Breakthroughs in Drug Delivery

By Marie Redding
Freelance Writer

Delivering Flu Vaccinations
In recent years, Becton, Dickinson, and Co. (Franklin Lakes, NJ) and Sanofi Pasteur joined efforts, collaborating to commercialize the first prefilled influenza vaccine utilizing a novel microinjection system for intradermal delivery. BD began developing the technology more than 10 years ago.  

Pending FDA licensure (anticipated in 2011), Sanofi Pasteur’s Fluzone will become the first vaccine available in the United States to use a microinjection system for intradermal delivery. Sanofi Pasteur announced in September that FDA accepted its Supplemental Biologics License Application.

Called the BD Soluvia microinjection system, it is a prefillable syringe that integrates BD’s microneedle technology and proprietary primary packaging, which are specifically designed to provide reliable delivery of drugs and vaccines into the intradermal layer of the skin.

Designed to be prefilled with a drug product, the microinjection system offers a ready-to-use presentation and eliminates the preparation time required with conventional vials, according to BD. The microneedle is affixed to the syringe, which further reduces the number of preparation steps and simplifies the medication administration process.

SafeShot calls its Epiphany Safety Syringe "the world's first affordable, single-handed, autoretractable, autodisabling, safety syringe."

“As compared with the current intradermal injection technique, BD Soluvia microinjection system helps simplify and improve the success of intradermal injections by utilizing a novel injection technique that is perpendicular to the skin,” says Eric Borin, vice president and general manager, BD Medical–Pharmaceutical Systems.

BD Soluvia’s microneedle is 1.5 mm long, compared with the 1 in. or 1.5 in. (25 mm–40 mm) length needles typically used with the intramuscular route for vaccination. The very fine needle helps to ensure that antigens are accurately and consistently deposited to the skin’s dermis, which contains immune cells that can stimulate an immune system response. The microinjection system is designed for fill volumes up to 130 µl of drug product. Each system also incorporates a needle-shielding mechanism, which may reduce potential for needlestick injury.

Intradermal injections provide the benefit of being minimally invasive. They deposit antigens in the dermal layer of the skin (located just below the outermost layer), rather than the muscular layer. The dermis contains a dense network of blood capillaries, which allow for quick drug uptake into the bloodstream and enhanced bioavailability relative to intramuscular and subcutaneous routes. The lymph flow within the dermis provides open access to the lymphatic system through draining lymph nodes by passing the metabolic first path effect of the liver.  These attributes allow for improved speed of drug uptake and pharmacological effect for many drugs, including those used to treat pain, shock, cancer, and metabolic conditions, such as diabetes. The dermal layer also contains populated contingent of immuno-competent cells characterized by a powerful capability to induce immune response. This unique characteristic of dermal tissue is a key element for improving immune response after vaccine delivery.

Safer Syringes
The need to find better ways to comply with Needlestick Safety regulations sparks the development of new safe syringe delivery systems. More countries are continuing to follow the example first set in 2000 with the U.S. Needlestick Safety and Prevention Act, while pharmaceutical companies and packaging suppliers are paying close attention.

Syringes, including prefilled and disposable unit-dose syringes used by hospitals and healthcare facilities, require the incorporation of safety features. This is mandatory in the United States, and the legislation is spreading around the world. Safer sharps can include spring-loaded retractable needles, active shield systems, guards that shield the tips, puncture resistant sharps containers, and blunt sutures.

Catalent Pharma Solutions and Innovate UK are collaborating to introduce Click In, a new proprietary safety shield device designed to be used with syringes that have a luer lock, luer slip, or staked needles.

Even though more countries are moving toward adopting new legislation regarding needlestick safety, there are many issues to overcome that affect pharmaceutical companies and packaging suppliers, according to Robert Beart, Emeritus Professor of Surgery at USC’s Keck School of Medicine and CEO of SafeShot. (Beart’s professional experience also includes serving as personal surgeon to several heads-of-state, including one U.S. President.)  

“Cost has been a major barrier to the adoption of safer syringes. There are cheap syringes on the market that are not safe, and there are a couple of syringes that work but are very expensive,” says Beart. “We’ve been able to develop a safe affordable solution to this issue. Our revolutionary new design can create a paradigm shift for all shots, drug injection, immunization, and inoculation in global markets.” 

In fact, safety legislation is spreading throughout Europe. On March 8, the European Union Employment and Social Affairs Ministers adopted a Directive to protect its 3.5 million healthcare workers from needlesticks and other sharps-related injuries. The new directive implements in law a framework agreement signed in July 2009 by the European Public Services Union and the European Hospital and Healthcare Employers’ Association. Full compliance for all healthcare employers is unlikely to be imposed until mid to late 2012.

“Due to the new legislation in Europe, disposable auto injectors and safety shield devices are becoming extremely important now,” says Sheila Dell, Ph.D., vice president of business development, Catalent Pharma Solutions (Somerset, NJ). “We’ve been finding that some of our customers are still not aware of the new legislation, which requires all prefilled syringes to have a safety shield device,” she says. 

Catalent recently partnered with a Manchester-based company, Innovate UK, to market a new safety shield device, as well as help its European customers comply faster with the new legislation. As a result of the joint marketing and distribution agreement between Catalent Pharma Solutions  and Innovate UK, a new proprietary safety shield device will be brought to market, called “Click In.” It is designed to be used with syringes that have luer lock, luer slip, or staked needles.

Catalent Pharma Solutions is currently showing it to pharmaceutical customers, and the device has been receiving an excellent response, according to Dell. The safety shield device is designed so that a syringe slides into it, where it clicks in place and is securely held.

According to Simon Cohen, managing director, Innovate UK, “Click In” offers a quick, turnkey solution for complying with new legislation. “Simplicity of action and ease of use are key advantages. There is no need to change or validate a syringe filling line,” says Cohen.

To use the safety feature, the injection is performed normally. After injection, the shield moves forward and locks in place when a button is pressed. It can then be put into a sharps container for disposal. “Since the device is not surface activated, there is no chance of splash contamination,” says Cohen. 

During the development of this safety device, Cohen explains that the main challenge faced was to make sure its design allowed flexibility in packaging options. “We wanted a system that could be added after fill as part of the packaging line, for an automated pre-fitted option. In addition, we wanted it to be offered as a stand-alone system that could be sent out with the product to be manually added by the clinician at point of use,” explains Cohen. 

Catalent Pharma Solutions is taking a proactive role in helping its customers comply with the new legislation. “We’re happy to be able to offer our customers an off-the-shelf product range of safety devices that represent a safe, simple, and secure solution to the problem of needle stick injury,” says Dell. “We’ve been heavily promoting this device to our worldwide pharmaceutical customers, making sure their prefilled syringes start to incorporate this safety device sooner, rather than later. It’s an inexpensive way to keep doctors, nurses, and caregivers safe.” 

Even as new safety regulations spread throughout the world, there are huge problems regarding the types of safety systems that are available, according to the experts at SafeShot. “As more safety products are developed, incidents involving needlesticks keeps rising,” says Beart.

“Most so-called safety products are basically a standard syringe with a lot of contraptions added on, which just make it more complicated and costly. Also, with some of these products, there is still the chance of getting pricked,” he says. “We’ve been able to solve issues of reuse to help prevent needlestick injuries at a cost that is comparable to traditional reusable syringes,” Beart explains.

SafeShot considers its Epiphany Safety Syringe, which was first developed a few years ago, an industry breakthrough. They tout it as ‘the world’s first affordable, single-handed, auto-retractable, auto-disabling, safety syringe.’ It adds only pennies to the cost of a traditional syringe, according to Beart. This is possible owing to Epiphany’s unique design that enables it to work without springs or other extra parts, which contributes to its low cost. 

Designed for single-use, the Epiphany Safety Syringe consists of a patented, vacuum-triggered barrel. After the shot is administered, the needle retracts into its barrel cylinder, where it is securely held for disposal. The syringe itself becomes its own sharps container.  “There is no chance of getting pricked, because once the needle is used, it is gone forever,” Beart says.
In September, SafeShot Technologies filed patents on a new low-dose version of its safety injection technology called Epiphany Ultra. Epiphany Ultra allows for safe injections of 1 mL and lower volumes using the same single-handed vacuum retraction technology used in its larger versions.  

“This is a huge milestone for our engineering team and company because of the precision required in designing an ‘Ultra Low Dose’ safety syringe that is as simple and affordable as the Epiphany Ultra,” says Beart.
 Since Epiphany’s introduction, SafeShot has been meeting with major pharmaceutical and medical device companies, and the team expects it to be commercialized by next year.

Epiphany and Epiphany Ultra can be used with a complete spectrum of drug delivery formats, including pre-fills, clinical, home, consumer and immunization/vaccination. “The design has the ability to adapt and fit into the current ‘tub filling’ technics and production filling lines used by many high volume pharmaceutical companies for their pre-filled offerings, with very little disruption of change,” says Beart.  

Beart feels they have succeeded in breaking the cost barriers that have prohibited healthcare facilities from broadly adopting the most effective safety technology available. “Our innovative design saves time in training, administering injections, and we are proud to say, it will ultimately save lives,” he says.

Conclusion
Needlesticks and other sharps-related injuries to hospital-based healthcare workers is associated with the transmission of Hepatitis B, Hepatitis C, and human immunodeficiency virus (HIV), but they have also been known to cause the transmission of more than 20 other blood-borne pathogens, according to the U.S. Centers for Disease Control and Prevention. 

Innovations are needed to maker injection safer and simpler. Affordability is also important in order for such safety solutions to become widely used.