Understanding What Is Category C in Medications and Pregnancy Risk

October 12, 2025 •

4 min read

The U.S. FDA officially phased out its A, B, C, D, and X pregnancy letter categories in 2015, replacing them with a more detailed narrative format. Yet, understanding what is category C remains relevant, as it provides important context for why the system was modernized and how drug risk during pregnancy is communicated today.

Quick Summary

This article explains the former FDA Pregnancy Category C, its limitations, and why it was replaced by the more comprehensive Pregnancy and Lactation Labeling Rule (PLLR) in 2015 for assessing medication risk during pregnancy.

Key Points

Category C Defined: It was a former FDA pregnancy risk classification for medications where animal studies showed a risk to the fetus, but there were no adequate, well-controlled human studies.
System Replaced: The entire letter-based system (A, B, C, D, X) was officially replaced by the Pregnancy and Lactation Labeling Rule (PLLR) in 2015.
Why the Change: The letter categories were flawed, often misinterpreted as a simple grading system, which could lead to biases and a lack of necessary context for risk assessment.
New Labeling Format: The PLLR requires a detailed narrative summary in three sections: Pregnancy, Lactation, and Females and Males of Reproductive Potential.
Modern Risk Assessment: Healthcare providers now perform a nuanced risk-benefit analysis based on the comprehensive narrative data, moving beyond the limitations of a single letter.
Communication is Key: The change emphasizes the need for informed conversations between patients and providers to assess medication risks during pregnancy.

The Former FDA Pregnancy Categories: A Historical Overview

From 1979 until 2015, the U.S. Food and Drug Administration (FDA) used a system of letter-based categories (A, B, C, D, and X) to classify the potential risk of medications to a developing fetus. These classifications were meant to provide a quick, simplified guide for healthcare professionals and patients, outlining the available information on a drug's safety during pregnancy. However, the letter system had significant drawbacks, which ultimately led to its discontinuation.

What Category C Specifically Meant

Within the old framework, Category C was defined by the following characteristics:

Animal studies showed adverse effects on the fetus: In tests on pregnant animals, the drug caused negative effects on the unborn offspring. These could include birth defects, smaller size, or other issues.
No adequate, well-controlled human studies: For ethical reasons, many drugs were never tested in clinical trials with pregnant women. Without this data, a clear risk profile in humans could not be established.
Potential benefits might warrant use: Despite the animal data and lack of human studies, a healthcare provider might still decide to prescribe a Category C drug. This decision would be based on a careful risk-benefit analysis, especially if the mother's condition required treatment and a safer alternative was not available.

The Shortcomings of the Letter-Based System

While intended to be helpful, the simplistic nature of the pregnancy letter categories often led to confusion and misinformation. The FDA eventually determined the system was "overly simplistic and was misinterpreted as a grading system," which did not effectively communicate the full risk profile of a medication.

Some of the key critiques included:

Misinterpreted as a simple grade: Many people mistakenly saw Category A as completely safe and Category X as completely dangerous, without understanding the nuances of the data. Category C was often misunderstood as being moderately risky, when in reality, the risk was largely unquantified in humans.
Exaggerated perception of risk: Many drugs fell into Category C simply because human data was unavailable, not because a risk was proven. This led to a disproportionately cautious approach, with potentially effective treatments being avoided out of fear.
Creation of bias: The system unintentionally created an "innocent until proven guilty" bias. A drug with no human or animal data might be a Category C, while an untested drug with negative animal data was also a Category C. This didn't accurately reflect the varying levels of available evidence.
Lack of detailed context: The single-letter summary offered no information on the timing of risk during pregnancy, the dosage, or the severity of the mother's underlying condition. It provided a one-dimensional view of a complex issue.

The Modern Approach: The Pregnancy and Lactation Labeling Rule (PLLR)

To address the failings of the old system, the FDA published the Pregnancy and Lactation Labeling Rule (PLLR) in 2014, with the change taking effect in 2015. The PLLR replaced the letter categories with detailed narrative summaries, organized into three new subsections in prescription drug labeling.

The Three New Subsections

Pregnancy (8.1): This section provides a comprehensive Risk Summary, including data from human and animal studies, information about any pregnancy exposure registries collecting data on the drug, and specific clinical considerations for healthcare providers and patients. It consolidates the old 'Pregnancy' and 'Labor and Delivery' information.
Lactation (8.2): This section, formerly 'Nursing Mothers', now includes information about the presence of the drug in human milk, the potential effects on the breastfed infant, and options for minimizing exposure.
Females and Males of Reproductive Potential (8.3): A completely new section, this provides information on pregnancy testing, contraception recommendations, and drug-related infertility.

Comparing the Old and New Drug Labeling


Feature	Old System (Pre-PLLR)	New System (PLLR)
Classification	Single letter categories (A, B, C, D, X)	Narrative summaries and data in three subsections
Information	Overly simplistic; often misinterpreted as a grade	Detailed, comprehensive risk summary, clinical considerations, and data
Flexibility	Rigid system that didn't account for nuance in risk assessment	Allows for a more personalized, case-by-case risk-benefit analysis
Data Sources	Heavily reliant on animal data for many categories (especially C)	Integrates human data, animal data, and clinical experience into narrative format
Patient Counseling	Limited information available; often led to anxiety or avoidance of necessary medication	Provides healthcare providers with richer information to counsel patients effectively

Practical Implications for Patients and Healthcare Providers

For healthcare providers, the PLLR necessitates a more thorough and evidence-based approach to prescribing for pregnant or breastfeeding patients. Instead of relying on a single letter, they must now review the detailed narrative, considering the specific clinical context of each patient. This shift empowers clinicians to have more informed discussions with their patients, allowing for a better-tailored risk-benefit assessment.

For patients, this means more transparent and detailed information is available. However, it also emphasizes the importance of open communication with their healthcare team. A simple letter-grade is no longer available as a shortcut, and a conversation with a trusted provider is the best way to understand the risks and benefits of any necessary medication. For up-to-date and specific drug information, reliable sources like the NIH's DailyMed database are invaluable tools.

Conclusion

While the concept of what is category C is a key part of medical history, it's crucial to understand that it is an obsolete classification system for medication risk during pregnancy. The move away from the simplistic letter categories toward the comprehensive narrative required by the PLLR represents a significant step forward in patient care. This modern approach provides healthcare professionals with more robust information to conduct detailed risk-benefit analyses, ensuring that decisions about medication use during pregnancy are as informed and individualized as possible. As the shift continues, referring to the detailed data in the new labeling is the gold standard for evaluating drug safety.

Frequently Asked Questions

No, the FDA pregnancy letter categories (including Category C) were officially discontinued in 2015. Medications approved since then use the new narrative-based Pregnancy and Lactation Labeling Rule (PLLR).

If a medication still displays the old letter categories, it was likely approved before 2015 and has not yet updated its labeling. While the label is outdated, the information reflects the past understanding that animal studies showed a risk, but human data was lacking.

A pregnancy exposure registry is an observational study that collects health information from women who use prescription drugs or vaccines while pregnant. This data helps improve understanding of a drug's effects and is now included in the updated labeling.

Healthcare providers now rely on the comprehensive narrative risk summaries found in drug labels under the PLLR. These narratives provide detailed information from human and animal data, allowing for a more nuanced and individualized risk-benefit analysis.

No, the PLLR only applies to prescription drugs and biological products. The labeling for over-the-counter medications remains unaffected by this rule.

The old system was criticized for being overly simplistic and misinterpreted as a letter grade. It didn't effectively communicate the nuances of risk, creating biases where untested drugs were perceived as equally or more dangerous than those with some known risk.

Yes, if the potential benefits to the mother outweigh the potential risks to the fetus. The modern approach focuses on a careful risk-benefit analysis based on all available data, not just an arbitrary letter grade.