Life Science & Medical Device Insights

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

Moving drugs and medications from one facility to another, or from one facility direct to the patient is a component of the pharmaceutical supply chain. The products can become impotent or unsafe if they are exposed to temperature or humidity out of their specified range.

Technology and the overall growth of unique symptoms and diseases have broadened both drug research and development. This growth has expanded the field of complex packaging and supply chain efforts. The expansion of science behind these drugs has changed the standard for Cold chain, which used to just mean 2-8°C, now there are products that must be shipped and stored at controlled ambient temperature (15-25°C), at body temperature (around 37°C),  or at extremely cold temperatures (such as -20°C or cryogenic ranges of -80°C to -192°C). High levels of humidity, alike, can cause pharmaceutical drugs to absorb moisture during final packaging, shipment, or storage, causing certain medications to degrade and lose efficacy.

Every different type of transportation comes with its own set of unique touchpoints. Four of the most common to consider are:

1. Prepping the pharmaceuticals for transport to the shipper location
2.  Passage to the shipper location
3. Physical loading
4. During transportation

It is predicted that the cold chain industry will increase by 65%  through 2020, as temperature-sensitive pharmaceutical products continue to elevate. Production networks are becoming more and more global which adds an even newer complexity into the mix. Manufacturing and logistics companies face a number of new obstacles created by this growth and difficulty. The combination of ways to monitor pharmaceuticals and thermally manage them throughout their lifecycle will not only protect the supply chain but also the patient.

Microtek Labs and American Thermal Instruments manufacture customized thermal solutions to ensure your brand is protected and your patient stays safe. Microtek Labs innovates new ways to use phase change materials to thermally manage a shipment, allowing the product to stay at the desired temperature, longer. 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 its efficacy or safety. Combining both of these solutions provides the ideal scenario for pharmaceutical applications.

Ch. 2: How the Rules for Shipping Pharmaceuticals are Impacted by Temperature

Means of transport for Pharmaceuticals are heavily regulated with temperature playing a major role in this, ranging from maintaining and managing the vaccine cold chain to drug sample storage and handling. Here are the basics of how it’s broken down in the United States
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 records, and their representatives shall store and handle all drug samples under conditions that will maintain stability, integrity, and effectiveness. It must be verified by the 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 provide an easy solution to allow you to be FDA CFR 21 compliant with their electronic data loggers. Time and temperature data are gathered at pre-configured intervals, as the shipment travels throughout the supply chain. This data is easily pulled from the logger and can be sent direct to your quality system or digitally stored in a cloud database.

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 a 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.

Ch. 3: Pharmaceuticals and Phase Change Material

How big of a role temperature control and regulation play in your life might surprise you. After all, you want your produce fresh, your flowers blooming and your chocolate melting only in your mouth, right? In order to maintain stable temperatures, those types of products require special handling and storage all through the process.

Industry-standard regulations and required documentation complicate standard shipping procedures to a high degree. Once you throw in all the items that require 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

Certain drugs exposed to extreme temperatures could be rendered ineffective or even harmful for this reason PCMs are a critical solution to be considered in the pharmaceutical supply chain world. And the importance of all medicine and other drugs being delivered on time and correctly to their recipients really can’t be understated. 

It’s important to know which items are perishable because, obviously, not everything that gets shipped needs strict temperature regulations. 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. This description includes pharmaceuticals.

It’s essential that during the logistics process that resources are dedicated to establishing, maintaining, and refining temperature control. 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. 

There is a level of qualification and monitoring that must be met in order to ensure that the temperature control of the pharmaceutical
goods is properly cared for. 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. A test is taken when the warehouse is empty, and again once it is stocked with products, to approve of temperature qualifications.

External factors play a role in shipping needs and temperatures control areas. They vary depending upon the time of year and the climates to which the items are shipped.

Manufacturers need to ship increased volumes of material over longer distances, as worldwide demand increases for new medications. These goods are often more valuable, in larger quantities, or more temperature-sensitive than they’ve been in the past. PCMs are critical to the pharmaceutical supply chain because they can keep products at a stabilized temperature range longer. 

PHARMACEUTICAL COOLING WITH Phase Change Material

Really what’s important when shipping and storing pharmaceuticals are that they’re kept at a consistent temperature, regardless of outside factors.

Oftentimes, the major concern with the  2-8C temperature range is that items have to be stored in very cold temperatures — but not freezing. Ice can damage and render useless many pharmaceuticals if they reach freezing temperatures or are frozen.

The versatility and customization of PCMs give more control of temperature. For example, ice cannot hold any temperature outside of 0C. PCMs can be customized to more specific temperatures for pharmaceuticals like 4C or 6C. This provides the cooling to stay under 8C, but removes the concern of going below 0C.

PCMs are also less dense than ice and therefore are lighter, which reduces shipping costs and allows more products to be loaded for transport.

CH. 4: Temperature-Controlled Pharmaceutical Storage

It is vital to maintain proper storage conditions for drugs, medicine, and other pharmaceuticals, to ensure quality. Meeting the conditions of ideal storage conditions for temperature, moisture, and “shelf life”, all based on the expiration date, is critical to maintaining the integrity, effectiveness, and safety of those products.

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

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

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

It’s usually recommended that most over-the-counter and prescription medications be stored at about 77 degrees Fahrenheit, which is more commonly known as “controlled room temperature. There are very strict specifications that need to be met during the manufacturing of medications, whenever possible, these products are designed to remain stable at room temperature. Obviously, different medications are more or less stable than others, but the majority remain at their most stable if they are stored and transported at room temperature.

Certain medicines 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. There are even a few medications that can maintain their composition when they are frozen.

Avoiding Excessively High Temperatures

There are a variety of factors that can expose your medications to potentially dangerous 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 can become a prominent concern during power outages.
• Travel: Your medication may sit in your luggage on hot tarmac or in non-air conditioned luggage handling areas.
• Car: Storing your medicine in your car for an extended period of time can expose it to high heat.
• 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.

WHAT’S CONTROLLED ROOM TEMPERATURE IN FAHRENHEIT?

As you probably know, most discussions around pharmaceutical storage and transportation are focused on the cold chain — which involves 2-8C.

Controlled room temperature or CRT (20-25C, 68-77 Fahrenheit) is just as important. There is generally less discussion around it because it’s often viewed as being easier to accomplish, but that doesn’t mean it should be overlooked or made it less important.

Holding something below 77 Fahrenheit in the summer or above 68 Fahrenheit in the winter presents just as many challenges as the cold chain.

That’s what makes PCMs so impactful. PCMs in temperatures 16C, 24C, and 28C (61F, 75F, and 82F) are excellent solutions to keeping something within specifications for CRT.

This is particularly important in the last mile of the distribution whether that is customer from pharmacy to home, pharmaceutical rep to doctor office (trunk/sample stock distribution), etc.

Ch. 5: Why We Use Phase Change Material for Cooling and Stabilizing Pharmaceuticals

In order to maintain a regulated temperature, phase change materials absorb and release thermal energy. According to the desired range, they’ll perform intelligent phase changes in temperature. With no power source necessary, temperature control is used to regulate the storage temperature of medicines. It is stable, reliable, and provides thermal cycling.

Required by regulations, distributors of pharmaceuticals must demonstrate that the medicines have not been exposed to conditions that may compromise their quality. Demands for ever more sophisticated and long-lasting temperature-controlled packaging have caused pharmaceuticals to have some form of temperature assurance during transit.

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

It was only a handful of years ago when cold-chain simply 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). For example, new solutions are undergoing testing in order to allow the safe transportation of goods at -40°C and -50°C, as requirements for different temperature ranges continue to expand.

The use of PCMs has allowed manufacturers to achieve these temperature-controlled ranges, shipping at the majority of these temperature ranges would have been quite difficult or even impossible until recently.

Successful transportation requires the expertise and detailed knowledge of a specialized shipping partner, 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.

Ch. 6: The Basics to Cold Chain Shipping Pharmaceuticals

It’s very important to highlight the importance of delivering medicine and other pharmaceuticals on time to hospitals, patients, and healthcare facilities. Cold chain shipping plays an essential role in this, from manufacturing to transport to delivery, ensuring that these products are kept at specific temperatures for every step of the journey.

However, the steps that go into this have evolved heavily over the past 20 years. The approach we take with the supply chain for shipping pharmaceuticals has changed through technology like phase change materials and more sophisticated temperature monitoring solutions.

The relationship between pharmaceutical companies and their drug delivery system has shifted course recently. the pharmaceutical companies
are expecting that ownership of the supply chain to fall to their partners – including cold chain managing and storage, rather than owning the entire process.

In order to ensure a drug delivers safe and effective, temperature mapping, qualification, and overall monitoring can help establish hot and/or cold areas through each shipment process.

There are a number of unique touchpoints to consider when it comes to temperature, with a variety of different medications and various transportation methods available:

• Preparation of the product for transport
• Transportation to the shipper location
• Physical loading
• In Transit
• Delivery to a dock or medical office
• Physical Handling before putting into storage

It’s vital to ensure that the product will stay at temperature and will remain monitored through the full duration.

Conditions of a Cold Chain System

There are numerous factors that should and need to be considered when implementing a cold storage system. A few criteria here:

• The temperature range and volume of the medicine
• Temperature controls
• Back up temperature controls
• The layout of the storage unit and airflow
• External temperature logging and data tracking
• Cargo placement (avoid areas where temperature variation is likely such as near bay doors)
• Have temperatures been tested?
• The volume of a medicinal product

The pharmaceutical industry approach to cold chain shipping is continuing to evolve, but the overarching goal is still the same: to guarantee that pharmaceuticals and healthcare products arrive on schedule and at the right temperature, every time.

Ch. 7: The Role of Pharmaceutical Packaging in Cold Chain

Pharmaceuticals are delicate, sensitive, and obviously expensive. That’s why there are entire industries built around packaging and shipping pharmaceuticals safely. From the factory floor to the point of delivery and everywhere in between, a pharma product’s integrity and quality must be maintained.

In the past, technology was limited so there were fewer options when it came to packaging pharmaceuticals for delivery. In fact, sometimes critically important medicines were packed in a styrofoam cooler with ice–the same way you pack food for the beach!

Today, however, pharmaceutical companies have adopted the cold chain system to ensure that their drugs are delivered on time and uncompromised.

The Cold Chain Process

When it comes to shipping pharmaceuticals, time and temperature control are the two most important factors. They’re also heavily regulated worldwide. The slightest change in temperature, even of just 2 degrees, can ruin pharma products and even make them dangerous to consume
or administer.

Here are the key steps in the cold chain process:

• Supply: The drugs, vaccines, or pharmaceutical products are made and packaged at a plant.

• Transportation: The medicines or pharma products are transported in a refrigerated or insulated truck. These trucks undergo routine inspections to make sure they are in satisfactory condition to keep inventory at the correct temperature.

• Storage: Pharmaceutical products may go into cold storage before they are distributed. This refrigerated warehouse can act as a middle ground before pharma products reach their final destination.

• Market: Generally speaking, the last step in the cold chain logistics process is delivery to the final destination where the pharmaceutical is sold
  or administered.

Maintaining Pharmaceutical Temperatures

Most pharmaceuticals ship at 55 to 77 degrees Fahrenheit to ensure product stability. This is where the cold chain comes in handy. Refrigerated trucks can maintain these temperatures, even when the weather outside is scorching hot because they’re designed to work independently of the tractors that haul them. Cold trailers feature their own refrigeration unit and a power source. This means cold trailers will keep temperature regardless of whether they’re being hauled by a tractor or are on a train, boat, or plane. These trailers work like other refrigerators and have three main components that help them stay cool: a compressor, condenser, and evaporator.

The compressor is supported by a small engine unit located inside the refrigerated trailer and takes in a refrigerant as a gas form and compresses it into liquid. The pressure heats the refrigerant fluid, which flows from the compressor to the condenser. The condenser helps exchange heat. Here the heated refrigerant is cooled by flowing through tubing to wide fins. The fins’ wide surface area allows the hot refrigerant to quickly cool. The compressor and condenser work together in a way that’s similar to how a car’s radiator works together to cool the engine.