According to Pharma Manufacturing, a U.S. pharmaceutical and biotech trade publication, 74% of cases in which the U.S. Food and Drug Administration (FDA) put new drug approvals on hold from 2020 to 2024 and requested additional information from corporations were due to chemistry, manufacturing and controls (CMC) issues. Not only efficacy and safety, but CMC capabilities have emerged as a key factor that determines the success or failure of new drug approvals.
CMC is cited as an important element in new drug development along with evaluating a drug's efficacy and safety. It is a framework that proves whether a new drug can be produced safely with consistent quality and whether it can be manufactured and managed to meet standards required by regulators. It is an essential element applied throughout the entire new drug development process, from preclinical trials to pivotal clinical trials, approval and commercial production.
◇ CMC tripped up HLB and Genexine… "Efficacy and safety alone won't win approval"
At the seminar titled "National CMC industry development strategy to secure global competitiveness," held on the afternoon of the 30th at the Korean Federation of Science and Technology Societies building in Gangnam-gu, Seoul, participants said with one voice that national-level CMC capability building is essential to strengthen the competitiveness of new drug development in Korea's pharmaceutical and biotech sector. The event was co-hosted by the Korea Drug Development Fund (KDDF) and the Korea CMC Service Industry Research Association (KCMC).
Attendees stressed that to move beyond the so-called "valley of death," the technology and funding gap, and secure global competitiveness, strengthening CMC capabilities to support the entire new drug development cycle is essential for Korea's biotech industry.
Domestic new drug development corporations have also been hobbled by CMC issues. HLB, pursuing a combination therapy of the liver cancer drug "Rivoceranib" and its Chinese partner Hengrui's immuno-oncology drug "Camrelizumab," has embarked on a third attempt after receiving two complete response letters from the U.S. FDA. In the prior two reviews, it was not the substance's efficacy or safety but CMC problems at Hengrui's manufacturing facilities that caused the setback. The industry is watching to see whether the CMC issues are resolved in the third approval decision, scheduled by the 23rd of next month.
Genexine, an affiliate of Handok, also recently had its application for the anemia treatment "Ephesa" rejected by the Ministery of Food and Drug Safety. This, too, was attributed not to safety or efficacy but to CMC deficiencies.
Kim Su-dong, KCMC chair (Ajou University professor), said, "Although a significant portion of failures in new drug development are related to CMC, it has been relatively neglected in both research and development (R&D) and industrial policy," adding, "After visiting the Ministry of Science and ICT, the Ministry of Economy and Finance and the National Assembly to work on building a CMC ecosystem that can support domestic biopharma corporations, we finally launched KCMC in March."
Gu Hyeok-chae, first vice minister of the Ministry of Science and ICT, who attended the event, said, "Korea has done relatively well up to the hit discovery stage, but there has been a lack of support in the subsequent clinical and commercialization stages," adding, "Because CMC is important at every stage from preclinical to pivotal trials, the government will take an interest and expand support."
◇ To run clinical trials, at least 5 billion won just for CMC… "Urgent need to build a national ecosystem for platforms and talent"
In particular, as various modalities (treatment approaches) such as cell and gene therapy (CGT) and antibody-drug conjugates (ADC) have emerged in recent years, manufacturing processes and quality standards have become more complex, further elevating the importance of CMC.
According to the industry, at least 5 billion won is needed just to prepare CMC to enter clinical trials in the early stages of new drug development. This is a significant burden for biotech ventures and small and midsize pharmaceutical and biotech corporations with limited financial resources.
Global contract development and manufacturing (CDMO) corporations such as Samsung Biologics, Lonza of Switzerland and WuXi Biologics of China are highlighting CMC capabilities and the ability to meet global regulatory requirements as core strengths. However, because their key customer base is concentrated among midsize drugmakers and global big pharma, access is not easy for biotech ventures and small and midsize pharmaceutical and biotech corporations.
Observers say CMC is important from a national competitiveness standpoint as well. Lee Jeong-tae, a KCMC director, said, "A significant number of domestic pharmaceutical and biotech corporations outsource CMC overseas, including to China," adding, "As a result, more than 100 billion won in capital and core process data leak overseas each year."
Overseas regulators have also been strengthening the emphasis on CMC recently. Han Gyun-hui, head of the Yonsei University Bioprocess Talent Training Program, said, "While the U.S. FDA and the European Medicines Agency (EMA) have recently eased some approval rules for biosimilars, they still treat CMC as a mandatory requirement," adding, "As opportunities expand for domestic biotech ventures to go overseas, specialized biopharmaceutical CMC education and workforce development are needed."
The industry believes there are limits to leaving the securing of CMC capabilities solely to the efforts of individual corporations at a time when competition in next-generation new drug development is heating up. As a result, there is a growing call for building a national CMC ecosystem that includes platform development, talent training and regulatory support.
To address these issues, KCMC and the Korea Drug Development Fund (KDDF) signed a memorandum of understanding (MOU) the same day and agreed to cooperate for the development of the national CMC industry. The two organizations plan to jointly promote efforts to strengthen the CMC capabilities of biotech ventures, train specialists and build an industrial ecosystem.
Lim Hyeong-gyu, head of the CMC Support Team at the Korea Drug Development Fund (KDDF), said, "CMC is not mere paperwork; it serves as a 'compass' that determines the direction of new drug research and development (R&D)," adding, "There are many cases in which domestic corporations secure strong candidates but face difficulties during development because they did not sufficiently consider manufacturability and quality assurance strategies from the outset."
Lim added, "In the era of next-generation modalities such as ADCs and CGT, the manufacturing process itself is R&D, so it is necessary to build a proactive CMC platform that can support stable production and quality control from the hit discovery stage."