The simple steps to successful active substance renewal in the EU

In the EU, the renewal procedure for existing plant protection active substances (under the “AIR” program) requires advance planning and careful management to comply with ever-evolving regulatory requirements. Read below for practical advice on how to prepare your renewal applications and discover how Labcorp can support you.

1. Form a task force or consortium

The major difference between an application for marketing authorization of a new active substance and for renewal of an existing active substance is that renewals are likely to involve more than one applicant and will therefore take the form of a joint submission. In fact, it is expected that stakeholders with joint interest in the same active substance will reach an agreement to cooperate in the reapproval process and submit a joint dossier.

For these joint submissions to work efficiently, it is important to first establish a task force or consortium of all companies that have an interest in the active substance. With many older chemicals out of patent, the list of interested companies may be long. Therefore, by establishing a consortium, the division of all costs associated with the renewal process, such as dossier preparation and submission, can be shared within a clear legal framework. Once renewal is granted, all parties share the active substance data, which can be used for the subsequent renewal of all associated plant protection product registrations.

2. Plan ahead and start early!

Preparation for renewal needs to start several years before the active substance expiration date. In the EU, the current regulation specifies that active substance applications must be submitted three years before the end of their approval period (normally 15 years). To meet this deadline, we recommend starting the process at least two years before that (i.e., five years before expiration). This allows sufficient time for the completion of several important activities, including:

• Data gap assessment: As a first step, it is essential to review all data available for the active substance against current data requirements and guidance. This allows you to identify what data are missing or suboptimal. Regulatory experience with previous or ongoing AIR evaluations allows the provision of suitable advice on which deficiencies are and are not likely to be accepted during renewal. For this reason, advice from regulatory experts is often sought to facilitate informed decisions on how to best present and defend the current data.
• Plan for addressing gaps in data: Once data gaps have been established, the next step is to devise a plan to address them for the submission, outlining the studies that could be defended (and defense strategy) and any new studies that may need to be conducted. At this stage, the challenge is the balance of the expenditure of any new studies against the overall return from the active substance. However, having both regulatory and scientific expertise under one roof enhances the processes of decision-making and prioritization.
• Organize a pre-submission meeting with the Rapporteur Member State (RMS) or request advice from the European Food Safety Authority (EFSA): A pre-submission meeting with the RMS, who are responsible for the first evaluation of the renewal, gives applicants the opportunity to have an open discussion about the active substance and their proposed plan along with their strategy for the application. In this meeting, any critical areas of concern or uncertainty should be discussed. Experience has shown these meetings are invaluable for both parties. Similarly, renewal pre-submission advice can be requested online from the EU’s independent scientific agency, EFSA.
• Notify and conduct studies: Given careful preparation and planning several years in advance, it is possible to conduct any required studies well ahead of the submission deadline. In accordance with the Transparency Regulation, details of all new studies must first be notified to EFSA at least five months prior to their intended commission date. The list of intended studies will be published for public consultation and comments provided to applicants.
• Prepare and submit the renewal dossier: The renewal dossier for the active substance should be prepared and submitted using IUCLID software to the appropriate standards and templates required, three years before expiration. The dossier must include all requests for confidentiality, in accordance with the Transparency Regulation. It is important to build a case in the dossier that will resonate with regulatory reviewers, anticipating and answering any potential concerns.
• Respond to RMS questions during their evaluation: the time for preparing responses is usually limited, and it is important to have a clear understanding what is being asked, so seek clarification if necessary. Try to answer as fully as possible.
• Review EFSA’s confidentiality decision: Once the RMS deems the dossier admissible, EFSA will assess all confidentiality requests and publish the nonconfidential dossier for public commenting for 60 days. The applicant can resubmit the dossier to address any confidentiality decisions.
• Comment on the Renewal Assessment Report (RAR) and EFSA conclusion: It is important to be prepared to respond to the draft RAR when it is issued, 13 months after dossier submission. Confidentiality requests must be submitted within two weeks of the issue of the draft RAR. A further two weeks is given for applicants to respond to any comments collated during the public consultation phase. Comments should be reviewed objectively and the applicant should be prepared to defend all studies and provide comprehensive answers to submitted questions. Any additional data requested by EFSA should be supplied within one month of the additional data request. Once EFSA drafts its conclusion, the applicant can respond within a period of 14 days. As soon as the conclusion has been finalized (75 days after applicant comments are received), the applicant must submit any confidentiality requests within two weeks before it is made available to the European Commission for its review.

3. Consider other important elements of active substance renewal

• Literature review: A review of all scientific peer-reviewed open literature available on the active substance and relevant metabolites must be included with the application. Labcorp has access to a number of free and subscription-based databases, allowing for a comprehensive literature search that meets the criteria as set out in the EFSA guidance. We take a tiered approach to identify papers that are both relevant and reliable for inclusion and consideration in the renewal dossier.
• Harmonized classification and labeling (CLH): A proposal for classification must be submitted to the European Chemicals Agency (ECHA) to obtain an opinion on harmonized classification of the active substance. Labcorp can prepare dossiers (including IUCLID technical dossiers) for CLH under Regulation (EC) No. 1272/2008 (CLP Regulation) to support the RMS application, prepare expert statements on technical and scientific issues regarding toxicity of active substances and support customers at ECHA risk assessment committee meetings.
• Maximum residue levels (MRLs): It is important to have appropriate MRLs (and/or import tolerances [Its]) in place for all uses of the active substance, not just the representative uses included in the active substance renewal dossier. MRL application and setting is covered by Regulation (EC) No. 396/2005 (MRL Regulation). Labcorp can support applicants in the preparation of a specific addendum to include in the renewal dossier if new or amended MRLs/ITs are required.

Figure 1: The route through active substance renewal in the EU

4. Work with Labcorp – a ‘one-stop shop’ for testing and regulatory

Given the complexity of managing these long-term regulatory renewals and study programs, working with a partner to support your submissions can be of great added value, ensuring effective communication and a clear agreement of roles and responsibilities to optimize the partnership.

Labcorp has a large team of independent regulatory consultants, scientific experts, experienced program managers and safety testing experts, all under one roof. Our regulatory consultants support our customers in all stages of the renewal process, possessing in-depth knowledge and decades of experience. Our global reach allows us to design studies that will not only satisfy EU but also global regulatory requirements.

It is important to be bold but realistic during the renewal process; look at your existing studies and plan a robust defense.

Also, remember that renewal of an active substance is an ongoing process and is only one step toward meeting your commercial objectives. The next stage is the renewal of products, introduction of new products and extensions of use of existing products containing the active substance. Advance preparation and attentive management of EU product submissions are equally as important.

All over the world, crop protection businesses face an ever-changing commercial and regulatory landscape—and with planning, partnership and a good CRO in place, you can accelerate your time-to-market.

Learn more about our Crop Protection Services.