Biologic Pharmaceuticals and Cold Storage Warehousing

Pharmaceutical Cold Chain Logistics Needed for Sensitive Biologics

The need for refrigerated cold storage warehouses and temperature-controlled transportation is on the rise due to the rise in biologic drug development

If you are like most Americans, you have seen the ads by pharmaceutical companies on television and social media touting the latest biologic drug product in the life sciences industry.  Biologics such as Enbrel, Humira and Neulasta are only a few of the brand name new therapies for cancer and chronic health conditions.  What difference will biologic drugs make in the crowded pharmaceutical industry?

Turns out, biologic drugs are set to have a significant impact on cold chain logistics, refrigerated warehousing and 3PL cold storage operations.  Let’s take a look.

Pharmaceutical and Life Science Goods:  Need for Temperature-Controlled Cold Chain Logistics

Supply chain management in the life science pharmaceutical industry is typically more complex and benefits from use of technology to enhance the outcome of risk management and quality control efforts.  Life science and pharmaceutical finished goods and components may be more sensitive, subject to damage or degeneration under specific conditions.  From start to finish, great care must be taken to ensure proper handling, storage and transport to ensure component and final product safety and quality.

The root cause of much of the damage to life science and pharmaceutical goods is simple.  Every year, all around the world, billions of dollars of pharmaceutical goods are stored and shipped at incorrect temperatures.  Frequently pharmaceutical products are delayed reaching their destination so that they do not arrive until after they have expired.  Not only does this result in tremendous volumes of wasted drug products but also a major risk to human lives, damaged reputations, lawsuits and shareholder distrust.

Plagued by the pharmaceutical supply chain’s complicated array of environments, pharmaceutical companies often resort to using technology to properly handle, store, ship and transport drug products for optimal quality control.  From packaging innovations, IoT and RFID tracking to sophisticated warehouse management software, use of technology in pharmaceutical cold chain logistics has become the norm.

    Rather than commonly using the term “cold chain”, today most pharmaceutical companies have started to utilize the term “temperature-controlled” when referring to the handling, storage and logistics involved with pharmaceutical and life science goods. The temperature-controlled spectrum ranges from:
    • Ambient (controlled room temperature) 20°C-25°C
    • Refrigerated 2°C to 8°C
    • Cryogenic Below 0°C to -150°C

    Increased Need for Temperature-Controlled Cold Chain Warehousing and Logistics

    The pharmaceutical industry is constantly designing new drug therapies to compete with or surpass the effects of traditional medicines.  The latest drug development efforts involve innovating well past the traditional chemical-based, small molecule therapeutics.  Could we even have imagined fifty years ago that pharmaceutical companies would be focused on stem cell therapy or using genes to help treat or prevent disease?  It’s a bold new world.

    Pharma companies have developed diverse new treatments for chronic illness and disease, to increase patient longevity and enhance the quality of human existence.  Whether therapies focus on the root cause of chronic ailments or disease or seek to minimize the impact of symptoms, drug development is costly and time consuming, requiring substantial investment and lead times.  Drug manufacturers must contend with extensive drug development processes involving clinical trials, regulatory compliance and Food and Drug Administration product review procedures.  Innovating new technology platforms for treatments has proven highly successful but has created new challenges for the pharmaceutical industry. 

    To gain a better understanding, let’s take a look at the types of drug products in use today, conventional and biologics.

     

    Small Molecule Drugs Vs. Large Molecule Biologics

    Traditional or conventional medications such as antacids, statins, aspirin and others are chemical in nature.  These drugs are produced by combining chemicals in building blocks to form a particular shape.  Known as small chemically manufactured molecules (SMOLs) or simply small molecule drug products, these medications make up the largest single group of drug products on the pharmaceutical market today.

    Traditional drug development for small molecule drug products involves the use of small, chemically manufactured active-substance molecules.  Processed into easily ingestible capsules or tablets, small molecule drug products can readily be dissolved in the body, absorbed into the bloodstream via the intestinal wall.  Small molecule drugs have a tiny structure and chemical composition which enables them to easily penetrate cell membranes. 

    Small molecule drug therapies can be formulated into orally delivered dose forms and are highly useful as they can be engineered to deliver a potent therapeutic effect to the patient in only a small dose.  This translates into a lower cost of goods for efficacy as compared to that of a large molecule therapy, as biologics typically utilize injectables as the principal delivery route.

    Conventional drug products often work as inhibitors.  The small molecules fit into parts of molecules in cells to block pain, pain signaling, etc.  Conventional drug development often involves designing or finding a small new drug that can block only a problematic process.  This requires precision.  The area inside cells includes a plethora of molecular components.

    Clinical trials for small molecule drug products tend to be much less complex and expensive that those of large molecule biologics.  Typically, the clinical supplies for SMOLs do not require cold chain logistics or temperature-controlled conditions, making shipment and storage of clinical supplies less expensive.

    By contrast, large molecule drug products, or biologics are not synthesized chemically.  Made from whole cells, either alive or dead, these biomolecules may originate from the internal components of cells such as enzymes, be the biomolecules that are produced by cells, such as the antibodies that are secreted by the immune system and may come from plants, animals, microorganisms or humans.  Unlike the chemicals used to create conventional medicines, the exact composition of biologic drugs may be unknown or even unknowable.  Biologics are typically found in liquid form, rather than in pills or tablets.  This is because the molecules in biologic medicines are fragile and tend to fare the best in liquid conditions.

    The earliest biologics were vaccines.  The United States Congress passed the first law in 1902, the Biologics Control Act to aid in ensuring the safety of biologics.  In the 1970s, drug manufacturers turned to recombinant DNA so that they would not need to extract many of the most important biologics from whole animals.  Today,  biologic drug products are often produced through use of recombinant DNA technology.

    Biologics are more complex than SMOL and more delicate in nature.   With small molecule drugs, the chemical structure of the finished drug product can be analyzed to ascertain the various components.  This is not the case with biologics as the biologic product is actually the process.  Biopharmaceutical manufacturers must impose strict quality control standards to ensure the consistency of biologic drug products.   In the production of biologics, the finished product cannot be completely identified and analyzed; the finished biologic may have components that cannot be identified using standard laboratory methods.  

    This is because the components of the living systems used to create the biologic product are complex and difficult to isolate.

     

    Biologic Drugs, Cold Chain Logistics and the Pharmaceutical Supply Chain

    In 2016, the pharmaceutical industry reported that biologic drug products made up 25% of the total pharmaceutical market, generating $232 billion in revenue.  The following year saw an increase in revenue as well as in the number of biologic therapies approved by the FDA.  The trend towards drug development of biologics has continued steadily, and even increased.  Half the drugs approved by the FDA in 2017 were biologics, large molecule complex drug products, that are produced within a living system such as a microorganism or in plant or animal cells.

    Because biologics are produced using living cells and/or systems, they tend to be especially sensitive to miniscule alterations of the manufacturing process.  Tiny changes in processes may result in pronounced alterations of the nature of the finished biologic product.  This can also impact the way that the biologic functions in the human body. Temperature-controlled conditions are typically mandatory for the safety and stability of the biologic drug product.

    FDA Expedites Biopharmaceutical Manufacturing Products

    Among the challenges facing biologic pharmaceutical manufacturers is that of new drug development and Food and Drug Administration approvals. Signed by President Obama on December 13, 2016, the 21st Century Cures Act was designed to help expedite drug development.  The legislation helps to speed up drug development efforts, and should prove especially useful for biologics.

    Cold Chain Logistics Necessary for New Drugs Approved in 2017 by FDA

    Of the 57 new drug products that were approved by the FDA in 2017, 28 (49%) are temperature sensitive products. Of the 28, 23 require refrigerated storage and transportation conditions.  The remaining 5 drug products require below 0, or cryogenic temperatures.  All 23 of the drug products which require refrigeration must be kept unfrozen in order for them to remain effective.

    In the pharmaceutical industry today, there are numerous instances in which cryogenic cold chain storage and transportation services are required: 
    • Tissue products
    • Bio samples used in clinical trials
    • Products including:
      • Grifols’ Fibrin Sealant requires -18°
      • Biomarin’s Brineura requires -35° to -15°

    New cellular/gene therapies:

    • Spark Therapeutics’ Luxturna -65°C
    • Novartis’ Kymriah -120°C (liquid nitrogen vapor)
    • Kite Pharma’s Yescarta -150°C (closer to liquid nitrogen)

    New Pharmaceutical Industry Cold Chain Trends

    Some cellular therapy products, including Novartis’ CTL019 (tisagenlecleucel) therapy for lymphoma has produced early success.  This is the first of the new CAR-T cell therapy products.  CAR-T therapy involves extracting T cells from a patient so that the cells genetics can be reworked.  The cells are then re-infused back into the same patient.  This temperature-controlled drug therapy has produced intense interest that seems to promise a flush of similar products if initially found to be effective.  Because of the sensitive nature of the CAR-T therapy products, cold chain logistics services would be necessary to get the therapy to the patient as well as from the patient.

    Cold chain logistics services are also in demand to handle the round-trip logistics activity involved with clinical trials.  In this instance, the investigational drugs go out and tissue, blood and other biologic materials from the patient are transported back for evaluation and study.  Major multinational 3PLs have become increasingly involved in providing the specialized cold chain logistics courier services needed for clinical trials.

    Many pharmaceutical products react negatively in certain conditions involved with humidity, light, vibration and shocks.  Radioactive therapeutic agents lose potency in a matter of days in some conditions.  As more large molecule therapeutics are developed, the pharmaceutical industry is recognizing increased need for experts in temperature-controlled storage and transportation as well as for technologies such as packaging to prevent product damage and ensure patient safety.

     

    Conclusion

    According to the 2017 Biopharma Cold Chain Sourcebook, Pharmaceutical Commerce estimated the global volume of 2017 cold chain drug products at $283 billion.  The biopharmaceutical manufacturing market in 2017 was approximately $1.17 trillion.  With a growth rate of approximately twice the overall pharma market, the biopharmaceutical manufacturing sector is making a serious dent in a crowded pharmaceutical industry with innovative new drug therapies.

    The advent of new large molecule therapeutics has given rise to the need for more temperature-controlled warehousing and transportation as well as for innovative new packaging.  This trend is anticipated to continue based upon current trends toward biologic drug development.  In addition, the increase in clinical trials and innovative therapies also increases the likelihood that more cold storage warehouses and cold chain logistics will be needed in the United States.

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