Animal health and feed additive products are crucial for maintaining the well-being and productivity of livestock and companion animals. By providing essential nutrients, managing health conditions, and optimising feed quality, these products help ensure the welfare of animals and the production of safe, high-quality food products.

However, bringing animal pharmaceutical and feed additive products to market is a long and difficult process. A complex regulatory landscape exists with a wide range of requirements in quality, safety and efficacy/utility documentation and studies that must be met before a product may be approved. That landscape is further exacerbated by differences in requirements between regions and product categories.

Successfully navigating this regulatory landscape can be a significant challenge for product developers, especially those new to the regulatory approval process. Misconceptions about timelines, product categories, and regulatory requirements can lead to lengthy delays and increased costs. For feed additives, the best-case scenario for generating data, submitting an application and gaining approval from the relevant regulatory authority after the review process could be 3-4 years while, for health products, this may take 6-8 years. In either case, however, the data generation and approval process can be delayed by years if a comprehensive and complete dossier is not submitted or if studies must be redone.

To mitigate the risk of delay and its fiscal impact, complying with the relevant guidelines and regulations is critical from the outset of product development. In this article, we shed light on the common challenges that occur on the journey to regulatory approval for animal health and feed additive products and demonstrate how planning and partnerships can help you navigate this complex landscape. Specifically, we will cover:

• Keeping up to date with current regulatory guidance
• Product formulation challenges
• Manufacturing and site qualification
• Safety and residue testing and setting tolerance levels
• Study site identification and patient recruitment for animal health products
• Compiling data packages for the US and Europe

Through understanding the common challenges and strategies for navigating the regulatory landscape, developers can enhance their chances of success and bring products to market more efficiently.

Demystifying common regulatory challenges for animal nutrition and health products

There are several key bottlenecks and challenges in regulatory approval that product developers should consider as they approach quality, safety, and efficacy/utility testing. Each of these challenges has the potential to delay timelines and add significant costs during the product development and submission process.

Keeping up to date with current regulatory guidance

Regulations and guidelines evolve as regulatory authorities keep up with new safety data, novel techniques, and government policies. As a result, the regulatory landscape can shift substantially during the years required for product development, potentially leading to unforeseen changes in requirements. But, there are steps developers can take to help mitigate risks. For example, in the US, developers are encouraged to work with the Center for Veterinary Medicine (CVM) to agree on the pivotal clinical study protocol prior to conducting the study. This allows product developers to mitigate the risk of regulatory changes affecting their clinical study.

It’s important to note that the health and feed additive spaces are regulated separately, with feed additive guidance updated more frequently in the European Union — typically every two to three years. Accordingly, product developers need to stay informed about potential regulatory changes on the horizon. By closely monitoring regulatory updates, developers can stay ahead of a curve and ensure their planned product testing and data dossier meet the latest requirements.

Product formulation challenges

A major challenge in product development is demonstrating the safety and efficacy/utility of a product, while ensuring that the final formulation is well characterised. Generating the necessary data to support the dossier is often a time-consuming and expensive process, especially for complex formulations requiring multiple iterations in clinical development.

As a result, the complexity of the formulation and robust data needed to support regulatory approval can create significant challenges for product developers. The risk of delays can be reduced with careful planning around the regulatory requirements regarding formulation and investing early in its development.

Manufacturing and site qualification

Good manufacturing practice (GMP) standards are essential for regulatory approval of animal health products. CVM/European Medicines Agency conduct regular inspections to ensure cGMP compliance. While GMP requirements apply to all manufacturers, there are more obligations for organisations importing investigational veterinary medicinal products manufactured outside of the region. These requirements, if not considered early, can lead to delays and additional costs.

Furthermore, in the US there are additional requirements for importing investigational medicinal or feed additive products. For instance, importing medicinal products requires appropriate notification to the FDA of the Investigational New Animal Drug holder.

Safety and residue testing and setting tolerance levels

Residue and tolerance testing are essential components of the regulatory approval process for veterinary products affecting food-producing animals. Designed to demonstrate safety of your product for human consumption, these studies are required to establish tolerance levels for compound residues in food products. However, conducting residue and tolerance testing poses unique regulatory challenges for product developers.

One challenge is generating new data to establish tolerance levels, which has to be done even if another sponsor has previously provided human food tolerance data for the same compound. Without their own raw data, or if it is not sufficient to ‘reset or confirm the tolerance’, the regulatory approval process can be delayed.

In both the US and EU, human food safety testing may require radiolabelled studies to track the depletion of compounds through the animal’s body and into food products. However, performing these studies can be difficult as they rely on specialist equipment, expertise, and study sites. Product developers must take a proactive, regulatory-focussed approach to food residue and tolerance testing to minimise delays and ensure their studies are compliant with regulatory requirements.

Study site identification and patient recruitment for animal health products

Clinical field studies are critical components of the product development process for medicinal products, but they have the potential to cause major delays. While good communication with the regulatory authorities is essential for planning and approving protocols in line with current guidance, logistical issues associated with setting up clinical field studies often prove to be the most common challenges. For example, identifying appropriate study sites and recruiting patients can be significant bottlenecks, particularly where patients are limited in your target indication.

Furthermore, clinical field study data are essential for regulatory submissions, and can take weeks or months to complete. Delays at the outset of these studies can significantly impact the approval timeline, leading to lost resources or increased costs. Product developers can ensure a smoother path to regulatory approval by building strong relationships with regulatory authorities and other clinical stakeholders to conduct thorough logistical planning around site identification and patient recruitment.

Compiling data packages for the US and Europe

While the US and EU share a common goal of ensuring robust quality, safety, and efficacy/utility data, they have different standards and requirements for submitting data. Consequently, submitting the same data package to regulatory authorities in both regions is insufficient. While there may be some overlap in the data required by each authority, developers must carefully plan their study designs and data dossier compilations to meet the unique submission and assessment requirements of each region for their chosen product category.

To optimise cost-effectiveness and efficiency in the submission process to authorities in multiple regions, product developers should thoroughly assess testing requirements. For example, it may be that there are simple measures that can be taken to ensure one study adheres to both US and EU requirements rather than having to complete two studies. By proactively addressing these requirements, developers can minimise delays and ensure that each dossier aligns with the submission guidelines of the respective authority.

Roadmap to regulatory success

In the complex regulatory environment of animal health and feed additive products, there is potential for delay and increased costs at every step of the development and approval process. Product developers can help mitigate these risks for their organisations by preparing for the regulatory submission journey as early as possible in the development cycle.

A regulatory roadmap to inform your development plan

Mapping the route from product categorisation to regulatory approval can help inform the product development plan, establishing relevant milestones, timelines, and potential costs. Having these identified early can help your organisation manage expectations with stakeholders and secure sufficient funding prior to embarking on the long and costly product development and approval journey.

Furthermore, comparing existing data with an up-to-date regulatory roadmap may reveal if it can be used for dossier submission. Some early testing, particularly around product composition and quality, may already meet existing guidelines and not require additional testing. Careful monitoring of the regulatory horizon for potential changes to guidelines and regulations should be factored into the regulatory roadmap to avoid unnecessary repetition of costly tests during product development.

Build relationships with CRO/CDMOs with regulatory expertise

Delays in the regulatory approval process can have significant repercussions, potentially leading to increased development costs and underserving both consumers and animals. To mitigate risk of delay, product developers must cultivate beneficial relationships with a range of stakeholders, including the regulatory authorities, manufacturers, clinicians, and regulatory experts to ensure that their roadmap supports the product development plan.

Partnering with an animal health CRO/CDMO with deep regulatory expertise can help you curate your regulatory roadmap and development plans as you progress through the product development cycle. Such partners can perform a gap analysis to identify what data are missing and which tests must be conducted, and also provide clearer visibility of the project’s costs and timings. By maintaining the regulatory roadmap/gap analysis as a living document, the development plan can be updated as gaps are filled, or as timelines or costs change.

Animal health CRO/CDMOs with regulatory experts can also help mitigate some of the general challenges faced by product developers from the outset. Many of the processes performed in early development such as formulation and product release profiling generate data that can be used in the regulatory submission, but only if it meets standards set out in the guidance. If you partner with an organisation with both development and regulatory capabilities, they can easily coordinate on specific data requirements, thereby helping to de-risk and streamline development processes in line with regulatory requirements.

CRO/CDMOs can also help with identifying correct product categorisation, informing on realistic timelines at each stage of product development, and providing insight to changing guidelines. Additionally, if a developer is seeking approval in both the US and EU, guidance from partners with experience in both regions may provide information on overlapping requirements and how to streamline costly testing processes.

What’s more, animal health CRO/CDMOs can ensure quality standards are met throughout the product development cycle and that the product is correctly characterised when the final formulation is established. In addition to adhering to required safety and GMP standards for manufacturing, CRO/CDMOs can also assist in identifying appropriate test sites and organise patient enrolment, minimising the risk of delays to already lengthy safety and efficacy/utility study periods.

Plan ahead and partner to ensure success

Navigating the regulatory landscape for animal health and feed additive products can be a daunting task, but it is necessary to ensure quality, safety, and efficacy/utility. Although the road to regulatory approval can be difficult and costly, the benefits of bringing a new product to market are clear: happier, healthier, and safer animals.

To overcome the numerous regulatory challenges and ensure a smoother path to approval, product developers must take a proactive and strategic approach. This includes planning early and integrating compliance measures into the product development process, as well as partnering with animal health CRO/CDMOs with expertise in regulatory affairs. By working closely with these experts, product developers can ensure that they meet all regulatory requirements and avoid potential setbacks, ultimately accelerating time to market and enhancing product success.

Are you ready to navigate the complex regulatory landscape? Let Argenta be your guide to help you ensure compliance while accelerating your path to success. Explore our comprehensive regulatory services today: https://www.argentaglobal.com/solutions/regulatory-services