Analysis of EU Pesticide Renewal Program Case Study of Prothioconazole

The European Union (EU) is a region with a stable demand for pesticides. According to Eurostat, from 2011 to 2018, the sales of pesticides remained at a consistent level of about 360 million kilograms per year.

In addition, the Member States of the EU, such as France, Spain, Italy and Germany, are in a leading position in the world in terms of both the level of agricultural development and the scale of agriculture. One can say that the pesticide in the EU still has great market potential, and the union is a good choice for strategic layout and development for pesticide manufactures.

How can pesticide companies enter the EU market? The most cost-effective way is to apply for the technical equivalence assessment for the technical material, that is, TE assessment. The TE assessment relatively has a short evaluation workflow, and the cost is low. Generally, companies only need to spend less than US$10,000 to get the approval letter within a few months or one year, and then their products can enter the EU market.

（Source: Eurostat）

TE assessment is a stepping stone for enterprises to enter the EU market, but TE is not enough for enterprises to better carry out market layout when the door is opened. According to the EU pesticide regulations, the registration of pesticide formulations requires two sets of data, one for technical material and the other for formulation. The manufacturers generally prefer to purchase the technical material from owners with a complete set of application data to support their pesticide registration.

Due to the lack of registration data, TE source owners cannot support the registration of downstream manufactures, so there will be certain restrictions on sales. Generally, TE sources can only be sold as an alternative source to those who can complete the registration of pesticides by their own. Sales profits will also be limited. If manufacturers of TE sources hope to take greater initiative in the EU market, joining the pesticide renewal program will be a solution for them.

After participating in the renewal program, the technical material approved during the renewal will become a reference source, which can be legally sold in the EU, and have greater autonomy in sales because of the full set of technical material data. In the subsequent trade, customers can be freely selected, and it will be relatively easy to obtain customers than other sources, and sales can obtain higher profits.

In addition, participating in the renewal can help keep abreast of the situation of the renewal at any time, help applicants avoid artificially set up technical barriers to trade through ways such as specification revision, and become a rule maker rather than just a participant in the game.

We all know that the management system of pesticides in the European Union is stringent, and the requirements for pesticides are very high. Therefore, if the products are officially recognized through the EU renewal and become a reference source in the EU market, it is high recognition of product quality and a high-quality plus for the enterprises to carry out brand promotion.
Based on the above reasons, although the cost of pesticide renewal is relatively high and the cycle is relatively long, this investment is necessary for leading domestic pesticide manufacturers.

I. EU pesticide renewal program

1. Introduction to Renewal Program

According to Regulation (EU) 1107/2009, the EU implements a periodic renewal system for pesticides. In recent years, the renewal regulations have changed frequently. The original Regulation (EU) No 844/2012 has gone through three major updates and is now replaced by Regulation (EU) 2020/1740. The new regulation will apply to active substances for which the approval date ends on or after March 27, 2024, (excluding substances that expire after March 27, 2024 due to an extension of the expiry date). Active substances expiring before March 27, 2024, remain subject to Regulation (EU) No 844/2012.

According to the renewal regulations, the validity period for approving active pesticide substances in the EU is generally 10 years (excluding low-risk pesticides and pesticides candidates for substitution). Before the expiry of the approval period of an active substance, it is necessary to start the renewal process to complete the evaluation before its expiration, realizing the smooth renewal of the approval period. At present, if pesticide enterprises plan to support the renewal, a full set of data meet the data requirements of Regulation (EU) 283/2013 and Regulation (EU) 284/2013 to be submitted to the EU at least three years before the expiry date of the active substance approval. The data requirements are the same as the current data requirements for new substance approvals.

Why would an applicant need to submit new data when the data requirements are the same for renewal and initial approval? Prothioconazole is taken as a case study to clarify.

According to the renewal application data submitted by Bayer in 2015, the renewal data file included new data in product chemistry, analytical methods, toxicology, ecotoxicology, environmental fate, and residue. The main reasons for submitting new data are as follows:

1) Changes in legislation. Prothioconazole was approved in 2008 under Directive 91/414/EEC, the predecessor of the current EU Pesticide Regulation, however the renewal was required in accordance with Regulation (EC) No 1107/2009. Due to the change of the regulation, the data requirements also changed. The renewal proponent will then need to submit new data to meet the new requirements.

2) Change of guidance documents. For example, in the part of analytical methods, the referenced guidance documents SANCO/3030/99, SANCO/3029/99 and SANCO/825/00 have been updated in the EU in recent years, and applicants need to carry out tests and provide corresponding data following the requirements of the new guidelines.

3) With the progress of science and technology, new test methods are available to perform the tests that could not be performed before.

4) Typical formulation change. In this renewal, in addition to the same specific preparation as the original substance approval, Bayer has added a new typical preparation, and the two preparations are different in composition and use, so new data needs to be supplemented.

2. Revision of Renewal Rules

The change of renewal regulation is also accompanied by a series of changes in implementation requirements. Based on years of experience with EU regulations, the author believes that the current renewal regulations are more friendly to applicants due to the reasons below.

1) Study notification requirements. According to the latest guidance document issued by EFSA in March this year, after March 27, 2021, the applicant is suggested to notify EFSA at least five months applying to the studies planned to support the renewal. Studies submitted directly without notification will have a risk of rejection during evaluation. Although the process becomes more cumbersome, it avoids the risk of applicants running unnecessary or unsuitable tests.

2) Changes in dossier format. The original dossier format for EU pesticide registration is CADDY, which is very difficult to make. In addition to experts in registration, it is also necessary to get involved in IT experts or turn to a special software company to help. Under the new regulations, the dossier format is changed to IUCLID, which is the same format as other EU regulations such as REACH and BPR. The difficulty of dossier compilation is greatly reduced.

3) Information transparency. According to the Transparency Regulation, the whole process of renewal will be more open and transparent. The dossiers submitted by applicants and official evaluation records of authorities, will be made public in OpenEFSA in a timely manner, and stakeholders will have easier access to this information than in the past. In addition, EFSA has launched Connect.EFSA to strengthen the good communication between the applicant and the assessor in the evaluation process and promote the smooth progress of the renewal work.

II. Analysis of EU Renewal Strategy

Participating in the EU pesticide renewal is a big decision for pesticide enterprises, and careful planning is needed. What should we pay attention to during the decision-making stage? The author believes that three “Rights” need to be considered: right time, right place and right substance. The three “Rights” will be analyzed in detail accordingly.

1. Right Time

In the European Union, after the approval of a new active substance, other technical manufacturers can only enter the market through TE assessment for most of the time. The EU has a unique work plan for pesticide renewal. If pesticide enterprises want to participate in the renewal, they must join under official renewal schedule. At present, there are six Active Ingredient Renewal Programs (AIR-Program). Each program is created generally based on the active substance approval period.

Taking Prothioconazole as an example, Bayer applied for substance approval of Prothioconazole to the United Kingdom on March 25, 2002, which was approved on August 1, 2008, with a validity period of 10 years and a deadline of July 31, 2018. Prothioconazole is a substance in the AIR-3 program according to its expiry date.

According to the renewal regulations, the applicant must submit the application for renewal three years before the expiry date, that is, before July 31, 2015. According to the relevant work plan, Bayer is the only supporter of Prothioconazole renewal, and they applied for renewal on July 28, 2015.

（Source: EC working document）

Anyone missing the deadline for renewal submission will not be allowed to apply. After the deadline, anyone who wishes to participate in the renewal can only negotiate with the existing renewal applicants to form a task force. At this point, the decision is in the hands of the current renewal applicants. Therefore, enterprises willing to participate in the renewal must pay attention to the approval period of the target active substance and the working document of AIR programs, making sure to apply for renewal to the authorities in time.

According to related regulations, the review period of the technical material takes nearly three years, but in recent years, most of the reviews have been postponed. For example, although Bayer applied for the renewal of Prothioconazole in 2015, the evaluation is still not complete, and the expiration date has now been extended to July 31, 2022. The EFSA review record suspended the review from October 22, 2018 to March 15, 2020 to allow the applicant to prepare additional information to support the application. The review was suspended again on October 16, 2020, due to the need for more data for endocrine disruption assessment. The review is expected to be relaunched after April 15, 2023. Therefore, the validity period of prothioconazole should continue to be extended.

(Source: EFSA website)

After the active substance renewal is completed, the renewal of the plant protection products will follow. Taking prothioconazole as an example, the number of prothioconazole formulations registered and the registration certification holders are relatively large. The countries with the most registered products are the United Kingdom and France, with more than 100 products. In addition, Germany, Belgium, Italy, Poland, and Sweden also have dozens of registrations. In addition to Bayer, there are dozens of registration certification holders, including Clayton Plant Protection (UK) Limited, SAGA SAS, GRITCHE, Life Scientific Limited, etc. Due to the postponement of the active substance renewal, the registration validity period of the preparations was also extended accordingly. For prothioconazole, the current registration validity period of trials in various member states have been extended to after 2022 or even later.
 
2. Right Place

Although the active substance renewal is conducted at the EU level, there will be a rapporteur member state (RMS) to perform the first step of the dossier review, issue an RAR (Renewal Assessment Report), and then submit it to EFSA for peer review and issue the final risk assessment report.

The choice of RMS has a huge impact on the overall assessment. At present, due to the impact of Brexit, the workload of Member States is very heavy, which is also an essential reason for the postponement of the EU's renewal programs in recent years. In addition, the evaluation capability of EU Member States varies greatly, and not every country can conduct an independent evaluation. The Czech Republic assesses different data such as product chemistry, toxicology, etc. by different departments, and the applicant needs to contact multiple PMs. As a result, the applicant's active and effective communication with RMS during the review process will be affected. Besides, different Member States have different evaluation styles; for example, Belgium has relatively more strict requirements for revaluation. Finally, Member States charge differently for the assessment. For instance, for the renewal of active substance, Sweden will charge up to €500,000 for the evaluation fee, while Germany will charge between €127,000 and €251,000.

According to the regulations, the RMS of renewal is designated by the European Union rather than being nominated by the applicant, so it is very important to know the style of the RMS. Being familiar with the "temperament" of the RMS will help with smoother communication during the review.

3. Right Substance

Whether the active substance will be banned is a popular topic that the renewal applicants should pay attention to. Choosing the right substance to support can prevent enterprises from flogging a dead horse. For pesticide registration, having a safe use has been a determining factor in the approval decision. But the European Union is not a completely risk-oriented region. In certain circumstances, the hazard of the active substance also plays a decisive role in whether the substance can be approved. Based on the risk of use and the substance hazard, the EU has banned many active substances of pesticides, which also makes it a very difficult area for pesticide registration.

According to Regulation (EC) No 1107/2009, there is a cut off criteria for approving an active substance. If one meets this criterion, the EU will not conduct a risk assessment on the active substance but directly prohibit its use. The cutoff criteria are as follows:

1) For human health, a substance is prohibited if it is classified as a CMR substance or an endocrine disruptor;

2) Environmentally, a substance is prohibited if it is regarded as PBT, POP, or vPvB.

For example, because prothioconazole and its metabolites may have potential endocrine-disrupting effects, the applicant is still supplementing additional information to exclude its endocrine disrupting hazards.

This article was initially published in AgroPages' '2021 CRO & CRAO Manual' magazine.

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