INTRODUCTION
When the FDA approved Sculptra® (poly-L-lactic acid injectable (PLLA) in 2004 for HIV lipoatrophy, there were many questions about this product, given its safety profile of dermal papules and nodules, which occurred frequently. More than a decade later, after receiving an aesthetic indication, the product has a much lower rate of adverse events. In order to understand how injectors are currently utilizing the product, a survey was sent to ask specific questions about reconstitution of this product to understand the methods a practitioner utilizes to prepare injectable PLLA.
History of PLLA Injectable Devices
PLLA is a polymer of lactic acid, which has been used for 3 decades in the medical world as a part of suture material (Vicryl®)1 and in many other medical applications. This polymer degrades along the same metabolic pathway as lactic acid. It has a well-characterized safety profile, as it is biocompatible and biodegradable.2 Sculptra®3 and Sculptra® Aesthetic4 are classified as medical devices that contain PLLA and have been approved for injection into the dermis for HIV lipoatrophy and more recently in the US for cosmetic indications, nasolabial fold contour deficiencies, and correction of other facial wrinkles. The 2 products have different approved indications, but both contain PLLA 150 mg, carboxymethylcellulose (USP) 90 mg, and non-pyrogenic mannitol (USP) 127.5 mg.3,4 These products come in vials as lyophilized milled powder and must be reconstituted with sterile water3,4 to wet and suspend the particles in an aqueous milieu before injection into the skin. Published studies have shown that controlled reactive fibroplasia to the implanted material causes dermal thickening,5 thus characterizing these products as biostimulatory fillers.6,7 Fillers such as hyaluronic acid would be considered to be replacement agents in this paradigm.
The product began in Europe as New-Fill in 1999. The original New-Fill directions for use were not explicit about reconstitution – neither diluent nor hydration time for the process, injection technique nor placement in the skin. The product was reconstituted with 3 mL of sterile water originally.1
In the EU, the approval for the aesthetic indication predated the HIV lipoatrophy indication. In 2004, the FDA approved this product as Sculptra® for HIV lipoatrophy.3 Four clinical studies were considered for the HIV lipoatrophy indication approval in the US. These included 2 studies conducted in Europe– Chelsea and Westminster,8 and Vega.9 The studies known as Blue Pacific,10 and Apex0021,2 had been granted IDEs (Investigational Device Exceptions) by the FDA, for the investigators to be able to conduct such research in the US prior to approval.
Each group of investigators had a different method to prepare the product for injection into the patient (Table 1).
The differences among the clinics conducting these trials included volumes of reconstitution, between 3-5 mL of sterile water with or without added lidocaine just before injection into the subject’s face for comfort (Table 1). Most clinics at that time used the product within minutes of reconstitution. Commonly, injectors had needles clog as they injected product into the dermis. Also at that time, there was no standardized protocol regarding injecting depth or technique; each clinic had its own method since there were no standardized instructions that were published for the “New-Fill†product. The investigator reported AEs of papules and nodules ranged from 6-44% in these studies.1,8-10 At the time, since primary care and HIV physicians performed many of the injections, the AE descriptions were
