1.1 Manufacture of active pharmaceutical ingredients (API) or active substances (pollution prevention and control)

Kurzbeschreibung

Manufacture of active pharmaceutical ingredients (API) or active substances. The economic activities in this category could be associated with NACE code C21.1 in accordance with the statistical classification of economic activities established by Regulation (EC) No 1893/2006.

Wirtschaftsaktivität (EU-Taxonomie)

Rechtsakt: 2023/2486, Anhang III, Abschnitt 1.1

Umweltziel: pollution prevention and control

NACE-Codes: C21.1

Beschreibung

Manufacture of active pharmaceutical ingredients (API) or active substances. The economic activities in this category could be associated with NACE code C21.1 in accordance with the statistical classification of economic activities established by Regulation (EC) No 1893/2006.

Technische Bewertungskriterien

Technical screening criteria Substantial contribution to pollution prevention and control 1. The activity complies with all of the requirements specified below relating to product substitution. 1.1. The API complies with one of the following requirements: (a) the API is a naturally occurring substance, such as vitamins, electrolytes, amino acids, peptides, proteins, nucleotides, carbohydrates and lipids, and, in line with the European Medicines Agency Guideline on the environmental risk assessment of medicinal products for human use (EMA ERA guideline) (1), is generally considered to be degradable in the environment (2); (1) European Medicines Agency Guidelines on the environmental risk assessment of medicinal products for human use, version of available at: https://www.ema.europa.eu/en/environmental-risk-assessment-medicinal-products-human-use-scientific- guideline. (2) Key metabolites are human metabolites likely to be excreted into the environment. Those metabolites are identified in (non-)clinical studies on the metabolism of medicinal products available in the marketing authorisation applications. Such metabolites are to be identified according to EMA/CPMP/ICH/286/1995, page 8. Key transformation products (TP) of these key human metabolites of the parent compound (API) are those that exceed 10 % of Dissolved Organic Carbon (DOC) or Total Organic Carbon (TOC) of the parent compound. OJ L, 21.11.2023 ELI: http://data.europa.eu/eli/reg_del/2023/2486/oj 90/164 (b) where the API does not comply with the requirements specified in point (a), the API, its key human metabolites and its key transformation products in the environment comply with one of the following: (i) are classified as readily biodegradable based on at least one of the test methods from the OECD Guidelines for the Testing of Chemicals, Test 301 (A-F), Ready Biodegradability (3), in accordance with the pass value for ready biodegradability as defined in that guideline; (ii) can be concluded to be mineralised based on a specific Test No 308: Aerobic and Anaerobic Transformation in Aquatic Sediment Systems (OECD 308) (4) of the OECD Guidelines for the Testing of Chemicals (5) compared to persistence criteria as defined in the EMA ERA guideline. 1.2. The API qualifies as an appropriate substitute to another API, within the same therapeutic area or the substance class, that is available in the market or was available during last 5 years and that does not comply with the requirements described in point 1.1. Compliance with this requirement is demonstrated through a publicly available analysis verified by an independent third party. 1.3. The manufacturing process of the API does not involve the use of substances, whether on their own or in mixtures, that meet the criteria set out in Article 57 of Regulation (EC) No 1907/2006 except where it is assessed and documented by the operator that no other suitable alternative substances or technologies are available on the market, and that they are used under controlled conditions (6). 2. The activity complies with the following requirements regarding the emission of pollutants: 2.1. Where the activity falls within its scope, the emission limit values are lower than the mid-point of the BAT-AEL ranges (7) set out in: (a) the best available techniques (BAT) conclusions for common waste gas management and treatment systems in the chemical sector for emissions to air of new installations (or for existing installations within 4 years of the BATC publication) where relevant conditions apply (8); (b) the Best Available Techniques Reference Document (BREF) for Manufacture of Organic Fine Chemicals (OFC) (9) for the manufacturing activity under conditions not covered by the BATC mentioned above; (3) OECD Guidelines for the Testing of Chemicals, Test 301 (A-F), Ready Biodegradability, version of 27.6.2023 available at: https://www. oecd.org/chemicalsafety/risk-assessment/1948209.pdf. OECD 301 (A-F) test is used to identify substances which are assumed to rapidly and ultimately biodegrade, i.e. mineralised under aerobic environmental conditions. (4) Higher-tier studies (OECD 308) result with so-called half-lives indicating the time after which 50 % biodegradation of the API is achieved. Half-lives acceptable to demonstrate sufficiently quick biodegradation, i.e. non-persistence, according to the Regulation (EC) No 1907/2006, Annex XIII, which is also referenced in the EMA ERA guideline, apply. (5) OECD Guidelines for the Testing of Chemicals, Test No 308: Aerobic and Anaerobic Transformation in Aquatic Sediment Systems, version of 27.6.2023 available at: https://www.oecd-ilibrary.org/environment/test-no-308-aerobic-and-anaerobic-transformation-in- aquatic-sediment-systems_9789264070523-en. (6) The Commission will review the exceptions from the prohibition from manufacturing, placing on the market or use of the substances referred to in points (f) and (g) once it will have published horizontal principles on essential use of chemicals. (7) The requirements under this point tackle the pollutants identified under the key environmental issues of each BREF document or the BAT-AEL of the relevant BAT conclusions Commission Implementing Decisions. Where BAT-AEL differentiate between ‘existing’ and ‘new plants’, operators demonstrate compliance with BAT-AEL for new plants. When there is not a BAT-AEL range but a single value, emission levels are below such value. When the BAT-AEL range is expressed as follows: ‘<x-y unit’ (i.e. the lower-end BAT-AEL of the range is expressed as ‘lower than’), the mid-point is calculated using x and y. Averaging periods are the same as in the BAT-AEL of the BREF documents outlined above. (8) Commission Implementing Decision (EU) 2022/2427 of 6 December 2022 establishing the best available techniques (BAT) conclusions, under Directive 2010/75/EU of the European Parliament and of the Council on industrial emissions, for common waste gas management and treatment systems in the chemical sector (OJ L 318, 12.12.2022, p. 157). (9) The Best Available Techniques Reference Document (BREF) for Manufacture of Organic Fine Chemicals, available at: https://eippcb.jrc. ec.europa.eu/sites/default/files/2019-11/ofc_bref_0806.pdf. OJ L, 21.11.2023 ELI: http://data.europa.eu/eli/reg_del/2023/2486/oj 91/164 (c) the best available techniques (BAT) conclusions for common waste water and waste gas treatment/management systems in the chemical sector (10); (d) the Best Available Techniques Reference Document (BREF) for the Large Volume Inorganic Chemicals – Solids and Others industry (11); (e) the Best Available Techniques Reference Document (BREF) for the manufacture of Large Volume Inorganic Chemicals – Ammonia, Acids and Fertilisers (12); (f) the Best Available Techniques Reference Document (BREF) for the production of speciality inorganic chemicals (SIC) (13); for the manufacturing activity under conditions not covered by the BATC mentioned above. Plants within the BAT-AEL range(s) moving to the mid-point ambition do not trigger any significant cross-media impact. Installations that have been granted a derogation in accordance with the procedure set out in Article 15(4) of Directive 2010/75/EU are not considered as fulfilling the technical screening criteria for the period of the derogation. 2.2. Where a continuous measurement methodology for a certain pollutant is available, the operator applies Continuous Emission Monitoring Systems (CEMS), Continuous Effluent Quality Monitoring Systems (CEQMS) and other measures ensuring the regular verification of non-deterioration of environment. 2.3. The operator applies solvent waste segregation for solvent recovery from concentrated waste streams, where technically applicable. Solvents included in Table 1 of the European Medicines Agency ICH guideline Q3C (R8) on impurities: guideline for residual solvents (14) are avoided. The maximum solvents loss from total inputs does not exceed a 3 % loss. Total volatile organic compound (VOC) recovery efficiency is at least 99 %. The operator verifies that no fugitive VOC emission occurs beyond the criteria specified below as to the parts per million volumetric (ppmv) thresholds by carrying out Leak detection and repair (LDAR) campaigns, at least every 3 years. Investments for the use of high integrity equipment are recommended, provided that these are installed in existing plants for cases mentioned under BAT 23 point (b) of the best available techniques (BAT) conclusions for common waste gas management and treatment systems in the chemical sector (WGC), whereas the pressure threshold is brought to 200 bar. The minimal verification schedule may be reduced in cases where quantification of total VOC emissions from the plant is periodically qualified with tracer correlation (TC) or with optical absorption-based techniques, such as differential absorption light detection and ranging (DIAL) or solar occultation flux (SOX) or other measures of equivalent performance. Diffuse emissions of substances or mixtures classified as CMR1A or 1B from leaky equipment do not exceed a concentration of 100 ppmv (15). (10) Commission Implementing Decision (EU) 2016/902 of 30 May 2016 establishing best available techniques (BAT) conclusions, under Directive 2010/75/EU of the European Parliament and of the Council, for common waste water and waste gas treatment/management systems in the chemical sector (OJ L 152, 9.6.2016, p. 23). (11) Best Available Techniques (BAT) Reference Document for the Large Volumes Inorganic Chemicals- Solids and Others industry (version of 27.6.2023: https://eippcb.jrc.ec.europa.eu/sites/default/files/2019-11/lvic-s_bref_0907.pdf). (12) Best Available Techniques (BAT) Reference Document for the manufacture of Large Volume Inorganic Chemicals – Ammonia, Acids and Fertilisers (version of 27.6.2023: https://eippcb.jrc.ec.europa.eu/sites/default/files/2019-11/lvic_aaf.pdf). (13) The Best Available Techniques Reference Document (BREF) for the production of speciality inorganic chemicals (SIC) (version of 27.6.2023: https://eippcb.jrc.ec.europa.eu/reference/production-speciality-inorganic-chemicals). (14) European Medicines Agency ICH guideline Q3C (R8) on impurities: guideline for residual solvents. Step 5, 2022, version of 27.6.2023 available at: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical- requirements-registration-pharmaceuticals-human-use_en-33.pdf. (15) Where the exemption under criterion 1.3 applies. OJ L, 21.11.2023 ELI: http://data.europa.eu/eli/reg_del/2023/2486/oj 92/164 The LDAR campaigns have the features described in BAT19 of the best available techniques (BAT) conclusions for common waste gas management and treatment systems in the chemical sector, which include detecting, repairing and maintaining leaks within 30 days of detection and a leak threshold that is lower than or equal to 5 000 ppmv for substances or mixtures other than those classified as CMR 1A or 1B, which are reviewed and updated for the continuous improvement of the installation. Solvent losses and recovery efficiency of VOC are monitored based on a solvent management plan using a mass balance for verification of compliance, in accordance with Chapter V of Directive 2010/75/EU. 2.4. Sewage, refuse, and other waste (including solids, liquids, or gaseous by-products from manufacturing) are disposed of in a safe, timely and sanitary manner. Containers or pipes for waste material are clearly identified. Analytical data demonstrating the conversion of these substances and their residues to non-hazardous waste materials are available at the facility and kept up to date. Do no significant harm (‘DNSH’) (1) Climate change mitigation Where the activity involves on-site generation of heat/cool or co-generation including power, the direct GHG emissions of the activity are lower than 270 gCO2e/kWh. For the refrigerant threshold, the Global Warming Potential does not exceed 150 in cooling of the substance. Where active pharmaceutical ingredients (API) or active substances are made from substances listed in Sections 3.10 to 3.16 of Annex II to Delegated Regulation (EU) 2021/2139, the GHG emissions do not exceed the limits set out in their respective criteria for DNSH to climate change mitigation. The substitution does not lead to an increment of lifecycle GHG emissions. Lifecycle GHG emissions are calculated using Recommendation 2013/179/EU or, alternatively, using ISO 14067:2018 (16) or ISO 14064-1:2018 (17). Quantified life-cycle GHG emissions are verified by an independent third party. (2) Climate change adaptation The activity complies with the criteria set out in Appendix A to this Annex. (3) Sustainable use and protec­ tion of water and marine resources 1. Waste water treatment The performance of waste water treatment processes conducted by or on behalf of the manufacturing plant does not lead to any deterioration of water bodies and marine resources. When activities fall within their scope, they meet the requirements of Directives 91/271/EEC, 2008/105/EC, 2006/118/EC, 2010/75/EU, 2000/60/EC, (EU) 2020/2184, 76/160/EEC, 2008/56/EC and 2011/92/EU. (16) ISO standard 14067:2018, Greenhouse gases – Carbon footprint of products – Requirements and guidelines for quantification, version of 27.6.2023 available at: https://www.iso.org/standard/71206.html. (17) ISO standard 14064-1:2018, Greenhouse gases – Part 1: Specification with guidance at the organization level for quantification and reporting of greenhouse gas emissions and removals, version of 27.6.2023 available at: https://www.iso.org/standard/66453.html. OJ L, 21.11.2023 ELI: http://data.europa.eu/eli/reg_del/2023/2486/oj 93/164 The activity implements best practices specified in the Joint Research Centre Best Environmental Management Practice for the Public Administration Sector (18). Where waste water treatment is conducted by an urban waste water treatment plant on behalf of the manufacturing plant, it is ensured that: (a) the load of pollutants released by the manufacturing plant has no negative effect in the treatment process of the urban waste water treatment plant; (b) the load and characteristics of pollutants do not pose any risk or harm to the health of the staff working in waste water treatment plants; (c) the urban waste water treatment plant is designed and equipped appropriately to abate the released polluting substances; (d) the overall load of the concerned pollutants discharged to the water body is not increased compared to the situation where the emissions from the installation concerned remained compliant with emission limit values set for direct releases; (e) the usability of the sewage sludge for nutrient (re)cycling is not affected. For installations where additional pollutant limits or stricter conditions have been included in their environmental permit compared to the requirements of the legislation mentioned above, these stricter conditions apply. 2. Soil and groundwater protection Appropriate measures are in place to prevent emissions to soil and regular surveillance is conducted to avoid leaks, spills, incidents or accidents occurring during the use of equipment and during storage. 3. Water consumption Operators assess the water footprint of the chemical production processes in line with ISO 14046:2014 (19) and ensure that they do not contribute to water scarcity. Based on this assessment, operators provide a declaration that they do not contribute to water scarcity which is verified by an independent third party. 4. The activity complies with the criteria set out in Appendix B to this Annex. (4) Transition to a circular economy The activity assesses the availability of and, where feasible, adopts techniques that support: (a) reuse and use of secondary raw materials and reused components in products manufactured; (b) design for high durability, recyclability, easy disassembly and adaptability of products manufactured; (18) Joint Research Centre, Best Environmental Management Practice for the Public Administration Sector, 2019, version of 27.6.2023 available at: https://op.europa.eu/en/publication-detail/-/publication/6063f857-7789-11e9-9f05-01aa75ed71a1/language-en. (19) ISO 14046:2014 Environmental management – Water footprint – Principles, requirements and guidelines, version of 27.6.2023 available at: https://www.iso.org/standard/43263.html. OJ L, 21.11.2023 ELI: http://data.europa.eu/eli/reg_del/2023/2486/oj 94/164 (c) waste management that prioritises recycling over disposal, in the manufacturing process; (d) information on product ingredients along the supply chain. (6) Protection and restoration of biodiversity and ecosys­ tems The activity complies with the criteria set out in Appendix D to this Annex.