Zach Marks, M.S., R.Ph., West Pharmaceutical Services05.14.14
Vaccinations for issues such as influenza typically are only at the forefront of healthcare news during a crisis. For parents of newborn children, however, the essential vaccinations for diseases such as diphtheria, tetanus, pertussis, measles, polio, tuberculosis, mumps, pneumococcal disease, rotavirus, rubella and, in countries where needed, yellow fever and Japanese encephalitis, must be completed within the child’s first year of life.
Unfortunately, it is likely that more than 24 million children—20 percent of those born each year—will not receive the full course of routine immunizations.1 While more children are being reached every year, many—and in particular those in developing countries—will not receive the life-saving injections they need for various reasons, including cost, difficulty of delivery and administration, accessibility of vaccines, drug shortages and supply chain issues.
In 2000, the World Health Organization (WHO) held a Millennium Summit and developed goals that included reducing the deaths of children younger than five years old. The availability and delivery of vaccines to at-risk children in developing countries is a major step toward achieving this goal. Novel vaccination strategies, such as intradermal delivery, currently are being evaluated. Though challenges exist, intradermal vaccination offers a variety of benefits to medical technology manufacturers and, ultimately, patients.
According to WHO, since 2000, the vaccine market has grown substantially, with much of the demand for newer and higher-priced vaccines coming from industrialized nations. Such countries have a reliable, properly functioning vaccine regulatory system, a strong supply chain and advanced healthcare facilities with trained personnel to aid in administration. Developing countries often do not have these options.
Critical vaccines that travel to the most remote regions often are subjected to extreme conditions during transportation which can threaten potency and limit overall effectiveness. Many live vaccines are lyophilized and require reconstitution prior to administration. This helps maintain stability and efficacy of the drug product prior to use; however, lyophilization, as well as the necessary cold storage and shipping condition associated with this technique, can increase costs. Additionally, once the vaccines reach their destination and are reconstituted, they must be used within three to six hours. Multi-dose vials can be cross-contaminated by reuse of syringes. In addition, vaccines can be wasted if multi-dose vials are reconstituted and then not dispensed within the three- to six-hour time period.
Vaccine delivery methods also pose a challenge. Many vaccines rely on the use of needles and syringes for administration, which may carry significant risk when used in developing countries where health issues such as lack of sharps waste management and reuse of needles are prevalent. Although a variety of options for vaccine delivery exist, including intramuscular (IM), subcutaneous (SC), nasal, oral and transcutaneous methods, recent advances have helped improve the efficacy of vaccine delivery through intradermal (ID) injection.
The skin contains a high concentration of antigen-presenting cells, making it an ideal location for injection. These cells perform an essential role in processing incoming antigens, resulting in powerful immune system responses. Delivery of vaccines to the epidermis or dermis may result in superior immune responses when compared to IM or SC injections.2 In addition to the enhanced immune response in patients, ID delivery offers a variety of benefits to pharmaceutical manufacturers, including dose sparing, increased availability of limited or expensive antigens and reduced cost per dose.
Unfortunately, the current method of ID delivery, the Mantoux technique, can be difficult to master. Developed by Charles Mantoux, the method requires that healthcare practitioners master inserting a needle at a five- to 15-degree angle approximately 1 millimeter deep into the skin to inject the vaccine effectively.3 When the injection is performed correctly, a bleb or wheal of 6 to 10 millimeters in diameter is formed on the skin indicating that the vaccine has been delivered to the dermal space. After a few minutes, the bleb disappears as the vaccine is dispersed and absorbed into the surrounding tissue. The difficulty associated with training and the inconsistency of injection efficacy have deterred vaccine manufacturers from testing ID injection and medical practitioners from using ID injection as a common immunization method.
Alternative methods of ID administration are being studied. Novel injection technologies can make intradermal injection easier and more consistent. Delivery devices may aid needle/syringe injection, while jet injection, transdermal patches and micro-needles offer new options to patients and caregivers. One requirement for the use of such technologies is ease of handling. In developing countries, healthcare providers may be in short supply, so minimal administrator training can aid in delivery. Use of a needle and syringe requires no specialized equipment, but training in the Mantoux method can be difficult. Patch injection devices do not use a conventional needle, so the injection itself may be less invasive and painful, as well as easier to administer, for patients. However, this method may require a reformulation of current vaccines, which may be time-consuming for pharmaceutical manufacturers requiring process development, stability and new regulatory submission of a novel device.
Jet injection provides a needle-free technology that eliminates cross-contamination if auto-disabled cartridges are used. However, jet injection devices can be expensive, and require a substantial capital investment, which is not a suitable alternative for developing countries since not all markets will have the resources to purchase this type of device. In addition, the extra cost of disposable cartridges may limit acceptance of this method of vaccination.
Syringe adapters can provide a guide for injection when using a syringe system. The device fits over a conventional hypodermic needle and syringe and precisely controls the angle and depth of needle penetration into the dermal layer. The ID adapter offers healthcare professionals a simple way to perform an ID injection, potentially without pharmaceutical manufacturers needing to reformulate their vaccine. Use of an adapter can offer greater confidence that the healthcare provider has administered the vaccine into the correct space. In addition, the ID adapter can be used with auto-disabled syringes, which prevents needle reuse and eliminates the risk of blood-borne disease transfer via the needle.
One of the major benefits of ID injection is dose sparing. This method of administration significantly can expand the vaccine supply in emerging markets. Patients may respond to a lower dose of a vaccine given intradermally than when the same vaccine is given at a higher dose subcutaneously or intramuscularly. This results in lowered cost per dose, less volume of the vaccine required in the cold chain and lower storage and transportation costs. Cost reductions can make a big impact on emerging markets, which tend to rely on multi-dose formats, and help make vaccines more accessible. In addition, intradermal administration may enhance immunogenicity for difficult-to-treat populations including infants and the elderly.
* * *
As the population in developing countries continues to grow and vaccine prices continue to rise, efficiency of delivery and use will be essential to ensuring that vaccinations are completed for both children and adults. ID administration can help reduce dose cost while potentially improving immunogenicity in traditional and hard-to-treat populations. Advances in delivery systems have made consistency of administration into the dermal layer possible without advanced training requirements and with minimal disruption to the pharmaceutical manufacturer. As more vaccines reach the market, and costs continue to rise, ID administration may provide an excellent alternative to traditional vaccination while maintaining the immune response. Improved delivery devices and systems can provide a low-cost, easy to use option for developing countries to help curb costs while ensuring safe delivery.
References
1. “State of the World’s Vaccines and Immunizations,” Third Edition, The World Health Organization, 2009
2. Kim, Y.C., et. al., “Delivery Systems for Intradermal Vaccination,” Current Topics in Microbiology and Immunology, DOI: 10.1007/82_2011_123, Springer-Verlag Berlin Heidelberg, 2011
3. Ibid
Zach Marks, M.S., R.Ph., serves as director of marketing at West Pharmaceutical Services. Marks joined West in 2002 as business development manager for the Clip’n’Ject reconstitution system. In 2007, his role was expanded with the acquisition of Medimop Medical Products. In 2010, Marks was promoted to his current position of director of marketing for self-injection and administration systems as well as the expansion of delivery systems in the Asia-Pacific region. Marks is a registered pharmacist with a B.S. in pharmacy and an M.S. in pharmaceutical science from Rutgers University.
Unfortunately, it is likely that more than 24 million children—20 percent of those born each year—will not receive the full course of routine immunizations.1 While more children are being reached every year, many—and in particular those in developing countries—will not receive the life-saving injections they need for various reasons, including cost, difficulty of delivery and administration, accessibility of vaccines, drug shortages and supply chain issues.
In 2000, the World Health Organization (WHO) held a Millennium Summit and developed goals that included reducing the deaths of children younger than five years old. The availability and delivery of vaccines to at-risk children in developing countries is a major step toward achieving this goal. Novel vaccination strategies, such as intradermal delivery, currently are being evaluated. Though challenges exist, intradermal vaccination offers a variety of benefits to medical technology manufacturers and, ultimately, patients.
According to WHO, since 2000, the vaccine market has grown substantially, with much of the demand for newer and higher-priced vaccines coming from industrialized nations. Such countries have a reliable, properly functioning vaccine regulatory system, a strong supply chain and advanced healthcare facilities with trained personnel to aid in administration. Developing countries often do not have these options.
Critical vaccines that travel to the most remote regions often are subjected to extreme conditions during transportation which can threaten potency and limit overall effectiveness. Many live vaccines are lyophilized and require reconstitution prior to administration. This helps maintain stability and efficacy of the drug product prior to use; however, lyophilization, as well as the necessary cold storage and shipping condition associated with this technique, can increase costs. Additionally, once the vaccines reach their destination and are reconstituted, they must be used within three to six hours. Multi-dose vials can be cross-contaminated by reuse of syringes. In addition, vaccines can be wasted if multi-dose vials are reconstituted and then not dispensed within the three- to six-hour time period.
Vaccine delivery methods also pose a challenge. Many vaccines rely on the use of needles and syringes for administration, which may carry significant risk when used in developing countries where health issues such as lack of sharps waste management and reuse of needles are prevalent. Although a variety of options for vaccine delivery exist, including intramuscular (IM), subcutaneous (SC), nasal, oral and transcutaneous methods, recent advances have helped improve the efficacy of vaccine delivery through intradermal (ID) injection.
The skin contains a high concentration of antigen-presenting cells, making it an ideal location for injection. These cells perform an essential role in processing incoming antigens, resulting in powerful immune system responses. Delivery of vaccines to the epidermis or dermis may result in superior immune responses when compared to IM or SC injections.2 In addition to the enhanced immune response in patients, ID delivery offers a variety of benefits to pharmaceutical manufacturers, including dose sparing, increased availability of limited or expensive antigens and reduced cost per dose.
Unfortunately, the current method of ID delivery, the Mantoux technique, can be difficult to master. Developed by Charles Mantoux, the method requires that healthcare practitioners master inserting a needle at a five- to 15-degree angle approximately 1 millimeter deep into the skin to inject the vaccine effectively.3 When the injection is performed correctly, a bleb or wheal of 6 to 10 millimeters in diameter is formed on the skin indicating that the vaccine has been delivered to the dermal space. After a few minutes, the bleb disappears as the vaccine is dispersed and absorbed into the surrounding tissue. The difficulty associated with training and the inconsistency of injection efficacy have deterred vaccine manufacturers from testing ID injection and medical practitioners from using ID injection as a common immunization method.
Alternative methods of ID administration are being studied. Novel injection technologies can make intradermal injection easier and more consistent. Delivery devices may aid needle/syringe injection, while jet injection, transdermal patches and micro-needles offer new options to patients and caregivers. One requirement for the use of such technologies is ease of handling. In developing countries, healthcare providers may be in short supply, so minimal administrator training can aid in delivery. Use of a needle and syringe requires no specialized equipment, but training in the Mantoux method can be difficult. Patch injection devices do not use a conventional needle, so the injection itself may be less invasive and painful, as well as easier to administer, for patients. However, this method may require a reformulation of current vaccines, which may be time-consuming for pharmaceutical manufacturers requiring process development, stability and new regulatory submission of a novel device.
Jet injection provides a needle-free technology that eliminates cross-contamination if auto-disabled cartridges are used. However, jet injection devices can be expensive, and require a substantial capital investment, which is not a suitable alternative for developing countries since not all markets will have the resources to purchase this type of device. In addition, the extra cost of disposable cartridges may limit acceptance of this method of vaccination.
Syringe adapters can provide a guide for injection when using a syringe system. The device fits over a conventional hypodermic needle and syringe and precisely controls the angle and depth of needle penetration into the dermal layer. The ID adapter offers healthcare professionals a simple way to perform an ID injection, potentially without pharmaceutical manufacturers needing to reformulate their vaccine. Use of an adapter can offer greater confidence that the healthcare provider has administered the vaccine into the correct space. In addition, the ID adapter can be used with auto-disabled syringes, which prevents needle reuse and eliminates the risk of blood-borne disease transfer via the needle.
One of the major benefits of ID injection is dose sparing. This method of administration significantly can expand the vaccine supply in emerging markets. Patients may respond to a lower dose of a vaccine given intradermally than when the same vaccine is given at a higher dose subcutaneously or intramuscularly. This results in lowered cost per dose, less volume of the vaccine required in the cold chain and lower storage and transportation costs. Cost reductions can make a big impact on emerging markets, which tend to rely on multi-dose formats, and help make vaccines more accessible. In addition, intradermal administration may enhance immunogenicity for difficult-to-treat populations including infants and the elderly.
* * *
As the population in developing countries continues to grow and vaccine prices continue to rise, efficiency of delivery and use will be essential to ensuring that vaccinations are completed for both children and adults. ID administration can help reduce dose cost while potentially improving immunogenicity in traditional and hard-to-treat populations. Advances in delivery systems have made consistency of administration into the dermal layer possible without advanced training requirements and with minimal disruption to the pharmaceutical manufacturer. As more vaccines reach the market, and costs continue to rise, ID administration may provide an excellent alternative to traditional vaccination while maintaining the immune response. Improved delivery devices and systems can provide a low-cost, easy to use option for developing countries to help curb costs while ensuring safe delivery.
References
1. “State of the World’s Vaccines and Immunizations,” Third Edition, The World Health Organization, 2009
2. Kim, Y.C., et. al., “Delivery Systems for Intradermal Vaccination,” Current Topics in Microbiology and Immunology, DOI: 10.1007/82_2011_123, Springer-Verlag Berlin Heidelberg, 2011
3. Ibid
Zach Marks, M.S., R.Ph., serves as director of marketing at West Pharmaceutical Services. Marks joined West in 2002 as business development manager for the Clip’n’Ject reconstitution system. In 2007, his role was expanded with the acquisition of Medimop Medical Products. In 2010, Marks was promoted to his current position of director of marketing for self-injection and administration systems as well as the expansion of delivery systems in the Asia-Pacific region. Marks is a registered pharmacist with a B.S. in pharmacy and an M.S. in pharmaceutical science from Rutgers University.