Ch. 1: Temperature and Humidity Control in the Pharmaceutical Industry

The pharmaceutical supply chain consists of moving drugs and medications from one facility to another, or from one facility direct to the patient. When these products are exposed to temperature or humidity out of their specified range, the products can become ineffective or unsafe.

Drug research and development are expanding based on technology and the overall growth of unique symptoms and diseases. With this growth comes a complex packaging and supply chain effort. Cold chain used to just mean 2-8°C, but with the expansion of science behind these drugs, there are now products that must be shipped and stored at body temperature (around 37°C), controlled ambient temperature (15-25°C) or at extremely cold temperatures (such as -20°C or cryogenic ranges of -80°C to -192°C). Equally, high humidity can cause pharmaceutical drugs to absorb moisture during final packaging, shipment or storage, causing certain medications to degrade and lose efficacy.

As outlined in the Guide to Temperature Controlled Logistics, each type of transportation comes with its own set of unique touchpoints. The 4 most common to consider are:

  1. Preparing the product for transport to the shipper location
  2. Transportation to the shipper location
  3. Physical loading
  4. During transit

As temperature-sensitive pharmaceutical products continue to rise, it is predicted that the cold chain industry will grow 65% by 2020. Production networks are also becoming more global, adding a new complexity into the mix. This growth and difficulty creates a number of obstacles for manufacturing and logistic companies. Combining a way to thermally manage and monitor pharmaceuticals throughout their lifecycle will protect not only the supply chain but also the patient.

American Thermal Instruments and Microtek Labs manufacture customized thermal solutions to ensure your brand is protected and your patient stays safe. ATI offers a wide range of temperature monitoring solutions to provide the necessary data needed to prove your product has not been exposed to environments that could hinder their efficacy or safety. Microtek Labs innovates new ways to use phase change materials to thermally manage a shipment, allowing product to stay at the desired temperature, longer. Combining these two solutions provides the ideal scenario for pharmaceutical applications.

Ch. 2: How Temperature Affects the Rules for Shipping Pharmaceuticals

Pharmaceutical transportation is heavily regulated and temperature plays a major role in this, ranging from drug sample storage and handling, to maintaining and managing the vaccine cold chain. Here are the basics of how it’s broken down in the US and Internationally:

US Regulation

FDA CFR 21 Part 205 - minimum requirements for storage and handling of prescription drugs and the maintenance of prescription drug distribution records.

  • Within security and storage it states that all prescription drugs shall be stored at appropriate temperatures and under conditions in accordance with requirements. If no requirements are set for certain prescription drugs, the drug may be kept at “controlled” room temperature to keep the strength and quality.
  • To document proper storage has been kept, manual or electronic temperature and humidity devices should be utilized.
  • When shipping these prescription drugs, each outgoing shipment must be carefully inspected for identity and damage from storage or improper conditions.
  • If any conditions create doubt on the drug’s safety, identity or quality, the drug shall be destroyed or returned to the supplier for investigation.

In general, manufacturers, authorized distributors of record, and their representatives shall store and handle all drug samples under conditions that will maintain stability, integrity and effectiveness. It must be verified by electronic record that everything has been done to ensure a safe and secure delivery and storage method all the way to the last mile.

Electronic Record - CFR Title 21 Part 11

  • FDA 21 CFR Part 11 compliance is essential for those FDA regulated companies that use electronic quality records and electronic signatures in place of their paper-based and ink-based counterparts to comply with FDA regulations faster and more efficiently.
  • Many companies want to make the FDA 21 CFR Part 11 compliance shift not just to comply with the FDA but to save on administrative time that otherwise would have been used to control documentation and quality management processes manually.
  • Divided into two main sections – Electronic Records and Electronic Signatures.
  • In basic terms, the requirement of Electronic Records is to provide secure data which can provide a high level of confidence as would be the case with paper records.
  • The advancement in electronic systems offers significant benefits for data retrieval and storage of data.

American Thermal Instruments’ electronic data loggers provide an easy solution to allow you to be FDA CFR 21 compliant. As the shipment travels throughout the supply chain, time and temperature data is gathered at pre-configured intervals. This data is the easily pulled from the logger and can be digitally stored in a cloud database or sent direct to your quality system.

International Regulation

WHO Regulations

WHO (World Health Organization) has standardized International packaging and shipping guidelines for vaccines.

  • WHO specifies low and high temperature ranges that are acceptable for international transport over 48 hours. Vaccine manufacturers must ensure their packaging complies and is fully validated based on the WHO standards.
  • They provide specifications for 3 classes of packaging – A, B, and C.
    • Class A identifies that the vaccine must be packed to ensure the warmest temperature in the package does not rise above 8°C for with an ambient temperature of 43°C for a period of 48 hours or more.
    • Class B must be packed to ensure the warmest temperature does not rise above 30°C with an ambient temperature of 43°C for at least 48 hours.
    • Class C designates that the package must be kept at 30°C or lower at an ambient temperature of 43°C and does not fall below 2°C in external temperatures of -5°C for at least 48 hours.
  • WHO regulations state that temperature monitoring devices should be included in all vaccine shipments. These act as a quick reference for possible temperature exposure and damage.
  • When using an electronic temperature device, WHO has minimum standards that should be met. These include but aren’t limited to – the ability to start and stop a device, an initial delay in start, history functionality to provide data, an LCD screen to provide visual display and alarm capabilities.

WHO has strict guidelines around route and arrival dates to also ensure the vaccines stay safe and effective.

  • Vaccines should travel by direct route whenever possible.
  • If they can’t ship direct, they must go through an airport with cold storage facilities and a temperate climate.
  • The time to reach the final destination must be 48 hours or less, unless otherwise agreed to by UNICEF or other agencies.
  • All vaccines must be kept in temperature-controlled environment throughout the shipment process.

Vaccine storage is unique based on the various temperatures that must be maintained. Microtek’s thermal management solutions, utilizing phase change materials, can help keep your product from getting too warm or cold for an extended length of time. This type of protection paired with a monitoring device allows you to stay confident that your product isn’t being affected by temperatures out of your control.

Want to learn more? Check out these 4 Basic Rules for Shipping Pharmaceuticals.

Ch. 3: How Phase Change Material Impacts Your Pharmaceuticals

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You might be surprised how big of a role temperature control and regulation play in your life. After all, you want your produce fresh, your flowers blooming and your chocolate melting only in your mouth, right? Those items require special handling and storage all through the process to maintain stable temperatures.

Standard shipping procedures are complicated enough with industry standard regulations and required documentation. Now, throw in items that need temperature protection and you get a whole checklist of rules to meet.

That’s what makes phase change materials so important.

How the Pharmaceutical Industry uses PCMs

PCMs are a critical solution to be considered in the pharmaceutical supply chain world because certain drugs exposed to extreme temperatures could be rendered ineffective or even harmful. And it really can’t be understated how important it is that all medicine and other drugs be delivered on time and correctly to their recipients. Check out the 4 basic rules for shipping pharmaceuticals.

That said, obviously not everything that gets shipped needs strict temperature regulations. That’s why it’s important to know which items are perishable. The International Air Transport Association (IATA) states that a shipment is perishable if its contents will deteriorate over a period of time if exposed to severe environmental elements. Many pharmaceuticals fit this description.

Most pharmaceutical goods remain between 2-8 degrees Celsius (36-46 degrees Fahrenheit), but there are extensions to this where temperatures of -20 degrees Celsius are used in warehouses to maintain products appropriate for this temperature. It’s essential that during the logistics process that resources are dedicated to establishing, maintaining, and refining the temperature control.

To ensure that the temperature control of the pharmaceutical goods is properly cared for, there is a level of qualification and monitoring that must be met. The warehouse, cooler, and trailer needs to be qualified based on tests to uncover if there are any areas that are prone to outside temperature ranges. To approve of temperature qualifications, a test is done when the warehouse is empty, and again once it is stocked with products.

Shipping needs and temperatures control areas also change based on the time of year and the climates to which the items are shipped.

As worldwide demand grows for new medications, manufacturers need to ship increased volumes of material over longer distances. What’s more, these goods are often more valuable, in larger quantities, or more temperature-sensitive than they’ve been in the past. PCM's can keep product at a stabilized temperature range longer, making them critical to the pharmaceutical supply chain.

Learn more about How Phase Change Materials Changed Temperature Regulation Forever.

CH. 4: Medicine Temperature Storage 101

Maintaining proper storage conditions for medicine, drugs, and other pharmaceuticals is vital to ensuring their quality. Expiration dates are based on ideal storage conditions for temperature, moisture, and “shelf life” and meeting those conditions is critical to maintain the integrity, effectiveness, and safety of those products.

Guidelines for the Storage of Essential Medicines and Other Health Commodities is a great practical reference for those managing or involved in setting up a storeroom or warehouse. The guide contains written directions and clear illustrations on many helpful topics, including:

  • Receiving and arranging commodities
  • Special storage conditions
  • Tracking commodities
  • Maintaining the quality of the products
  • Constructing and designing a medical store
  • Waste management
  • And more

This resource was written to meet the needs of district-level facilities; however, the guidelines and information it contains apply to any storage facility, of any size, in any type of environment. Pay special attention to pages 57-63!

It's usually recommended that most over-the-counter and prescription medications be stored at what's known as "controlled room temperature, which is typically about 77 degrees Fahrenheit. Medications are manufactured under very strict specifications, and, whenever possible, these products are designed to remain stable at room temperature. Obviously, some medications are more stable than others, but most remain at their most stable if they are transported and stored at room temperature.

There are some medicines that can be maintained in temperatures as low as 52 degrees Fahrenheit, such as the liquid form of the antibiotic amoxicillin, or interferon beta, which is used for the treatment of multiple sclerosis. A few medications can even maintain their composition if they are frozen.

Avoiding Excessively High Temperatures

There are a number of factors that can expose your medications to dangerously high temperatures. Here are some of the most common:

  • Hot weather: If you don't have air conditioning (and keep it on 24/7 during hot spells), high outside temperatures can cause your home to become warm enough that medications "overheat." This is a particular concern during power outages.
  • Car: Storing your medicine in your car for an extended period of time can expose it to high heat.
  • Travel: Your medication may sit in your luggage on a hot tarmac or in non-air conditioned luggage handling areas.
  • Pharmacy: If your pharmacy loses power for an extended period of time before you picked up your prescription, you may be unaware of the problem.
  • Delivery: If you get your medicines from a mail-order pharmacy, they could be delivered in a non-temperature regulated truck or may sit in your mailbox for an extended period of time.

Ch. 5: Why Pharmaceutical Companies Use Phase Change Material for Cooling and Temperature Stabilization

Phase change materials absorb and release thermal energy in order to maintain a regulated temperature. They perform intelligent phase change in temperature according to a desired range. This temperature control is used to regulate the storage temperature of medicines without the need for any power source. It is reliable, stable and provides thermal cycling.

Phase Change Material

See How PCMs Work

Regulations require distributors of pharmaceuticals to demonstrate that the medicines have not been exposed to conditions that may compromise their quality. Pharmaceuticals must have some form of temperature assurance during transportation, which has brought demands for ever more sophisticated and long-lasting temperature controlled packaging.

Since phase change materials have high latent heat and a range of different melting points, they are ideal for use in various thermal management applications. This is especially useful for thermal regulation with the transportation of medical and pharmaceutical products to ensure quality and effectiveness, even with an unsteady supply chain.

Only a few years ago, cold-chain just meant 2-8°C, but increasingly products today must be shipped at ‘body temperature’ (around +37°C), ‘controlled room temperature’ (15-25°C), or at extremely cold temperatures such as -20°C, and in even lower cryogenic temperatures (-80°C and -192°C). Requirements for different temperature ranges continue to expand and new solutions are undergoing testing in order to allow the safe transportation of goods at -40°C and -50°C, for example.

Shipping at most of these temperatures ranges would have been very difficult or even impossible until recently, but the use of PCMs have allowed manufacturers to achieve these temperature-controlled ranges.

At a time when materials are of high value, time- and temperature-sensitive, and quite often critical to a clinical trial or a medical emergency, a successful transit requires the expertise and detailed knowledge of a specialized shipping partner.

Looking for temperature monitoring and control solutions? We’d love to talk to you! Contact us to get started.