EU restrictions on per- and polyfluoroalkyl substances (PFAS), common synthetic chemicals, could put in peril the pharmaceutical industry’s ability to manufacture and supply essential medicines and risk regulatory compliance with marketing authorizations for medicinal products, warned Alice Redmond, chief strategy officer at the consultancy firm CAI.
In their current form, the plans could have a wide reaching effect from packaging to the production of raw materials and finished products. While some products could benefit from a derogation, for others, companies will have to invest in R&D to come up with alternatives to these substances, said Redmond.
In an interview with the Pinks Sheet, she advised companies to undertake a full audit of their portfolios to understand which marketing authorizations may be affected before restrictions start entering into force.
PFAS And REACH Regulation
Per- and polyfluoroalkyl substances are synthetic chemicals used in a broad range of products and which are increasingly regarded as environmental pollutants, some of which are linked to negative effects on human health, according to the European Chemicals Agency (ECHA).
These so called forever chemicals contain carbon-fluorine bonds and are “one of the strongest chemical bonds in organic chemistry,” and are therefore resistant to degradation during use and in the environment, says the ECHA.
To limit the impact of these chemicals in the environment, in early 2023 five EU member states proposed banning the substances with some derogations under the EU Regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). The plans would affect a myriad of sectors from medicine and food production to the fashion industry.
In 2023, the ECHA carried out a six-month consultation on the proposals, to which the pharmaceutical industry group, EFPIA, responded claiming that some 47,677 global marketing authorizations could be affected and that more than 600 medicines from the World Health Organization’s Essential medicines list could be at risk.
“If the proposed restriction is implemented, a large number of important medicines will no longer be available. This is not only based on unavailability of replacement materials, but also because the time needed for regulatory processes to re-acquire approvals exceeds the given transition periods,” said EFPIA in its consultation response.
Redmond warned that the proposals could worsen ongoing medicines shortages in the EU. “Industry is already in a mess with drug shortages. Now, if we add this on top of it, it becomes a situation whereby patients are waiting, and nobody wants that.”
According to the proposals, restrictions would enter into force during the third quarter of 2025, and after an 18 month transition period all PFAS use would be banned unless there is a derogation in place.
Derogations
The ECHA’s committees for risk assessment (RAC) and for socio-economic analysis (SEAC) are currently reviewing which products may receive a derogation from the restrictions. For example, 12 year derogations have been discussed for implantable medical devices, such as pacemakers, said Redmond.
However, derogation discussions relating to human medicines still have some way to go, she added. “What’s agreed is only 10% of medicinal products, the rest are all still in consultation and discussion.”
She advised companies to conduct a full audit of their products from raw materials to finished products to see which might benefit from a derogation. “Companies have to provide really strong risk-based evidence to justify the need for derogation. So this is an enormous time crunch for them,” she said.
Redmond explained that an important part of industry’s strategy was to “understand what poses a risk and what doesn’t.” Fluorine compounds have been naturally used in medicines for many years, which means there is substantial data on their impact, she added.
“Years Of Work”
Where derogations are not possible, the biggest issue will be finding alternatives to PFASs that do not “compromise stability and the inertness of the product.” This could mean “years of work,” and companies will likely have to invest in further R&D.
The cost of transitioning to the changes will also hit budgets, she said. In addition to R&D costs, there will be “significant changes” to manufacturing processes. Regulatory agencies would also likely have to increase their number of staff to review the number of regulatory submissions they receive, she said.
Redmond also advised companies that they should develop a comprehensive strategy for phasing out these substances and mitigating risks as well as engaging with industry groups and regulators to come up with a plan to look at derogations.
