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Global notification strategy for the EU and Pacific Rim countries

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Chemical Regulation

Global notification strategy for the EU and Pacific Rim countries

otification of new chemicals can be a costly process and in order to recoup the costs of the testing burden placed on companies by the regulatory authorities it is necessary to have a marketing/ notification strategy in place before this testing is started. This requires input from regulatory experts at the start in order to assess what testing needs to be performed, and where to perform it, in order to maximise the use of such data and minimise repeat testing (some will be unavoidable due to local testing requirements in some countries). We want to present the scenario of a manufacturer which has notified its product at the 1-10 t/yr level (Annex VII) in the EU under REACH and is considering notification at a similar tonnage in as many South Asian Pacific Rim countries as it is financially viable to do so. What does the manufacturer need to consider? Firstly, as testing and notification can take a considerable amount of time, the manufacturer needs to consider the economics of the intended countries. Is their Gross

Domestic Product (GDP) growth predicted to increase in the next five years (say) to support projected sales in that countries or do they have a niche market for that product in a particular country. They also need to consider how the product would reach the country, i.e. does it have a good shipping route/port and whether the cost of transport is likely to be prohibitive and reduce the potential profit margin to an unacceptable level. For the purposes of this article we intend to consider the countries listed in Table 1. From Table 1 below, where countries are listed in ascending order of GDP, it can be seen that several countries on the Pacific Rim have a significant GDP and are predicted to continue to grow over the next few years, so the next step is to consider how much additional testing (if any) would be required above that already required for the notification in the EU. The basic data set for a REACH 1-10 t/yr (Annex VII) Notification for a solid, with low water solubility and low

Table 1: Pacific Rim countries, their transport routes and predicted GDP increase Rank* Country 2 4 12 15 18 19 24 29 32 38 40 63
* PPP

GDP (PPP) $ billion Predicted GDP (PPP) Container port in world top 50 Increase in GDP (PPP) 2011* 2017* busiest ports (2011 - 2017) $ billion (%) 11,300 4,400 1,554 1,124 914 876 602 447 390 315 300 122 20,366 5,324 2,148 1,829 1,229 1,261 902 653 568 432 490 150 Shanghai (1st) and 7 others Tokyo (25th) and 3 others Busan (5th) Jakarta (24th) and 1 other No Kaohsiung (12th) Leam Chabang (22nd) Port Klang (13th) and 1 other Manila (37th) Singapore (2nd) Saigon (28th) No 9066 (80%) 924 (21%) 594 (38%) 705 (63%) 315 (34%) 385 (44%) 300 (50%) 206 (46%) 178 (46%) 117 (37%) 190 (63%) 28 (23%)

China Japan South Korea Indonesia Australia Taiwan Thailand Malaysia Philippines Singapore Vietnam New Zealand

Values taken from data published by the International Monetary Fund 2012 Purchasing power parity in US$

Chemical Regulation
Table 2: Basic data set for a REACH 1-10 tonne/year (Annex VII) Notification for a solid, with low water solubility and low volatility Study Acute oral Acute dermal Skin irritation/ corrosion in vitro Eye irritation/ corrosion in vitro Skin sensitisation (LLNA) Bacterial mutation (AMES) In vitro chromosomal aberration Biodegradation (general) Biodegradation (specific)a Acute fish toxicity (general) Acute fish toxicity (specific)a Acute daphnia toxicity Algal growth inhibition ASRIT Bioconcentration in fish (specific)d e Acute earthworm toxicity 28-day rat toxicity studye
P
a b c d e

EU 1-10 t/yr Yes No Yes Yes Yes Yes a No Yes No No No Yes Yes No No No No

Australia >1 t/yr Yes Yes Yes in vivo Yes in vivo Yes Yes Yes Yes No No No Yes Yes No No No Yes

China 1-10 t/yr Yes Yes P P Yes Yes Yes No Yes No Yes Yes Yes Yes No Yes c Yes

Japan 1-10 t/yr No No No No No Yes No No Yes a No No No No No Yes b No No

South Korea >1 t/yr Yes No Yes in vivo Yes in vivo Yes Yes a Yes a Yes No Yes No Yes Yes No No No No

Guidance indicates in vitro may be acceptable (but see later in article) Further testing may be required depending on results May be required if not readily biodegradable and log Pow 3.5 May be required depending on physicochemical properties Study required to be performed in country of notification or to specific testing requirements It is recommended that a JMETI design is used in all cases if it is likely that a notification at greater than 10 t/yr is planned for Japan in due course

volatility, assuming all physicochemical and spectral data are available, is shown in Table 2. In many of the Pacific Rim countries there is currently no system of new chemical notification regulation or list for existing and/or new chemicals, for example Indonesia, Singapore and Vietnam. A notification system will be enforced in Taiwan and Malaysia in the near future. The regulatory process in New Zealand is noticeably different to the rest of the world and is based on assessment of groups of chemicals. In general the testing requirements for most countries in the region at 1-10 t/yr are very similar and often there is a possibility for testing to be reduced or waived if the new chemical has already been successfully notified in one or more countries. For example, in the Philippines a

limited notification can be performed if the test material is already notified, i.e. EU, Australia. From the information in both tables it is worth considering what additional studies are required for notification above those for the EU and if the GDP of the country (and the future growth) support the extra expense. China, Australia and South Korea all require additional testing, for example a chromosomal aberration study and/or a 28-day toxicity study. But is it a good financial decision to perform the studies just for a notification in Australia? Australia does not have a major container port so the cost of sending the new test material may be prohibitive. However, if the notification is for China and Australia then it would make sound financial sense to perform the study as China has the largest GDP and the most major container ports per

Chemical Regulation
country in the world thus aiding the importation process. Similarly it may be worth considering whether a local study in China will meet the regulatory requirements elsewhere, as it is not to full GLP standards, or if a GLP study is required? Any additional data generated may have an impact on your EU dossier as new data will have to be submitted in an update to the EU dossier. The study requirements for Japan (above those for the EU) are very similar to China with the exception of the ecotoxicology study noted below. With the advent of REACH the emphasis in the EU has been on the use of in vitro and read-across data, however some countries, such as China from our experience, are unlikely to accept in vitro information even though it may be stated in their regulations that in vitro data can be submitted. This situation needs to be carefully confirmed before irritation studies, in particular, can be commissioned. In several countries (Japan and China for example) there is a requirement for biodegradation studies and/or ecotoxicological testing to be performed in a test species/ system in a laboratory in that country. This may mean that a study needs to be duplicated as a biodegradation study performed in China will not be accepted in other countries but one must be performed in China even if a study from outside this country already exists. Similarly countries may have specific requirements for studies not needed elsewhere in the world such as the JMETI biodegradation study which requires all degradates to be identified and these may then also require a low volume exemption notification. There may also be the requirement to perform, what is considered in the EU as a higher level test (10-100 t/yr), i.e. not performed for a 1-10 t/yr notification. For example, a 28-day toxicity study is required for a 1-10 t/yr submission in China and a 1 t/yr submission in Australia. In China there is a need to submit a risk assessment, albeit only a qualitative one, for a 1-10 t/yr (Level I) submission, which requires a lot of information on manufacturing processes and/ or uses in China. It is worth noting that once the study set for China has been completed, with the addition of a reproductive toxicity screening study, there will be sufficient data to support a 10-100 t/yr (Annex VIII) submission in the EU. However, a significant additional effort would be required to move to the next tonnage band in China. In both Australia and Korea there is no tonnage band above the 1 t/yr level. Country specific testing can impact significantly on timings as there may only be a small number of laboratories sanctioned by the regulatory authorities and these may have a large backlog of work such as is currently the situation in China. Foreign companies can commission studies in China directly with the Chinese laboratories. However, in our experience, this is not advisable and it is best to use an Agent based in China who has experience in dealing with the Chinese laboratories. LSR Associates has an experienced Chinese partner company who is fully accredited and can arrange such matters on behalf of a manufacturer or importer. It is very difficult for anyone to influence the timings of the studies in Chinese laboratories, which can seem unnecessarily bureaucratic and slow to a western way of working. A particular country may also have specific requirements for the notification dossier, i.e. for final reports (or at least the summaries) in the dossier package to be translated into the language of the country or for paper copies as well as electronic copies to be submitted. Additionally, an agent or satellite company in the country of notification may be needed to submit the dossier as companies registered outside the country are not permitted to do so. In China, for example, there are very specific criteria set out in Decree no 7 (the Chinese Regulations) that an Agent must meet in order to be able to offer its services to companies registered outside of China. Currently many of the countries in the Pacific Rim that do not have a system of notification for new chemicals have put, or are in the process of putting, legislation in place to accept Globally Harmonised System classification and labelling. However, whilst it has been proposed, not all countries have the regulations in place for its implementation. There is also a transition period, which varies from country to country, during which chemicals will be accepted and in many countries this also applies to mixtures (although the timeframe is longer). In conclusion, a careful and thorough review of existing data available is needed at the outset. Then once countries have been selected for notification, country specific testing/notification requirements should be reviewed prior to the commissioning of any studies. This will help to reduce timings and costings whilst maximising the probable acceptance of submissions.

Key Points

study and a quantitative risk A toxicokineticrequired for a Level II (10-100 t/yr) assessment is recognition A mutualand Canada. system Australia notification in China. operates between

LSR Associates has performed New Chemical notifications in most Pacific Rim countries including
for Korea Look out in updates on the progress ofmonthly REACH the LSRa NewsWatch newsletter. 540 different notification types in China.