Beyond the Cold Chain : Evolving Needs of Pharmaceutical Distribution
The distribution of pharmaceutical products simply does not mean placing the temperature-sensitive items in cold-insulated boxes and sending them to destinations unknown. The process is more complex than that. Beyond the pharmaceutical cold chain. What are the evolving needs of the pharmaceutical cold chain logistics industry
Unexpected events can endanger the effectiveness of expensive speciality medicines. Temperature monitoring management systems are required to overcome those challenges. These systems monitor the environmental conditions of the biologicals to ensure that they meet the special pharmacy accreditation standards. Monitoring is essential to detect changes in the environment that surrounds cold chain shipments, to ensure that constant temperatures between 2°C (35°F) and 8°C (46°F) are maintained.
The farther medical product travels, the less control the manufacturer has. As such, cooperation between the organizations involved throughout the distribution chain is essential to prevent hot or cold deviations during the shipping process.
It is also vital to protect against damage from dropping packages, vibration, humidity, pressure, or too much light.
To achieve accreditation from the pharma company requires close adherence to pharmacy operation standards based on appropriate temperatures set by the manufacturer.
It is vital to follow standard operating procedures (SOP) when checking the temperatures of freezers and ice packs in the shipping process, safeguarding that they are within the correct levels and will not cause thermal shocks.
One accrediting institution is the Utilization Review Accreditation Commission (URAC). It requires a documented program for the distribution of cold chain products, with specific standards for packaging and transportation.
It requires controls that utilize the correct packaging, directives to maintain a steady recommended temperature and methods to determine whether a package can be on hold in the case of a potential delay, such as extreme weather. It also requires an annual review of quality management in the delivery process, along with concerns about the cold chain delivery systems.
It is worth noting that pharmacists are not properly trained on how to use cold packs or how internal package temperature can be affected by frozen gel packs. Expert advisors may need to be employed to ensure proper cold chain management.
The Value of Cold Chain Logistics
Cold Chain Logistics is a $10 billion part of the $1 trillion global pharma industry. The majority of drugs need temperature-controlled transportation and demand for safe drug transport is increasing every day. According to the World Health Organization, more than 90% of all vaccines require a temperature-controlled supply chain.
The increasing need for temperature control for this cold chain logistics is imperative as today’s drugs, especially the “large-molecule,” i.e., biologics, are becoming more prone to damage from deviations of temperature. Maintaining temperature is a constant challenge, as regulations, complications in global production, new market development and new modes of transportation continue to expand. According to industry experts, as much as 5% of medical products are lost to temperature fluctuations.
The World Health Organization reports that the Effective Vaccine Management assessment, which was deployed in more than 70 countries between 2010 and 2012, discovered that only 29% of countries met minimum recommended standards for temperature control.
Vaccine Market Trends
Clearly the move to biologic medicines and personalized, patient-centric cures are becoming more common in the pharmaceutical market. Due to the nature of these drugs, they need to be in specialized temperature-controlled containers to maintain their potency.
Without proper control, since they contain living cells or complex chemical molecules, medicines could lose their efficacy and could represent hazards to the patient because of the presence of toxic degradation compounds.
The cold chain delivery systems responsible for delivering these products have become increasingly complex, tortuous, and diverse. Today’s complicated cold-chains have several parties involved, across several shipping venues, to form a seamless link to deliver the products through climate zones, storage facilities, and patient health clinics and hospitals.
Even if there is a perfect thermal management system working and strictly enforced, it is still not enough. Human error or unforeseeable circumstances are some of the causes of temperature fluctuations. Vials left exposed to ambient temperature, power outages, equipment breakdowns, or improper temperature setting levels might spell disaster for the patients whose lives depend on quality medical products.
Other situations where there can be breakdowns in the cold chain include the delivery of medications into isolated places in the world, where the storage facilities are not available to guarantee safe final-mile delivery.
Solving these problems will help meet the regulatory requirements on temperature management to ensure that the pharma products are going to be effective at the point of administration to patients. Significant challenges occur once the product departs the cold chain facilities and enters areas where correct procedures for the handling and storage of sensitive drugs are unknown. Even less may be known about the results of taking thermally-compromised medicines.
The Regulatory Statement
Another important requirement is that regulatory authorities ensure that a manufacturer takes care of product quality, not only during storage and transport, but until the drugs are finally delivered to the patient.
For example, the International Conference on Harmonization states that “The storage conditions and the lengths of studies chosen should be sufficient to cover the storage, shipment, and subsequent use.”
This regulation presents a big challenge for the pharma manufacturer since the conditions for product safety must be guaranteed even after it leaves the hands of the manufacturer in the primary cold chain. This, for example, would include the transfer and storage of pharmaceutical products to and from pharmacists, retailers, hospitals, and community doctors, and even extends to when consumers receive and store the product at home.
Sometimes when a drug’s potency has been degraded to the point of being toxic, government regulations stipulate it must be discarded and destroyed.
For example, the Centers for Disease Control and Prevention in the US states that, “It is hazardous to administer vaccines where the temperature record is unknown or uncertain. It is better to not vaccinate than to administer a dose of vaccine that has been mishandled.”
Domestic Storage and Safety of Pharma Medicines
Checking the bathroom medicine cabinet and the kitchen pantry for medicines that are no longer effective
Homeowners oftentimes do not read the fine print on every label when they buy their medicines. Even fewer know if the product they bought is safe or suited to their needs. Almost none of them will keep a record of the temperatures of their medicines.
A study was conducted that provided end-users of a temperature-sensitive drug with a data recorder to monitor the actual storage temperature conditions in their homes. Out of 255 participants, only 17 (6.7%) had stored their medication properly within the prescribed range. Of those who did not, 24.3% had stored their medication for more than two hours outside of the recommended range.
This shows that storing these medications outside of the prescribed temperature settings may adversely affect their potency.
Remote Monitoring and Controls
There is a probability for breakdowns in the cold chain in the delivery of vaccines, clinical trial materials, and other life-saving drugs to remote countries of the world. In these scenarios, the infrastructure is insufficient and personnel are often untrained for meeting the standards for safe final-mile delivery. Necessary preventive measures for removing the compromised products from the supply chain are rarely in place.
In many countries, due to the difficulty of obtaining proper drugs, expensive prices, and the absence of community medical services, people have stockpiled drugs in their homes for “just in case” use. This often leads to seriously out-of-date medicines being kept in improper storage spaces.
One study in Sudan, for example, found that 97.7% of households were storing medicines. Aside from drugs used for on-going treatment, other medicines leftover from previous treatments, or acquired from OTC sources when available were being saved for future treatments. The climatic conditions in these countries increased the risk of deterioration and expiry.
These findings demonstrate the urgent need to educate consumers on temperature management. A dependable point-of-use temperature instrument is a way of ensuring that drugs consumed or used at home are within acceptable margins for safety in terms of temperature history.
There are also many drugs that discarded because there was no indication of their temperature history, even though they were still fit for use. An accurate temperature indicator can ensure that drugs can be consumed during their “safe period,” reducing unnecessary drug wastage and lessening the consumption of potentially dangerous drugs.
The Unexpected Challenge of Low Temperatures
The challenge of temperature control is not just about high temperatures. Medicines, especially vaccines, can be vulnerable to cold conditions. According to the World Health Organization, “protecting vaccines from freeze damage remains one of the most poorly addressed problems in vaccine management.”
Shipping and storage guidelines usually recommend that vaccines and biologics must remain at temperatures between 2°C (35°F) and 8°C (46°F), based on stability parameters over time.
The WHO regulation explains, “Vaccines are highly thermo-sensitive biological substances which have a fixed shelf-life and lose viability over time. The loss of viability is irreversible and accelerated if proper storage and temperature conditions are not maintained. A vaccine vial must remain between 2°C and 8°C (35°F and 46°F) throughout the entire cold chain system – when it is transported, when it is stored in a refrigerator or cold store, and when it is used at an immunization session.”
Although many temperature-sensitive drugs fall into the nominal 2 to 8°C category, others need very specific storage conditions and must be kept in the same condition until the point of consumption.
The HPV vaccine, for example, can tolerate higher temperatures, but is extremely sensitive to freezing and cold conditions.
A systematic review stated that “accidental freezing is pervasive and occurs across all segments of the cold chain. Between 14% and 35% of refrigerators or transport shipments were found to have exposed vaccine to freezing temperatures, while in studies that examined all segments of distribution, between 75% and 100% of the vaccine shipments were exposed.”
It’s hard to tell how many drugs are discarded as being found unfit for human consumption prior administration. An unknown number of drugs are taken that are outside the safety margins.
To a large extent the problem can be resolves through equipping individual medicine containers with inexpensive temperature indicators that are accurate, reliable, and easy-to-handle.
Such safety features will minimize wastage and improve curative outcomes. It will also give the drug suppliers improved market advantage and positive brand reinforcement.
Furthermore, the integration of electronic temperature indicators will provide additional protection against counterfeiting and improve consumer confidence.