Are monoclonal antibodies hazardous drugs? An Evidence-Based Answer

October 9, 2025 •

2 min read

By 2013, the global sales of monoclonal antibodies (mAbs) already constituted about half of all biopharmaceutical sales, a figure that has only grown. This prevalence raises a critical question for healthcare workers: Are monoclonal antibodies hazardous drugs that require special handling?

Quick Summary

Most standard monoclonal antibodies (mAbs) are not classified as hazardous drugs. However, antibody-drug conjugates (ADCs), which are mAbs linked to a cytotoxic agent, are considered hazardous and require strict handling precautions.

Key Points

Not a Monolithic Class: The hazardous status of a monoclonal antibody (mAb) depends on whether it is a standard ('naked') mAb or an antibody-drug conjugate (ADC).
Most mAbs Are Not Hazardous: Standard mAbs generally do not meet the NIOSH criteria for hazardous drugs because their large molecular weight limits skin absorption.
ADCs Are Hazardous: Antibody-drug conjugates (ADCs) are linked to a cytotoxic payload, making them hazardous drugs that require full USP <800> handling precautions.
Risk Assessment is Key: Healthcare facilities should perform a risk assessment for each individual mAb to determine appropriate safe handling procedures.
Handling Varies Widely: Handling for non-hazardous mAbs involves standard precautions, while ADCs require engineering controls like CSTDs and extensive PPE.
NIOSH List is the Standard: The NIOSH List of Antineoplastic and Other Hazardous Drugs is the primary reference for identifying which drugs require special handling.
Hidden Risks Exist: Even with non-hazardous mAbs, there are potential long-term risks from occupational exposure, such as immunogenicity and allergic reactions.

Understanding Hazardous Drug Classification

The National Institute for Occupational Safety and Health (NIOSH) defines hazardous drugs based on characteristics such as carcinogenicity, reproductive toxicity, or genotoxicity. This definition underpins the NIOSH List of Antineoplastic and Other Hazardous Drugs and guides safe handling practices like those in USP General Chapter <800>.

The Status of Monoclonal Antibodies on the NIOSH List

Standard, unconjugated monoclonal antibodies are generally not classified as hazardous by NIOSH. Their large molecular size typically prevents absorption through intact skin. While concerns exist about long-term, low-dose exposure, these mAbs are not usually categorized as hazardous like traditional chemotherapy. There is ongoing discussion, with some organizations noting that some mAbs are listed as hazardous due to their use in cancer treatment rather than direct cytotoxicity.

The Major Exception: Antibody-Drug Conjugates (ADCs)

A key exception is antibody-drug conjugates (ADCs). ADCs link a mAb to a potent cytotoxic agent or radioisotope, targeting the toxic substance to specific cells. Because of the attached hazardous payload, ADCs are classified as hazardous drugs and require strict handling. Examples of ADCs listed as hazardous by NIOSH include Brentuximab vedotin and Trastuzumab emtansine.

Comparison: Unconjugated mAbs vs. Antibody-Drug Conjugates (ADCs)


Feature	Unconjugated ("Naked") mAbs	Antibody-Drug Conjugates (ADCs)
NIOSH Hazardous Status	Generally No (unless listed for other toxicities)	Yes
Primary Risk	Immunogenicity, allergic reactions, infusion reactions	Cytotoxicity, genotoxicity, reproductive toxicity from payload
Handling Requirements	Standard precautions; risk assessment advised. ONS recommends two pairs of chemo-tested gloves.	Full hazardous drug precautions (USP <800>), including closed-system transfer devices (CSTDs) and full PPE.
Disposal	Clinical / Biohazardous waste	Cytotoxic / Hazardous waste

Safe Handling Recommendations

Handling procedures vary based on the type of mAb.

Handling Unconjugated mAbs

A precautionary approach is often recommended for unconjugated mAbs due to potential long-term exposure risks. Guidelines suggest using PPE like two pairs of chemotherapy-tested gloves and gowns, eye protection if splashing is possible, and preparing in a segregated area. A risk assessment for each drug is advised.

Handling Antibody-Drug Conjugates (ADCs)

Handling ADCs requires strict adherence to USP <800> standards. This includes using a biological safety cabinet, Closed-System Transfer Devices (CSTDs), and comprehensive PPE, including two pairs of gloves and low-permeability gowns. All waste must be disposed of as hazardous cytotoxic waste.

Conclusion

Determining if a monoclonal antibody is hazardous requires evaluating its specific structure. While unconjugated mAbs are generally not hazardous, requiring standard precautions, antibody-drug conjugates (ADCs) are hazardous due to their toxic component and necessitate stringent handling protocols. Healthcare facilities must assess each mAb to ensure proper protection for staff and patients.

For more detailed guidance, consult the official NIOSH list: https://www.cdc.gov/niosh/docs/2016-161/default.html

Frequently Asked Questions

No. While many are used in oncology, only those that are conjugated to a cytotoxic drug (ADCs) or otherwise meet NIOSH criteria are considered hazardous. Many 'naked' mAbs used in cancer care are not on the hazardous drug list.

An antibody-drug conjugate (ADC) is a type of medication that combines a monoclonal antibody with a potent cytotoxic (cell-killing) agent. The antibody targets specific cells, like cancer cells, delivering the toxic payload directly to them.

Most monoclonal antibodies are very large molecules, typically with a molecular weight that prevents them from being absorbed through intact skin, a common standard for which is the '500 Dalton Rule'.

Even for non-hazardous mAbs, many guidelines, including those from ONS, recommend wearing two pairs of chemotherapy-tested gloves, a disposable gown, and eye protection if there is a risk of splashing, as a precautionary measure.

A CSTD is an engineering control that mechanically prohibits the transfer of environmental contaminants into a drug vial and prevents the escape of drug aerosols or vapors. NIOSH recommends using CSTDs when handling mAbs that are classified as hazardous, such as ADCs.

Waste from non-hazardous mAbs can typically be disposed of as clinical or biohazardous waste. However, all waste from antibody-drug conjugates (ADCs), including empty vials, tubing, and contaminated PPE, must be segregated and disposed of as cytotoxic hazardous waste.

Yes, there is a potential risk of developing immunogenic or allergic reactions from long-term, low-grade occupational exposure to monoclonal antibodies, even if they are not classified as hazardous.