Letters to the Editor: Improving the Accuracy of Botulinum Toxin Injections Cannot Rely on Syringe Devices

Dear Editor:

There is no doubt now that the use of botulinum toxin (BoNT) in aesthetics has been a revolution for the noninvasive treatment of patients. In the last several decades, the use of BoNT has changed from fixed doses delivered at fixed time intervals into fixed anatomical sites, all of which were required for regulatory approvals, to patient-centric treatments of variable doses delivered into variable anatomical points at time intervals individually tailored to each patient. This complete change in approach has also helped to exchange the “frozen look”  for the “natural look” for the majority of patients.

The commentary by Yoelin et al,1 a call for improved accuracy of BoNT injections, deals with a subject that has received little attention in the last 20 years—namely, the physical injection technique of the product. Their article is, in reality, a promotional commentary for an injection device in which they have commercial interests and so must be read with caution. They build on a 2019 study2 that examined various aspects of their device in the laboratory, together with a 15-user satisfaction survey. There is little surprise that their device gave accurate injection volumes when compared with freehand administration.

Yoelin et al mention two other toxin injection devices that are available. The 3Dose™ Injector device, originally from TSK Laboratory Europe B.V. (Oisterwijk, the Netherlands) but now from Vlow Medical B.V. (Eindhoven, the Netherlands), was first introduced by TSK in 2015 as a single unit. A second unit, with a different injection dose range, was introduced in 2017. The Vlow Medical B.V. website presents testimonials and published literature on the device. Over the five years of availability, the device has become a useful adjunct to treatment for some injectors.

Yoelin et al. also comment that the Juvapen device (Juvaplus; Neuchâtel, Switzerland) has “no published, peer-reviewed article demonstrating injection accuracy.” Whilst strictly correct, the 2016 study by Bertossi et al3 examined the treatment of 50 patients using a grid system for the upper third of the face, where half of the patients were injected using the Juvapen device and the other half were injected using a normal syringe. The patients injected with the Juvapen experienced much less pain on injection. Direct patient clinical experience far outweighs any laboratory testing of such devices.

There are numerous other devices available to the toxin injector. Galderma (Lausanne, Switzerland) offers, free-of-charge, a zero dead-space syringe calibrated to Dysport/Azzalure units to assist the injector without concerns about dilutions and injection volumes.

With this plethora of devices available, it would be wrong to specifically focus on any one product when discussing how they might assist and improve toxin injection techniques. What is really needed is a side-by-side comparison of the devices in actual clinical use. However, such a study is unlikely due to competing interests.

Moreover, Yoelin et al failed to take into account an exceptionally important aspect of all BoNT products, which is often missed or neglected in discussions about the number of units administered. The labeled potency of each vial is only a nominal value. In reality, this can vary by ±20 percent or more, dependent on the product.4 These limits are due to the biological assays used to measure final product potencies, not manufacturing factors, and are established during the registration procedures in conjunction with the relevant regulatory authorities. With such wide variations, the benefits of highly accurate injection volumes from these devices are almost entirely negated. This variability of final product potency may well explain differences between products seen in clinical results and is why so-called conversion ratios between product units cannot be firmly set.

With regard,

Andy Pickett, BSc, PhD

Affiliations. Dr. Pickett is with Toxin Science Ltd., Chester, United Kingdom and the Botulinum Research Center, Institute for Advanced Sciences in North Dartmouth, Massachusetts.

 Funding. No funding was provided. 

Disclosures. The author declares no conflicts of interest related to the content of this letter. 

Correspondence. Andy Pickett, BSc, PhD; Email: andy@toxinscience.com.


  1. Yoelin SG, Kwolek MS, Block JE. Commentary on botulinum toxin injections: a call for improved accuracy. J Clin Aesthet Dermatol. 2020;13(8):13–15.
  2. Kwolek MS, Block JE. Maximizing botulinum toxin injections for cosmetic and therapeutic applications with a single use, disposable, exact dose injection assist device. Clin Cosmet Investig Dermatol. 2019;12:35–46.
  3. Bertossi D, Mortellaro C, Nocini P. New clinical analysis and device for Botox injections. J Craniofac Surg. 2016;27(6):1554–1557.
  4. Botulinum Toxin Type A For Injection. In: European Pharmacopoeia. Monograph 2113 (in revision September 2020).


We very much appreciate Dr. Pickett’s interest in our article emphasizing the need to evaluate the syringe delivery technique for BoNT in aesthetic applications. We concur that the topic is underappreciated but of growing importance as the clinical paradigm has shifted toward neuromodulation with microdosing to achieve a natural appearance. Our contribution focused on improving dose accuracy which represents, along with placement and depth, the methodological triumvirate of proper injection technique. In fact, we conjecture that injection dose accuracy is the most difficult proprioceptive feature to master with precision and consistency.

As noted in our article and in Dr. Pickett’s reply, only three devices have been developed specifically to assist the injector with improved dose accuracy in neurotoxin delivery and the supporting literature is scant. The KB Medical injection-assist device (KB Medical LLC, Irvine, California) is the only device with published findings of comparative dose accuracy and precision versus freehand delivery in the peer-reviewed literature.1 In fact, accuracy values achieved with standard freehand delivery were ten times worse than with the injection assist device and precision estimates ranged from 2.2 to 5.4 times worse with freehand. Despite Dr. Pickett’s assertion that “clinical experience far outweighs any laboratory testing,” regulatory clearance of any of these devices in the United States will require strict independent laboratory testing of device accuracy before they can be available commercially to injectors.

We share Dr. Pickett’s enthusiasm that the clinical use of injection-assist devices may be associated with less injection site pain. We have also noted this interesting finding anecdotally. Additional human use studies will be necessary to confirm this observation. Indeed, these devices may offer several secondary advantages beyond assisting the injector with exact dosing. For example, we have previously reported that product waste at the injection site due to needle dripping was almost three times worse with freehand injection compared to injections performed with the KB Medical device.1

We agree that the wide laboratory tolerance limits on BoNT batch potency are unknown to most injectors. Xavier et al2 found that the average potency across seven separate samples of BoNT was 99% ± 5.7% (mean ±95% confidence interval), suggesting only modest batch-to-batch variability in the real world.

As highly-experienced injectors, we remain confident that these injection-assist devices represent new tools in our clinical armamentarium. We encourage an ongoing evaluation of these devices as instructional tools for new injectors as well as for experienced injectors to facilitate a broader scope of aesthetic applications.

With regard,

Steven G. Yoelin, MD;
Marilyn S. Kwolek, MD;
and Jon E. Block, PhD

Affiliations. Drs. Yoelin and Kwolek are in private practice in Newport Beach, California and Danville, California, respectively.  Dr. Block is an independent consultant in San Francisco, California.

Funding. No funding was provided. 

Disclosures. Drs. Kwolek and Block are Co-founders of KB Medical LLC (Las Vegas, NV).

Correspondence. Jon E. Block, PhD;
Email: jb@drjonblock.com.


  1. Kwolek MS, Block JE. Maximizing botulinum toxin injections for cosmetic and therapeutic applications with a single use, disposable, exact dose injection assist device. Clin Cosmet Investig Dermatol. 2019;12:35–46.
  2. Xavier B, Perobelli RF, Walter ME, et al. Content/potency assessment of botulinum neurotoxin type-A by validated liquid chromatography methods and bioassays. Toxins (Basel). 2019;11(1).