24 April 2023

Modernization of the current variations system

The pharmaceutical industry is calling for a modernization of the current variations system to reflect advancements in technology and regulatory needs. The industry is calling for a modernization of the current framework to better reflect scientific progress, improve operational efficiency, and reduce administrative burden for both regulatory authorities and the industry.

In recent years, the number of resources spent on maintaining medicinal products has increased significantly. This has resulted in generic medicine companies spending as much on 3-year regulatory maintenance as they do on R&D for new product development. The costs of variations may play a role, particularly in the generic and well-established medicines industry, on the decision to maintain some medicinal products on the market, that potentially can lead to unavailability of medicinal products on some markets.

The increase volume in variations has been attributed to several specific events. Some of these are legislative nature, such as the Falsified Medicines Directive, while others are politically driven, like Brexit. Additionally, changes in guidelines and increased requirements (safety variations) have also contributed to this trend. The number of variations per MA and per year have increased about 75% since 2010.

In 2008, the industry requested the introduction of minor variations Type 1A, which simplified the process but had the unintended consequence of increasing the overall number of variations submitted by companies. This increase in volume, especially of Type IA variations, has significantly increased the workload for regulatory agencies, making it more challenging for both companies and regulators to focus on important changes that have the most potential impact on product quality, safety, and efficacy.

Particularly optimizing the process and reducing the average time spent on processing variations (mainly Type IA) could deliver a real efficiency gain for both regulators and industry.

A lean approach that would differ from the current method of submitting variations to health authorities is requested. A non-variation based regulatory pathway should be developed to maintain purely administrative data without the need for classical variations filing. This would simplify the regulatory process and reduce the workload for regulatory agencies. Information on the supply chain or changes thereof shall be provided via digital means to the databases accessible by each health authorities (i.e. SPOR database), instead of classical variation procedures. The authorities shall have full access to the information and shall keep full visibility of the supply chain.

Therefore, minor variations Type IA/IAIN are the most appropriate for optimization of the submission process due to the administrative nature, no assessment by the health authorities, direct implementation by the MAH and no impact on the quality, safety and efficacy. In total, approximately 26 different variation updates (combined type IA/IAIN) were identified as examples that can be transformed, to ‘data only’ submissions directly to the SPOR database.

The pharmaceutical industry coalition is calling for the modernization of the current variations system as it has not kept up with the evolution of technology and regulatory requirements. The coalition suggests considering the targeted amendment of the EC Variations Regulations 1234/2008 and Variations Classification Guideline under the mandate of the new European Commission 2019-2024.