Reliance for post-authorisation changes: pilots for the pharmaceutical industry

The European Medicines Agency (EMA) collaborates with national authorities from countries outside of the European Union (EU), with the World Health Organization (WHO) and with the pharmaceutical industry to test a global model for handling major post-authorisation changes. This happens via pilot programmes that enable national authorities to use EMA's assessments to inform their own decision-making processes. This approach is based on the principle of reliance. It can help authorities streamline processes, make better use of resources and facilitate patient access to quality-assured medicines.

EMA and WHO are supporting a pilot programme that enables pharmaceutical companies to submit EMA-approved post-authorisation changes (i.e. variations) to multiple non-EU national authorities.

These pilots allow national authorities to use EMA's assessments to reach their own regulatory decisions. This happens almost simultaneously with the related post-authorisation changes. It is called a concurrent review. 

National authorities keep full scientific and regulatory independence in their decision-making.

Pharmaceutical companies take the initiative to start a pilot.

As of February 2025, there are 10 ongoing pilots involving up to 100 national authorities. They mostly cover major quality-related post-authorisation changes that can impact the supply of medicinal products.

For more information, see:

• Multilateral coalitions and initiatives
• World Health Organization (WHO)
• Post-authorisation

Pilot objectives

The reliance pilots aim to accelerate review and approval timelines. They do so by exploring relevant regulatory pathways, in line with WHO's good reliance practices.

They also aim to:

• facilitate patient access to quality-assured medicines;
• make better use of resources;
• help authorities align on regulatory requirements, also referred to as convergence;
• improve transparency between the pharmaceutical industry and regulatory authorities, and among regulatory authorities.

Regulatory authorities use reliance extensively when they approve medicines. However, they do not apply reliance widely to assess post-authorisation changes. These changes can be complex, time-consuming and unpredictable, which increases the risk of shortages.

Insights and recommendations from these pilots will help achieve a more efficient global model based on standardised reliance practices to assess post-authorisation changes. This will benefit both regulatory authorities and the pharmaceutical industry.

For more information, see:

• World Health Organization good reliance practices in the regulation of medicinal products

How to apply for pilots

EMA invites pharmaceutical companies interested in participating in a pilot to contact EMA at [e-mail].

Applicants must submit the same documents to all participating national authorities, as indicated below:

• Variation package, as used in the EU
• EMA's Committee for Medicinal Products for Human Use (CHMP) final assessment report and approval letter

Applicants can also submit a question-and-answer document. It should contain an overview of the pilot and details about the post-approval changes. If applicable, it can also cover any information on good compliance practices.

They should comply with mandatory local requirements and respect the classification of post-authorisation changes set by each participating national authority.

National authorities have the option to fully or partially rely on EMA's assessment. They must still adhere to their own regulatory and legal frameworks.

They should also try to align country-specific requirements to EMA's documentation requirements.

Early dialogue and clear communication between the applicant and national authorities is key for the success of a pilot.

Pilot steps

The timeline below describes the recommended steps of a pilot.

The steps can be split into two phases:

• Engagement - where applicants present a pilot to national authorities
• Execution - where the national authorities assess the post-authorisation changes and make their decision

These steps are expected to take around 6.5 months.

1. Applicant interested in a pilot contacts EMA

   Applicant should provide EMA with a question-and-answer document detailing the pilot's steps

2. Applicant engages with national authorities

   Applicant checks the interest of national authorities in participating in the pilot

3. Kick-off meeting between applicant and national authorities (optional)

   National authorities receive information on the pilots and post-authorisation changes

4. Applicant submits documentation to all national authorities per their regular submission processes

   Applicant shares the same documentation to all national authorities, including variation package, EMA assessment report, approval letter, questions and answers, and good manufacturing practices certificate (if needed)

5. National authorities review submitted documents and ask questions to the applicant

   National authorities share their questions with the applicant. They can also ask EMA for clarifications on its assessment report

6. Applicant replies to the questions from national authorities

   Applicant can optionally share responses to all received questions with all national authorities, who can use it to support their own reviews.

7. National authorities make their independent decisions

   Approval or refusal of post-authorisation changes
8. Show more 4 itemsHide 4 items

Pilot metrics

There are a few important metrics that applicants should collect to evaluate the performance of a pilot. Find them below:

• Country engagement - which countries were involved in a pilot, percentage of countries that accepted to participate and reasons for countries not wanting to join a pilot
• Level of reliance - whether national authorities can recognise EMA's assessment or whether they need additional scientific evaluation
• Time - how long did national authorities take to approve the post-authorisation changes
• Level of harmonisation - how many additional changes the applicant made to their dossier to comply with local requirements
• Potential resources saved - both time and human resources needed to manage the post-authorisation changes submitted

EMA role

If required, EMA can hold pre-submission meetings to discuss a pilot.

If needed, it can also:

• attend a pilot's kick-off meeting alongside WHO - in these meetings, applicants provide national authorities with details on the post-authorisation changes, timelines and pilot logistics;
• offer national authorities the opportunity to seek clarifications on its assessment report from the team that produced the report and the rapporteur;
• provide applicants with an invitation letter which they can share with interested national authorities;

Furthermore, EMA supports the pilots with other activities, including:

• informal discussions with applicants to discuss the pilots and high-level principles of reliance;
• ad-hoc updates on the progress of the pilots;
• discussions in relevant platforms on lessons learned, ways forward and reliance models.