Sebastian Joseph is principal consultant, director, Development Consulting and Scientific Affairs, PharmaLex India, Noida, India.

Sebastian Joseph

Submitted: Oct. 25, 2019; Accepted: Sept. 9, 2020

Microplastics, plastic particles with a diameter of ≤5 mm, represent an area of concern for scientists and policy makers as a result of environmental persistence and adverse impact on the environment and human health. To restrict the use of intentionally added microplastics, the European Chemicals Agency (ECHA) has proposed a restriction dossier that describes various measures aimed at minimizing the use of microplastics in various industrial segments, including pharmaceuticals. The restriction dossier proposes a ban on certain consumer and professional uses, while other uses would be subject to labeling/information requirements and annual reporting. As of now, ECHA’s opinion on microplastic use for pharmaceuticals recommends following the obligation for labeling and reporting. The dossier proposes reinforcement of the existing provisions under the medicinal product regulations (and in particular the Summary of Product Characteristics), hence a labeling requirement is also recommended. Further decision may be taken by the European Commission on an overall restriction of microplastic use in pharmaceuticals and other industrial segments.

Plastic has widespread uses in various industries and forms the part of society’s day-to-day life. However, plastic/plastic debris can also have a negative impact on the environment and human health. Plastic/plastic debris is present in a variety of sizes and shapes, but when the plastic particles are smaller than 5 mm in size, they are called “microplastics,” and these microplastics are currently a hot topic for scientists and policy makers.

There is currently no harmonized definition of a microplastic because of the differences in the definitions and scope used in various national legislation and voluntary measures adopted across various countries for these materials. The European Chemicals Agency (ECHA) proposed the regulatory definition of a microplastic as a “material consisting of solid polymer-containing particles, to which additives or other substances may have been added, and where ≥1% weight by weight (w/w) of particles have (i) all dimensions 1 nm ≤ x ≤ 5 mm, or (ii), for fibers, a length of 3 nm ≤ x ≤ 15 mm and length to diameter ratio of >3. Polymers that occur in nature that have not been chemically modified (other than by hydrolysis) are excluded, as are polymers that are (bio)degradable” (1).

Applications of microplastics in pharmaceuticals

Microplastics are used for different applications in different industrial segments such as agriculture and horticulture (in fertilizers and plant protection products), cosmetic products (both rinse-off and leave-on products), detergents and maintenance products (e.g., as fragrance encapsulation in laundry detergents and fabric softeners, as well as in products for cleaning and polishing), paints, coatings and inks (in professional and consumer uses), chemicals used in the oil and gas sector, construction industry, pharmaceutical products and medical device, and food supplements and medical food industry (1).

Microplastics are classified either as excipients or APIs, according to the 

 (1–2). As a result of the taste-masking and controlled release (CR) properties offered by microplastics, these materials find applicability in human and veterinary medicines, mainly in solid formulations (tablets and capsules). Microplastics are also used as additives, such as binder, disintegrant, diluent, or lubricant, in solid dosage forms. In parenteral and inhalation drug formulation, microplastics have application in microencapsulation (1–2).

According to the Annex to the Annex XV Restriction Report (2), microplastic particles exhibit their CR properties through one of the following mechanisms (2):

“Diffusion through a polymer matrix or a polymer membrane.” Examples of potential microplastics used in the formulation of diffusion-CR medicines are polymethacrylate, carbomer polymers, ethyl cellulose, polyvinyl acetate phthalate, polyethylenevinyl acetate, poly(ε-caprolactone), cellulose acetate (phthalate).

“Ion exchange via cross-linked resins also known as ion exchange resins.” Examples of potential microplastics include calcium/sodium/hydrogen polystyrene sulfonate, cholestyramine, polacrilex, polacrilin potassium, methacrylic acid with divinylbenzene, and so on.

“Osmotic control via semi-permeable membranes” (water insoluble, nondegradable polymer).

Annex to the Annex XV Restriction Report states that, “It is important to note that … coated tablets, encapsulation membranes, or osmotic systems can be recognized as microplastics as long as the ‘end product,’ which is consumed/ingested, lies within the targeted size range of a microplastic particle” (2). If the core/granule/tablet or osmotic system dimensions are > 5 mm, they do not fulfill the definition of a ‘polymer-containing microplastic’ at the point of use by the consumer, but it is possible for secondary microplastics to be excreted from the body (1–2).

Concerns with microplastic uses and exposure through pharmaceuticals

Release of microplastics in the environment is a cause of concern due to their persistence and bioaccumulation, which can adversely affect the ecosystem. The microscopic size of microplastics makes them readily available for ingestion and potentially liable to transfer within food chains (1–4). Microplastics from medicinal products may be released to the wastewater and ultimately to the environment through the pharmaceutical manufacturing activities and through the excretions and incorrect disposal of unused medicine by the patients.

As noted earlier, microplastics are intentionally used as CR agents and taste-masking agents in human and veterinary medicines. Therefore, it is possible that microplastics are released from medical products via two pathways—excretion of ingested microplastics from the body and improper disposal of unused medicines. This potential release could be minimized by precautionary measures and by a European Union (EU)-wide action (2).

Action proposed by ECHA for regulation of microplastics

In the framework of the EU Plastics Strategy (2018/2035(INI)) (5), at the request of the European Commission (EC), ECHA has assessed the health and environmental risks posed by intentionally added microplastics and submitted a restriction proposal for microplastic particles that are intentionally added to mixtures used by consumers or professionals. This restriction proposal states that, “If adopted, the restriction could reduce the amount of microplastics released to the environment in the EU by about 400,000 tons over a period of 20 years” (1).

Annex XV Restriction Report (Version 1.2) suggests a ban on the use of microplastics in certain consumer and professional applications (1). For other uses of microplastics, the report specifies that products would be subject to labeling/information requirements and annual reporting (1).

Accordingly, in the Annex XV Restriction Report (Version 1.2), restrictions comprising three types of measures were proposed (1):

A restriction on the commercialization of microplastics in isolation or in mixtures where their use will inevitably result in environmental release, irrespective of the conditions of use. Annex XV Restriction Report (Version 1.2) proposal states, “polymers shall not, from entry into force (EIF), be placed on the market as a substance on its own or in a mixture as a microplastic in a concentration equal to or greater than 0.01% w/w” (1).

The necessity for labeling requirement is to provide information on the potential environmental risk and instructions for appropriate disposal of a product to reduce environmental release. Annex XV Restriction Report (Version 1.2) proposal states, “A labelling requirement to minimize releases to the environment for uses of microplastics where they are not inevitably released to the environment but where residual releases could occur if they are not used or disposed of appropriately” (1).

An enhancement of the quality of available information through reporting so that any future environmental risks may be evaluated. Annex XV Restriction Report (Version 1.2) proposal states, “A reporting requirement to improve the quality of information available to assess the potential for risks in the future” (1).

For the purpose of the restrictions set out in the Annex XV Restriction Report, in order for a polymer to be considered as a microplastic all criteria included in the definition must be met—polymer, solid particle/fiber, dimensions, concentration limit, non (bio)-degradability (1,6). The public consultation on this proposed restriction was completed between March 20, 2019 and Sept. 20, 2019 (6).

Additionally, for specific sectors, a period of implementation and exemptions have been suggested so that societal costs are minimized without delaying emissions reduction unnecessarily. “In this manner industry will have enough time to develop and transition to suitable alternatives, including biodegradable polymers where this is appropriate,” the restriction report specifies (1).

Identifying a microplastic according to ECHA restriction proposal

ECHA has proposed a tiered approach for the identification of the microplastic as covered within the scope of restriction proposal (6):

Tier 1a—are relevant solid particles present?

Tier 2—are polymer-containing particles present?

Tier 3—is the concentration limit exceeded?

Although the restriction proposal does not specifically provide an order to the microplastic definition set by which microplastics may be identified, ECHA advises that the initial step should be a check for the presence of solid particles or polymers in the commercialized substance or mixture. Upon the simple check, if either solid particles or polymers are not present, or they are present below the suggested concentration limit of 0.01% w/w, then it may be concluded that the substance or mixture under evaluation will not be affected by the proposed restriction.

Is pharma out of scope for the restrictions?

In short, the answer is partially. In terms of risk management options, a ban of microplastics in medicinal products was considered but finally dismissed, for the following main reasons:

There are sector-specific EU regulations that already govern market suitability, the benefit–risk analysis (on human health), and the market-safety surveillance of medicinal products for human and veterinary uses.

Regulating the use of microplastics under REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals) in addition to the existing regulations may result in a lack of clarity for the actors in these two supply chains.

In addition, a restriction on these already heavily-regulated uses could affect the availability of medicines, particularly as it is not clear if there are alternative medicines available for the pathologies where microplastics are used either as an excipient or an active substance.

Meanwhile, to address the issue of microplastics that are released into the environment as a result of improper disposal of unused medicines, it is proposed by ECHA that there is a reinforcement of the existing provisions under the medicinal product regulations (and in particular the Summary of Product Characteristics [SmPC]), hence a labeling requirement is also proposed (1,6).

In general, ECHA’s restriction proposal states that polymers “shall not, from EIF, be placed on the market as a substance on its own or in a mixture as a microplastic in a concentration equal to or greater than 0.01% w/w” (1). However, this restriction does not apply to medicinal products for human or veterinary use.

Even though medicinal products seem to contribute substantially to the release of microplastics into the environment, it has been concluded that the best course of action is to propose the following restriction option:

 To gather more systematic information on the use of microplastics, so that a decision can be made on which EU action (e.g., REACH, Medicinal product regulation, other) would be the most efficient to address the issue and avoid potential double regulation.

The reporting requirement states that “from [EIF +12 months], any downstream user using a microplastic derogated from use restriction shall send to ECHA, in the format required by Article 111 of REACH, by January 31 of each calendar year:

the identity of the polymer(s) used in the previous year,

a description of the use of the microplastic,

the quantity of microplastics used in the previous year, and

the quantity of microplastics released to the environment, either estimated or measured in the previous year.

“ECHA shall publish a report summarizing the information received by March 31 every year” (1).

Labeling requirement with a two-year transition period.

 To address the problem of microplastic release via inappropriate disposal of unused medicines, ECHA is proposing to reinforce the existing medicinal product regulations with an obligatory indication on the package leaflet (PL) of medicines. The indication will provide sufficient instructions for patients on how to properly dispose of any unused medicines. For example: ‘This medicine contains microplastics. Any unused medicines should be returned to the pharmacy or disposed according to the local regulation. Unused medicines should not be flushed down the toilet nor placed in liquid waste disposal systems.’

The labeling requirement states that “from [EIF + 18 months] any manufacturer, importer, or downstream user responsible for the placing on the market of a substance or mixture containing a microplastic derogated from the restriction proposal shall ensure that the label and/or safety data sheet (SDS)—where applicable—‘instructions for use’ (IFU) and/or ‘package leaflet’ provides, in addition to that required by other relevant legislation, any relevant instructions for use to avoid releases of microplastics to the environment, including at the waste life-cycle stage” (1).

“The instructions shall be clearly visible, legible, and indelible. The label shall be written in the official language(s) of the member state(s) where the mixture is placed on the market, unless the member state(s) concerned provide(s) otherwise. Where necessary because of the size of the package, the information labelling shall be included on the instructions for use” (1).

After the initial proposal, the further steps included the scrutinization of proposal by the Committee for Risk Assessment (RAC) and the Committee for Socio-economic Analysis (SEAC) of ECHA as well as by the enforcement forum, including the public consultation that was open until Sept. 20, 2019. As reported on June 10, 2020, “ECHA’s RAC supports restricting the use of intentionally added microplastics while recommending more stringent criteria for biodegradable polymers … ECHA’s SEAC agreed on its draft opinion on the costs and benefits of this proposal for society … A 60-day consultation of SEAC’s draft opinion will start soon. The consolidated opinion of both committees is expected to be ready by the end of 2020. The decisions on REACH restrictions are taken in the European Commission by the EU Member States and scrutinized by the Council and the European Parliament” (7). It is then up to the EC to propose an amendment to the REACH Regulation if the restriction meets the legal requirements (8–11).

ECHA, “Annex XV Restriction Report: Proposal for a Restriction—Intentionally Added Microplastics (Version 1.2),” 

ECHA, “Annex to the Annex XV Restriction Report: Proposal for a Restriction—Intentionally Added Microplastics (Version 1.2),” 

European Parliament, “A European Strategy for Plastics in a Circular Economy: European Parliament Resolution of 13 September 2018 on a European Strategy for Plastics in a Circular Economy (2018/2035(INI)),” 

ECHA, “Questions and Answers on the Restriction Proposal on Intentionally Added Microplastics (Version 1),” 

ECHA, “RAC Backs Restricting Intentional Uses of Microplastics,” 

EC, “European Commission Welcomes ECHA’s Opinion on Restricting Microplastics Intentionally Added to Products,” 

EC, “ECHA Public Consultation on the Restriction Dossier For Microplastics Intentionally Added to Products,” 

, Internal Market, Industry, Entrepreneurship and SMEs, Mar. 28, 2019.

Parth Soni* is assistant manager, Development Consulting and Scientific Affairs, PharmaLex India, Noida, India, Parth.Soni@pharmalex.com. Sebastian Joseph is principal consultant, director, Development Consulting and Scientific Affairs, PharmaLex India, Noida, India.

*To whom all correspondence should be addressed.


Vol. 45, No. 1
January 2021
Pages: 40–43

When referring to this article, please cite it as P. Soni and S. Joseph, “ECHA’s Microplastic Ise Restriction—Impact on Pharmaceuticals,” 

Articles

To restrict the use of intentionally added microplastics, the European Chemicals Agency has proposed a restriction dossier that describes various measures aimed at minimizing the use of microplastics in various industrial segments, including pharmaceuticals. In this paper, the authors discuss these restrictions.