Drug Master File for API 237→653…'easing of regulation'

First half year DMF cases surged by 2.8 times…attributed to the abolition of GMP inspection·certificate substitution

DMF cases fluctuated with changes to the regulation…dropped after 2021 and then rebounding this year

The number of Drug Master File, DMF, cases in the first half of this year surged by 2.8 times compared to the same period last year.

 

This is the highest for a half-year period.

 

Analysis suggests that this is due to the easing of Active Pharmaceutical Ingredient (API) registration requirements at the beginning of the year.

 

The government had previously eased regulations to allow GMP evaluation to be replaced by GMP certificates for API registration starting this year.

 

'Record-High' DMF Registrations of 653 Cases in the first half of 2025...Up 2.8x YoY According to the Ministry of Food and Drug Safety (MFDS) on June 26, the number of API registrations by Korean pharmaceutical and biotech companies in the first half of this year reached 653 cases.

 

Compared to 256 cases in the first half of last year, this year's marks a 2.8-fold increase in one year.

 

It has already surpassed the total number of API registrations for the entire 2024 (545 cases).

 

In terms of half-yearly API registrations, it has exceeded the 537 cases in the first half of 2021, reaching an all-time high.

 

Half Yearly Cases of Drug Master Files (DMFs) for API (unit: number of cases, source: MFDS)

The robust increase in DMF cases is attributed to the government's easing of regulations.

 

Earlier this year, MFDS reformed the DMF system to replace on-site inspections with GMP certificates.

 

Previously, DMF applications required on-site inspections, along with manufacturing facility data, production country manufacturing certificates, and 11 types of GMP documents.

 

From this year, on-site inspections have been abolished.

 

Additionally, documents can now be replaced by GMP certificates issued by the government agency of the production country or a PIC/S member country.

 

The administrative processing period has also been shortened from 120 days to 20 days.

 

An MFDS official explained, "Previously, to register API, the applying company had to undergo a GMP on-site inspection, but from this year, it can be substituted with a certificate," and added, "It seems that nearly 1,000 piled-up DMF applications were processed in large numbers this year, leading to a surge in DMF cases." Concerns over API quality verification...MFDS states "On-site inspections maintained for high-risk Items" Regarding this deregulation, some in the pharmaceutical industry express concerns that API quality control could become lax.

 

Critics argue that, with registration now possible solely based on GMP certificates, it will be challenging to identify quality issues beforehand through document-based evaluations.

 

This easing of regulation is a complete reversal from MFDS's previous stance.

 

Since the introduction of the DMF system in 2002, MFDS has consistently strengthened quality control.

 

In 2014, GMP evaluation standards were reinforced with PIC/S membership.

 

At this time, 11 types of GMP documents and on-site inspection standards were introduced.

 

In 2019, DMF registration became mandatory not only for new items but also for previously approved items.

 

In 2021, the on-site inspection system was further strength with a focussing on high-risk items.

 

During a briefing last year, MFDS explained that they adjusted the evaluation system in response to the administrative bottleneck caused by a surge in DMF applications, which also delayed the review of finished pharmaceutical products (FPP).

 

Overall, MFDS's policy is to shift its GMP approach to be 'FPP-centric.' Regarding concerns about API quality, MFDS states that on-site inspections are exceptionally maintained for high-risk items, and GMP certificate requirements have been strictly set in line with international standards.

 

Indeed, for high-risk items such as biopharmaceuticals and sterile APIs, on-site inspections and submission of evaluation data are still required.

 

Furthermore, on-site inspections are maintained as before for drug approval and suitability judgments.

 

They also plan to introduce the concept of a 'Site Master File' to understand the quality management system of manufacturing sites comprehensively.

 

Up and down of cases based on regulatory changes...Decline after 2021 peak→ rebounding This Year The number of DMF registrations by Korean pharmaceutical and bio-companies has fluctuated significantly each year due to system changes and policy factors.

 

Over the past eight years, DMF cases have exhibited fluctuating trends: ▲347 in 2017 ▲516 in 2018 ▲571 in 2019 ▲714 in 2020 ▲967 in 2021 ▲671 in 2022 ▲487 in 2023 ▲545 in 2024.

 

With 653 cases in the first half of this year alone, there is a possibility of exceeding 1,000 cases by year-end.

 

The surge in DMF cases in 2021 coincided with the implementation of a policy that made API registration mandatory, even for previously approved items.

 

In 2019, MFDS expanded the scope of DMF to include 'previously approved items' from the original 'newly approved items.' It is analyzed that commercial drugs were required to complete registration by 2021, leading to a concentrated influx of DMF applications.

 

A reform of the drug pricing system around the same time also influenced the increase in DMFs.

 

In July 2019, the government introduced a 'step-wise drug pricing system.' Generics that did not meet the highest price criteria could maintain their previous drug prices if they submitted data from bioequivalence tests and demonstrated the use of registered APIs.

 

This led to a surge in DMF applications from pharmaceutical and biotech companies seeking to maintain drug prices.

 

After 2023, the situation changed.

 

In February 2023, the submission of DMF documents for drug price maintenance concluded.

 

With most DMFs for previously approved items also finalized, the number of registrations began to decline.

 

Indeed, DMFs, which had reached 967 cases in 2021, nearly halved to 487 cases by 2023.

 

However, with the lowering of DMF hurdles this year, the number of registrations is showing a rebounding trend.