Counterfeit Drugs-Learning form the Past

Counterfeit medicine is a menacing problem in the health care sector of human beings. The possible counterfeit products may be available in human and veterinary drugs, medical devices, biological products, foods, dietary supplements or cosmetics.
Counterfeit Drugs-Learning form the Past

ABSTRACT

The large-scale prevalence of counterfeit medicine which was once thought to be in less developed nations is now alarming highly affluent ones. The reluctance of mighty drug companies to share the risk information is a major impediment in combating this menace added to this on-line drug purchase is compounding the problem. However, WHO has taken a number of proactive initiatives in monitoring the spread of SSFFC through task forces such as IMPACT and web based medical products rapid alert systems and also Interpol services. Trace and track surveillance methods of supply chains employing high end technology viz., e-Pedigree, EPCIS and DPMS are yielding results. The grey areas in this serious health hazard scenario still are the lack of data on analytical reports and more so bio-analytical screening of the exposed population.

INTRODUCTION

Counterfeit medicine is a menacing problem in the health care sector of human beings. The possible counterfeit products may be available in human and veterinary drugs, medical devices, biological products, foods, dietary supplements or cosmetics. This review exclusively deals with counterfeit drugs in allopathic medicines. This medicine may be a fake medicine, contaminated or contain the wrong or no active ingredient. It may have the right active ingredient but improper dose.

World Health Organization in 2006 defined a “counterfeit” as “a medicine, which 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 or wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging.

The main types of counterfeit pharmaceuticals:

1. Incorrect Active Pharmaceutical Ingredient (API) or poly- morph

2. Correct API but incorrect excipients

3. Re-packaged, out-of-date but genuine pharmaceuticals

4. Harmless but does not contain the active ingredient/s

World Alert

Many pharmaceutical companies and governments are reluctant to publicize the problem to health staff and the public, apparently motivated by the belief that the publicity will harm the sales of brand-name products in a fiercely competitive business. Publicly, at least, several industry sources say the justification for secrecy is to avoid any alarm that could prevent patients taking their genuine medicines. They argue that this secrecy, and the subsequent lack of public health warnings, is harming patients and that it is also not in the long- term interests of the legitimate pharmaceutical industry. The regulatory agencies advocate mandatory reporting to govern- mental authorities, which should also have a legal duty to investigate, issue appropriate public warnings, and share information across borders. This is not a role for the pharmaceutical industry, which has a serious conflict of interest.

Although the major pharmaceutical manufacturers were aware of counterfeit medicines among their frontline products they were reluctant to share the information. Amongst them they formed a Non-profit Organization, Pharmaceutical Industry Survey (PSI) based in Virginia,USA. The PSI currently has the member- ship of 28 major pharmaceutical companies and has one of the most comprehensive and updated data bases on fake drug information but is not available in public domain. The veil of secrecy of its contents and investigation reports is so tight that even its member companies cannot share the contents, leave alone WHO, health workers or general public. However, after a public outcry and adverse publicity it has agreed to release information to national regulatory agencies on a “need to know basis”. Most of the statistics are released through PSI Counterfeit Incident System (CIS) which are limited to instances of legitimate supply chain penetration. However, it should be noted that data from CIS is proprietary to its members and not made available to the public other than in yearly aggregate trend reporting on PSI’s website.

The menace of counterfeit medicines was first alerted in late 1980’s through newspaper articles, BBC talk shows etc. Most literature on fake drugs appears in public domain through investigative journalism with very little scientific enquiry through reputed scientific journals.

This leads a situation of only a transient uproar. Therefore, their effects on consumers are difficult to follow up and mostly hidden from normal public through a maze of official health statistics. At the 1998 World Health Assembly this problem was extensively discussed and WHO decided to be taken up a more pro-active role. In 2006 it has launched International Medical Products Anti- Counterfeiting Task Force (IMPACT).

WHO Member State Mechanism

In defining, tracking and tackling fake drugs the WHO proposed a Member State Mechanism- under which some countries of UN/WHO system form a group. Due to differing patterns of legislations on crime and punishment amongst them, the nomenclature on Not Standard Quality (NSQ) and or even the word counterfeit does not address the definition. Therefore, at the 63rd World Health Assembly it was proposed that until a proper definition is framed they are referred as substandard, spurious, falsely– labeled, falsified counterfeit medical products or acronym SSFFC. The Member State Mechanism is a global format in which countries can deliberate to address the presence of SSFFC products. Global Surveillance and Monitoring System for SSFFC medical products was established in 2013 with 130 countries and about 20 high volume supply chain conglomerates. Network of about 500 personnel from the national regulatory agencies have been trained to use the system and over 950 SSFFC medical products are under scanner.

Contents of SSFFC medicine

Perhaps the best description of not only SSFFC contents but also NSQ was given in a publication by Rahul and Vasudha 12 have described the contents as

  1. Falsified medical products may contain no active ingredient, wrong active ingredient or the wrong amount of active ingredient

  2. They are found to contain corn starch, potato starch or chalk.

  3. Some products have been toxic in nature with either fatal levels of wrong active ingredient of other toxic chemicals

  4. SSFFC medical products are often produced in very poor and unhygienic conditions by unqualified personnel, and contains unknown impurities and sometimes contaminated with bacteria.

  5. Even if the active pharmaceutical ingredient (API) is correct or not in range of therapeutic dose the medicament is still dangerous or fatal.

Counterfeit medicines are part of the broader phenomenon of standard pharmaceuticals. The difference is that they are fraudulently mislabeled with respect to identity and or source. This product mostly has no therapeutic benefit; they can cause drug resistance and even death. Trade in counterfeit is extremely lucrative thus making it more attractive to criminal networks.

Figure-2: PSI collected data on counterfeiting, illegal diversion and theft incidents for fourteen consecutive years:
Figure-2: PSI collected data on counterfeiting, illegal diversion and theft incidents for fourteen consecutive years:

A report released by the Centre of Medicine in the public interest in the United States, projects counterfeit drugs sales to reach US $ 125 billion in 2020, a 110% increase from2005. Counterfeit drugs can include life style drugs, lifesaving drugs, patent/generic drugs and even medical devices. Hence, the patient safety is at risk, as it permits substandard drug delivery to patients. Counterfeit drugs are fraudulently manufactured, where drug identity or its source is misrepresented to wrongly influence the judgment of patients and healthcare professionals. The Fig-1 indicates the percentage of counterfeit drugs available in different line of therapy.

A formulated drug such as tablet, capsule, syrup, etc, contains of two components. An API and the excipients which facilitate the administration, preservation and absorption of the drug molecule. The risk from these counterfeits can arise from any of these components. The bulk drug is imported or smuggled and formulated with cheap materials like corn starch, crude lactose or chalk which are susceptible to microbial contamination.

Counterfeit drugs can be introduced during any one of the following stages:

  • Drug manufacturing of product by using the fake Active Phar- maceutical Ingredient (API).

  • Packaging by inserting incor- rect dosage

  • Recycling by repacking used or expired drugs and

  • Through internet by concealing address and other details.

2.1. Examples of counterfeit drugs

A few reported cases are presented to highlight the scale of the scourge

  • Approximately one-third to one-half of packets of artesunate tablets, the pivotal, life-saving anti-malarial drug, purchased in Southeast Asia were fakes, containing no active ingredient at all. A nongovernmental organization in a Southeast Asian country bought 100,000 inexpensive “artesunate” tablets only to find that they were counterfeit.

  • A total of 192,000 Chinese patients are reported to have died in 2001 from fake drugs, and in the same year Chinese authorities “closed 1,300 factories while investigating 480,000 cases of counterfeit drugs worth 57 million USD”. In 2004, Chinese authorities arrested manufacturers of grossly substandard infant milk powder and closed three factories after the death of over 50 infants .

  • In North America, counterfeit atorvastatin, erythropoietin, growth hormone, filgrastim, gemcitabine, and paclitaxel have been reported recently.

  • Nigeria in 2001 threatened to ban the import of all drugs from India, a major supplier, because of the high prevalence of counterfeits amongst the imports.

  • In Haiti, Nigeria, Bangladesh, India, and Argentina, more than 500 patients, predominantly children, are known to have died from the use of the toxin diethylene glycol in the manufacture of fake paracetamol syrup.

  • During the 1995 meningitis epidemic in Niger, the authorities received a donation of 88,000 Pasteur Merieux and SmithKline Beecham vaccines from neighboring Nigeria.23The drugs were found to be counterfeit, with no traces of active product. Some 60,000 people were inoculated with the fake vaccines.

  • Counterfeit antiretrovirals (stavudine-lamivudine- nevirapine and lamivudine-zidovudine) in central Africa raises the prospect of a disastrous setback in the treatment of AIDS in sub-Saharan Africa, unless vigorous action is taken now.

  • In Africa malarial deaths are estimated to be a million a year. About 60% are children below five years of age. Halofantine, paediatric syrup (Halfan) a GSK product was faked and sold, which resulted in several deaths. This has alarmed health care professionals to the scale and range of distribution syndicates involved in the sale of fake syrup and adult tablets. The GSK group after relent- less campaigns by BBC radio talks, has agreed to undertake a technical study of the seized fake Halfan.

  • In 2013-2014 The seizure of large quantities of counterfeit prescription drugs containing fentanyls has thrown light on growth in overdose deaths in the United States, according to a report from the US-DEA which states global threat describes how “hundreds of thousands of counterfeit prescription pills, some containing deadly amounts of fentanyls have been introduced into U.S. drug markets.” Center for Disease Control (CDC), Atlanta, reported that deaths from synthetic opioids (including fentanyl) upto 79%. A substantial portion of the synthetic opioid deaths appeared to be related to the influx of fentanyl.

  • In 2015 FDA has alerted health care practioners and the public that a counterfeit version of Botox was found in the United States and may have been sold to doctors and medical clinics all over the world. Botox is extensively used in cosmetic facial procedures.

  • In May 2016, DEA was informed that counterfeit version of a FDA approved cancer drug, BiCNU (carmustine for injection) 100 mg, has been detected in some foreign countries.

Trace and Track Methods

It is now clearly understood that SSFFC products enter through supply chains which are porous and not monitored. Added to these inadequacies are complex legal challenges which may differ between countries or between different regions within a country. After setting up of web-based system by the WHO on tracking the movement of counterfeit drugs on a trial basis in the western pacific region, it gradu- ally expanded its activities to cover more WHO geographical regions. This network medical product the Rapid Alert System (RAS) alerts the authorities to take quick action.

In an effort to counter this issue, countries and organizations are pursuing the need for serialization. The serialization process provides the complete scenario of a given product’s chain of custody from the manufacturer to the point of dispensing. To support this number of trace and track procedures have been introduced. Some of them include existing methods like barcoding, Electronic Product Code (EPC) and a host of new technologies like Drug Pedigree Message Standard (DPMS).

The DPMS system calls for mass serialization which involves e-Pedigree method using Radio Frequency Identification (RFID), 2d-bar codes. These systems provide a window for recording and storing the complete movement of a product from entering the supply chain to the end –user. The e-pedigree regulation has a double advantage of not only tracking of counterfeit drugs but also diverted or smuggled genuine drugs gone beyond the use by date label. In India pioneering work in development and application of these software-based measures have been undertaken in big way by TCS Life Science and Health Care Unit.

E-Pedigree: E-Pedigree “means a record in electronic form containing information regarding each transaction resulting in a change of ownership of a given medical product from manufacturer, wholesalers until final sale to a pharmacy or health care professional furnishing, administering or dispensing product. It is therefore an interoperable electronic surveillance system for movement of medical products literally from “bench to bedside”.

Many anti-counterfeit technologies are available for manufacturers and brand owners, ranging from simple and effective to complex and sophisticated. The Global e-Pedigree software market and related features can be broadly segmented as following four types.

Visible features or overt features help end-users to verify the authenticity of the pack. These features are clearly visible, and it is hard to make any changes. A few visible features are holograms, OVD, color shifting security inks, security graphics, sequential numbering, and marking on the product.

Hidden features or covert features are used to enable brand owners to identify a fake product. General users will not be aware of their presence nor have the means to verify them. A few hidden features are invisible printing, embedded images, digital watermarks, hidden marks, anti-scan designs, laser coding and substrates.

Forensic techniques many high-end technology solutions are conducted in the laboratory and require testing to prove authenticity scientifically. These are a subset of hidden technologies, but the main difference is the scientific methodology required for authentication. A few such techniques are chemical taggants, biological taggants, DNA taggants, isotope ratios, and micro-taggants.

Track and trace technology serve a few important functions such as tracking items through the supply chain, providing traceability of the history of any item, and enabling authentication of the data at any time. Serialization, barcodes, RFID tagging, and topography or unique surface markings are a few of the techniques used in this technology.

Two Dimention Bar code

The label works like an ATM pin voucher. The user scratches off the cover and texts what is underneath to a free phone number, to find out if a product is genuine. Quick response (QR) codes are also being tested. These printed squares are an advanced version of the 2D barcodes. Anyone with a camera- enabled phone and web access can scan the code and be taken instantly to the pharma company website to authenticate the drug. A committee set up by the Indian Ministry of Health has approved a proposal to put 2D barcodes and scratch-off labels on medicines and which also stipulated the compulsory implementation of a track and trace system from 1 January, 2012. According to the public notice issued by the Directorate General of Foreign Trade dated January 10th, 2011, exported pharmaceutical products should have track and trace capability using barcode technology as per GS1 global standards.

Radio Frequency Identiftcation (RFID)

RFID uses the low-end of the electromagnetic spectrum. It is a generic term for technologies that use radio waves to automatically identify people or objects. By comparison these waves coming from radars are less dangerous than the waves coming FM radio. Radio frequency identification, or RFID There are several methods of identification, but the most common is to store a serial number that identifies a person or object, and perhaps other information, on a microchip that is attached to an antenna (the chip and the antenna together are called an RFID transponder or an RFID tag). The antenna enables the chip to transmit the identification information to a reader. The reader converts the radio waves reflected back from the RFID tag into digital information that can then be passed on to computers that can make use of it.

Initially many drug manufacturers were reluctant to tag their product due the additional cost and a lurking suspicion that technology may not be tamper proof. Despite these cutting edge software tools there should be a constant vigil to prevent tampering as counterfieters have worked their way around this secure system and first instances of RFID tampering have surfaced. This has called for additional security features.

Hemalatha and Srinivasa Rao have recently suggested electronic solution using the GSM/code division multiple access technology and internet which will be able to remove the gaps in the supply chain and a bio-metric based solutions at each step.

Analytical Tools

Analytical chemistry plays an important role in the assessment and maintenance of food quality and safety both in industry and for enforcement authorities at the national and international levels. Chemical analysis is a term used in a broader sense to encompass quality and utility of substances. During the past three decades, investigations on drug impurities and contaminants have made phenomenal advances, largely to the development of efficient separation techniques like column, paper, high performance thin layer chromatography (HPTLC), high pressure liquid chromatography (HPLC) and gas chromatography as well as sensitive methods of instrumental analysis such as ultraviolet (UV), infrared (IR), nuclear magnetic (NMR), electron spin resonance (ESR), optical rotatory dispersion (ORD), circular dichroism (CD) and mass spectroscopy. Some of the reported analytical protocols on purity and adulterants in drugs are cited here on a representative basis.40,41 HPTLC is the main screening method used today to decide if a drug product meets label specifications. There are simple, inexpensive, selective and semi-quantitative can be applied to detect steroid drugs in herbal preparations.

Advanced techniques are playing a key role in identifying black sheeps in the pharmaceutical field. NIR measurements combined with chemo-metric data processing are an effect method. An example is Omcilon -A “M” in the paste is tested in the packaging condition and found adulteration containing triamcinolone acetonide where Neomycin as active ingredients. NIR spectra Raman spectroscopy is non- destructive and can be used to asses both authenticity of the packaging as well as the pharmaceutical product. So, this method is particularly suited in the analysis of repackaged and out-of-date products.

X-ray powder diffraction a reliable technique counterfeit control. Analysis of original Viagra tablets (sildenafil) & their imitations. This method is reliable and very fast and correctly predicts the presence or absence of active substance. Nuclear magnetic resonance (NMR) screening analysis involves solvent extraction and quantification using appropriate internal standards. Desorption electro spray-ionization linear ion-trap mass spectrometry for counterfeit anti-malarial tablets. pediatric syrups Halfan.42 Handheld devices are currently gaining more importance and numerous instruments are being developed. Mainly portable devices like the handheld Raman and IR spectrometers are being utilized owing to their non-destructive, rapid, and reliable properties. An increased demand for these is seen not only by the pharma companies, but also by health authorities, regulators, and law enforcement agencies.

There are very few attempts to evaluate the adverse reactions by bioanalytical methods in the patients exposed to fake drugs. This is a key area which may alert the medical profession to a hitherto unrecognized therapeutic risk.

CONCLUSIONS

WHO has dropped the term counterfeit and renamed as falsified to indicate the inferior quality drugs.44 Counterfeit drugs are not only dangerous but also causes economic loss and declining faith of the public in the nation’s health care system. Regulatory authorities should be motivated to promote the implementation of Good Manufacturing, Good Distribution and Good Pharmacy Practice guidelines and quality assurance systems to ensure supply chain integrity in addition they should improve the quality assurance, guidance on the role of quality control laboratories in combating counterfeit drugs. Mass serialization strategies must constantly upgrade. The governments need to promote networking and collaboration among national and international drug regulatory authorities and to develop guidance for pharmacovigilance systems to include reporting and investigating suspected cases of counterfeit by making their foot prints less visible. The entry of on-line dispensation of drugs has compounded the situation. Newer security features must be incorporated and the existing safeguards must be re-looked and implemented mutatis mutandis. Therefore, all the genuine stake holders who are in hot pursuit after these mass killers must follow the adage “if you want to stay where you are, you have to keep running”.

REFERENCES

  1. World Health Organization Depart- ment of Essential Drugs and Other Medicines (1999) Counterfeit drugs: Guidelines for the development of measures to combat counterfeit drugs. Geneva: World Health Organization. Available: http://whqlibdoc.who.int/ hq/1999/WHO_EDMQSM_99.1.pdf.

  2. Institute of Medicine Countering the Problem of Falsified and Substandard Drugs. Institute of Medicine. 2013. * http://www.iom.edu/Reports/2013/ Countering-the-Problem-of-Falsified- and-Substandard-Drugs.aspx

  3. World Health Organization (1998) Report of the International Workshop on Counterfeit Drugs. WHO/DRS/ CFD/98.1. Geneva: World Health Organization.

  4. Cockburn R (1989 April 18) Warnings delayed over fake asthma inhalers. The Times (London) 8: *

  5. Reidenberg MM, Conner BA (2001) Counterfeit and substandard drugs. Clin Pharmacol Ther 69: 189–193. *

  6. Cockburn R, Newton PN, Agyarko EK, Akunyili D, White NJ. The global threat of counterfeit drugs: why industry and governments must communicate the dangers. PLoS Med. 2002;2:e100

  7. Oleson S, Pal A.S.N,Stergachin A and Coupes M ( 2010) ,Pharmacovigilance activites in 55 low and middle income countries, Drug Safety 33 (8),689-70

  8. Chakravarty S, Unnithan S, Ram A (2001 January 29) Deadly doses. India Today 58–61.

  9. “IMPACT: “Counterfeit Drugs: an update on estimates”,1 Nov 2006 Internet: http// www.who.int/impact/ about/en

  10. IMPACT Draft Principles and Elements for national Legislation against Coun- terfeit Medical Products”WHO 2007 http// www.who.int/ entity/impact/en

  11. Cockburn R,Crime, fear and silence: Making public the fake pharmaceutical drug racket [presentation]. First Global Forum on Pharmaceutical Anti- counterfeiting; 2002 September 22–25; Geneva, Switzerland.

  12. Rahul. M and Vasudha W (2015),”ICRIER Working paper on Drug Quality and Safety issues in India” Published in Oct 2015.Accessed on 20-10-2016 via internet

  13. Perrone M Counterfeit drug becom- ing big Business worldwide USA Today.2012; Feb 16

  14. World Health Organization (1998) Report of the International Workshop on Counterfeit Drugs. WHO/DRS/ CFD/98.1. Geneva: World Health Organization.

  15. Dondorp AM, Newton PN, Mayxay M, Van Damme W, Smithuis FM, et al. Fake antimalarials in Southeast Asia are a major impediment to malaria control: Multinational cross-sectional survey on the prevalence of fake anti- malarials. Trop Med Int Health 2004; 9: 1241–1246.

  16. United Nations Composition of Macro Geographical (Continental) Regions, Geographical Sub-Regions, and Selected Economic and Other Groupings. https://unstats.un.org/unsd/methods/ m49/m49regin.htm

  17. Yardley Bogdanich W, Hooker J. From China to Panama, a Trail of Poisoned Medicine. 2007. * http://www.nytimes.com/2007/05/06/world/americas/06poison.html?pagewanted=all

  18. Fackler M. China’s fake drugs kill thousands. San Francisco Examiner. 2002 July 29 *

  19. Yardley J. Infants in Chinese city starve on protein-short formula. New York Times. Sect 2004, May 5: A: 3 (col 1). *

  20. Charatan F. Fake prescription drugs are flooding the United States. BMJ.2001; 322: 1443. *

  21. Rudolf A, India agrees to help Nigeria tackle the import of fake drugs. BMJ.2003; 326: 1234. *

  22. O’Brien KL, Selanikio JD, Hecdivert C, Placide MF, Louis M, et al. Epidemic of pediatric deaths from acute renal failure caused by diethylene glycol poisoning. JAMA.1998; 279: 1175–1180. *

  23. Broussard P. From Nigeria to Niger strange vaccines against meningitis,Le Monde.1996; Oct 26

  24. National Agency for Food and Drug Administration and Control, List of identified fake products [cited June 2002] *

  25. Ahmad K. Antidepressants are sold as antiretrovirals in DR Congo. Lancet.2004; 9410: 363: 713. *

  26. Wolff JC, Thomson LA, Eckers C (2003) Identification of the ‘wrong’ active pharmaceutical ingredient in a counterfeit Halfan drug product using accurate mass electrospray ionisation mass spectrometry, accurate mass tandem mass spectrometry and liquid chromatography/mass spectrometry. Rapid Comm Mass Spectrom.2003; 17: 215–221.

  27. Counterfeit Prescription Pills Containing Fentanyls: A Global Threat” can be accessed at www. DEA.gov.accessed [cited on 5-11-2016]

  28. Patil A ,Alexander O, Andres A, Alicia K and Roy R G (2016) Fentanyl and a Novel Synthetic Opioid U-47700 Masquerading as Street “Norco” in Central California: A Case Report, Ann Emergency Med,(in Press) dx.doi.org/10.1016/j.annemerg- med.2016.06.014

  29. FDA alert on Botox : Botoxwww.fda.gov/Drugs/DrugSafety/ ucm443217.htm FDA released on 16-4-2015.

  30. Drug Supply Chain [email protected] * www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChain-Security/ucm348584.htm

  31. Attaran A, Barry D, Basheer S, Bate R, Benton D, Chauvin J, Garrett L, Kickbusch I, Kohler JC, Midha K, Newton PN,Nishtar S, Orhii P, McKee M. How to achieve international action on falsified and sub-standard medicines. BMJ. 2012;345: e7381. PubMed

  32. Sanjeev S, Debiprasad P, Leveraging RFID and 2D Barcodes : e- Pedigree and Beyond. Tata Consultancy Services Life Science and Health Care Net source 2009.

  33. Tremblay M. Medicines counterfeiting is a complex problem: a review of key challenges across the supply chain. Curr. Drug Safety. 2013;843–55. . PubMed

  34. Mackey TK, Liang BA. Pharmaceutical digital marketing and governance: illicit actors and challenges to global patient safety and public health. Global Health. 2013; 9: 45. PubMed

  35. Peasgood S. The Counterfeiting Conun- drum: How Technology Will Slam the Scam.]. Available from: www.cantech- letter.com/2014/10/counterfeiting

  36. Central Drug Standard Control Organisation Implementation of bar-coding on export consignment of pharmaceuticals and drugs for tracing and tracking purpose. http://cdsco.nic. in/implementation_bar_coding_p_ notice_59(RE-2010).htm

  37. Potdar,M ,Chang, E and Potdar,V. Ap- plications for RFID in pharmaceutical industry, in Mohanty, S.P. and Sahoo, A. (ed), International Conference on Industrial Technology, 2006; Dec 15: 2860-2865. Mumbai, India: IEEE Computer Society Press

  38. Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clin Ther. 2013; 35: 694–700. *

  39. Hemalatha R and Srinivasa Rao A, 2015 Electronic solutions for combating counterfeit drugs, J.Pharm Bio Allied Sci. 2015;7 (3): 230-32 *

  40. Ahuja.S and Alsante KM, Handbook of Isolation and Characterisation of Im- purities in Pharmaceuticals, Academic Press, 2003: 2nd Ed; 47.

  41. Tino R, Martino MM, Gilard V, Balayssac S. 2010 Counterfeit drugs: analytical techniques for their identification. Anal Bioanal Chem.; 398:77- 92 http:// dx.doi.org/10.1007/s00216-010-3748-y.

  42. Meena S and Krishna Reddy Ch., 2011 paper presented at Modern Analytical techniques in Standardization and Bioestimation of Herbal drugs held Sri Ramakrishna Institute of Pharmaceu- tical Sciences Coimbatore (adjudged for best paper award)

  43. Thayer A M. Instrumentation Firms Develop Portable Technology To Detect Counterfeit Drugs. Chem Eng News.,2012; 90:11–15. http://cen.acs. org/magazine/90/09033.html.

  44. Indian News Daily The Hindu 2016, 26th Nov:10

* Find these articles online

Related Stories

Aster Medical Journal
www.theamj.org