Industry officials: Varied global postapproval change requirement pose challenges for drugmakers

BASEL, SWITZERLAND – Multiple country-specific requirements for postapproval changes are affecting drugmakers’ ability to implement changes in manufacturing facilities or processes. This situation leads to unpredictable timelines and potential delays in providing access to improved medicines. This was highlighted by two industry representatives during a session at DIA Europe 2025 on 19 March.

Officials also highlighted the findings of a recent report from the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) in collaboration with Clarivate. The survey revealed notable differences in the level of convergence regarding postapproval changes across 21 countries in the Middle East, Africa, Latin America, and the Asia-Pacific region that are members of the World Health Organization (WHO).

Angelika Joos, executive director of science and regulatory policy at MSD, pointed out that divergent postapproval change requirements hinder modifications to pharmaceutical products.

Joos indicated that, due to this divergence, companies must prepare to submit to multiple change requests to authorities and be able to manage their existing inventory to ensure enough product availability until the change is approved.

“The different submission timelines are something that we have to consider. In some regions, it is very fast, and in some regions, it is long. In some regions, it is predictable, and in some areas it is unpredictable. It is a very complex change management process because you have to think how long it will take to get the change approved, so how much inventory do we have to build up from the old manufacturing sites.”

She said there is a risk of a drug shortage if the old inventory is exhausted before changes are approved. There is also delayed access to medicines and vaccines with the latest process or capacity enhancements.

Changes submitted in the EU or the US as minor that are submitted globally through standard pathways have long review timelines and often require more data to support the change.

Joos said that to comply with these diverse requirements, companies must dedicate a significant workforce to generating and maintaining additional country-specific documentation.

The complex regulatory framework complexity ultimately has a “ripple effect” on patients’ access to the latest medicines and vaccines, impacting process, quality and capacity enhancements, she said.

She added that many markets do not have “do and tell” or “tell, wait, and do” pathways for postapproval changes as part of their regulatory frameworks.

Joos stated that the industry is currently focusing on harmonizing and submitting a global core dossier to as many regulators as possible. This work is being conducted under the auspices of the International Council for Harmonisation (ICH), the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S), the World Health Organization (WHO), and the Pharmaceutical Quality Knowledge Management (PQKM) pilots conducted under the auspices of the International Coalition of Medicines Regulatory Authorities (ICMRA).

IFPMA survey

Isabelle Colmagne-Poulard, head of international global regulatory and scientific policy at Merck, said that there is a significant level of divergence among WHO member countries regarding postapproval changes, referencing the IFPMA Clarivate report.

The survey highlighted wide variability in the postapproval change requirements among 21 countries it looked at. It compared the degree of alignment of specific postapproval changes for pharmaceutical products in these countries with the WHO guideline, Guideline on procedures and data requirements for changes to approved biotherapeutic products under Annex 3, TRS No. 1011.

The countries included in the survey were Argentina, Brazil, China, Colombia, Egypt, Ghana, India, Jordan, Malaysia, Mexico, Nigeria, Peru, Rwanda, Saudi Arabia, Singapore, South Africa, South Korea, Taiwan, Thailand, Turkey, and Vietnam.

The survey indicates that the highest level of convergence pertains to pharmacopeial changes, while the lowest level is related to facility changes.

In APAC countries, 76% of the members had low convergence with the WHO guidelines, while 11% demonstrated medium convergence and 13% showed a high level of convergence.

Among the countries in Latin America, 58% had low convergence, 36% had medium convergence, and only 6% achieved high convergence with the WHO guidelines.

For countries in the Middle East and Africa, 62% had low convergence, 13% had medium convergence, and 25% had high convergence with the WHO guidelines.

A low convergence level indicates that one or none of the three Chemistry, Manufacturing, and Controls (CMC) parameters set by the World Health Organization (WHO) are in alignment. A moderate convergence level occurs when two of the parameters align with WHO guidelines, while a high convergence level indicates that all three parameters are fully aligned. These parameters include categories of changes, requirements for supporting the change, and approval timelines.

Colmagne-Poulard indicated that the upside from the survey is that all 21 countries have regulations concerning variations, all utilize a risk-based system for classifying postapproval changes, and all maintain timelines for approvals.

“I believe that global regulatory convergence, utilizing a scientific and risk-based approach, allows for more efficient management of postapproval changes, particularly when tailored for biologics. There is excellent guidance available, especially from ICH Q12 and WHO on change control,” shse said.

In the GMP realm, Stephan Rönninger, director of quality compliance for external affairs for Amgen in Europe, questioned the need for country-specific import testing for products in countries that are participating in mutual reliance activities such as participating in PIC/S or the pilots conducted by ICMRA.

“Why … do you have to do this import testing? It causes waste and destroys good medicines; you ruin them through the retesting,” he said.

Industry officials: Varied global postapproval change requirement pose challenges for drugmakers

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