Revoking the ODD status of immunostimulants remains unresolved

The Central Pharmaceutical Affairs Council (CPAC) was convened. Yet, the Ministry of Food and Drug Safety (MFDS) is still reviewing

External experts have yet to reach a conclusion

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Discussions over 'revoking the orphan drug designations' of major injectable immunostimulants, which came under intense scrutiny during last year's National Assembly audit over efficacy controversies and excessive prescribing, remain unresolved nearly a full year later.

With this year's parliamentary audit scheduled for October, the Ministry of Food and Drug Safety (MFDS) is expected to face heavy legislative pushback if it fails to present concrete regulatory outcomes.

On the 21st of last month, the MFDS convened an advisory session of the Central Pharmaceutical Affairs Council (CPAC) to discuss revoking orphan drug designations for injectable formulations of Viscum album (40 products) and immunocyanin (2 products). Under current pharmaceutical regulations, designated orphan drugs are exempt from mandatory clinical re-evaluation. Consequently, the regulator initiated preliminary administrative steps because the patient populations for their approved indications have surpassed the statutory orphan threshold of 20,000 patients.

However, regulatory authorities have not yet reached a definitive conclusion. Both therapeutic agents remained on the updated orphan drug list gazetted earlier this month. In response, the MFDS stated, "We are currently reviewing whether to revoke the orphan drug designations while taking the advisory opinions of the CPAC into consideration".

Industry sources report that the advisory council adjourned without reaching a clear conclusion, leaving the deliberation suspended. Without a definitive consensus from the expert advisory body, the MFDS will likely struggle to make a unilateral regulatory determination.

Analysts observe that the CPAC wrestled intensely with the substantive validity of 'revoking orphan status.' Deliberations likely included contentious debate over the broader repercussions of mechanically enforcing the epidemiological prevalence criterion, as well as whether destabilizing formally approved indications to curb out-of-pocket, off-label prescribing conforms to the administrative legal principle of proportionality.

The critical issue remains that while regulatory reviews remain stalled, the out-of-pocket, non-reimbursed prescription market continues to expand rapidly.

According to a recent analysis of the "Second Half 2025 Non-Reimbursed Healthcare Reporting System" by the Ministry of Health and Welfare and the National Health Insurance Service, non-reimbursed medical expenses for thymosin alpha-1, which is an immunostimulant facing parallel efficacy challenges, reached KRW 27.4 billion in September 2025 alone. This marked a 67.1% surge within a single year, with prescribing heavily concentrated in long-term care and traditional medicine hospitals. Even after the National Evidence-based Healthcare Collaborating Agency (NECA) concluded that the therapy lacked sufficient clinical evidence and lawmakers repeatedly demanded efficacy reassessments, market prescription volumes remained entirely unchecked.

The MFDS continues discussion internally. While the ministry took administrative steps under pressure from the parliamentary audit, internal voices acknowledge that shifting the burden of policing a KRW 200 billion non-reimbursed prescribing market onto pharmaceutical manufacturers by mandating costly clinical trials represents an excessive administrative overreach. The pharmaceutical industry has adopted an uncompromising defensive posture, preparing to pursue aggressive legal countermeasures, including petitions for injunctions to stay execution and formal administrative litigation, should the revocation and re-evaluation orders proceed.

With sharp criticism from the National Assembly's Health and Welfare Committee anticipated in the upcoming audit, industry attention is focused on whether the MFDS, caught between regulatory enforceability and litigation risk, can reach a definitive resolution before the audit convenes.