The measure at the heart of the shift is Commission Regulation (EU) 2023/2055, adopted in September 2023, which amends Regulation (EC) No 1907/2006, better known as REACH, by adding a restriction on synthetic polymer microparticles, or SPMs, to Annex XVII. These are the tiny solid plastic particles, generally smaller than five millimeters, that come from deliberately manufactured microscopic materials or from the breakdown of larger plastic items. Because they resist biodegradation, they accumulate in ecosystems, and early research has linked them to inflammation, oxidative stress and cellular damage, with possible effects ranging from impaired reproduction to increased mortality in organisms that ingest them. The full extent of the risk to human health remains uncertain, which is precisely why regulators have moved to cut emissions at the source, with the EU targeting a thirty percent reduction in microplastics released into the environment by 2030.

The regulation broadly bans placing substances and mixtures containing intentionally added SPMs on the market, but it carves out critical sectors, including medicinal products, where polymers play an essential role in delivering therapies. That exemption, however, is not a free pass. Medicines that contain qualifying SPMs are still subject to information obligations, effective from October 2025, and to reporting obligations, with the first reports covering calendar year 2026 due to the European Chemicals Agency by 31 May 2027. The technical definition matters enormously here. A polymer counts as an SPM if it is solid, constitutes at least one percent by weight of particles, or forms a continuous surface coating on them, and if at least one percent of those particles measure five millimeters or less in all dimensions, or up to fifteen millimeters long with a length-to-diameter ratio above three. Many polymer powders used in tablets fit that description easily.

Exclusions are where the regulatory science gets interesting, and where the burden of proof falls squarely on industry. Polymers escape the SPM designation if they result from polymerization occurring in nature and have not been chemically modified, if they are proven degradable under the prescribed test methods, if their water solubility exceeds two grams per liter, or if they contain no carbon atoms at all. Because polymeric excipients can vary with source material and processing conditions, exclusion evidence must be tied to the specific grade and manufacturing site. The authors of the new paper, a team from excipient supplier DFE Pharma, propose a four-step workflow that separates evaluation of intrinsic material properties from the application of dosage forms. Step one screens material chemistry and production process, step two examines physicochemical properties such as solubility and particle size, step three assesses biodegradability, and step four determines whether information and reporting requirements apply to the finished medicine.

Compliance is complicated by the reporting mechanics themselves. Estimates of annual SPM emissions rest on lifecycle assumptions, in a field with no standardized methodology or historical reference data, and dossiers must be prepared in IUCLID format and submitted through the REACH-IT portal, tools that sit outside the traditional pharmaceutical regulatory framework. Reported information is made available to national authorities such as ANSES in France and the Umweltbundesamt in Germany, meaning information requests may arrive through environmental departments rather than regulatory affairs or quality assurance units. For oral medicines, potential environmental release arises mainly from disposal pathways such as unused or expired medicines, so defensible assumptions and transparent data provenance are essential for reproducible, year-on-year tracking. Although the restriction is EU-based, it applies to any product placed on the EU market, including those from non-EU manufacturers, effectively globalizing the paperwork.

To demonstrate the framework in action, the team ran a portfolio screening of their excipient range, extending the list with commonly used ingredients from marketed oral solid dosage forms. Disaccharides such as lactose, sucrose and trehalose were excluded outright as small organic molecules rather than polymers, as were mannitol, sorbitol, dicalcium phosphate, magnesium stearate, silicon dioxide and sodium stearyl fumarate. Naturally occurring, unmodified polymers such as microcrystalline cellulose, native potato starch and pregelatinized starch also escaped, since physical processing with heat and moisture does not introduce new chemical substituents. The case of microcrystalline cellulose, however, exposed a genuine gray zone: it is made by controlled hydrolysis of cellulose, and if regulators judged that processing to constitute chemical modification, the material would fail step two, since its particles fall within the SPM size range and it is insoluble. Fortunately, cellulose is widely recognized as biodegradable and even serves as a reference material in biodegradation studies.

The chemically modified polymers posed the hardest questions. Sodium starch glycolate, croscarmellulose sodium, hydroxypropyl methylcellulose, ethyl cellulose, polyethylene glycol, polyvinyl pyrrolidone, copovidone and crospovidone all lack automatic exclusions, and without explicit proof they may fall within the SPM definition. Two cross-linked, carboxymethylated superdisintegrants emerged as candidates for testing: Primojel, a sodium starch glycolate derived from potato starch with all particles below 125 micrometers, and Primellose, a croscarmellulose sodium from cotton-based cellulose with a similar size profile. Both were evaluated in a carbon dioxide evolution test, OECD 301B, conducted under good laboratory practice by an accredited external laboratory. The results were striking: mineralization reached 63.8 percent of theoretical carbon dioxide content for Primojel and 75.5 percent for Primellose at sixty days, clearing the sixty percent threshold for group two screening and justifying exclusion claims under the regulation for both products.

The testing itself is neither quick nor cheap. GLP-compliant biodegradation studies demand significant resources and may run for weeks or months, with advanced environmental simulations stretching to twenty-four months, making rapid screening unfeasible and prioritization essential. Standardized tests also have well-known limitations: variability in microbial inoculum, temperature and nutrient composition can produce inconsistent results across laboratories, and laboratory protocols may not faithfully reflect the complexity of real ecosystems where excipients ultimately end up. Uncertainty near decision thresholds is a particular concern, so when results hover close to a cutoff, companies should substantiate decisions with replicate measurements or confirmatory tests. Evidence from one supplier cannot automatically be transferred to another, since even materials sharing a pharmacopeial name and CAS number can differ in degree of substitution, cross-linking density, molecular weight distribution and particle morphology, a lesson the industry already learned painfully during the nitrosamine crisis.

The stakes extend beyond paperwork into formulation science itself. If compliance ever forced substitution of an in-scope excipient, the change could alter disintegration, drug release and manufacturing robustness, because the functionality of superdisintegrants and controlled-release agents depends on their exact polymeric structure. The authors argue that SPM-related decision-making should therefore be integrated early into formulation design and supplier qualification, alongside quality-by-design activities, rather than treated as a late-stage compliance scramble. Suppliers who can document that their excipients fall outside the SPM scope will gain a competitive edge as sustainability expectations rise. Looking ahead, other jurisdictions are moving at different speeds: the United States has focused on microbead bans in rinse-off cosmetics while the FDA and EPA monitor microplastics through research programs, the UK operates its own REACH framework without an equivalent restriction, and Canada, China and India have adopted product-specific measures mostly aimed at cosmetics. The authors warn that divergent definitions, thresholds and reporting formats could multiply the burden on global supply chains, and they call for regulators introducing new microplastics rules to harmonize with the substantial work already done at EU level. Coordinated effort among excipient suppliers, drug manufacturers and regulators, they conclude, will be essential to sustain polymer innovation in drug delivery while meeting the world’s escalating environmental expectations.

Subject of Research: EU REACH restriction on synthetic polymer microparticles and its compliance implications for pharmaceutical excipients and drug delivery

Article Title: Microplastics matter: practical implications of the EU REACH restriction for the pharmaceutical industry

Article References: Janssen, P. H. M., Rijpkema, W. A., Bisharat, L., Orbons, M., Jaspers, M., & Dickhoff, B. H. J. (2026). Microplastics matter: practical implications of the EU REACH restriction for the pharmaceutical industry. Frontiers in Drug Delivery, 6, Article 1854462. https://doi.org/10.3389/fddev.2026.1854462

Image Credits: AI Generated

DOI: 10.3389/fddev.2026.1854462

Keywords: microplastics, synthetic polymer microparticles, REACH, pharmaceutical excipients, European Chemicals Agency, biodegradability testing, drug delivery, OECD 301B, superdisintegrants, regulatory compliance, sustainability, pharmaceutical manufacturing