Will the Indian API cause problems?

Concerns over the impact of impurity detection in tramadol combi

NNDT impurity detected in several generic products using API sourced from India

85% of DMF from India…If impurity detection expands, market restructuring is inevitable

Q3 tramadol·AAP prescription sales amounted to KRW 114.9B…Top-selling products likely to see benefit

An impurity issue has emerged as a major variable in the tramadol-acetaminophen combination drug market, valued at approximately KRW 150 billion annually.

 

Following the detection of impurities in three generic products using Indian-sourced active pharmaceutical ingredients (API), the pharmaceutical industry is watching closely for the potential expansion of the impurity issue across all API from India.

 

In this case, the market is expected to be reorganized around products that use non-Indian sourced API.

 

85% of tramadol DMFs are produced in India...Concerns Over Widespread Impurity Detection According to the Ministry of Food and Drug Safety (MFDS) on October 29, following the excess detection of the impurity NNDT (N-nitroso-desmethyl tramadol) in a tramadol monotherapy product in July, the recall target has recently been expanded to include tramadol + acetaminophen combination products.

 

To date, impurities have been detected in three tramadol + acetaminophen combination products.

 

The MFDS issued recall orders for specific batch number products of: ▲Dongkoo Bio & Pharma’s 'Jimuradol Tab' ▲Ausco Korea Pharma's 'Acetadol Tab' ▲Union Korea Pharm’s 'Atracen Tab.' All three products in which impurities were detected are known to have used India-sourced API.

 

The concern is that a significant portion of the tramadol + acetaminophen combination products currently distributed in South Korea relies on API sourced from India.

 

Currently registered sources of tramadol API: YELLO-India, BLUE-Israel, RED-Switzerland, GREEN-Korea

Indeed, examining the Drug Master File DMF status for tramadol-related API shows that 62 of the 73 registered raw material manufacturers (85%) are located in India.

 

The remaining 11 sites include 8 in Israel (11%), 2 in Switzerland (3%), and 1 in Korea (1%).

 

Many domestically supplied products likely rely on Indian-sourced API.

 

KRW 150 Billion Market...Top-selling products not at risk of impurity expected to benefit The three products where impurities were detected have negligible prescription sales.

 

According to pharmaceutical market research firm UBIST, the cumulative prescription sales for these three products combined were less than KRW 400 million in the third quarter of this year.

 

While the market impact is currently limited, analysis suggests that market restructuring will be unavoidable if impurity detection expands across Indian-sourced API.

 

This is because securing new raw material manufacturers outside of India is difficult, and the administrative process for changing API registration alone takes approximately six months, which would lead to a market supply gap.

 

The tramadol + acetaminophen combination market in Korea has seen steady growth in the moderate-to-severe pain treatment sector.

 

It increased by 24% over the last four years, from KRW 120.7 billion in 2020 to KRW 127.1 billion in 2021, KRW 138.2 billion in 2022, KRW 144.6 billion in 2023, and KRW 149.6 billion last year.

 

Cumulative sales reached KRW 114.9 billion in the third quarter of this year.

 

Quarterly prescription sales of tramadol-acetaminophen combination drugs (DARK GREEN: original product, LIGHT GREEN: generic products; unit: KRW 100 million, source: UBIST).

The original product, Janssen Korea's Ultracet, recorded cumulative sales of KRW 24.1 billion in the third quarter, a slight decrease from KRW 24.3 billion in the third quarter of last year.

 

Generic products collectively saw a 5% increase in the same period, rising from KRW 86.3 billion to KRW 90.9 billion.

 

The growth of top-selling generics was particularly notable: Samjin Pharm's 'Synerjet' grew by 23%, from KRW 6.9 billion to KRW 8.6 billion; Myung Moon's 'Traphen' grew from KRW 5.2 billion to KRW 6.6 billion; and Genuone Sciences' 'Painless' increased from KRW 4.4 billion to KRW 5.1 billion.

 

In this circumstance, if the impurity issue spreads, non-detected products are expected to quickly replace the market.

 

Currently, the market-leading products are understood to be not at risk.

 

The original product, Ultracet, has registered a Swiss manufacturer as its API supplier.

 

The top generic product, Samjin Pharm's Synerjet, manufactures its finished drug in-house using an Israeli-sourced API.

 

Neither of these two products was requested to submit data in the MFDS's comprehensive investigation of NNDT impurities in tramadol.