Issue link: https://www.e-digitaleditions.com/i/1163217
Concern about microplastics has been growing for some time, particu- larly in Europe. Historically, micro- plastics contamination of the marine environment has been attributed to factors such as large plastic wastes, scrubbing agents in toiletries, tire ero- sion, and abrasion of synthetic textiles during washing. Pharmaceutical and excipient manufacturers generally haven't viewed microplastics as an issue that would significantly impact medicinal products. That changed in January of this year when the Euro- pean Chemicals Agency (ECHA) issued a proposal to restrict the use of intentionally added microplastics (Annex XV Restriction Report, available at: tinyurl.com/Annex-XV). In the repor t, ECHA defined microplastics as materials consisting of a solid polymer or a polymer con- taining particles to which additives or other substances may have been added and where at least 1 percent w/w of particles have all dimensions in the range of 1 nanometer to 5 milli- meters. Essentially, under the ECHA proposal, a "microplastic" is any non- biodegradable synthetic polymer that's a solid particle within the dimensions specified. ECHA has identified polymeric excipients and some active substances in controlled-release medicines as potential microplastics. The agency included medicinal products in the restriction proposal based on the assumption that intentionally added microplastic particles in controlled-re- lease solid oral dosage applications are excreted and released into the envi- ronment as solid microplastics and therefore fall under the scope of the microplastic definition. The assumption that all ingested solid polymeric excipients are eventu- ally released into the environment as microplastics is not supported by sci- ence. An excipient in a medicinal product is subjected to different physical, chemical, and metabolic processes once ingested and may not be excreted as solid particles. Also, products where the microplastic par- ticles cease to exist at the point of use are derogated from restriction, such as in instances where they dissolve or swell in contact with water to such an extent that they can no longer be considered solid particles. This would apply to polymeric excipients that no longer fall under the scope of micro- plastics once excreted. T he EC H A pr oposal f u r the r states that "coated tablets, encapsu- lated membranes, or osmotic sys- tems can be recognized as micro- plastics as long as the 'end product' which is consumed /ingested lies within the targeted size range of a microplastic particle." A tablet or encapsulated product with a contin- uous polymer film coating would be considered a microplastic if the max- imum dimension is 5 millimeters or less. This would include mini tablets, which are critical for elderly patients and others who have difficulty swal- lowing large tablets. The proposal does not prohibit the use of "microplastics" in medicinal products but does include labeling and reporting requirements that will impact both excipient and drug prod- uct manufacturers. Drug product manufacturers will be required to report to ECHA the identity and quantity of the polymer(s) used and released on an annual basis. Also, excipient and drug product manufac- turers placing a product on the market will be required to provide instruc- tions on the label or package leaflet for avoiding release of microplastics to the environment and proper disposal. Medicinal products represent a minor amount of total microplastics emissions, and the benefits to patients outweigh any perceived risks. In addition to controlled-release prod- ucts, polymeric excipients are used in a range of immediate-release solid and liquid applications and play an important role in drug product for- mulation, stability, and delivery of active ingredients. Reformulating medicinal products to r eplace s y nthet ic poly me r ic excipients likely isn't viable since refor mulation can take 10 to 15 years and few alternatives, if any, currently exist. Requiring tablet and capsule product labels to indicate that the product contains plastic would likely lead patients to misin- terpret the labels as additional risk and would misrepresent the exten- sive safety evaluations undertaken prior to regulatory approval. The current proposal and any future regulatory initiatives based on inaccurate science could unintention- ally cause drug shortages and stifle innovation with very little benefit to the environment or patients. It's criti- cal for the global pharmaceutical industry to provide input to ECHA, as the proposed regulation would impact the entire drug product supply chain, including manufacturers, importers, and downstream users and could have unintended consequences for medici- nal products in the future. T&C M e e r a R a g h u r a m i s d i r e c t o r, regulator y strategy and policy at Lubrizol Life Science and chair of IPEC- Americas' regulatory affairs committee. b a c k p a g e How proposed EU microplastics legislation could impact the pharma industry