Vaccine and Pharmaceutical Formulation and Stabilization Technologies

Optimizing product stability

Protecting valuable products from temperature extremes

Overexposure to extreme heat or cold can ruin desperately needed vaccines and essential medicines. Keeping these critical health products at the appropriate temperature range of 2°C to 8°C requires a cold chain: a global distribution network of equipment and procedures for maintaining product quality (potency) during transport, storage, and distribution. Despite these efforts, a growing body of evidence indicates that temperature excursions—when temperature-sensitive products are exposed to extreme heat or cold—occur with high frequency in both developed and developing countries.

The potential for temperature extremes to damage vaccines and essential medicines is highest in areas where power outages or gas shortages prevent refrigerators from operating or where health care products must be transported over long distances to reach remote populations. Vaccines containing an aluminum adjuvant are particularly sensitive to freezing, which can occur when vaccines are placed too close to the walls of ice-lined refrigerators, the evaporator in certain refrigerators, or the frozen ice packs inside insulated transport carriers. When health workers suspect temperature damage, the vaccine or medication is often discarded—at great cost to health care programs. When temperature damage goes unnoticed, patients may receive ineffective vaccine or medication.

Working to ensure potency and impact

Thermostable formulations can resolve many of these issues, providing an extra level of “insurance” for product quality and potency during cold chain breaks. Optimized product stability through heat and freeze protection can also add value for producers by improving bulk production efficiencies, reducing the risk of recalls (following breaks in the cold chain, when the vaccine is under the manufacturer’s warranty), and decreasing the cost of temperature-controlled transport and storage. In addition, by preventing the damage caused by temperature extremes, thermostability can help to ease outreach logistics, facilitating coverage gains in remote settings beyond the peripheries of the cold chain.

Tremendous efforts have been made in recent years to advance stabilization technologies that can aid the development of vaccines and pharmaceuticals with enhanced thermostability. Innovations include new tools for characterizing the structure of proteins to inform formulation design, developing biophysical assays for the high-throughput screening of formulations, and analyzing as well as optimizing established and novel drying techniques and processing methods.

Feasibility of temperature-stable products

PATH has a long history of inventing, adapting, testing, and validating emerging concepts, advanced formulation designs, stabilization technologies, and processing methods that can help to ensure product effectiveness and impact under the toughest temperature conditions. In addition, we have explored the key logistical, regulatory, procurement, and policy issues associated with the development and use of temperature-stable vaccines and essential medicines in developing countries.

  • Extending heat stability. Our work on various antigen types with numerous technical collaborators has yielded major improvements in the heat stability of the vaccines tested—offering game-changing possibilities for improving vaccine effectiveness and outreach in low-resource settings. Visit our page on extending heat stability to learn more »
  • Preventing freeze damage. We have also worked to address the longstanding but under-recognized problem of vaccine freezing through the development of a method that protects liquid formulations containing an aluminum salt adjuvant or its equivalent (e.g., aluminum hydroxide, aluminum phosphate, or calcium phosphate) from freeze damage. Visit our page on PATH’s freeze-protection technology to learn more »

In a guest editorial published in Human Vaccines and Immunotherapeutics, we reflect on our achievements and major lessons learned in optimizing vaccine product stability, and provide eight recommendations for developing and commercializing vaccines with improved stability:

  1. Stabilization efforts should be integrated into early vaccine development.
  2. There are circumstances where it makes sense to stabilize existing vaccines.
  3. Freeze stabilization is possible for vaccines containing aluminum adjuvants.
  4. Heat stabilization requires a customized approach, and results will be variable.
  5. The full benefits of heat-stable vaccines will only be realized after programmatic and policy changes are made to storage guidelines.
  6. Improvements in vaccine heat stability are inextricably tied to product format and careful consideration should be given to the end-product attributes and priorities during vaccine development.
  7. Some heat-stability improvements result in inferior product formats whereas others enable new, beneficial formats.
  8. Products with enhanced stability can benefit both vaccine producers and purchasers.

Many of our achievements and major lessons learned in the stabilization of human vaccines can also be applied to drugs and some veterinary vaccines. Visit our page on fast-dissolving tablets to learn more »

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