Degradation And What It Means To The Supply Chain

Product degradation is often overlooked compared with other supply chain issues. but if left unchecked can lead to the market entry of substandard medicines, whether through ignorance or gross negligence.

When it comes to discussions about supply chain vulnerabilities, counterfeit drugs are front and centre for good reason. According to estimates from The World Health Organisation, up to 30% of drugs sold in Africa, Asia and Latin America are fake and the International Policy Network reports that more than 700000 people die each year from counterfeit malaria and tuberculosis drugs alone (1). Counterfeits also impact pharmaceutical companies, which are losing as much as $75 billion in business each year (2).

(JANIS CHRISTIE/GETTY IMAGES)

However, there is another serious threat to the supply chain that is often overlooked: pharmaceutical degradation. Degradation, as with counterfeiting, enables substandard drugs to fall into the hands of patients and is most prevalent in developing countries where inadequate storage facilities are commonplace and proper regulatory oversight is often lacking. Unlike counterfeiting, however, degradation is not solely the result of malicious activity and can stem from a variety of issues. There is no effective method for monitoring what occurs between point A and point B in the supply chain, but the main contributors tend to be humidity, temperature and expiration.

Humidity and temperature

In developing countries, materials often degrade because of shifts in temperature and humidity. This can occur during transport; for instance, storage containers offloaded at the port of entry may sit in the tropical sun for an extended period of time while waiting to clear customs.

The transportation phase is not the only culprit. Following delivery, pharmaceuticals are frequently stored in warehouses that lack a suitable air conditioning system. The US Centers for Disease Control and Prevention estimate that 17–37% of providers expose vaccines to improper storage temperatures (3), which can diminish the levels of a drug's active ingredient or alter the excipient matrix and, ultimately, hinder its effectiveness.

Expiration

The concept of monitoring expiration dates seems fairly rudimentary. However, drugs that have passed their expiration date still frequently make it into the supply chain. This could happen as a result of ignorance, with the retailer being unaware that the expiration date had passed before delivery. The more common reason, however, is gross negligence where retailers repackage and re-label pharmaceuticals before putting them back into the supply chain. This is most prevalent in countries lacking sufficient regulation and where drugs are often sold at markets. To a lesser degree, repackaged drugs are also an issue in Europe because of parallel trade, where drug repackaging is legal. In these instances, there is no way to know how old a product is unless it is properly tested.

Technology solutions

In many regions it is difficult to consistently monitor the factors that can influence drug degradation, but technology can help pharma manufacturers, distributors and others involved in the supply chain to screen products to determine if they are potentially substandard.

One of the most common technologies used today — besides laboratory testing — is the Global Pharma Health Fund's Minilab, which is used across 70 countries worldwide and leverages four types of tests to identify poor quality products. Pharmaceuticals containing less than 80% of the API will not pass the test. At just under $10000, Minilabs are relatively affordable, but require potable water, electricity and a conditioned-controlled environment where the testing is conducted.

Another option is spectroscopy, which has gained considerable momentum since becoming available in portable, handheld instruments. There are several technologies that use spectrometry, but I will focus on infrared (NIR) and Raman spectroscopy in particular because these techniques exist in handheld formats and don't require contact with a sample.

NIR is a well-known spectroscopic technique that measures molecular vibrations to identify individual chemical components of a drug or raw material. NIR requires an investment of manpower to create and maintain robust material libraries, but provides quick, reliable results once properly installed. It also has the advantage of not requiring contact with a sample. Compared with Raman spectroscopy, however, it has the disadvantage of being less selective and of requiring more up-front development work to build robust reference libraries.

Raman spectroscopy is less well known than NIR, but is becoming more popular because it is available as a portable, handheld instrument. These instruments can be used essentially by anyone because they quickly identify chemical components without coming into direct contact with the substance. In other words, handheld instruments can scan through sealed glass, plastic bottles, bags and blister packs at ports of inspection or any other place in the supply chain using a laser that illuminates a sample and measures the molecular shift. Handheld Raman spectroscopy is currently being used by a number of large pharmaceutical manufacturers, as well as regulatory bodies worldwide.

Conclusion

Pharmaceutical degradation may not have the visibility of counterfeiting, but it still poses a potential threat to patients and must be considered by pharma companies. Technology, however, can help ensure that substandard materials are removed from the supply chain and kept out of the hands of patients. Handheld Raman instruments represent a simplistic solution.

Duane Sword is vice president of Thermo Scientific's Portable Optical Analysis business unit.

References

1. J. Harris, P. Stevens and J. Morris, Keeping it real: combating the spread of fake drugs in poor countries (International Policy Network, May 2009).

2. P. Gumbel, "How to Stop the Counterfeit-Medicine Drugs Trade", Time (October, 2009). www.time.com

3. FiercePharma Manufacturing, "Potency drops investigated in H1N1 vaccines" (January 2010). www.fiercepharmamanufacturing.com