[Edaily Reporter KIM SAE-MI ] PharmaResearch(214450)is seeking U.S. Food and Drug Administration (FDA) medical device approval for its flagship product, “Rejuran,” but is expected to face significant hurdles before actually entering the U.S. market.

According to an E-Daily report on the 24th, PharmaResearch is preparing to seek FDA medical device approval for Rejuran—which is currently on the market—with the goal of entering the U.S. market around 2031–2032. Industry experts believe that, given the mechanism of action of polynucleotides (PN), the nature of the raw material—animal-derived DNA—and manufacturing and quality control (CMC) considerations, the process of establishing a precedent for the first approval in the U.S. will not be easy.

PharmaResearch: “PN Is Different from PDRN… Preparing for Approval as a Medical Device”

PharmaResearch has made it clear that it intends to seek approval for Rejuran through the FDA’s medical device track. A PharmaResearch official stated, “It is being approved as a medical device not only in the U.S. but also in other countries,” adding, “Rejuran contains PN, and its composition is fundamentally different from that of PDRN. While PDRN is listed as a pharmaceutical ingredient even in Korea, Rejuran contains PN, so we are preparing for approval as a medical device.”

PharmaResearch estimates that Rejuran could enter the U.S. market around 2031–2032. However, the company explains that since there is no precedent for a PN-based skin booster being approved by the FDA, securing additional data—including clinical trial results—will require a significant amount of time.

Some in the industry continue to point out that, given Rejuran’s mechanism of action, it is difficult to rule out the possibility that it could be classified as a drug in the U.S. If it follows the drug approval track, clinical procedures equivalent to those for new drugs may be required, which could significantly increase both the approval timeline and costs.

One dermatologist noted that if Rejuran’s efficacy is explained as a mechanism that induces regeneration by transmitting signals to cells—rather than simply being a substance that physically fills the skin—it may not be easy to have it recognized as a simple medical device in the U.S. He pointed out, “If the mechanism involves signaling to cells, the question arises as to how the U.S. would classify it as a medical device.” Another bioindustry official also expressed concern, stating, “The more we emphasize Rejuran’s pharmacological effects, the greater the likelihood of getting bogged down in regulatory red tape.”

There is also a counterargument that, given that both PN and PDRN are substances derived from finely fragmented DNA extracted from fish, it remains to be seen whether regulatory authorities will deem them completely distinct substances. A biotech industry official researching PDRN pointed out, “PN and PDRN are fundamentally the same substances in that they are both created by cutting DNA from fish such as salmon; the main difference lies in the size of the DNA fragments,” adding, “Since existing literature presents their biological mechanisms, there are aspects that suggest they have pharmaceutical characteristics.”

From Animal-Derived DNA to CMC: ‘A Mountain of Obstacles’

The nature of the raw material—animal-derived DNA—is also cited as a hurdle to overcome in the FDA approval process. Rejuran is a product in which PN, processed from DNA extracted from fish, is injected directly into the skin. Given that it involves the injection of foreign biological genetic material into the body, U.S. regulatory authorities are likely to scrutinize the safety of the raw material and the potential for an immune response more strictly.

An industry official explained, “Since Rejuran’s raw material is DNA extracted from fish, U.S. regulatory agencies may view it as a product that directly injects genetic material derived from a foreign organism into the human body.” They added, “When foreign DNA enters the human body, the innate immune system can recognize it through mechanisms such as CpG motifs, so there is a possibility that additional immunogenicity safety evaluation data will be required.”

In particular, the source noted, “We will need to demonstrate the safety of the raw material, immunological safety, and consistency in production and quality. However, scientifically proving safety is an entirely different matter from simply stating, ‘We’ve used it so far without major issues.’” They added, “This does not mean approval is impossible, but it will likely involve a very arduous process.”

CMC is also identified as a major hurdle. This is because, in the process of manufacturing PN by cutting long DNA extracted from fish into small pieces, the final product may consist of DNA fragments of various sizes rather than having a single, consistent molecular weight. In this case, it becomes crucial during the FDA review process to establish product specifications and demonstrate that consistent quality is maintained across each production batch.

An industry official pointed out, “In the PN and PDRN manufacturing process, the final product may vary depending on the species and origin of the raw material, as well as the processing method,” adding, “Consistent quality control across batches is crucial.” He noted, “When DNA is physically cut to produce the product, the heterogeneity of the raw material can become an issue,” and stated, “The key will be how high a level of consistency the FDA requires for CMC and between batches.”

Industry estimates suggest that, considering the time required to secure these clinical and CMC data, U.S. approval could take 6 to 10 years and cost approximately 100 to 150 billion won.

Original Patents Expire Before U.S. Market Entry… Defending Against Latecomers Remains a Challenge

Challenges remain even after successful approval. The domestic original patent held by PharmaResearch—the foundation of Rejuran—relating to early DNA manufacturing is set to expire in January 2028. The protection periods for some patents directly related to the initial version of Rejuran will also end around the same time.

Of course, the expiration of domestic patents does not immediately mean that patent protection in the U.S. will disappear as well, since patent rights are applied independently by country. Considering that PharmaResearch anticipates entering the U.S. market in 2031–2032, there will be a time lag between the expiration of the domestic patents that have protected the initial Rejuran technology and the company’s entry into the U.S. market. This raises another challenge: determining which patents will be available to fend off competitors when the product is commercialized in the U.S.

The importance of the U.S. market is growing steadily. While Rejuran has pioneered the domestic skin booster market and driven PharmaResearch’s rapid growth, the recent slowdown in domestic growth rates has revealed limitations in sustaining the same growth momentum relying solely on the domestic market. Since expanding into overseas markets is essential for PharmaResearch to take the next leap forward, the success or failure of its entry into the U.S.—the world’s largest aesthetic medicine market—is considered a key factor that will determine its medium- to long-term growth potential.

PharmaResearch maintains that it is continuously securing follow-on patents, such as those for high-concentration DNA compositions and next-generation tissue-regenerative compositions. However, specific patent defense strategies—such as which patents will be used to protect the existing Rejuran, for which FDA approval is currently being sought, in the U.S., and to what extent follow-on patents can block competitors from circumventing the market—have not yet been clearly disclosed.

An industry insider commented, “I believe approval is possible if PharmaResearch follows the proper procedures to demonstrate safety and clear regulatory hurdles,” but added, “Since this is essentially a first-of-its-kind case, the process is bound to be quite arduous.”