Samer Aburous, senior expert global notification Symrise AG, discusses how best to ensure acceptance of data in multiple jurisdictions.
Compliance with global chemical management regulations is crucial when it comes to the worldwide marketing of chemical materials. One of the major pillars of chemical compliance is the availability of data on the properties and effects of chemical substances. Hence, companies need to consider the global acceptability and permissibility of their data, to avoid undesirable business conditions caused by possible fines, delays and expensive remedies as a result of non-compliance through inadequate data.
Chemical substances are widely used in different areas of our daily life such as food, medicine, personal care, home care, pesticides and in many other personal, professional and industrial applications. This wide use and resulting exposure require ensuring production, use and disposal is safe by means of safety assessments based on the properties of the chemicals of concern.
Many jurisdictions demand testing data to comply with their legislation for managing and controlling the use of chemicals in different applications. There are variations in the types of data required under different laws; however, much of this is in common between many of the regulatory systems.
Data on chemicals can be obtained using different approaches, such as laboratory testing, quantitative structure activity relationship (Qsar) and read-across (RA). Existing testing data can also be purchased from other parties for use under different systems. To ensure the global acceptance of data and their optimal use, companies need to have a wide vision of the prospective data needs and the requirements applied in different regions and systems.
When considering laboratory testing, several points need to be taken into account depending on the planned use of the resulting data.
Accreditation and testing guidelines
Firstly, the testing lab needs not only to have the experience and knowledge to perform the study, but also should have the required accreditation, such as OECD good laboratory practice (GLP) or other local certifications. Some chemical control legislation requires certain studies to be performed in a domestic testing laboratory.
The selection of the testing guideline is also important. OECD testing guidelines are widely used and accepted but some systems may have specific requirements regarding the tested species and level of detail asked for in the study report. But also some of the new OECD testing guidelines may not be yet validated in some regions.
‘Some of the new OECD testing guidelines may not be yet validated in some regions’
It is strongly recommended to find out the specific requirements of the regulatory regime under which the data will be used and to communicate that in a timely fashion to the testing laboratory.
Examples of such requirements include:
- China requires biodegradation and some ecotoxicity studies to be performed in accredited testing labs in China, using Chinese species (where applicable);
- study of partition coefficient for the South Korean CCL (the Korean Act on the Registration and Evaluation of Chemical Substances) needs to be performed under GLP conditions; and
- Japan’s chemical regulation requires a higher level of documented details in the testing reports of some studies. The testing laboratory may need to use a different template to comply with this.
Furthermore, particular attention needs to be paid to the appropriate identification of the test subject, which is key in judging the reliability of the generated data. It is not advisable to only use the commercial name. The chemical identity (chemical name and Cas number), purity and impurity profile (for example, gas chromatogram) needs to be well documented and preferably included in the test report.
Sharing data
Existing testing data may be shared between companies and this holds benefits for both data holder and grantee. Purchasing existing data will normally reduce the time and cost of completing the data set for any specific registration. The following considerations are key in deciding whether to perform a new, or purchase an existing, study:
- availability and reliability of existing data: upon confirming that a specific study is available, it is essential to check that the documentation and details are adequate to judge its quality and reliability;
- type of data (for example, data on animals): all possible efforts need to be made to avoid performing, or even worse repeating, a study on animals. Maintaining animal welfare principles should be given highest priority;
- planned use of the purchased data: knowing that purchasing data for multiple-use (multiple regions and/or multiple legislations) will cost as much as a new study, it may be wise in this case (with the exception of animal studies) to perform a new study to have all the advantages of a data holder; and
- budget and time constraints: obtaining access to existing data is normally faster and cheaper, particularly for long-term and repeat-dose studies.
Finding existing data on a specific chemical may not be an easy task but rewards the effort, especially when it comes to animal studies. It is worth pointing out that all known names and identifiers of a chemical need to be used when searching for corresponding data. The following websites and services are useful for finding existing data:
- Echa;
- the AMBIT chemical safety prediction tool;
- databases such as Pubchem, ChemIDplus, eChemportal;
- the OECD QSAR toolbox;
- the US-EPA chemistry dashboard; and
- Australia’s Nicnas website.
Before purchasing access to an existing study, its quality and reliability needs to be carefully assessed. Give particular attention to the testing method used and laboratory qualifications, test item identity, documentation of testing conditions and results.
Additionally, any deviations from the standard testing guidelines should be evaluated critically. In some cases, the availability of an original study report in hard form may represent a determining factor because some systems (for example, cosmetic ingredient registration in China) require the submission of these.
Agreements on data sharing are essential to regulate the conditions and terms under which access to data is given. Standard agreement templates, provided by industry associations, can be used to manage data sharing for different purposes and regions. However, companies need to properly adapt the template and use the correct terminology to reflect the conditions of sharing. In particular, special attention needs to be paid to adjust the clauses related to the specific purpose of sharing (registration, reporting, internal assessment), validity area, responsible authorities and the correct name of the legislation (when applicable).
Qsar and RA
Qsar and RA approaches can be also used to fill in some data gaps. However, such data may not be accepted in some regions. It is important to ask for advice from the responsible authority or a consultant before preparing and submitting data based on these approaches. Generally, Qsar and RA data are accepted in Europe, China, USA, Canada, Australia, Korea and the Philippines.
‘For other more complex properties and substances, Qsar models may not be reliable but may provide data to support other approaches’
Different free and commercial models are available to generate reliable Qsar data on some physico-chemical and environmental toxicity and fate properties of mono constituent substances. For other more complex properties and substances, Qsar models may not be reliable but may provide data to support other approaches.
The scientific validity of the Qsar data is confirmed by following the five OECD principles. More than one valid model can be utilised for an endpoint, taking the outcome of the most reliable as the key result supported by results from the other models. Good documentation of the model used and results obtained will help in the evaluation of the generated data and increases the likelihood of its acceptance.
Unlike the Qsar approach, the RA approach can generate data on many properties and be used with multi constituent substances and UVCBs, given that the constituents of both the target and source substances are well identified. Availability of testing data is an essential element in selecting source substances; however, special attention needs to be given to the similarity to the target substance, bearing in mind also the involved chemical functional groups and their relevance to the addressed endpoint.
Again, the importance of good documentation of RA data should not be underestimated, and the report needs to account for the following points:
- RA hypothesis;
- identity of source and target chemicals, including their purity and impurity profiles;
- data matrix for source and target chemicals;
- justification of RA approach; and
- conclusion.
The evolving nature of chemical management regulations requires careful and continual monitoring of changing data requirements and use possibilities. Additionally, available tools and search engines need to be utilised well to generate alternative, or look for existing, data on chemicals.
Dedicated training is required for some tools (for example, the OECD QSAR Toolbox) but this is worth the time. Comprehensive and long-term compliance plans make decisions on data collection simpler and more efficient.