Tackling the menace of fake drugs in India

 

- Ganadhish Kamat

Menace of fake drugs is not new in India. Reports of seizure of fake drugs and arrest of culprits keep appearing in the news at periodic intervals from various parts of the country. Last few days I came across many such articles about seizure of fake medicines in various parts of India. Some prominent cases include -

1. 25 crore fake cancer drug case busted by Delhi police where the suspects filled empty vials of international and Indian brands with antifungal drug fluconazole.
2. Case of spurious medicines such as Ultracet, Amaryl, Gluconorm, and Defcort tablets manufactured in two UP cities (Gaziabad & Shamli) cracked again by Delhi police.
3. Case of fake medicines (mostly antibiotics like cephalosporins and amoxycillin-clavulanic acid) manufactured by Meg life science (a fictitious company with headquarter in Sirmaur district of Himachal Pradesh) containing chalk powder and starch valued at Rs 33.3 lakh seized in Telangana by the Drugs Control Administration.
4. Another case busted by Telangana DCA of a drug manufacturing unit in Uttarakhand that was producing and selling counterfeit drugs containing chalk powder with labels of reputed pharmaceutical companies such as Cipla and GlaxoSmithKline.

As per WHO report published in 2017, around 10.5 percent of medicines sold in low and middle-income countries, including India, are substandard and falsified. The falsified medicines may contain no active ingredient, wrong active ingredient or less amount of the active ingredient. They may contain innocuous substances like starch or chalk powder in place of the drug or may even contain substance which are toxic in nature. These medicines are often produced in poor and unhygienic conditions by unqualified personnel, and may contain unknown impurities and contaminants including microbial contamination. As these are designed to appear identical to genuine product, they are difficult to detect. The key findings in the WHO report include -

• Substandard and falsified medical products may cause harm to patients and fail to treat the diseases for which they were intended.
• They lead to loss of confidence in medicines, healthcare providers and health systems.
• They affect every region of the world. However the proportion is higher (around 10%) in low- and middle-income countries.
• Substandard and falsified medical products from all main therapeutic categories have been reported to WHO including medicines, vaccines and in vitro diagnostics.
• Anti-malarial and antibiotics are amongst the most commonly reported substandard and falsified medical products. This may contribute to antimicrobial resistance and drug-resistant infections.
• Both generic and innovator medicines can be falsified, ranging from very expensive products for cancer to very inexpensive products for treatment of pain.
• They can be found in illegal street markets, via unregulated websites through to pharmacies, clinics and hospitals.

This article is focused on counterfeit or falsified drugs as it is a serious concern for the genuine manufacturers as well as the government because of the serious risk it poses to the people and also loss of revenue and disrepute it brings to genuine manufacturers whose medicines are counterfeited. (Please read my article Improving Quality of drugs in India  https://pharmaqsutra.blogspot.com/2021/06/improving-quality-of-drugs-regulatory.html for addressing substandard drugs).

Government regulatory agencies as well as the manufacturers have taken various measures to prevent counterfeiting. 

Measures tried out in the past by the manufacturers -

Various measures taken by the manufacturers include Overt and Covert measures. Given below are various measures tried out by the pharmaceutical industry and their merits and demerits -

Overt measures include -

• Color-shifting inks - Change color when viewed from different angles, making them difficult to duplicate.
• Embossing - Creates a raised design or pattern on the packaging surface, making it harder for counterfeiters to reproduce.
• Holograms - Can provide first line authentication as they are hard to replicate and consumers easily recognize them. Covert features like microtext, scrambled images, and UV-sensitive inks can be second line authentication. 
• Barcodes & QR codes - Can be implemented as overt features that retailers/consumers can scan to verify the product's genuineness.
• Variable data verification using text messaging - Unique code is printed on the pack, user can send that code to number mentioned on the pack as SMS to get confirmation whether the product is genuine or not. 

Merits - All these overt measures makes it difficult for the counterfeiter to copy. These measures help the users to easily ascertain that the product they are using is genuine. SMS verification gives foolproof method of verifying authenticity of the product.  

Demerits- Although difficult, they are not impossible to copy with right tools except for SMS verification. Many counterfeiters have successfully copied all these features making it difficult for the users to distinguish fake product from genuine. Although SMS verification is good method, very few users actually use it because of inability to read English, type lengthy alphanumeric code in text message or shear laziness. The consumers who are regularly using a product may be able to detect missing anti-counterfeit feature but for drugs prescribed for specific one time ailment, it is impossible for the consumers to detect if any feature is missing in the pack.  

Covert methods include - 

• UV luminescence, 
• Fineline/microtext, 
• Micro hidden elements detected with a hand held microscope, 
• Variable data printing - Uses unique numbers or barcodes with specialty inks, including invisible inks.

Merit - These methods make it almost impossible for the counterfeiters to copy or even to detect.

Demerit - As they are covert methods, the users also can not detect them or use them to verify the authenticity of the product. They can only help the manufacturer to protect themselves from prosecution by the regulatory agency incase the medicine is declared as NSQ (Not of Standard Quality).

Measures taken by the Government

Apart from the measures taken by the manufacturers, the government does periodic inspections at the wholesalers and retailers and collects samples for analysis. In 2020-2021, the Indian government analyzed 84,874 drug samples, of which 2,652 were declared substandard (3.12%), and 263 were declared spurious or adulterated (0.31%). Like any other sampling, such sampling can detect substandard or falsified medicines only by chance. The probability of detection will depend on whether the defective lots are uniformly distributed in the country, defect rate, population (number of total lots in distribution) and the sample size (number of lots sampled). There is no information about how many lots of various drug products are in distribution in India at any given point of time and hence it is not possible to determine the percentage of the number of lots analyzed. Considering 10% defect rate and about 1% sampling, probability of detection of substandard or falsified medicine should be around 9.85%. From the data of 84,000 samples it looks like the sampling is less than 1% or the sampling locations may not be truly representative.

In an attempt to deal with counterfeit medicines in India the Government of India amended Rule 96 of Drugs Rules, 1945 with effect from 1st August 2023 vide Gazette notification GSR 823(e) to make it mandatory to print Barcode or QR code on the packs of 300 medicines listed in Schedule H2. The rule requires printing or affixing Bar Code or Quick Response Code on its primary packaging label or, in case of inadequate space in primary package label, on the secondary package label that store data or information legible with software application to facilitate authentication.

The stored data or information is required to include the following particulars, namely: —

1. Unique product identification code.
2. Proper and generic name of the drug.
3. Name and address of the manufacturer.
4. Batch number.
5. Date of manufacturing.
6. Date of expiry; and
7. Manufacturing license number.

The rule is well intended but has numerous shortcomings which makes it ineffective in preventing counterfeiting. The shortcomings are listed below -

• The logic behind selection of only 300 brands is not clear. Probably top selling brands were selected based on the turnover or the market share in the segment. This method of selection could have left out many products with significant sales and market share for example, Crocin (3rd largest Paracetamol brand) is not in the list, while Dolo and Calpol are included. Such exclusion leaves scope for counterfeiters to focus on high selling brands which are not in the list.
• Very few people will have ready access to the schedule H2 which lists the products requiring QR code/ Barcode. Without referring the list there is no way for the consumer or pharmacist know that the product should have such code which should be verified for establishing the authenticity of the product. Even if counterfeiters continue to push fake product in the market without codes, chance of getting identified as fake is very little as very few people will know which product is required to have the code.
• The rule requires inclusion of Unique Product Identification code without specifying that it should be Universal Product code or GTIN number. Thankfully most companies have used GTINs.
• The next requirement is about including Proper and Generic Name of the drug. While generic name is well known term, I could not understand what Proper name means. I looked in the Drug law to find the definition but could not find one although the term Proper name has been used multiple times. Since the statement has "and" between the two terms, they appear to be two different terms.
• Except for the Unique product identification code mentioned in the requirement, rest all the information is part of the standard labeling requirement. Incorporation of Unique product code and capturing all this information additionally in Bar code or QR code cannot prevent counterfeiting. Anyone can easily generate QR code using free software available on internet or copy the QR/Bar codes from the pack and print on their fake products.
• The rule is silent about how authenticity of the product will be verified. Many questions arise in the mind such as -
• Are Pharmacists supposed to check the authenticity of the product before dispensing or the patient is supposed to check it?
• If manufacturer uses Bar code how the verification will be done by the patient?
• Are all the pharmacies. equipped with bar code scanner?
• QR code can be scanned using smart phones, but how many patients have access to smartphones and data?

Possible solutions for curbing counterfeit drugs - 

Option 1 - Use of 2D barcodes with Serialization and Track & Trace system

This has now become norm in all the advanced countries. Serialization ensures that if details are copied from one pack, multiple pack with same code can not be dispensed. Track and trace helps in tracking full history of the product throughout the supply chain. Since the barcodes requires special readers to decode the information, the responsibility of verification will have to be with various partners in the supply chain such Depots, Wholesalers and retail pharmacies. Government will have to create a central repository where the manufacturers can upload the information about the information encoded in the 2D matrix code and the parent child relationship for each lot. Every time the ownership of the goods changes, respective partner in the supply chain will have to carryout transactions to reflect the changes in the data base so as to establish full traceability from manufacturer to retailer.

Option 2 - Use of QR code with serialization

If the government does not want to create the repository as mentioned above, The information about the serialization can be maintained on the manufacturer's server or on the cloud and the QR code on the pack can lead the user to the requisite path to access the information. For this system to work following checks will have to be built -

1. The QR code should be printed on each saleable pack of the medicines.
2. The QR code should be unique for each pack ID (serialization) and the background information should link it to other information such as GTIN & Unique product code etc.
3. There should be mechanism for detecting multiple scans of the code and such event should alert the person scanning the product and also send alert to company with the  location.
4. Verification of the code by Pharmacist should be made mandatory before dispensing.
5. Consumer awareness should be created through media campaigns so more and more people verify authenticity of medicines they take.

This system will be able to detect counterfeit but will not show the history of the ownership during supply chain.

Following are the challenges in implementing these options - 

1. Printing of 2D matrix code or unique QR code on individual unit will slow down the line output.
2. Implementation will require significant investment and drive up the cost. (Considering the risk to patients due to counterfeit medicines, this cost increase is justifiable)
3. Option 1 will require collation and establishing parent child relationship (ePedigree) from primary pack to final shipper pack. This will increase the complexity of the process.
4. Printing of such codes on Strip and blister packs could be difficult due to -
1. The blister foil is already crowded with lot of information mandated by law.
2. Knurling on the foils may interfere in reading of the codes.

        The printing and readability problems can be addressed by taking following measures -

1. Creating specific space in the artwork to print the code such that it always appears on the portion without knurling and using print registration technology to print the code in designated space.
2. Simplifying the labeling rule to remove some text such as schedule warning etc which can be embedded in the code or controlled from background. (As such these warnings are rarely complied with.)  

Conclusion -

The problem of counterfeit or falsified medicines in India is very serious as it poses significant risk to the patients. Because of the size of the country, large number of manufacturers, wholesalers, retailers foolproof solution to this problem is not easy. However if all the stakeholders that is manufacturers, wholesalers, retailers, the government and the healthcare givers come together, no problem is difficult to address. The solutions proposed by me will require significant investments and may drive up the cost however considering the risk the counterfeit medicines can pose to patients, it is worth. I suggest the government regulatory agency should form a forum involving various stakeholders and also some IT experts to deliberate on this issue. This forum may come out with more cost effective and better solution. Government may also consider giving financial aid to small manufacturers for implementing anti counterfeit measures.