REGULATION & COMPLIANCE requirement . If they are unable to do so , they will ask the registrant for additional information .
Consequences of decision
A compliance check decision requesting additional information starts a formal process and , critically , has a hard deadline at the end of it . Not submitting the requested data by the deadline can lead to a dossier being considered non-compliant and enforcement actions started by member state competent authorities .
The deadlines set by ECHA add pressure to a situation and they are also not always realistic . Whilst they usually account for the actual time necessary to conduct a study , often no consideration is given for time needed for some of the additional – but also necessary – tasks .
For example , reputable laboratories are always in demand and space is at a premium . Waits of six months or more to start a study are not uncommon . And , when registrants are in a consortium , discussions on cost- and data-sharing can add a long delay to even commissioning a test .
Another pressure brought by the evaluation process is the cost . While it is still possible to apply Annex XI adaptations in response to a decision , ECHA will expect the SIRs to be met by the ‘ gold standard ’ experimental methods . However , when common requests are pre-natal developmental toxicity studies and the extended one generation reproductive toxicity study ( EOGRTS ) – with a likely combined cost of well over € 2 million – the incentive to ensure that such a request is not received becomes clear .
Increased detail
When considering an update ahead of a potential evaluation , the first consideration should always be to improve what is already in the dossier . It is clear from compliance check decisions I have seen , and updates to IUCLID ’ s validation assistant ( VA ) rules , that an increased level of detail is now expected compared with when REACH first came into force .
Figure 2 - Key areas of focus for improving a dossier
For example , it is not uncommon to be asked for greater detail on specific effects . Sometimes this is on a certain developmental effect , but even details that appear inconsequential can be requested during an evaluation .
One option is to provide tabulated results to help ECHA ’ s evaluators reach a conclusion on safety without having to resort to a compliance check decision or information request . You may want to consider the inclusion of historical data also , notably for the leading toxicological effect seen in a study or , for example , where you want to justify that a particular effect is not relevant to humans .
Any registrant who has attempted to use read-across as an adaptation to a SIR will know that the bar set by ECHA is very high . This area is certainly worth investing time to improve in any update , especially as dossiers with existing read-across are likely to be flagged for earlier evaluation .
Improving a read-across justification might involve generation of new data . This can be in vitro ( e . g . genotoxicity , metabolism ) or in vivo . The idea is to provide ECHA with as much opportunity to perform a side-by-side comparison of the source and target substance ( s ) as possible .
These are sometimes described as bridging studies : the OECD 422 is a good choice , as it covers a number of key endpoints ( repeated-dose , reproductive and developmental ) and thus can support read-across for several higher-tier studies , such as the EOGRTS .
The IUCLID VA is a key tool to help registrants maintain their dossiers , and the rules are regularly updated . Running the VA on an older dossier is likely to identify immediate areas for improvement . These can be either submission checks ( sometimes described as technical completeness failures ) or quality checks ( which are suggestions for improvements ). These suggestions should not be ignored ; they can include specific details of studies , which are important for an evaluator .
Remember as well that there is an additional manual completeness check carried out at ECHA after submission . This includes checks of the Chemical Safety Report and any
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