BYRYZN — filler or booster

What is set out on the official BYRYZN site is as follows.

One thing to point out here. The 62026-I10-23-2790 written on the official site is an advertising review number, not a marketing approval number. An advertising review asks “may this advertising copy be used?”, while a marketing approval asks “may this product be sold?”. Having a validity period attached is also characteristic of an advertising review. The difference between the two numbers is set out in what one line of approval number can and cannot tell you. We too were unable to obtain the original text of BYRYZN's marketing approval number while writing this piece — because the Korean Ministry of Food and Drug Safety (MFDS) medical device database blocks automated lookups.

Hugel's official research and development page introduces BYRYZN under the heading “hyaluronic acid filler”, with the year of approval given as 2021. Which means the manufacturer itself classifies it as a filler.

The term was made in marketing and in clinical practice, and it is entered nowhere in any regulatory framework.

How the FDA solved this problem

In May 2023, in approving a product of the same class (SKINVIVE by JUVÉDERM), the FDA did not use the existing wrinkle indication but made a new sentence.

“Indicated for intradermal injection to improve skin smoothness of the cheeks in adults over the age of 21.”
— intradermal injection to improve the skin smoothness of the cheeks in adults over the age of 21

So the regulator did not use the words “skin booster” either. Instead it set up a separate indication — not “smooths wrinkles” but “makes the skin smooth” — and specified the site as the cheeks. Those two things are the official description that comes closest to what this product family actually is.

There is a study that actually measured the elastic modulus (G′) of products sold as skin boosters under the same conditions. The result is unexpected.

All of them are “skin boosters”, and yet G′ spreads from 8 Pa to 553 Pa, a 69-fold gap. A product at a concentration of 12 mg/mL (153–165 Pa) is also more than ten times stiffer than a product at 20 mg/mL (8–13 Pa) — meaning the more concentrated one can be the softer. What the authors confirmed was that what sets the stiffness is not the concentration but the degree of cross-linking.

There is one conclusion to draw from this — the name “skin booster” tells you almost nothing about the substance inside. The differences among products sold under that one name are larger than the difference between a skin booster and an ordinary filler. BYRYZN's measured G′ is not published, so we could not put it in this table.

For ordinary volumising fillers, another study reports G′ of 128 Pa for Belotero Balance, 207 Pa for Juvéderm Ultra XC and 864 Pa for Restylane-L. However, the measurement frequency and strain differ, so those figures cannot be set directly side by side with the table above. Please use only the ordering within each study.

Among domestic booster products there are many with no peer-reviewed paper at all. BYRYZN has one.

What to look at alongside this paper

The title is “The efficacy of intradermal hyaluronic acid filler as a skin quality booster”. The researchers themselves framed this as “a filler used as a booster”. And there are three things you should look at with it.

• There is no control group. All 20 received the procedure and there was nothing to compare against. So “it improved because of the procedure” cannot be proved by this design. That is simply what a pilot study is.
• Observation ended while the improvement was already shrinking. 40% at week 8 → 33% at week 12. Beyond that nothing was measured.
• The interval between sessions is 2 weeks. That differs from the 4-week interval commonly quoted in Korea. We did not find a study comparing which of the two is better.

We also note a point where the labelling does not line up. This paper gives the manufacturer of the test product as “ACROSS Co., Ltd., Gangwon-do, Korea”, while the official BYRYZN site gives the manufacturer as Hugel Inc. We were not able to confirm the relationship between the two companies. It may be contract manufacture or a change of company name, and it may be something else. We will not write it down one way or the other while we have not confirmed it.

For this product family, the largest set of adverse events disclosed, and in the most reliable form, is the FDA approval label. These are the results of the initial procedure in the US pivotal trial.

A palpable lump is closer to the rule than the exception. That said, most resolved within 7 days. And the label wrote down the exception as well — in 3 people mild to moderate lumps did not resolve until 12–15 months after the procedure. Adverse events related to the procedure were 3.0%, and of those 76.2% resolved within 30 days.

How you read this number matters. 63.3% does not mean “this is dangerous”; it is closer to meaning “this is simply what this procedure is like”. Put gel into the shallow dermis at many separate points and having it palpable for a few days is the normal course. The question is whether you were told this before the procedure. Experienced without having been told, it becomes a side effect; experienced having been told, it becomes the course.

Rare but long-lasting — delayed-onset nodules

Nodules appearing weeks to months after the procedure are a separate problem. The figures cited by reviews in this field are as follows.

All four of these figures are secondary citations, and we were not able to confirm the original paper behind each of them. Please take them only as figures cited by a review.

Two sentences written by the same review connect back to the properties table above — “placement of HA within the dermis, particularly in its superficial layer, is associated with an increased risk of granuloma formation”, and “a high-G′ product placed superficially is more likely to be palpable or visible”. The fact that G′ spreads 69-fold between products sold as skin boosters takes on its real meaning here.

The explanation that “it hurts less because it contains lidocaine” has a basis. It is as well to know two things alongside it.

In a 2024 meta-analysis, HA fillers with lidocaine, compared with those without, gave significantly lower pain (VAS) with a standardised mean difference of −2.47 (95% CI −4.15 to −0.79, p = 0.004). By contrast, there was no difference in the degree of wrinkle improvement (p = 0.36) or in overall adverse events (p = 0.51). Tenderness was slightly lower (RR 0.91, p = 0.002).

• 0.3% is the standard value for this product family. The label of the same-class product approved by the FDA also states HA 12 mg/mL + lidocaine 0.3% w/w. It is not a special formulation but the customary concentration in this field.
• The trials included in that meta-analysis are all trials of deep injection into the nasolabial folds. We did not find a randomised trial verifying lidocaine's pain reduction for the method of injecting at many points into the shallow dermis.

For reference, there is one striking piece of data on point (1). In a review of 33 MRI follow-up cases of volumising filler placed deep in the midface, filler was detected in all 33 of the cases reviewed, and in some the procedure had been 8–15 years earlier (residual rate 84.47% ± 4.43%). However, this is data on deep-layer volumising filler and cannot be carried across as it stands to the method of placing a small volume in the shallow dermis. The reason we set this out here is not to argue that “it lasts a long time” but to make clear that the received idea that “HA all disappears within 3–12 months” has itself never been verified.

One more thing — the frequently cited criterion that “residual BDDE below 2 ppm is safe” is a value in common use in the academic literature. We were not able to confirm the actual regulatory document (an MFDS notification or an international standard) that set this criterion. So a phrase such as “the MFDS criterion of 2 ppm” is not accurate.

This is why we wrote this piece. “Filler or booster” looks like word play, but it is in fact the question that sets your expectations. Told it is a booster, you come to expect “the skin getting better”; told it is a filler, you anticipate “it fills as much as was put in, and it may be palpable for a few days”. The approval documents, the only paper and the FDA label all point to the latter. We are not telling you not to have this procedure; we are saying that it is better to have it knowing what it is you are receiving.

Written and reviewed by Lee Chi-Hak, MD, medical director of Miso Clinic in Daegu, South Korea. Every study cited above is given together with its design, its size and the limitations the authors themselves recorded, and where we could not find data, we have said that we could not find any.