Impact of Counterfeit Drugs on Healthcare Combating Alternatives : An overview

By - 02/07/2008

1086 reads

Average:

Your rating: None Average: 5 (1 vote)

R. Hemalatha

R.Hemalatha

As the counterfeit drugs are making their presence every where causing huge social and economic costs besides undermining the confidence of the common man on health care system, there is urgent need to combat the problem.

This article summarizes the various adoptable alternatives available viz simple forensic methods, passive/overt systems such as holograms and Active/covert systems such as RFID, Taggants and 2D-encryption discussing their relative advantages and disadvantages. The changes proposed in the Drugs and Cosmetic act are also listed. There is imperative need to educate people about this ubiquitous menace with whose effective participation this problem can be tackled.

1.0 Introduction

Manufacturing counterfeit medications and packaging is an alarmingly simple and inexpensive process. The counterfeit drugs have been in existence for quite a long time and have made a negative impact in the recent history of industrial scale drug production in India and abroad. Recent evidence / seizures on counterfeits establish the scope and scale of the problem. Globally, counterfeiting is not just limited to high value branded drugs. It now includes everything the pharmaceutical industry produces globally from high value life style, therapeutic and life saving prescription drugs to generic therapies for malaria, AIDS/HIV and TB. Many pharmaceutical manufacturers who spend billions of dollars on research, production and marketing a particular drug are being knocked off as attenuated drugs, useless placebos or dangerous substances by counterfeits manufactured in basement laboratories throughout the world especially in places like south America, former Soviet Union and India.

Given the enormous return on investment, it is believed that this business already financially surpasses the world wide heroin-trafficking industry. The organized crime and terrorists turn to counterfeit goods to generate cash flow. The growing trade in counterfeit products will create social and economic costs and further burden the global healthcare expenditures.

According to latest WHO report, counterfeit medicine is defined as¹

“any product that is deliberately and fraudulently mislabeled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products and counterfeit products may include products with correct ingredients or with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging”

2.0 The Nature and Scope of the Problem of Counterfeits

As the counterfeits are made either without any active ingredient or insufficient quantities or with the addition of some toxic substance such that the counterfeit drug has no or has a decreased therapeutic, diagnostic or prophylactic value. With little or no active ingredient a person does not receive all the therapeutic, diagnostic or prophylactic benefit and will either not recover or will have a delayed recovery. Toxic ingredients, of course, can poison humans at times with fatal results. In case of infectious diseases (the major cause of disease in under developed world), the counterfeit drugs lead to selection of drug resistant pathogens, increased morbidity, mortality and a significant economic burden on developing regions of the world.

No pharmaceutical product is by the way safe from counterfeiters. Although expensive medicines, such as oncology products, human growth hormone and widely prescribed life style products like erectile dysfunction drugs, are natural targets, there is still major profit to be made by counterfeiting virtually any medication as well as other products and devices used in health care like glucose monitoring solutions, mesh implants, catheters, stethoscopes and device components for assembling intra-aortic pumps, cardiovascular and orthopedic solutions.

Significant cross border price differentials often attract many small and medium pharma manufacturers to counterfeit and parallel trade. When drugs intended for a particular market at a reduced price make it into a higher price market, with the diverter pocketing the profits. There is also rapid growth in internet pharmacies. Many of the internet pharmacies are based in places other than where they appear to be located. The internet allows official drug monitoring bodies to be bypassed and provides counterfeiters with ready access to consumers and markets.

A recent WHO report estimates the prevalence of counterfeit drugs to be about 1% in developed countries and at over 10% in some of the developing countries ². The most important aspect is this global problem, is that while such estimates are only meant to provide insight into the problem, the occurrence of even a single case of counterfeit medicine is simply unacceptable to society.

The counterfeiting may take place at various stages of production/distribution process of drugs

a)Counterfeit active / bulk ingredients:

If the ingredients used in the manufacture of drugs is spurious, this may result in reduced bio-availability and do not produce the desired therapeutic effect. And / or may also result in presence of toxic or undesirable constituents in the drug.

b)Counterfeit finished / diverted products:

The counterfeit finished products, which enter the supply chain, may have less or no active ingredients of the drug cause much of the damage. a) It reduces the faith of the public on the drug, b) may sometimes put patients health at risk.

c)Counterfeit labeling / mislabeled Product:

This is one of the by product of finished / diverted product and eat into the drug manufacturers earnings besides causing irreparable damage to the health care. There is also an ongoing problem of product diversion and reintroduction of expired products into the supply chain.

3.0 Alternatives Available to Address the Problem

Detecting counterfeit products is one of the ways the industry can combat this problem. But unfortunately, the complex and diverse trade and distribution systems through out the world can make detection difficult. On obtaining the suspect sample, the initial question is “ is this the authentic product?”. If a conclusion cannot be obtained from the packaging and other information, analysis must be performed for comparison with the authentic product.

3.1 Forensic methods

One or more properties of the drug may serve as “identification tag” for a drug or for a manufacturers product. These properties include ³

a) Chemical characteristics

i)Excipient identity, ii) Impurity profile, iii) Crystal form, iv) Morphology or particle size, v) Thermal behavior

b)Analytical profiles

i) Major and minor components, ii) Impurities, iii)Isotopic ratios

Techniques such as infrared Spectroscopy, X-ray powder diffraction, Thermal gravimetric analysis, microscopy and various forms of chromatography have been used to check the authenticity of samples.

However, all these methods are to be done in a well equipped laboratory and are unavailable to the common consumer. Therefore, the trend is to develop a cost effective, simple device that can be used by a common man.

A handheld refractometer ⁴ normally used to examine the specific gravity of urine specimens has been found to be effective to test and detect counterfeit drugs. One has to take the sample of the drug, pulverize and dissolve the powered in alcohol and filter out any undissolved portion. A drop of this solution is placed in the refractometer, which gives a shadow line indicative of refractive index. That index can be converted to specific gravity, which can compared to a standard already established for that particular drug. This is a relatively low technology approach that people in developing countries who have limited resources can use.

However, these techniques involve opening of the package of the drug. Once a drug package is open, the product usually cannot be marketed. Therefore the present focus is on developing tools that can be used without opening the package of the drug. Researchers used a new form of Raman spectroscopy, a tool for identifying molecules. The method called Spatially offset Raman⁴ Spectroscopy, can analyze through paper packaging, plastic containers, capsule shells and tablet coatings to verify the ingredients in pharmaceutical product.

However, as the consumer groups have strongly advocated that it is ultimately the responsibility of the pharmaceutical company to protect their products and take all necessary measures to identify a bonafide drug. Pharmaceutical industry is trying many alternatives to protect their brands.

3.2 Passive Overt systems

The overt technologies are readily visible and include features such as

i) Packaging that is difficult/costly to duplicate such a blister packing and ii) Holograms or Color shifting ink.

Though these are the first defense, which can provide simplified means for consumers to deduce the authenticity of a drug. The major advantage of such passive approaches is that they can be applied at the item level. The major problem however, is that they are generally costly and not effective in the long term as often these can also be reverse engineered. For example holograms can cost as much as 10-25paise depending upon their level of sophistication and therefore can add significantly to the MRP of low end medicines that are staple of the indigenous pharmaceutical market². Another problem is that, the hologams themselves can also be eventually duplicated by counterfeiters making the initial investment by the brand owner ineffective when such knock-offs enter the market. Finally, passive technologies do not provide the brand owner with an implantable supply chain management. And/or track-trace ability.

3.3 Active/ Covert Systems

Covert technologies are not visible to the naked eye and include the use invisible chips and security markers or taggants, which can be mixed with inks, coatings or the packaging material.

3.3.1 Radio-frequency identification (RFID)

The technology is based on an electronic chip that emits radio frequency waves encoding a specific code or ID. Down the supply chain this information is captured by a specialized chip reader. The major advantage of RFID is that no line of sight is required as the chip can be embedded in cartons or pallets in a hidden manned that resists tampering.

The major problem with RFID technology is its cost, readability. The cost estimates vary in India but each chip is typically in the range of 5 to 15 rupees ². This may be acceptable cost if the chips are used for product batches (e.g., cartons or pallets), but the price becomes unacceptable at the item level. Also, to decode and compare the information on the chip a reader is required which also adds to t he cost besides making this technology useless to the common consumer.

Further, readability has constraints of high error rates which have technical origin. The error rates of 2.5 per cent and above have been reported with RFID technology². The problem with error rates comes down to physics as radio waves are easily impeded by metals and liquids. It is therefore difficult to predict how radio signals will be bounced around inside a pallet or carton of goods. This scale of error rate is not acceptable in any large-scale operation.

In line with this view, the European Federation of Pharmaceutical Industries and Associations (EFPIA) announced on May 30, 2007 in Brussels that they had chosen the 2-D barcode to carry the identity of medicines as the preferred anti-counterfeit tool 'instead of the less reliable and more expensive RFID'.

3.3.2 Taggants and Tracers

The taggants can be made from food-grade materials such as cellulose or gelatin and can be incorporated in to the packaging in various ways such as ⁵

An adhesive
A coating on a label or other packaging substrate
A stripe on the side of the cap
In combination with the dessicant.

The taggant acts like a fingerprint in establishing product authenticity. Taggants are typically multicolored particles that are added to masterbatches. Taggants are also derived from crosslinked melamine particles and undisclosed rare earth elements. These taggant particles are available in size ranging from less than 20 to 600 microns. More than 37 million color codes can reportedly be developed from combinations of eight colors and other chemicals in a 10 layer wafer-shaped structure⁶. Identification characteristics can be made more complex by adding nanoparticles, besides spectral, elemental, or infrared materials, each of which emits a particular signature when scanned and almost infinite number of unique codes can be created by mixing in quantities of less than two parts per million. This low concentration means that it is nearly impossible to find, much less reverse engineer, the taggant. Energy-sensitive chemicals may also be added to the taggants that cause scanners to beep. When a laser scans the chemicals, the particle absorbs the light and reflects it back to the scanner, activating an audio signal.

The taggant authentication can occur on three levels, including simple presence detection, pattern matching of the taggant with a camera based system and the removal of the taggant to confirm its identity. The authentication mechanisms include a portable scanner or UV light picking up and lab analysis that confirms the type of chemical in use and its concentration within a given area of compound. The benefit of most detection systems is that they are simple and can be used in the field by law enforcement and customs agents as well as manufacturers and end-users and can be disguised as an everyday object such as cell phone or pen. These can detect taggants as effectively as a laboratory analysis.

The process of compounding the taggants with the drug ingredients, or applying a taggant-equipped coating to solid dosage forms, is under active study. Such methods will provide product authentication at the pill level.

Other covert technologies available include

i) inks that are visible only when exposed to infrared or ultraviolet light

ii) Micro Printing technologies that conceal a message in tiny type

iii)Pattern printing – this is a technique that creates a pattern that is only revealed when a screened key is placed over the printing area. Messages can be printed in two directions so that two different messages can be hidden.

Taggants are relatively expensive and therefore are specified for higher-end products like medical devices and pharmaceutical packaging.

However, Tracers, are inert chemical compounds and are not as sophisticated as taggants in composition, but they provide a high degree of covert protection that is difficult to duplicate. Tracers are usually developed in-house by chemical engineers and provide relatively simple means of detection with lab equipment or scanners. Tracers are not as expensive as taggants, Like taggants, they do not affect the properties, performance, or processability of compounds. Both these type of additives can be used with many thermoplastics, with transparent and opaque materials, and are suitable for molding and extrusion. There are, however, differences in heat resistance. Taggants are thermally stable to 200 degrees C.

3.3.3 2D - Encryption

The third category of solutions is the software-based 2D-Encryption technology. Although the concept behind this technology has been around for some time, recent advances in computing machinery along with sophisticated algorithms for data encryption have propelled this field to the point, where it is now commercially available to the pharmaceutical industry as an effective tool for combating counterfeit activity.

Every product is given a unique digital identity generated by a computer-based encryptor. Every product from the item to the pallet level can be given its own unique digital code. The encrypted code itself is usually a 16-digit alphanumeric code that can be displayed in scripted format and by way of a linear or 2-D data matrix barcode. 2-D barcodes are printed on packaging during manufacture, providing each medicine with the identity before it enters the supply chain.

Besides the encryption and decryption of the codes, the software that supports this technology allows brand owners to fully manage their supply chain, so that the needed e-pedigree is made possible. The drug manufacturers can track their shipments from the factory through all intermediate nodes right down to the retail level. An additional advantage of such a powerful supply chain management tool is that pharmaceutical companies are better able to manage recalls, if any.

Also, 2D-encryption allows the consumer to authenticate a drug. As the codes can be printed on blister packs and vials in script form, the consumer can simply verify the authenticity of the drug by entering the code into an internet site or by using mobile phone SMS. The widespread use of mobile phones in India makes it possible to actually authenticate a product at the point of sale. Genuine drugs will pass authentication and the consumer will be sent a message to this effect. Counterfeit drugs will either contain no code or have an invalid code, which will not pass the authentication process. It is impossible for a counterfeiter to make up arbitrary codes, because the possibilities of combinations are astronomically large for a 16-digit alphanumeric format. Furthermore, the brand owner may choose to only allow a single authentication of any given code for maximum security. In this way, if a counterfeiter manufactures multiple fake products containing a single valid code, further authentications of that code will fail. The brand owner can get intelligence to identify failed authentications and can take measures to track down the source of the counterfeit drug.

The features of 2D-Encryption that are now getting substantial attention can be summarized to include its extremely low cost, track-and-trace capability and supply chain management that is bi-directional. Most importantly, mass encryption is a tool that empowers the end-user to verify the authenticity of a product. This last point can serve as a highly effective marketing tool for pharmaceutical companies that implement technologies in which consumers are given the ability to undertake their own diligence. In doing so, consumers are not only protecting their own purchase but are actually helping the brand owner by serving as their detectives of counterfeit products in the marketplace.

Finally, Weak legislation is often identified as the single most important factor driving counterfeit trde. At present, out of 191 WHO member states, about 20% are known to have well developed drug regulation, 50% are at various stages of implementing drug regulation and the remaining 30% either have weak or no drug regulation ⁷. Enacting deterrent anti-counterfeiting legislation alone will not solve the problem It needs to be enforced. For Indian context, the Drugs and Cosmetics amendment Bill 2007 contains stringent provisions such as a maximum penalty of life imprisonment and a fine of not less than 10lakh for those engaged in manufacturing spurious and fake drugs⁸.

Conclusion

Where as the simple forensic methods can be used by small clinics and primary health centres to check the authenticity of the drugs they dispense pharma companies may use the boom in Information technology and communications network to validate their supplies through the supply chain by various covert technologies. Most experts recommend layering protective technologies by selecting a combination of overt and covert techniques as liability issues, consumer confidence and brand erosion costs are driving pharmaceutical manufacturers to adopt technologies to combat this ever increasing problem.

India with its flowering economy is emerging as a strong player in many industries such as IT and pharmaceuticals. Given the country's image that has been portrayed abroad - a major supplier of counterfeit drugs - a genuine effort to combat this problem and to reinvent the impression and global perception India as a supplier of medicines of reliable quality, the Indian pharmaceutical industry must take measures to combat the scourge of counterfeit medicines and take the lead in ensuring the safety of its supply chain. The efforts of Indian pharmaceutical companies will be rewarding to the Pharma industry, the consumer and the Image of India as a whole. Finally, it is difficult to manage problem of this magnitude without effective participation of people. There is intrinsic need to educate people about this ubiquitous problem and involve them in the fight against counterfeit products in which the ultimate beneficiary is the consumer himself.

References:

1. Discussion paper;:Combating Counterfeit Drugs: Building effective International collaboration – International conference – Rome, Italy 16-18 Feb, 2006.

2. Magnar Loken, and Avi Chaudhuri , “Countering counterfeits”, Sept., 2007

3. Berbard A. Oslon, Mathew W. Boerer. Fred M. Perry and Robert A. Forbes “Screening for Counterfeit drugs using near infrared Spectroscopy”, Pharmaceutical Technology, June 2002

4. www.Sciencedaily.com – counterfeit drugs can kill: Nanotechnology fingerprints can Certify authenticity, 2007, Low-tech Handheld Device Det4cts Counterfeit Drugs, 2001, New Method For Detecting Fake Drugs Without Opening The Package, 2007

5. Halllie Forcinio “New systems for Counterfeit protection and Quality control”, Pharmaceutical Technology, 2005

6. Toeinmeier, Patrick A., Compounders thwart counterfeiting with covert additive techniques, Plastics engineering, Sep. 2005.

7. Mohan RK Nimmagadda, “Impact of counterfeits, parallel trade on global healthcare value chain”, www. Pharmabiz.com, Dec., 2007

8. P.A., Francis “Editorial: Surveying spurious drugs”, www.Pharambiz.com, Dec 2007

About Author: