Sam Chun Dang Pharm said it received a response from the U.S. Food and Drug Administration (FDA) regarding the generic drug approval process and launched a broad promotion campaign saying there is "no clinical risk at all."
Sam Chun Dang Pharm has been pursuing the FDA's pre-ANDA process with the goal of developing the first generic of Novo Nordisk's oral diabetes drug "Rybelsus." The company said the latest response "served as a turning point that eased a significant portion of the regulatory uncertainty."
However, based on the FDA's official guidelines and explanations from approval experts and industry officials, some noted it is a separate question whether a pre-ANDA response alone can be interpreted to mean that "approval can proceed with only a BE study."
Sam Chun Dang Pharm(000250), which has repeatedly faced disclosure controversies in the past over contract size and business outlook, is also seen as needing more thorough verification for this announcement.
◇ANDA does not normally involve clinical trials
An ANDA (Abbreviated New Drug Application) is a marketing application submitted to sell a generic drug in the United States. Phase 1, 2 and 3 clinical trials to reestablish the safety and efficacy of an already approved reference drug are not required in principle.
Instead, a generic must demonstrate it is therapeutically equivalent to the reference drug. To do so, it must prove pharmaceutical equivalence—same active ingredient, strength, dosage form and route of administration—and bioequivalence (BE), showing that the rate and extent of absorption in the body do not differ statistically. Approval is typically sought by submitting BE studies in healthy volunteers and chemistry, manufacturing and controls (CMC) data.
Accordingly, CEO Jeon In-seok of Sam Chun Dang Pharm's explanation that "no separate clinical trials are required" aligns with the general features of the ANDA system.
However, this only means it does not repeat the large-scale safety and efficacy trials required for new drug development; it does not mean there is no risk at all, as Jeon phrased it. The FDA has not yet formally reviewed the BE study results.
"...the pre-ANDA program includes product development meetings and pre-submission meetings and is intended to clarify regulatory expectations for prospective ANDA applicants early in product development, assist applicants in developing more complete submissions, promote a more efficient and effective ANDA assessment process, and reduce the number of assessment cycles required to obtain ANDA approval."(The pre-ANDA program consists of a product development meeting and a pre-submission meeting. Its purpose is to clarify regulatory expectations for prospective ANDA applicants early in development, help applicants prepare more complete submissions, promote a more efficient and effective ANDA assessment process, and reduce the number of assessment cycles needed to obtain final approval.)U.S. Food and Drug Administration (FDA) ‘Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA’
◇"It is very unusual for the FDA to use definitive wording"
The pre-ANDA pursued by Sam Chun Dang Pharm is a prior consultation program for developers of complex generics. The FDA classifies complex generics as drugs that include complex active ingredients (such as peptides or mixtures), dosage forms, routes of delivery, or drug–device combination products.
The oral semaglutide under development by Sam Chun Dang Pharm also qualifies as a complex generic designed to enable oral absorption of a peptide-based GLP-1 receptor agonist.
A domestic approval expert who requested anonymity said, "Pre-ANDA is a process in which, for complex generics where equivalence is hard to prove using conventional methods, the developer discusses a new demonstration strategy with the FDA in advance," adding, "Regarding the strategy proposed by the developer, the FDA may provide scientific feedback such as 'we can review it' or 'please submit additional data.' However, this is merely directional feedback and does not confirm that approval can proceed with only BE studies."
The expert said, "Even if a developer asks whether 'BE studies alone are sufficient,' the FDA typically responds conservatively along the lines of 'we will decide during the review of the submitted materials,'" adding, "Even when equivalence appears almost certain, the FDA does not use definitive wording."
The expert added, "Therefore, the phrase 'approval can proceed with only BE studies' is more likely the company's interpretation of the response rather than the FDA's official judgment."
In response, Sam Chun Dang Pharm said, "We quoted the FDA's response verbatim." However, it did not disclose the full reply, citing the inclusion of confidential business information.
When ChosunBiz asked whether it planned to release even partial content excluding trade secrets, the company said, "We are cautious because excerpting only some parts could create additional controversy in the process of interpreting the sentences."
◇There is a long way to go before approval
An expert said, "If the FDA expressed a willingness to review the strategy the company proposed, that is indeed a positive sign," but added, "However, that does not mean the appropriateness of the BE results has been confirmed. The FDA will ultimately review the BE data during the ANDA assessment, and there are many steps to clear afterward, including manufacturing site inspections."
When a developer submits an ANDA, the FDA first conducts a filing review. Once filing is accepted, the substantive review begins, during which the agency may request additional information via an Information Request (IR) or a Deficiency Response Letter (DRL). The outcome may be approval, tentative approval, or issuance of a Complete Response Letter (CRL).
In the past, U.K.-based Hikma Pharmaceuticals also received a CRL from the FDA after submitting an ANDA for its generic of the asthma treatment "Advair Diskus," and later resumed the approval process after additional studies and supplemental submissions.
Some in the industry also say it is hard to judge success based solely on the BE results that Sam Chun Dang Pharm disclosed. Although the company revealed certain metrics, the raw data and detailed analyses were not disclosed, making it difficult for outsiders to verify whether they meet FDA standards.
There is another factor that will determine final approval: the manufacturing site inspection. An expert said, "Inspections of generic manufacturing sites proceed at virtually the same level as for new drugs, and for complex generics, the weight on process validation can be even greater."
The industry views the manufacturing site inspection as the biggest hurdle in the FDA approval process. An official at a domestic drugmaker with new drug development experience said, "It is not uncommon to spend hundreds of millions of won to undergo mock inspections by external professional bodies in preparation for FDA inspections," adding, "Recently, the FDA has been strictly evaluating not only production facilities but also data integrity."
Coincidentally, Sam Chun Dang Pharm was recently ordered by the Ministery of Food and Drug Safety to suspend manufacturing operations for failing to comply with good manufacturing practice (GMP) and for violations related to oversight and recall procedures for certain products. Although this administrative action is separate from the U.S. FDA approval review, it is drawing industry attention because manufacturing and quality control capabilities are key variables in generic approvals.
The Financial Supervisory Service is also closely watching Sam Chun Dang Pharm's case. Using various controversies surrounding the company and the broader industry as a catalyst, the agency launched a task force (TF) in April to improve disclosures in the pharmaceutical and biotech sectors and plans to announce related guidelines as early as this month or by early August.
Attention is on whether standards will be set for how definitively companies can phrase disclosures about early development results or consultations with regulators. In response to a related inquiry from ChosunBiz, an FSS official said, "It will be at the level of providing general direction," adding, "Given the diversity of company-specific cases, it was not easy to craft uniform standards."