Monday, August 1, 2023

If you have not heard about the potential devastating impact of a ban of all PFAS substances including essential fluoropolymers and fluoroelastomers—which have been shown to pose no risk—you can learn more from the ASME BPE, BioPhorum and BPSA. These groups are preparing to submit or have submitted comments to the ECHA, which you can read here.  The BPSA submittal is in preparation and will be posted here as soon as it is available.

Monday, June 26, 2023

The proposed restriction of per- and polyfluoroalkyl substances (PFAS) is a growing topic of conversation in the bioprocess and biopharma industry. Regulatory bodies have concerns regarding the hazardous properties of these chemicals as they are increasingly detected as environmental pollutants, with some linked to negative effects on human health. There are over 9,000 chemicals being lumped together with the blanket categorization of PFAS due to a fully fluorinated carbon atom in their molecular structure. This broad category of PFAS is an insufficient way of looking at these chemicals, and a more scientific approach should be taken to discriminate between the subcategories. Fluoropolymers, which are widely used in single-use bioprocessing, are a distinct class of PFAS substances, and although they fit the PFAS structural definition, they have documented low-risk properties.

Dr. Barbara J. Henry, a toxicologist with W. L. Gore & Associates, has a wonderful analogy likening birds to PFAS: while all birds have similarities (feathers, beaks, the laying of eggs), there are many differences between birds that prohibit them from being described accurately using solely that terminology. Some birds fly while others do not, but more apt to this analogy, some are dangerous predators while others are docile songbirds.

The bioprocessing industry uses a wide range of fluoropolymers in their single-use systems including but not limited to polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE) and fluorinated ethylene propylene (FEP). Fluoropolymers have documented low-risk properties compared to other PFAS: thermally, biologically and chemically stable, negligibly soluble in water, nonmobile, nonbioavailable, nonbioaccumulative and nontoxic. These properties are what make fluoropolymers essential for bioprocess applications. Although fluoropolymers fit the PFAS structural definition, they have very different physical, chemical, environmental and toxicological properties when compared with other PFAS¹. Borrowing from the bird analogy, these fluoropolymers would be the docile songbird of the PFAS category. In 2018, Barbara J. Henry et al. published a paper justifying the separation of fluoropolymers in the hazard assessment by labeling them “polymers of low concern” (PLC) and stating that grouping them with PFAS for regulatory purposes would be scientifically inappropriate.

The Organization for Economic Co-operation and Development (OECD) has the following criteria for a PLC:

These criteria predict negative impact on human and animal health and environmental hazards. When stacked against these criteria, fluoropolymers were found to have low health and environmental concerns, unlike some of their counterparts in other subcategories of PFAS.

The bioprocess and biopharma industries have been using fluoropolymers in their single-use assemblies for years because the materials provide many advantages that are essential to the pharmaceutical manufacturing process, such as broad sterilization compatibility, chemical inertness, low extractables, integrity in cryogenic applications, robust chemical compatibility and many others. The movement to ban and control the use of PFAS has valid health and environmental concerns due to the nature of other subcategories, but fluoropolymers are being caught in this overly broad classification.

In Europe, the definition of substances of very high concern (SVHC) is being broadened to include substances that are non-toxic, and Germany is leading a proposal to add PFAS, including fluoropolymers, to the SVHC list. The European Chemicals Agency (ECHA) received a proposal from the national authorities of Denmark, Germany, the Netherlands, Norway and Sweden to restrict PFAS under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). This proposal was published on February 7, 2023, and is currently in a six-month consultation period that ends on September 25, 2023. Once implemented, industries without a noted derogation period will have a ban with an 18-month transition period. There are identified industries that have been granted a derogation period to allow for a transition to other materials, such as medical devices with a noted 12-year derogation period; however the biopharmaceutical industry seems to be missing from the report. As a result of this, and the significant impacts to the bioprocessing industry, many organizations have rallied to bring awareness to the ECHA restriction proposal. These include the Bio-Process Systems Alliance (BPSA), The American Society of Mechanical Engineers – Bioprocess Equipment (ASME-BPE), and BioPhorum. As a member of each of these organizations, Qosina has been involved in helping bring awareness to this topic and to help formalize responses to the PFAS restriction proposal during the comment period.

In the United States, the Environmental Protection Agency (EPA) is pursuing a hazard approach rather than a risk-based analysis. Additionally, the FDA and the EPA are not pursuing an “essential use requirement,” which would allow for drug manufacturers to apply for exemption from the control of fluoropolymers. These approaches, coupled with the scientifically inappropriate classification of fluoropolymers, present a great danger to the bioprocess industry due to continued use of these materials in the manufacturing process. A study by Emily Hammel found that 94% of pharmaceuticals on the market include substances in their process materials that include one fully fluorinated carbon (-CF3). Among this 94%, Prozac and Lipitor, two of the most prescribed drugs in the world, find their processes at risk ². If fluoropolymers remain included in the ban of PFAS, the supply of these drugs and many others would be impacted as regulatory re-filings, and process changes would be required, assuming an alternative material existed.

If alternative materials are not available, the industry could be faced with a 5–10-year new product development process to identify materials for different uses and applications. If alternative materials could be identified, there are several challenges that would be encountered to source and qualify them. This could include additional costs affecting overall drug prices, leading to reduced access and impacts to manufacturing process performance such as drops in product yield and quality, reduced productivity and delays in production, causing supply issues. With a change in material, filing updates may be required, and there is the potential for delayed response due to an increased number of requests to the regulatory authorities. These delays could limit the production and supply of critical biopharmaceutical products globally.

In summary, a restriction on the use of fluoropolymers would prevent critical materials necessary in pharmaceutical and biopharmaceutical manufacturing processes from being used and will have negative impacts on the availability of life-saving therapies. There are many advocacy groups campaigning for the reclassification of fluoropolymers. The EPA is working to take a risk-based approach to PFAS, and the OECD issued a document titled, “Reconciling Terminology of the Universe of Per- and Polyfluoroalkyl Substances: Recommendations and Practical Guidance.” The support for a scientifically appropriate classification and a risk-based assessment of PFAS has garnered attention and discussion of regulators, industry subject matter experts and drug manufacturers, as they attempt to enact the most sensible and safe approach to the use of PFAS in SUS.

1. A Critical Review of the Application of Polymer of Low Concern and Regulatory Criteria to Fluoropolymers, Barbara J Henry, et al., February 9, 2018↩
2. Implications of PFAS Definitions Using Fluorinated Pharmaceuticals, Emily Hammel, et al., March 2, 2022 ↩