Sasidharan S Menon **
Subject Matter Expert (SME) – Design & Evaluation
Controlled Environment for Contamination Control
Today, the Indian pharmaceutical industry is valued at $ 22 billion with experts projecting the market to grow at a CAGR of eight per cent during 2010-14, according to the Indian Drug Manufacturers’ Association (IDMA). With this, the exports have also grown. In India India
Objective
There is a growing need for awareness in this market and objective of this article is to introduce Phase Change Materials (PCMs) - an innovative, efficient and cost effective way of transporting temperature-sensitive pharmaceutical products and how it can bridge the gap between the regulatory policies & guidelines and the need of the consumer concerning product safety.
Challenges in temperature sensitive drugs, vaccines, clinical sample transportation
Healthcare manufacturers need to safeguard their products and offer evidence of complying to maintain a certain temperature range throughout the movement of goods. Biopharmaceuticals and vaccines contribute to a majority of shipments of temperature-sensitive pharmaceuticals, which are typically high in monetary value and have low product volume. With the surge in mail order shipments, increasing scrutiny by regulatory agencies and the desire to lower costs , the need to develop an effective and reliable cold chain management protocol has become a necessity of utmost importance.
Different Products require different temperatures
One of the main driving factors behind the increased temperature control requirements is the simple question whether temperature sensitive products that requires controlled storage conditions need be shipped under the same temperature conditions. Here, the term “temperature sensitive” needs some clarification. A particular product may suffer degradation if it is heated to +100°C, for example, but is stable otherwise. The likelihood of it being exposed to these conditions in transit between sites is effectively zero while another product may be affected by any temperatures outside +15°C to +25°C conditions. Both of these products will have storage conditions of +15°C to +25°C but it does not make sense to transport these with the same level of temperature control. Regulators hint that necessary actions have to be taken during storage & transportation to ensure product integrity and patient safety (World Health Organization, 2003). It hence becomes imperative to choose packaging and storage solutions as per regulatory requirements with stringent temperature monitoring during the products’ life cycle.
Operating Temperature °C
|
Application
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-30°C to -20°C
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Fresh Frozen Plasma
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-20°C to -23°C
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Blood serum, proteins, Plasmids, DNA, RNA, Anti Sera samples
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-5°C -10°C
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Tissues on slides
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2°C - 8°C
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Vaccines, Insulin, Blood Products.
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20°C- 24 °C
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Blood platelets, Cancer testing drugs, Freeze-Dried or Lyophilized Tissues
|
Source:
1. 1. Standards Australia on behalf of Committee HT/10. AS 3864-1997 Medical refrigeration equipment - For the storage of blood and blood products. Standards Australia. NSW, 1997.
2. American Association of Blood Banks. Technical Manual 16th edition. AABB Press. Bethesda
Loss of product efficacy
The term cold chain in the pharmaceutical industry applies to certain pharmaceuticals that require the maintenance of a specified temperature range in order to retain their therapeutic effectiveness. The essential temperature range must be adhered to throughout all phases of these drug products’ lifecycle, from the time they are manufactured until the time they are administered to patients (Weir & Hatch, 2004). Since temperature is one of the most important parameters to control during drug transportation, regulatory agencies have published guidelines on cold chain management. A disruption in the cold chain can cause temperature abuse and fluctuations such as cycles of freezing and then thawing, which can significantly weaken or even destroy the potency of certain immunizations (Edstam JS, 2004). Between 75% and 100% of vaccine shipments are accidently exposed to freezing temperatures due to breaks in the cold chain (Matthias, Robertson, Garrison, Newland, & Nelson, 2007).The conventional methods to ship temperature sensitive products use dry ice, water-based gels, and bottles containing freezing liquid. However, these materials can store at only two temperatures ie, 0°C or -80°C. Due to the small amount of pharmaceutical mass, the product quickly reaches the freezing temperatures, potentially causing irreversible damage and reduction in potency. The small heat capacity makes the pharmaceutical products susceptible to rapidly reaching equilibrium temperature with the frozen gel packs (Figure 1).
Also, as per CDSCO guidelines, special care should be taken while using Dry Ice as the extreme low temperature causes other problems such as shrinkage of the rubber stopper in vials, degradation of the air-quality in the container (Central Drugs Standard Control Organization).
Hence, the need for a technology that can be customized to maintain constant temperatures as per product specifications and the advent of Phase Change Materials (PCMs) minimizing the risk of over freezing due to lesser payloads or limitations in maintaining precise temperature ranges. The figure 2 below illustrates the performance of a minus 23 PCM over a duration of 48 hours subjected to varying ambient temperatures.
What is PCM
Water is a natural form of Phase Change Material (PCM) and most temperature control packaging use water by utilizing its high thermal energy storage capacity during its change of phase from liquid to solid or vice versa. The properties that make water an ideal material for storage & transport of materials for applications requiring temperature maintenance in the range of -2°C to 4°C are as follows,
· Consistent, repeatable, reliable phase change material temperature of 0° C.
· High latent heat of fusion.
· Non-Toxic.
· Easily packaged into pouches or bottles.
· Inexpensive and easily Available.
A good phase Change Material should mimic these properties but change phase at different temperatures.
A Phase Change Material (PCM) has the ability to store and release large amounts of heat/energy while maintaining a constant temperature as shown in figure 3. PCM’s have tremendous potential to fulfill the growing need of energy for cooling and heating applications across various industries.
Figure 3
Application of PCM
Phase Change Materials fall under the sub category of energy exchanging smart materials. Energy exchanging smart materials is defined as those materials that are able to store latent and sensible energy in the form of light, heat, electricity or hydrogen and exhibit reversibility. These are also called as “passive” cooling materials as these work without requiring any moving parts or complicated moving components and avoids the requirement of expensive retrofits or professional installation. PCMs can be placed among the products in HDPE bottles or HDPE pouches and reused for more than 3000 cycles which translates to over 10 years of life before losing its efficacy by 2-3%. Shown below in figure 4 are typical pharmaceutical packaging boxes with different PCM encapsulations.
These packages can maintain temperatures for up to 72 hours which takes care of major challenges of long transit period in air shipments. From a carriers’ perspectives there are three major aspects in moving temperature-sensitive cargo which are warehouse management, loading and flight, which in addition to road transport and other exigencies would be around 48hrs - 60hrs to reach the destination from the point of origin. We are looking at a new technology which got great potential to address product quality and patient safety.
Other Applications
PCM has its application across various industries where there is a need for temperature control and regulation. Example of its application in other industries is summarized below
1. Cold Chain Industry – PCMs have been proven to be very useful in cold chain industry. The major applications are to maintain temperatures during power failures. Major deep freezer manufacturers have started using phase change materials in their freezer to avoid the spoilage of products during power cut-offs, which is a major problem in India. Many FMCG companies in the dairy industry have started fast adopting phase change materials for last mile distribution into rural areas.
PCM integrated into the end product – Deep freezers at the retail
2. Building HVAC - PCM based thermal energy storage systems help in reducing capital costs, operating cost and increase efficiency by utilizing off peak electricity during the night hours. PCMs help store this energy during the off peak hours in large insulated tanks, which can be harnessed during the day time for serving the cooling needs of the building. This
3. Solar Applications- PCMs are being used to store the solar energy in the form of thermal energy which can be used in the absence of sunlight. This enables the solar based systems to work at night without use of external sources of heat/electricity.
PCM application to store Solar energy
4. Temperature-controlled clothing- PCMs can be incorporated with fabrics in various ways and can be used to provide comfortable temperature even in extreme temperature conditions.
Many more possibilities are yet to be exploited with PCMs extending its application into retail products, home appliances, automobiles etc.
Works Cited
Central Drugs Standard Control Organization. (n.d.). Guideline on Good Distribution practices for biological products.
Edstam JS, D. (2004). Exposure of hepatitis B vaccine to freezing temperatures during transport to rural health centers in Mongolia. Prev.Med, 384-388.
Matthias, D., Robertson, J., Garrison, M., Newland, S., & Nelson, C. (2007). Freezing temperature in the vaccine cold chain: Asystematic literature review. Vaccine 25, 3980-3986.
Weir, E., & Hatch, K. (2004). Preventing Cold Chain failure. Canadian Medical Association journal, 9.
World Health Organization. (2003). Guide to Good Storage practices for pharmaceuticals. WHO technical report series.
Datasheets/ technical Info - Pluss Polymers (P) Ltd., Gurgaon, India
**Mr Sasidharan S Menon, an Electrical Engineer by profession, is in the field of clean rooms and controlled environments for Pharma and Healthcare sectors since 1982 and can be contacted at contact@sasidharanmenon.com
