Duane Sword is Vice President Marketing & International Sales at Thermo Fisher Scientific.

Duane Sword

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).  

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.  

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.  

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.  

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. 

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.  

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

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", 

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

Articles

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.

Degradation And What It Means To The Supply Chain

The full version of this counterfeiting feature can be read in the July issue of our digital magazine: http://www.pharmtech.com/ptedigital0710

To date, the pharmaceutical industry's primary defence to counterfeiting is to create more sophisticated packaging that makes imitation more difficult, such as packaging involving barcoding and RFID. However, counterfeiters are becoming increasingly sophisticated and this approach ultimately only secures the packaging rather than the product itself. Also, implementing an RFID strategy can be very costly from an operational standpoint because it requires additional manpower and also introduces some technology hurdles that must be overcome before it can be more broadly applied. For example, each individual pallet or package requires an individual RFID chip, which despite decreasing prices, still costs about 7–15 cents. In the case of the Viagra implementation in 2006, Pfizer ultimately spent $5 million on just the pilot phase of their RFID tagging initiatives.

  Additionally, there are also unsettled questions about whether the RF energy used to read the tags may impact sensitive biologics.

One analytical technique that has gained significant traction in the fight against counterfeits is Raman spectroscopy, which was originally created for use in condensed matter physics and chemistry where it was used to study vibration, rotational and other low-frequency modes in a system. The biggest difference between Raman spectroscopy and RFID is that the former tests the actual drug and/or raw materials, which is important for markets where the product is sold without its original packaging. Raman spectroscopy also accurately identifies chemicals through sealed glass, plastic bottles, plastic bags and blister packs, which means that the operator does not come into direct contact with the substance. This avoids potential contamination and preserves the integrity of any evidence that can be used against counterfeiters.  

In recent years, Raman spectroscopy has become available as a lightweight, handheld instrument that can identify even slight differences in drug formulations. This type of instrument can be deployed to authenticate the raw materials and/or finished products on the spot at points throughout the supply chain, including:  

Ports of inspection — to allow enforcement to execute random sample testing of raw materials and finished products before they enter the supply chain, thereby eliminating the risk to consumer health.

Distributors — by making handheld analytical instruments available at massive distribution centers, businesses can catch counterfeit materials and/or drugs before they are sent to the various worldwide locations, after which they can be very difficult to track and recall should a problem be identified at a later point in time.

Point of sale — conducting field inspections at the point of sale is the critical place where these instruments should be deployed to ensure counterfeit drugs are not ending up in the hands of patients. Additionally, these inspections send a clear message to counterfeiters because they are done publicly at pharmacies and open markets.

The World Health Organisation (WHO) estimates that counterfeit pharmaceutical levels range from less than 1% in the developed world to more than 30% in less developed regions. In less developed countries, there are gaps throughout the supply chain because standards are not as strict as they are in more developed regions. Open markets, where the unauthorised re-sale of medicines often takes place, are also very prevalent in these regions.  

Bringing technologies to less developed countries should be a top priority, and these technologies should ideally be portable and easy to use with minimal training, which handheld Raman instruments may be able to offer.  

Some countries already have an anti-counterfeiting strategy in place. For instance, Nigeria's National Agency for Food and Drug Administration and Control (NAFDAC) has launched a text messaging service called the Mobile Authentication Service (MAS) that allows anyone in Nigeria to check the authenticity of their medicines. More than 80% of the population in Africa have mobile phones, which makes systems such as these highly accessible to the general public.  

In combination with its MAS system, Nigeria is also using our handheld Raman instruments to identify even the slightest difference in drug formulation. After just two weeks of deployments, the instruments had helped authorities seize more than 60000 counterfeit drugs.

  The technology was also used to help NAFDAC intercept a consignment of counterfeit Lonart DS anti-malarial tablets worth 10 million naira.

  Arrests were made in connection with the incident, which sends a clear message to counterfeiters that there will be consequences.  

Nigeria's aggressive anti-counterfeiting campaign is now being emulated in other developing countries. For instance, Indonesia's national agency for food and drug control (BPOM) is now using TruScan and others are also evaluating the technology.   

Although supply chains in developed regions, such as the EU and the US, are tighter than those in less developed countries, they are still not 100% secure against counterfeiters, which is why it is still necessary for manufacturers in these areas to implement anti-counterfeiting strategies. Counterfeit identification rates will be lower in these regions compared with less developed countries, but every case counts. The biggest risk in these countries lies in medicine purchases made 

 the internet. As such, it is very important to educate consumers to allow them to better tell whether the medicine they are buying is legitimate. There are little things consumers can do to check the medicine they are taking is authentic, such as checking the seal to confirm it's not broken, reviewing the expiration date and buying medicines only from legal pharmacies. 

Another significant risk facing developed countries stems from globalisation. Many businesses outsource the manufacture of drugs or raw materials to foreign countries, which creates the potential for substandard or counterfeit products and ingredients to enter the supply chain. One example of this is the 2008 Heparin incident when it was discovered that Heparin, which is used daily in many hospitals worldwide, was contaminated with a toxic substance. The contamination occurred in China and resulted in hundreds of patient injuries and more than 80 deaths.  

The FDA and the European Medicines Agency rely on manufacturers to meet certain standards, but many medicines now have foreign sources beyond the reach of these agencies. This situation will not be resolved unless new policies and regulations are put in place.  

Counterfeiters will inevitably focus on products that are easiest to counterfeit, as well as the countries with the least amount of enforcement. The challenge for manufacturers is to keep pace with counterfeiters by making it as difficult as possible for drugs to be copied. This will be achieved by deploying serialisation technologies, such as RFID, as well as chemical identification instruments that can provide a quick "pass" or "fail" analysis of a medicine on the spot. 

is Vice President Marketing & International Sales at Thermo Fisher Scientific.

1. RFID Journal, "Pfizer's RFID Pilot Is the Start of Something Big" (2006). 

2. Federal Communications Commission, "Radio Frequency Safety" (2009). 

3. Thermo Fisher Scientific, "Thermo Fisher Scientific Helps Nigerian FDA Fight Counterfeit and Substandard Pharmaceuticals Using State-of-the-Art Portable Raman Instrument" (2010). 

To date, the pharmaceutical industry's primary defence to counterfeiting is to create more sophisticated packaging that makes imitation more difficult, such as packaging involving barcoding and RFID.

How Raman Spectroscopy Is Benefitting Developing And Developed Countries

To date, the pharmaceutical industry’s primary defence to counterfeiting is to create more sophisticated packaging that makes imitation more difficult, such as packaging involving barcoding and RFID. However, counterfeiters are becoming increasingly sophisticated and this approach ultimately only secures the packaging rather than the product itself. Also, implementing an RFID strategy can be very costly from an operational standpoint because it requires additional manpower and also introduces some technology hurdles that must be overcome before it can be more broadly applied. For example, each individual pallet or package requires an individual RFID chip, which despite decreasing prices, still costs about 7–15 cents. In the case of the Viagra implementation in 2006, Pfizer ultimately spent $5 million on just the pilot phase of their RFID tagging initiatives.

 Additionally, there are also unsettled questions about whether the RF energy used to read the tags may impact sensitive biologics.

 Duane Sword. Vice President Marketing and International Sales at Thermo Fisher Scientific.

 One analytical technique that has gained significant traction in the fight against counterfeits is Raman spectroscopy, which was originally created for use in condensed matter physics and chemistry where it was used to study vibration, rotational and other low‑frequency modes in a system. The biggest difference between Raman spectroscopy and RFID is that the former tests the actual drug and/or raw materials, which is important for markets where the product is sold without its original packaging. Raman spectroscopy also accurately identifies chemicals through sealed glass, plastic bottles, plastic bags and blister packs, which means that the operator does not come into direct contact with the substance. This avoids potential contamination and preserves the integrity of any evidence that can be used against counterfeiters. 

In recent years, Raman spectroscopy has become available as a lightweight, handheld instrument that can identify even slight differences in drug formulations. This type of instrument can be deployed to authenticate the raw materials and/or finished products on the spot at points throughout the supply chain, including:

The World Health Organisation (WHO) estimates that counterfeit pharmaceutical levels range from less than 1% in the developed world to more than 30% in less developed regions. In less developed countries, there are gaps throughout the supply chain because standards are not as strict as they are in more developed regions. Open markets, where the unauthorised re-sale of medicines often takes place, are also very prevalent in these regions. 

Bringing technologies to less developed countries should be a top priority, and these technologies should ideally be portable and easy to use with minimal training, which handheld Raman instruments may be able to offer. 

Some countries already have an anti‑counterfeiting strategy in place. For instance, Nigeria’s National Agency for Food and Drug Administration and Control (NAFDAC) has launched a text messaging service called the Mobile Authentication Service (MAS) that allows anyone in Nigeria to check the authenticity of their medicines. More than 80% of the population in Africa have mobile phones, which makes systems such as these highly accessible to the general public. 

In combination with its MAS system, Nigeria is also using our handheld Raman instruments to identify even the slightest difference in drug formulation. After just two weeks of deployments, the instruments had helped authorities seize more than 60 000 counterfeit drugs.

 The technology was also used to help NAFDAC intercept a consignment of counterfeit Lonart DS anti‑malarial tablets worth 10 million naira.

 Arrests were made in connection with the incident, which sends a clear message to counterfeiters that there will be consequences. 

Nigeria’s aggressive anti‑counterfeiting campaign is now being emulated in other developing countries. For instance, Indonesia’s national agency for food and drug control (BPOM) is now using TruScan and others are also evaluating the technology.  

Although supply chains in developed regions, such as the EU and the US, are tighter than those in less developed countries, they are still not 100% secure against counterfeiters, which is why it is still necessary for manufacturers in these areas to implement anti-counterfeiting strategies. Counterfeit identification rates will be lower in these regions compared with less developed countries, but every case counts. The biggest risk in these countries lies in medicine purchases made via the internet. As such, it is very important to educate consumers to allow them to better tell whether the medicine they are buying is legitimate. There are little things consumers can do to check the medicine they are taking is authentic, such as checking the seal to confirm it’s not broken, reviewing the expiration date and buying medicines only from legal pharmacies.  

Counterfeiters will inevitably focus on products that are easiest to counterfeit, as well as the countries with the least amount of enforcement. The challenge for manufacturers is to keep pace with counterfeiters by making it as difficult as possible for drugs to be copied. This will be achieved by deploying serialisation technologies, such as RFID, as well as chemical identification instruments that can provide a quick “pass” or “fail” analysis of a medicine on the spot. 

1. RFID Journal, “Pfizer’s RFID Pilot Is the Start of Something Big” (2006). www.rfidjournal.com 

2. Federal Communications Commission, “Radio Frequency Safety” (2009). www.fcc.gov

3. Thermo Fisher Scientific, “Thermo Fisher Scientific Helps Nigerian FDA Fight Counterfeit and Substandard Pharmaceuticals Using State-of-the-Art Portable Raman Instrument” (2010). www.ahurascientific.com

To date, the pharmaceutical industry?s primary defence to counterfeiting is to create more sophisticated packaging that makes imitation more difficult, such as packaging involving barcoding and RFID.