How Vaccine Sensitivity Affects Potency: A Guide

How does vaccine sensitivity to temperature affects its potency? Vaccines owe their efficacy to a lot of factors. Its potency is heavily influenced by dynamic external factors that plague it from its conception to distribution.

Awareness of these sensitivities is vital because once the potency is lost, it cannot be regained. Hence, it is necessary for the organizations within the supply chain to first, determine the vaccines and their corresponding sensitivity; then, continue monitoring them before administration.

In this article, we describe the sensitivities of the known vaccines and how to care for them to offset any possible diminishing of potency.

Difference between vaccines and diluents

Understanding vaccine sensitivity means understanding its most important partner—diluents. Some vaccines are inactivated or in powdered form, known in pharmaceutical terms as lyophilized or freeze-dried. Activating them before injection requires a combination with diluents (liquid form) or another vaccine—a process called reconstitution.

Reconstitution must be done by following the guidelines set by the manufacturer. Diluents are not interchangeable and only go to its partner vaccines. Because of the variety of these products, vaccinators must carry out reconstitution with care.

A diluent can be any water solution (aqueous solution), simple salt solution, or another vaccine that is just as sensitive as vaccines to the same external factors.

Types of sensitivity

Heat sensitivity

All vaccines lose potency over time, but heat speeds up the process. The presence of high temperatures and the absence of cooling equipment contribute to diminishing effectivity. That’s why it’s necessary to determine the type of vaccine and diluents, always considering the manufacturers’ guidelines.

The table below shows the type of vaccines and their level of sensitivity to heat. The vaccines inside each group are arranged in alphabetical order, not in order of sensitivity. But the groups above the table are more sensitive than the groups below. The boldly written vaccines are freeze-dried, thus in need of reconstitution.

On the other hand, diluents comprise of two types: pharmacologically active and pharmacologically inactive.

Inactive diluents are packed separate from the vaccines because they are more heat-stable and less temperature-sensitive than the vaccines they accompany. These diluents can be stored and transported at room temperature until the service level. But in few cases where the inactive diluents are encased with the vaccines, these products must undergo the cold-chain process just as much as vaccines.

Active diluents are strictly packed together with the vaccines. They are more temperature-sensitive, thus requiring cold-chain capacity requirements.

Despite inactive diluents being heat-stable, manufacturers require all types of diluents and vaccines to be kept at 2°C to 8°C (35°F to 46°F) during storage and transport and after reconstitution at the clinic.

Freeze sensitivity

Many vaccines can withstand a freezing environment. Lyophilized measles-containing vaccines and oral polio vaccine (OPV) are freeze-stable. But some vaccines containing aluminium salt adjuvants (aluminium phosphate or aluminium hydroxide) clump together when frozen. The immunological properties are then gravely affected.

Injecting a previously frozen vaccine results in a reduced immune response and potentially increased incidence of local transmission.

Vaccines with diphtheria toxoid, tetanus toxoid, and hepatitis B antigens, also the diluent for meningitis A conjugate vaccine contain aluminum salt adjuvants. (Take note: some vaccines like oral cholera, inactivated polio, influenza vaccines, are easily damaged by freezing even without aluminum adjuvants.)

The figure below separates vaccines that get damaged by freezing and those that do not.

Unlike some vaccines, all diluents must be kept from freezing temperatures. The vials that hold most diluents are brittle enough to crack in an icy environment. Though mostly water and simple salt solutions, some diluents also contain salt adjuvants.

Photosensitivity

Ultraviolet light can diminish the efficacy of photosensitive vaccines the likes of BCG, measles, and rubella. The reason manufacturers enclose these vaccines in vials of dark glass is to protect against UV exposure. Generally, all vaccine primary containers should be kept from sunlight and UV-emitting artificial light sources like fluorescent tubes and bulbs. Purpose-built freezers of see-through glass doors can affect the vaccines when opened from their secondary cartons.

Below is a table of vaccine products that are light sensitive and their recommended handling.

There are many ways you can prevent the loss of vaccine potency: knowing the type of vaccine, the type of sensitivity of these vaccines, and the specific measures to protect from these sensitivities.

Even though environmental factors like light and temperature diminish the effectivity of a supposed good vaccine, a well-prepared cold-chain supply network is helpful. A supply chain that studies the products enough and provides all the equipment will likely up the chance of delivering effective and potent vaccines.

Recommended Storage Temperatures for Vaccines

The manufacturers’ guidelines should always be referenced when considering the storage of vaccines. There may be country-specific legislation and legal requirements, in the absence of this the World Health Organization (W.H.O) have published guidelines.

With few exceptions, vaccines should be maintained at 2°C to 8°C (35°F to 46°F) for as long as possible. OPV require storage in freezers at -25°C to -15°C (-13°F to 5°F). Freeze dried vaccines that are bundled with their diluent should never be frozen.

In some cases there may be limited cold-chain capacity diluents may be kept outside of the cold chain environment between 2°C to 25°C (35°F to 77°F) until clinic level. At this stage, it is important that the manufacturers’ instructions are followed regarding cooling the diluent prior to reconstitution. However, where there are sufficient cold-chain storage capacity diluents should be kept together with their corresponding vaccines and protected from freezing.

Conclusion

It is essential to be aware of the vaccines you are handling, transporting or storing and their specific requirements. The cold chain should not be broken, photosensitive vaccines protected from exposure and freeze sensitive vaccines never frozen. There are some vaccines that can withstand temporary exposure to elevated temperatures, this will be detailed in the manufacturers’ guidelines and is known as the drug stability budget.

A data logger or realtime monitoring system can be employed to protect the vaccines. Data loggers are retrospective and can inform you if the vaccines have been exposed to temperature excursions. A realtime monitoring system can give advanced warning of pending excursions as they happen, potentially saving thousands of dollars worth of vaccines.