EMEA filing for first vaccine using Soluvia microinjection system

The submission for the first influenza vaccine to use the BD Soluvia system has been accepted for review by the European Medicines Agency (EMEA). In clinical trials involving more than 7,000 adult or elderly subjects, the ID vaccine triggered higher levels of seroprotective immune response against all tested influenza strains than standard intramuscular (IM) influenza vaccination, Sanofi Pasteur reported. Most vaccines are injected into muscle. With BD Soluvia, a prefillable microinjection system integrated with a thin needle only 1.5mm in length, the vaccine can be delivered accurately within the dermal layer of the skin. As BD pointed out, this layer contains a dense network of lymphatic vessels feeding local lymph nodes, which gives the vaccine rapid and efficient access to the immune system. The dermal layer also contains a high concentration of potent immune cells that play a key role in initiating the immune response following vaccination, BD added. Another plus is ease of use, with a minimally invasive procedure that ensures the antigen is consistently deposited in the dermal layer. BD has independently conducted clinical trials with BD Soluvia involving more than 700 subjects and 3,500 injections, to make sure the system is safe and easy to handle. These demonstrated that the tiny microneedle "is barely perceptible when it enters the skin and ensures the administration of the injected solution to the dermal layer irrespective of the subject's gender, age, ethnicity and body mass"​, the company said. In the trials conducted by Sanofi-Pasteur, ID delivery of the influenza vaccine using BD Soluvia was shown to be especially effective at enhancing the immune response in the elderly. The French company sees this as an important distinction, given that the immune system tends to weaken with age, making the elderly not only more susceptible to infection but less responsive to vaccination. ​"When infected with flu virus, the elderly may not be able to mount an adequate immune response and, as a result, they remain vulnerable to the more serious complications of flu,"​ commented Dr Robert Booy, co-director of the National Centre for Immunisation Research and Surveillance in Sydney, Australia. "For this reason, there is a strong need to increase the immune response to vaccination in persons over 60 years of age, and the data show that the new ID vaccine can effectively provide improved responses in this age group." ​​Philippe Laurent, vice-president, medical affairs for BD Medical, described BD Soluvia as "a breakthrough technology that is intuitive to use and allows accurate and consistent delivery of substances such as flu vaccine into the dermal layer"​. According to the US medical technology specialist, the microinjection system has the potential to improve patient acceptance of injections and enhance immunisation practices. "BD is deeply committed to continuing the development of BD Soluvia for the intradermal route of administration for use with infectious disease and emerging cancer vaccines,"​ said Alex Conroy, president, BD Medical - Pharmaceutical Systems. The so-called 'Mantoux technique' of ID administration was first introduced in 1908. It involves stretching the surface of the skin and inserting a needle almost parallel to the skin surface so as to penetrate the thin dermal tissue layer. The relevant medicine or vaccine is then administered by slow injection. Despite the documented immunological and pharmacological advantages of ID vaccine delivery, the Mantoux technique is not commonly used due to difficulties in performing the procedure easily, reliably and effectively in a clinical setting, noted Laurent and colleagues in a paper published last October in the journal Vaccine​ (25 (2007) 8833-8842). These difficulties include the need for training and practice as well as problems with inelastic skin or age-related changes that can hamper correct placement of the needle in the dermal layer. Moreover, dose inconsistency "is unavoidable due to inherent variability in on-site syringe filling and air bubble purging processes"​, the authors point out. The 'dead volume' of vaccine left in the vial and syringe after injection is a major source of wastage during the injection process. These factors have also tended to blunt the pharmaceutical industry's interest in developing vaccines delivered via the ID route, Laurent et al note. Currently, only BCG and rabies vaccines are indicated for ID administration using the Mantoux technique. Nonetheless, in 2004 reports of flu vaccine shortages in the US raised the possibility of using ID delivery to spare vaccine dose. In published clinical trials, hepatitis B, rabies and flu vaccines administered via the ID route showed the potential for obtaining comparable humoral responses to those generated by IM injection, but at a fraction of the dose, the BD researchers said. These studies "rekindled interest among researchers, ​clinicians and public health officials in ID vaccine administration"​. A number of these studies were performed using the Mantoux technique and precursors of the Soluvia microinjection system. The system tested by Laurent and colleagues for performance and safety in humans and animals features a 30-gauge microneedle specifically designed for perpendicular insertion into the skin. The microneedle is pre-attached to a delivery system that limits the needle's depth of insertion to 1.5mm from the skin's surface. The microneedle is attached to a glass syringe pre-filled with the vaccine dose and a needle-shielding system that covers the needle after injection. The main benefits of the microinjection system confirmed in this study were consistency of dermal infiltration and accuracy of the delivered fluid volume. The system requires minimal advance instruction and incorporates a needle protection system to reduce the risk of inadvertent needlestick injury, the researchers noted. It would also be "very difficult to reuse (for those markets where inappropriate injection system reuse is an issue)"​, they added. Sanofi-Pasteur's application to the EMA is the first worldwide for any vaccine using BD Soluvia. The system is under development with other, unnamed partners for vaccines targeting prostate and breast cancer as well as melanoma, Conroy told In-PharmaTechnologist.com. One of these projects is in Phase II clinical trials but the rest are still at the research stage or in very early clinical development.