COUNTERFEIT MEDICINES: A REAL THREAT TO THE SOCIETY

COUNTERFEIT MEDICINES: A REAL THREAT TO THE SOCIETY

Sonal Sekhar*¹, C. Adheena Mary ², Rijo Mary George ² and Shalini Sasidharan ²

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University ¹, Manipal -576104, Karnataka, India

Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham University ², AIMS Health Sciences Camapus, Kochi-682041, Kerala, India

ABSTRACT

Counterfeit drug is a pharmaceutical product which is produced and sold with the intent to deceptively represent its origin, authenticity or effectiveness. It may contain inappropriate quantities of active ingredients, may be improperly processed within the body or may contain ingredients that are not on the label, and is often sold with inaccurate, incorrect, or fake packaging and labeling. It is estimated that more than 10% of drugs worldwide are counterfeit, and in some countries more than 50% of the drug supply is counterfeit. In 2003, the WHO estimates that the annual earnings of counterfeit drugs were over US$32 billion. These are inadequate measures to determine the correct prevalence of the problem. There are several technologies that may prove helpful in combating the counterfeit drug problem include radio frequency identification which uses electronic devices to track and identify pharmaceutical items and electronic pedigree  (e-Pedigree) system to track drugs throughout its distribution channel.

RFID

INTRODUCTION: History of counterfeiting stands long back. It was scaring news when it came in the news papers about the mass poisoning that caused the death of more than 14 children in France. It was a result of counterfeiting. The sweet tasting costly base of syrup, glycerol, the safe one, was replaced by less costly diethylene glycol. A  wide  range  of  cases  has  been  reported  for  counterfeit  medications  through  out  the  years.

In  2006,  lack  of  sufficient  active  ingredient  has  detected  in  the  legal  supply  of   Lipitor,  a  drug  use  for  lowering  cholesterol,  at  United  Kingdom.  Xenical,  a  drug  for  obesity   has  sold  in  United  States  via  internet  sites  operated  outside  USA  with  no  active  ingredients  in  2007.

In  2008,  Viagra  and  Cialis  for erectile  dysfunction  has  smuggled  into Thailand  from  an  unknown  source  from  an  unknown  country.  One  of  the  most  severe  one  was  in  2009,  in  China  an  antidiabetic  traditional  medicine  used  for  lowering  the  blood sugar,  with  six  times  the  normal  dose  of  glibenclamide  leads  to  the  death  of  2  people  and  the  hospitalization  of   9.

If  not  regulated  properly  counterfeit  medications  can  cause  serious  harm  to  the  humanity.  Apart  from  that  it  may  lead  to  the down regulation  of  the  distribution  of  drugs  and  can  adversely  affect  the  worth  of  entire  healthcare  system ^1-3.

On  the  26^th  March  2010,  FIP  was  invited  to  moderate  a WHO  Open  Forum  on  the  International  Medical  Products  Anti-Counterfeiting  Taskforce (IMPACT) ²  which  brought  together  48  WHO  Member  States  and  28  international  development  agencies,  NGOs  and  private  sector  organizations  from  around  the  world  to     share  information  on   the  work  of  IMPACT,  and  review  the  feed-back  from  WHO Member  States  on  the  use  of  the   term  "counterfeit medicines"  and/or  equivalent  in  national  legislation.

This  meeting  presented  a detailed  overview  about  the works  of  IMPACT  since  2006.  In  this  meeting, it  is  recognized  that  the  imminent  rapid  growth  of  counterfeit  medicines  will  only  be  stopped  through  global  cooperation  among  governments,  international  agencies,  legislators,  law  enforcement  units,  health care professions,  patient groups   and  industry  representatives  from  all  countries  of  the  world.  It is  also  with  the  social  imperative  that  pharmacists  as  health  care  professions  need  to  take in  the  way  we  fight  against  counterfeit  medical  products  in  our  daily  practice.  The    misnomer  of  "it  will  never  happen  to  me"  is  a  dangerous  one. FIP  continues  to  work  very  closely  with  the  WHO  Counterfeit  Medicines  Programme  and  IMPACT ^{4, 5}.

The  World  Health  Professions  Alliance (WHPA)  today  urged  further  action  against  counterfeiting  of  medical  products.  Speaking  for  more  than  26  million  health  professionals  in  more  than  130  countries,  WHPA  is  extremely concerned  that  the  infiltration  and  sale  of  counterfeit  medical  products  in  the  legitimate supply  chain  can  cause  death  and  misery  to  tens  of  thousands  of  patients  around  the world.

The  WHPA  announced  that  it  is  stepping  up  its  commitment  to  this  issue,  with  the  launch  of  the  ‘Be  Aware,  Take  Action'  campaign  against  counterfeiting  of  medicinal  products.  This  campaign  focuses  on  public  health  and  patient  safety  issues  and  enhances the  role  of  health  professionals  and  associations.  Through  regional  workshops  dedicated  to  anti-counterfeiting,  the  WHPA  aims  to  strengthen  advocacy  for  appropriate  investments in  the  education  and  capacity  of  health  professionals  to  detect,  report  and  prevent         counterfeit  medical  products.  In  addition,  the  WHPA  Be  Aware,  Take  Action  toolkit  and   other  campaign  resources  are  provided  for  health  professionals,  healthcare  advocates  and  patients.   The  harm  caused  by  counterfeit  medicines  is  greatest  in  those  communities  least  able  to  afford  effective  regulatory  systems  and  quality  health  care.  WHPA  recognizes  also  that  for  health  professionals  to  be  able  to  effectively  play  their  role,  national authorities  must  set  up  effective  systems  for  the  collection  of  information  and  increase national  drug  and  medical  device  regulatory  capacity  to  support  the  enforcement  of  pharmaceutical  guidelines ^{6, 7}.

At  December  2010,  the  Madras  High  Court  upheld  the  detention  of  13  people  allegedly  involved  in  selling  spurious  drugs,  some  fake  and  some expired,  under  the  Goondas  Act. The  Goondas  Act  allows  suspected  spurious  drug  sellers  to  be  detained  while  being  prosecuted,  rather  than  released  on  bail,  to  deter  them  for  continued  selling  until  their  trial  date.  The  detainees  are  accused  of  collecting  expired  medicine  and  returning  them  to  the  pharmaceutical  retail  market  as  valid  drugs  by  altering  the  batch  numbers  and  expiration  dates ⁸.

The  Cambodian  Ministry  of   Health  reported  a  92%  decrease in  the number  of  illegal  pharmacies  nationwide  and  a  71%  fewer  unlicensed  health  clinics  over  the  past  year,  on  December  22, 2010. The  European  Union  ambassadors  approved  an agreement  to  regulate  medicines  sold  over  the  internet. The  agreement  approved  by  the  EU  ambassadors  will  create  regulation  intended  to  protect  legal  suppliers  of  medicine.

New  rules  will  require  internet  pharmacies  to  register  with  authorities  in their  home  country  and  ensure  that  the  products  sold  are  licensed  for  sale  in  the  country  of purchase   reports, the European Voice, on December 24, 2010. A  recent  EC  report  claimed  that  India  was  the  largest  source  of  the  2.7  million  counterfeit  drugs  seized  by  its  custom  department  in  2006 ⁹.

Mobile  Product  Authentication (MPA) (Fig. 1)  is  a  technology  developed  by  Sproxil  which  is a  preventive  measure  for  consumers  to  identify  whether  the  drug  is  counterfeit  or  not. By  this  technology, using  a  cell  phone,  customers  can  text message  an  item-unique  code  and  get  an  instant  response  confirming  the  brand's genuineness. We  can  then  send  highly  relevant  targeted  offers  to  the  consumers  right  at  the  point  of  sale. This is the world-first innovation by Sproxil. The  scratch-off  technology  is  proven  its  trend  in  the  emerging  markets. The  mobile  operator  market  chose  scratch-offs  instead  of  holograms  for  popular  pay-as-you-go  subscription  schemes ^{10, 11}.   

FIG. 1: MOBILE PRODUCT AUTHENTICATION TECHNOLOGY

With  Cascading  Authentication,  we  can  make  sure,  only  trusted  agents  handle  the products ,  while  each  one  of  the  supply  chain  agents  can  individually  verify  the  authenticity  of   products  as  they  disperse  through  the  distribution  network (Fig. 2).

FIG. 2: TRACKING DRUG DISTRIBUTION THROUGH MOBILE PRODUCT AUTHENTICATION

The use of counterfeit medicine is increasing day by day. So we should be aware of the possible harm these fake ones may cause and should take adequate precautions to get rid of them. A counterfeit medication or a counterfeit drug is a medication or pharmaceutical product which is produced and sold with the intent to deceptively represent its origin, authenticity or effectiveness. WHO defines counterfeit medicine as a medicine which is deliberately and fraudulently mislabeled with respect to identity and/or source.

Now a day these counterfeit medicines are entering into the market through some channels and creates some serious life threatening problems. Counterfeit medicines have been recognized by the WHO as a threat to public health since 1985, but the manufacture of the product appears to be increasing. They mimic the genuine drug in such a way that sometimes they may not be caught by the regulatory authorities also. Counterfeit medicines are found more in the drug markets of developing countries (10-50%) than in developed countries (1%) due to various reasons like poor regulatory control on drug market and economy of the population. That is in developing countries expensive drugs are available at a cheaper rate through black market. So public awareness about the consequences of consuming counterfeit medicine is the main factor in controlling the spread of these medicines in the market ^{12, 13}.

Types of counterfeit drugs and their consequences: Illegal drugs are often produced and sold with the intent to deceptively represent their origin, authenticity or effectiveness. The nature of these fraudulent drugs ranges from those containing no active ingredient (eg. when a bag of powdered lactose claimed to be cocaine), with insufficient active ingredient or with some diluents (e.g., Baking soda or lactose) or sometimes with a wrong active ingredient (e.g., when methamphetamine is sold as cocaine) or with a fake packaging ^{14, 15}. The various types of counterfeit drugs are

• Counterfeit drugs containing same dose of the active ingredient
• Mislabeled medications
• Counterfeit drugs containing an incorrect dose of the active ingredient
• Counterfeit drugs which do not contain the active ingredient
• Counterfeit drugs containing a potentially harmful substance
• Counterfeit drugs containing an unlisted active ingredient
• Genuine medicines marketed for incorrect or recreational use

Counterfeit drugs containing same dose of the active ingredient: They are close replicas of the genuine drug with the same dose of the active ingredient. They constitute only 5% of the fraudulent medicines. The health risk associated with this type of medicines is very less compared to other types which are different medicines or different dose of same medicine than the originals they claim to replicate. Even though they contain the same active ingredient as the originals they are of poor quality as it is not manufactured according to the rules of good manufacturing practice approved worldwide. They carry the health risk associated with manufacturing process. Since the manufacturing of counterfeit medicines is illegal the base line ingredients cannot be purchased from reliable suppliers and the source of active ingredient remains unknown.

The dissolution profile of the drug may vary, so the amount of drug available for absorption by the body may vary and finally the efficiency of the drug is less. The inactive ingredients in this type of drugs are not documented and they can be detected only by laboratory analysis. Sometimes these inactive ingredients can cause health risks. For example a study of malaria medications sold on the black market in three African countries reported that >50% of the medicines in circulation were counterfeit with the same dose of active ingredient. However the active ingredient was from a different source and had a different dissolution profile to the original ¹⁶.

Mislabeled medications: Mislabeled medicines are those which are sold in the package of another brand medicine. The label of counterfeit medicine also contains batch number, manufacturing number and other details which are fraudulent. It may or may not contain the same active or inactive ingredients as the original. These mislabeled medicines are often supplied through e-pharmacies in developed countries. For example in 2006 the US government issued a public warning against buying brand name medicines off the internet. This was after the case of prescription weight loss medication Xenical (orlistat).Upon laboratory investigation; counterfeit medications labeled Xenical were not found to contain orlistat. Some of the counterfeit medicines contain sibutramine another weight loss medication with different action in the body as the active ingredient. They were taken in different doses compared to orlistat. Some contained talcum powder and chalk instead of active ingredient. The packaging appeared authentic but the batch number; (a genuine one) did not matched with the expiry date for the batch by the manufacturer ¹⁷.

Counterfeit drugs containing an incorrect dose of the active ingredient: Sometimes counterfeit medicines contain active ingredient in incorrect dose (either too high or too low).This can lead to many health related problems. In case of fatal diseases it can lead to the death of patient due to ineffective dose. In case of antibiotics low dose therapy may not kill the bacteria but may lead to the emergence of resistant strains. In 2000 in Cambodia counterfeit malaria tablets caused death of 30 people ¹⁸.

Counterfeit drugs which do not contain the active ingredient: Sometimes Drugs are marketed without any active ingredients. For example instead of cocaine some powdered lactose is marketed. More than 60% of the counterfeit drugs identified by WHO in 2000 was without any active ingredient. Another example is of sibutramine instead of orlistat in Xenical ¹⁹.

Counterfeit drugs containing a potentially harmful substance: Sometimes harmful substance may replace the active ingredient in the genuine drug. This can lead to many health problems. For example, in the case of Xenical the genuine drug orlistat is replaced by sibutramine which is a pharmacologically active drug used to reduce weight but by different mechanism. The dosing schedule of orlistat and sibutramine also varies that is orlistat is needed once daily and sibutramine thrice daily. Also the interactions and contraindication as may vary. Over hundred children died in Nigeria in 1993 due to the harmful substance in the counterfeit cough syrup. Similar cases were reported in China and India in 1990-2007 and in panama due to ethylene glycol in cough syrup instead of glycerol. In 2002 more than 190,000 deaths occurred due to poly ethylene glycol contamination in paracetamol syrup ²⁰.

Counterfeit drugs containing an unlisted active ingredient: This type of counterfeiting is commonly found in recreational drugs which may contain some herbal ingredients. Even though they are natural they may exhibit some pharmacological actions in the body. So it should be taken into consideration and use of such type of drugs should be discussed with the health care provider.

All types of drugs are prone to counterfeiting or fraudulent manufacturing. In developing countries both expensive and inexpensive drugs are available in the black market. According to a report of WHO about one third of counterfeit drugs identified were counterfeit antibiotics. In developed countries counterfeit drugs are often treatments for lifestyle diseases like obesity, erectile dysfunction etc. All these counterfeit drugs are associated with some health risks, if not seeking proper medical advice or treatment.

For example in case of infectious disease the patient condition may get worsen even though he is taking the fraudulent drug .Similarly in chronic conditions like erectile dysfunction, it may be an indicator of some other conditions like diabetes or atherosclerosis which may lost an opportunity to get diagnosed by the use of these drugs from black market ²¹.

Counterfeit drugs can be purchased from many outlets and in rare cases they get into the legal supply chain. In United Kingdom recently counterfeit drugs for treating high blood cholesterol and bipolar disorder were identified in the legal supply chain. In developing countries they are available in black market and in the unregulated informal sector. In developed countries internet has been exploited by the fraudulent drug manufactures to create market for their product.

Some measures to prevent the use of Counterfeit medicines ¹⁷:

At International level: National and international authorities and pharmaceutical manufactures have put in place measures to curb the spread of counterfeit medicines into the market ⁸. Usually the counterfeiters work in borders, i.e. they manufacture the drug in a developing country where regulatory issues are minimum and then transport to a developed country to increase the  legitimacy of their appearance on the market and then to the market of  either developed or developing country. In order to control the manufacturing of counterfeit drugs in countries with poor regulatory controls international authorities like WHO had established International Medical Products Anti counterfeiting Taskforce in 2006.

At National level: Most developing countries have strict regulatory controls in place to secure their markets from counterfeit drugs. In Australia, the Therapeutic Goods Administration prohibits the manufacture sale, import or exports of counterfeit drugs and has assessment mechanisms like customs inspection to identify those who break the law. It is difficult for the national government to implement legal measures if the counterfeiting or website is based in another country. Government bodies may use public education as a strategy to prevent illegal drugs from entering the market. They may provide public warning against purchase of drugs from internet and notify the public when fake drugs are known to be on the market. Government may also announce product recalls if drugs are suspected or known to be counterfeit. Government may provide advice to the pharmacist and other health care professionals to identify the counterfeit drugs on their shelves and the patients who have consumed it ²².

At the level of pharmaceutical manufactures: Genuine drug manufactures now responded to counterfeiters by introducing physical-chemical indicators. Physical chemical indicators are pharmacologically inactive substances mixed in low concentration with the drug and they can be identified only by specific laboratory tests⁹.Using tracking technology we can track the source of any fake drug in the supply chain. Identifying the methods used by counterfeiters in mimicking the genuine drug is an important step to stop their marketing. But as it is an organized crime the counterfeiters are using such technologies which make it difficult to identify. They can change the method more rapidly that is when one method is detected they can employ another one as yet unidentified to prevent their product being unidentified.

CONCLUSION: Counterfeit medicines represent an enormous public health challenge. It poses a public health risk because their content can be dangerous or they can lack active ingredients. Their use can result in treatment failure and contribute to increased resistance in the case of antimalarials that contain insufficient active ingredient or even death. Unlike substandard medicines where there are problems with the manufacturing process by a known manufacturer, counterfeit medicines are made by people with the intent to mislead. The extreme difficulty in tracing the manufacturing and distribution channels of counterfeit medicines makes their circulation on markets difficult to stop. To fight counterfeit medicines effectively, a range of stakeholders is needed, not just health professionals.

ACKNOWLEDGEMENTS: We deeply express our profound and sincere gratitude to Manipal University, Manipal; all the staff of Deptartment of Pharmacy Practice, Manipal College of Pharmaceutical Sciences; and Dr. K. G. Revikumar, Principal, Amrita School of Pharmacy, for the valuable guidance and encouragement

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