consumes the file, and it's much harder to contain once it's there.
What's Changing
SPL itself isn't new, but two FDA rules are putting new pressure on the content that goes into it.
The 12-digit NDC rule. In March 2026, FDA published a final rule moving every National Drug Code to a single 12-digit format: a 6-digit labeler code, a 4-digit product code, and a 2-digit package code. The rule takes effect March 7, 2033, followed by a three-year transition period running to March 2036 for updating labels and using up old labeling stock.
FDA will update NDCs in drug listing SPL files automatically. The labeling itself is a different story. The NDC appears on the carton, the container, and in the prescribing information, and every one of those documents will need to move to the new format consistently. FDA has advised companies to begin updating their labeling as soon as possible. The rule also changes barcode requirements, permitting other data carriers such as 2D barcodes. (For more on the wider barcode shift, see our GS1 Sunrise 2027 guide.)
Seven years sounds like plenty of time. For a large portfolio, it means a long series of label updates, each one a chance for an NDC to be converted on one document and not another.
The proposed Patient Medication Information rule. In May 2023, FDA proposed a new, standardized one-page patient document called Patient Medication Information (PMI), which would replace Medication Guides for outpatient prescription drugs and be submitted to FDA for approval. The comment period closed in November 2023, and FDA is still reviewing comments ahead of a final rule. It isn't law yet, but if finalized, it adds another approved labeling document that has to stay consistent with the prescribing information it summarizes.
Internationally, the direction is the same: more labeling content managed as structured data rather than static documents. In the EU, that shift is happening through ePI, covered in our ePI and dual-channel PIL guide.
The Text Risk That Doesn't Get Enough Attention
Where SPL compliance most often breaks down in practice isn't the XML structure. It's the text. SPL labeling content has to match the FDA-approved labeling exactly. A missing word, an altered dosage figure, or a character encoding change is a discrepancy between what was approved and what was submitted.
The risk is higher than it looks because SPL content is usually produced by converting or re-authoring text from another format. PDF-to-XML conversion in particular can introduce encoding errors, hidden characters, and text that looks correct on screen but contains different underlying characters. Structural validation tools check that the SPL file is well-formed. They don't check that the words match the approved label.
What Regulatory Teams Should Be Checking
Compare SPL text against the approved labeling at the character level. Not just a structural check, and not a visual read of a long XML-derived document. The approved labeling is the master. The SPL must match it exactly.
Treat every labeling update as a new comparison. Each change, whether it's a safety update, a new indication, or a 12-digit NDC conversion, creates a fresh obligation to confirm the SPL still matches.
Check consistency across every document that carries the same data. An NDC, a dosage strength, or a storage condition appears on the carton, container, prescribing information, and patient labeling. When one changes, all of them need checking against each other, not just the one that was edited. This is the same version control discipline we cover in our Document Version Control in GxP Labeling guide.
Manual review can't do this reliably at portfolio scale. Automated comparison between the approved labeling and the SPL text is the only defensible way to confirm they match, every time.
Content Compare verifies SPL text against approved labeling at the character level, and compares NDCs, dosage details, and other shared data across every carton, container, and labeling document. See how it works on your own labeling.
