Take action on PFAS to protect your critical processes.

There is a general consensus that per- and polyfluoroalkyl substances (PFAS) are harmful to health. Increased restrictions on their use are expected but, with many industries and applications not having an equivalent non-PFAS material immediately available, a wholesale ban will have a significant negative impact on many processes that rely upon them. Such a ban is possible in future; however, the socio-economic impact assessment is expected to support derogation for critical industries and processes. This would include the manufacture of medicinal products for human use.

PFAS: What action should the bioprocessing industry take?

The next ECHA milestone is expected soon (as early as 2025). This will share the opinion of the review committee regarding the the risk assessment and draft socioeconomic analysis. A 60 day period for comment will follow. If you’ve not already reviewed the potential impact on your process, now is the time to evaluate this in preparation to take full advantage of this window for comment.

It is recommended that you review the use of PFAS in your process, understand each material and their impact on each application. Review the risk profile of the material and the specific use. Consider the full lifecycle of the material and, if alternatives are not known, consider if control strategies can be managed that may prevent environmental contamination. Seek input from materials, application, technology and product experts as needed.

Irrespective of the outcome of the ECHA review committee it is prudent to plan ahead and to establish a preliminary site action plan.

What can I do to reduce the use of PFAS?

PFAS can be found throughout bioprocessing. In some non-critical applications, there may already be equivalent PFAS-free alternatives available. For these, change is relatively easy once you have identified and categorized the materials and their uses. For materials that have the potential to directly impact the critical quality attributes of an API or finished drug product, or to significantly impact the drug manufacturing process, change requires deeper investigation. However, with the right drive, control and proof of equivalence, this is also achievable.

* With surface added chemistry containing the potential for PFAS

Table 1: Overview of common PFAS materials in bioprocessing

A different approach may be required for those processes or technologies that rely upon PFAS for which there are currently no alternatives that can perform at a level that is equivalent. For these, there is a choice. Where a PFAS-free material with performance equivalence is not available, a manufacturer may choose to accept a compromise to the process that may arise from the introduction of a PFAS-free process design. For existing processes, this change may require, notification to, and/or approval from, the relevant regulatory agencies. In each case it is likely to require evidence to show that there is negligible risk to the patient from a change in product safety, efficacy or quality. However, assuming that a complete ban is not enforced, difficult choices may still need to be made. If the change impacts the efficiency or economy of the process, the speed of development, or supply of the drug to a waiting population, it simply may not seem practical to make the change.

It is anticipated that situations such as this will be considered in the ECHA review. It would appear to be reasonable for any potential environmental issues that result from the continued use to be diligently investigated, controlled and documented.

Take a risk-based approach to PFAS reduction: An air filter case study.

Gas and vent filtration is found throughout a typical bioprocess. Among other duties, they provide critical contamination controls to both upstream and downstream processes. The microporous membranes typically used in sterilizing grade air filters are often made from PTFE, a material well known for its stability and hydrophobicity. But, with the shift towards single-use manufacturing and irradiation of manufacturing systems in place of steam sterilization, PVDF alternatives that are compatible with irradiation sterilization and almost as hydrophobic as PTFE were a strong replacement in many applications. Now, with both these materials in question, a deeper dive into their risks is a good place to start that may provide an outline for the review and use of PFAS in bioprocessing in a wide range of applications.

* Landfill only. Risk is low with controlled temperature incineration
† High molecular weight PFAS with high resistance to breakdown and leaching
‡ Low molecular weight PFAS with risk of leaching into process and environment

Table 2: Overview of product lifecycle stages of impacted materials commonly used in filtration membranes

Polyvinylidene fluoride (PVDF)

Prior to 2006, many PVDF resins used in microporous membrane filters were manufactured using a PFAS surfactant in addition to the 1,1 difluoroethylene (VDF) monomer that makes up the PDVF backbone. Due to environmental concerns, these fluorosurfactants have since been replaced with non-PFAS containing alternatives. While the PVDF produced still classifies as a PFAS, once polymerized, the PVDF polymer is generally considered to pose a low risk during the use of products containing these membranes. The current regulatory-driven expectation for extractables or leachables datasets that characterize bioprocess materials and support patient safety risk assessments, provides further verification that small molecular-weight PFAS chemistries are not present or able to pose a risk to patients.

However, the manufacturing and use phases are only part of the overall lifecycle of any polymer. While landfill of materials used in the production of drugs is uncommon, incineration may still pose a risk. If incinerated at too low a temperature the risk of environmental pollution increases. A study comparing municipal and industrial incinerators [1] highlighted this potential, however full incineration at 860°C for 2 seconds has been shown to be sufficient to mineralize the polymer and reduce the risk of environmental pollution of PFAS to a negligible level . Responsible handling during manufacture and disposal may therefore be considered effective controls that manage the risk and maintain this at a low level.

Polytetrafluoroethylene (PTFE)

Some PTFE manufacturers are working to develop PFAS-free processing aides; however this requires time and development, and the majority of PTFE today is manufactured with the use of PFAS fluorosurfactants. Like PVDF, when polymerized, the tetrafluoroethylene (TFE) monomers are not thought to pose a risk of leaching or degradation during the use phases in a typical pharmaceutical application. Recent publications also conclude that incineration is effective at mineralizing the PTFE and to mitigate the end-of-life risk.

Polyethersulfone (PES)

By itself, PES is not considered a PFAS. It is a common polymer used in microporous membranes used for critical filtration processes such as sterilizing grade liquid filters. However, in some use cases the addition of a surface chemistry can add a degree of hydrophobicity. This extends their use to some gas and vent applications. The most effective surface chemistries include fluorinated chemicals and, while the base matrix of the membrane does not contain PFAS, these surface chemistries may actually pose a higher risk of leaching into the environment than membranes using a PFAS backbone polymer.

Alternative non-PFAS surface chemistries have been identified but these typically impart limited hydrophobic characteristics compared to existing materials. These hydrophobic characteristics may not be required for all use cases but are beneficial for robust operations in critical processes. For example, air filters using membranes with reduced hydrophobicity may be prone to wetting in demanding applications such as bioreactor vents. Here, any wetting may reduce airflow through the filters to cause the bioreactor to fail and the batch of drug to be lost.

For critical air filtration processes there is currently no direct equivalent that achieves the same level of hydrophobicity as PTFE or PVDF. While it may appear beneficial to reduce the total mass of PFAS by using surface treated PES membranes, the real risk may not be lower and may even be higher than a polymerized PFAS material, even when both materials are handled appropriately throughout their lifecycle.

So, what action should the bioprocessing industry take now?

Innovation has always been a key industry enabler, but it may take more than a decade to develop PFAS-free materials with equivalent properties that can effectively support critical applications in bioprocessing. While the efforts to develop these materials must continue, controls within the bioprocessing sector and informed material choices are likely to be able to effectively reduce the risk of environmental pollution from PFAS.

The risk-based mindset common in pharmaceutical manufacturing is already mature and ready to be deployed to carefully control the use of PFAS and to document the review and controls needed. Outputs from informed risk assessments may contribute to exceptions for critical industries when coupled with appropriate controls that cover the entire lifecycle of the material. These assessments benefit from the expertise, knowledge and understanding of the whole supply chain.

Science-based approaches to all aspects of sustainability, including specific environmental and material concerns, will continue to grow in importance. A pragmatic and open approach to the need for change, balanced with an equal drive to maintain the stability of the supply of existing and new drugs, will be critical. But some form of change is inevitable. Our shared challenge is how to empower, support and action changes that safeguard global health without having an impact on the drug development and manufacturing processes that aim to improve it.