Life Sciences: Protecting your pharmaceuticals
Ch. 1: Temperature and Humidity Control in the Pharmaceutical Industry
The pharmaceutical supply chain consists of moving drugs and medications from one facility toanother, 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:
- Preparing the product for transport to the shipper location
- Transportation to the shipper location
- Physical loading
- 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:
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.
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.
Ch. 3: How Phase Change Material Impacts Your Pharmaceuticals
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.
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
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.
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 online resource and 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 the 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.
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 PCM has 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.
Ch. 6: The Key to Cold Chain Shipping Pharmaceuticals
The importance of delivering medicine and other pharmaceuticals on time to hospitals, healthcare facilities, and patients really can’t be understated. Cold chain shipping plays an essential role in this, ensuring that these products are kept at specific temperatures for every step of the journey–from manufacturing to transport to delivery.
However, the steps that go into this have evolved heavily over the past 20 years. Through technology like phase change materials and more sophisticated temperature monitoring solutions, the way we approach the supply chain for shipping pharmaceuticals has changed.
Recently, the relationship between pharmaceutical companies and their drug delivery system has shifted course. Rather than the pharmaceutical companies owning the entire process, they’re expecting that ownership of the supply chain to fall to their partners – including cold chain managing and storage.
Temperature mapping, qualification, and overall monitoring can help establish hot and/or cold areas through each shipment process to ensure a drug delivers safely and effectively.
With so many different medications and various transportation methods available, there are a number of unique touchpoints to consider when it comes to temperature:
- 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
Ensuring that the product will stay at temperature and will remain monitored through the full duration is critical.
Conditions of a Cold Chain System
There are many factors that need to be considered when implementing a cold storage system. Here are just a few criteria:
- 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 medicinal product
The way the pharmaceutical industry approaches cold chain shipping is continuing to evolve, but the goal remains the same: to ensure that pharmaceuticals and healthcare products arrive on time and at the right temperature, every time.
Ch. 7: How Pharmaceutical Packaging Impacts the Cold Chain Process
Pharmaceuticals are expensive, which is why there are entire industries built around packaging and shipping them to the property temperature and humidity range. From the manufacturing plant to the end-user and everywhere in between, the integrity and quality of the product must
be a priority.
Before recent technological advances, there were limited options when it came to packaging pharmaceuticals for delivery. For example, quite often there were medicines being packed in a styrofoam cooler with ice–the same way you pack food for a picnic!
However, these days pharmaceutical companies utilize the cold chain system to ensure that their medicines get from A to B without
How Cold Chain Works
Time and temperature control are the two most important factors when it comes to shipping pharmaceuticals. Because of that, these factors also face heavy regulations around the world. A temperature change of just 2 degrees can make these products useless–or even dangerous–to
There are 4 key components in the cold chain process:
- Supply: The medicines, vaccines, and other pharmaceutical products are made and packaged at the manufacturer.
- Transportation: The pharmaceutical products are transported in refrigerated or insulated vehicles, which are built to keep inventory at the correct temperature.
- Storage: Depending on the need or location, these products may go into cold storage before they are shipped. A refrigerated warehouse can act as a middle ground before pharmaceutical 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
Pharmaceutical Temperatures: the Numbers Game
Most pharmaceuticals need to be shipped between 55 to 77 degrees F to ensure product integrity. That’s why the cold chain is so important. Refrigerated trucks can maintain these temperature levels, regardless of what the weather outside is like. Additionally, cold trailers feature their own refrigeration unit and power source, regardless of whether they’re being hauled by a tractor, train, boat, or plane. Like any refrigerator, they have three main components: a compressor, a condenser, and an evaporator.
The compressor is powered by a small engine located inside the refrigerated trailer and takes in a refrigerant as a gas form and compresses it into liquid. The pressure warms the refrigerant fluid, which flows from the compressor to the condenser. 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.
CH. 8: What is the Correct Temperature for Storing Medication?
From manufacture through storage, distribution points, and across the extended supply chain, medicines travel through numerous touch points and hand-offs to reach a healthcare facility, pharmacy, or another point of purchase. Because a drug’s chemical/physical properties can change when exposed to temperatures outside of the manufacturer’s recommended range, maintaining safe conditions during storage and transport
Pharmaceutical companies entrust shipments to their supply chain and there is very little room for error. Even short-term exposure outside of recommended temperature ranges can compromise a drug’s integrity and prove harmful, even fatal, to those taking the medications.
The World Health Organization (WHO) offers some strict recommendations for medication storage. It advises that pharmaceuticals be maintained in cool dry areas with good ventilation and away from strong odors or direct sunlight. What’s more, relative humidity levels should be at approximately 50%, and at temperature ranges as designated by the manufacturer.
While the recommended temperature for storing medication will vary from one drug and type to another, most are maintained at 2° to 8° C (59° to 77° F). Failure to preserve safe conditions can result in changes to a drug’s texture, color, or create an odor or foul taste. Any of these conditions are clear indications that a drug is no longer effective or safe.
In addition to temperature, moisture, such as humidity, can affect the integrity of some drugs. Low humidity (generally levels below 45%) may cause certain medicines to dry out. This can create problems from manufacture through distribution and storage.
At the same time, high humidity (above 60%) can change the characteristics of some drugs and create conditions for the growth of viruses, bacteria, mold, and fungi. Because humidity can inhibit a drug’s effectiveness and cause some to become toxic, it is recommended, that household drugs be refrigerated rather than stored in a “medicine cabinet” found in many bathrooms.
Warehousing and Distribution
From very simple to very complex, supply chains come in all levels of sophistication. Temperature-sensitive shipments, such as pharmaceuticals, are often distributed through a tightly regulated stage known as a “cold chain”.
According to Pharmaceutical Commerce magazine, the annual global sales of biologic drugs (produced from or contain components of living organisms) and vaccines – both requiring strict temperature control – exceed $340 billion. The publication also reports that cold chain logistics account for nearly 18% of all biopharma logistics spending.
Because the storage and distribution of vaccines (as well as cell/gene therapies) require lower temperatures, the delivery of a lifesaving COVID 19 vaccine has created logistical challenges. This includes streamlining the cold chain to accelerate delivery while reducing touchpoints and the likelihood of exposure to adverse conditions.
Cryogenic and controlled room temperature are two popular temperatures for storing medications. Cryogenic freezing storage temperatures can range from -238° to -310° F and below. These extreme temperatures suspend biological activity prohibiting degradation from taking place. Cryogenic freezing is ideal for sensitive samples and materials like blood, tissues, reproductive specimens, and clinical trial materials.
Controlled Room Temperature (CRT) storage is customary for many types of biological materials. Specifically, CRT storage requires temperature maintenance of 68° to 77° F. There are some pharmaceutical products and biological samples that should not be subjected to lower temperatures, as freezing could result in degradation.
Through its American Thermal Instruments (ATI) brand, CAVU Group has been providing healthcare, life sciences, consumer products, and industrial sectors with cold chain temperature monitoring solutions for more than 35 years. The company offers a complete line of chemical, electronic, and cloud-based technologies allowing temperature data to be tracked and analyzed easily – from origin through destination. In this way, CAVU is helping to ensure brand integrity and consumer safety.
Temperature for Storing Medication Matters
Today, drug research and development have evolved to large-molecule biologics. Unlike small-molecule drugs, most large molecule drugs are complex, composed of more than 1,300 amino acids, and are identical versions of human proteins. However, this advancement comes with its challenges as more types of drugs are reliant on strict temperature parameters to maintain their integrity.
The best temperatures for storing medication depends on the specific drug type and manufacturer’s specification. This holds true for prescription as well as over-the-counter medications. And drugs that are improperly stored can result in litigation, lost market share, massive recalls, and worst of all harm to the end-user.
From capsules and pills to liquids, sprays, inhalers, injectables, and beyond, pharmaceuticals come in a wide variety of forms. But regardless of type or chemical composition, all medicines must be maintained within safe environments through their lifecycle.
CH. 9: Shipping Temperature-Sensitive Pharmaceutical Products
Supply chain management across all industries is critical to move product efficiently and effectively. It’s necessary to maintain the expected quality of any product that is shipped. However, moving temperature-sensitive pharmaceutical products is a much more complex and challenging process. It requires specific protocols in order to guarantee effective and safe transport.
Shipping containers must be validated to meet the expected extremes of temperatures within various environments. Each delivery system must be aware of know the requirements to maintain the quality of the drug, the amount being shipped and length of time to deliver. Consider temperature requirements and if heat or cold packs need to be added to meet the appropriate temperature for safe travel.
Identify the optimal shipping method by analyzing trends in shipping lanes, seasons and logistics partners. Consider overnight shipping versus ground shipping to ensure the method and the packaging are the right solution to protect the integrity of the product. Understanding route optimization will help ensure you deliver an effective product.
Time and temperature are critical for shipping pharmaceuticals. Knowing temperature is important, however, knowing the exact time a product has stayed at certain temperatures is critical to ensure the quality of the product. Monitoring adds a security check to guarantee that the packaging paired with the transportation method is keeping the product at appropriate temperature at all time – no matter the season, shipping time, etc. Consider that the product may travel from a very hot climate to a very cold climate quickly. The temperature at every part of the journey must be monitored and logged. Consider a mix of on-product monitoring along with box or pallet monitoring. This will allow for targeted quality inspection. With real-time data, you can track exposure to extreme temperatures at the vial, bottle or product level, instead of recalling or throwing out an entire shipment.
Storage To The Last Mile
It’s critical to track product at every stage – from warehouse to administration. Beyond the logistics of moving the product to patients, doctor’s offices and distributor centers, there are many factors you need to confirm as your product travels that last mile. Do you know your end locations have the right conditions for storage? Can you guarantee the product will stay safe until the patient receives it? The pharmaceutical manufacturer is the one responsible for the efficacy and safety of the drug. Brand protection is only secure if you can guarantee that the product quality endures at all phases of transport, all the way up to when it’s administered to the patient.