What You Don’t Know Can Hurt You: Where PFAS Hide in Pharmaceutical Manufacturing

Pharmaceutical manufacturers may know where they intentionally use Per- and polyfluoroalkyl substances (PFAS). The harder question is whether they know where all PFAS entering and leaving the facility actually come from.

Beyond fluorinated active pharmaceutical ingredients (APIs), from the visible PFAS in the marketed drug product, contributing PFAS may also originate upstream from the drug manufacturing process, and/or as invisible PFAS used in the manufacturing process but not present in the marketed drug product (Scotney et al, 2026). They may leave through finished marketed drug products, wastewater, solid waste and other release pathways.

That makes PFAS exposure a mass-balance problem, not just an inventory exercise. Understanding the full picture starts with mapping where PFAS enter, move through and exit the operation.

PFAS in Pharmaceutical Manufacturing

PFAS are a broad class of fluorinated chemicals valued for properties such as chemical resistance, thermal stability, durability and low surface energy. In pharmaceutical manufacturing, those characteristics can be difficult to replace, which is why PFAS are intentionally used in both drug chemistry and the materials that support manufacturing and product delivery.

PFAS, including visible, contributing and invisible PFAS, used in pharma generally fall into two broad categories:

• Polymer PFAS, or fluoropolymers, include materials such as PTFE, PFA, FEP, PVDF and fluoroelastomers. Their durability, chemical resistance and compatibility with cleaning and sterilization make them useful in tubing, piping, gaskets, seals, filters, membranes, valves and single-use systems. Similar materials may also appear in blister packaging, coated stoppers, syringe components, sterile barrier systems and drug delivery devices.
• Non-polymer PFAS are smaller fluorinated molecules and can include certain APIs, starting materials, intermediates and process chemicals. Fluorination may be deliberately incorporated into a drug molecule to influence properties such as metabolic stability, potency, binding, permeability and bioavailability.

Taken together, intentional PFAS uses can span the pharmaceutical lifecycle, from drug development and production equipment to packaging and delivery.

Polymer and non-polymer PFAS can behave very differently in the body and environment. Fluoropolymers are large, highly stable molecules with low bioavailability, while non-polymer PFAS are smaller molecules with a much broader range of behaviors and potential health and environmental effects. That means fluoropolymers, legacy PFAS such as PFOA and PFOS, and non-polymer PFAS should not be treated as one uniform risk category.

That difference also matters from a regulatory perspective. Some jurisdictions distinguish fluoropolymers from smaller PFAS, while others regulate PFAS more broadly as a class. Not every fluorinated pharmaceutical always meets the regulatory definition of PFAS, either. The result is an uneven landscape in which different PFAS uses may be treated very differently depending on the material, application and jurisdiction.

PFAS In, PFAS Out: Where PFAS Risk is Hidden

Some PFAS enter pharmaceutical manufacturing intentionally. Others arrive without ever being specified or purchased as PFAS.

Intentional inputs may include fluorinated APIs, process chemicals, fluoropolymer tubing and seals, filters, single-use systems, packaging components and drug delivery materials. These uses are generally easier to trace because they serve a known function and are more likely to appear in formulations, specifications or purchasing records.

Unintentional inputs are harder to see. PFAS may enter through contaminated process water, raw materials, proprietary supplier formulations, outsourced CDMO processes or other material inputs with incomplete documentation. Transformation products, those terminal PFAS resulting from precursor PFAS intentionally added, can add another layer of complexity; for example, terminal PFAS such as trifluoroacetic acid (TFA) may form during wastewater treatment.

Once PFAS are inside the facility, they can leave through multiple pathways, including:

• finished pharmaceutical products
• process wastewater
• cleaning and rinse water
• sludge and treatment residuals
• packaging and other solid waste
• manufacturing process losses such as air emissions or refrigerant losses

This is what makes PFAS exposure a mass-balance challenge. A manufacturer may have a good handle on what it intentionally uses and still have an incomplete picture of what enters through less visible pathways or what ultimately leaves through wastewater, air and solid waste. Proprietary supplier materials, CDMO processes and process water are all potential gaps in that picture.

The result: a traditional materials inventory can tell you what you bought, but not necessarily the full story of PFAS moving through, and being released from, the facility.

Mapping PFAS Across the Facility

Understanding PFAS exposure requires more than knowing where PFAS might be present. Manufacturers need to understand how those sources fit together across the facility and where the most significant uncertainties and exposures lie.

That can be surprisingly difficult. Supplier formulations may be proprietary or incomplete, and PFAS-containing components may be buried several tiers down the supply chain. CDMO processes can add another layer of limited visibility. Analytical challenges complicate the picture further: pharmaceutical waste streams range from process and cleaning water to solvent-bearing streams, sludge and biologics waste, and the PFAS profile can vary considerably among them. Standard analytical methods may not capture every compound or perform equally well across these complex matrices.

The goal of PFAS mapping is therefore not simply to create an inventory list of PFAS-containing materials. It is to build a defensible picture of PFAS across the operation: what is known, what is uncertain, where exposure is most significant and where important data gaps remain.

That visibility matters because not every PFAS use or release pathway carries the same risk. A clear facility-wide map helps manufacturers distinguish essential uses from incidental exposure and understand where regulatory, environmental, supply-chain or business risks may be concentrated.

Without that baseline, PFAS risk remains difficult to quantify, and even harder to explain or defend.

A Clearer Picture of PFAS Risk

Battelle helps manufacturers close those visibility gaps by combining pharmaceutical industry expertise with advanced PFAS analytics, including methods optimized for complex pharmaceutical wastewater and emerging approaches for ultrashort-chain and other difficult-to-measure PFAS. That work can be supported by specialists across formulation, regulated manufacturing, product-contact materials, packaging, medical devices, toxicology and regulatory strategy, allowing PFAS exposure to be evaluated in the context of the full pharmaceutical operation.

That understanding does not solve the PFAS challenge by itself. But it provides the foundation for making better decisions about what comes next.

Download Managing PFAS in Pharmaceutical Manufacturing: A Risk Management Approach for the Pharmaceutical Industry to explore the full PFAS lifecycle and Battelle’s framework for assessing and managing PFAS risk.