Current Status and Challenges of Serialization in Pharma Industry

Introduction

Like any other commodity, medicines are also vulnerable to the falsification and counterfeit by the peoples, groups involved in it. In all aspect medicines are lifesaving and cannot be compared with other commodities, however the counterfeiters do not have any such distinction. Data of 2019 OECD/EUIPO report shows that between 2014 and 2016 custom seized items mentioned medicines as 10th most counterfeit product. In 2016, this illegal business of counterfeit pharmaceuticals amounted to USD 4.4 billion. This is 0.84% of total worldwide imports of pharmaceutical products. This figure rises to 10% globally, although in some developing countries it is as high as 50%. The World Health Organization (WHO) estimate, these substandard and unsafe medicines accounts for over 700,000 deaths annually and 50% of medicines available via the internet are counterfeit [1, 2, 3].

This challenge of falsified, counterfeit medicines is not recent and pharmaceutical industry and regulators are fighting the challenge since long. Various changes in packaging were made to ensure that the medicine reaches to intended population safe without tampering or adulterating. Tamper evident packaging is helpful to avoid such incidences but only to some extent. Due to advances in the packaging easy availability of ‘me too’ or ‘look alike’ printed packaging component circumvents the earlier efforts to counter falsification. Hence the need of better technological solutions which are difficult to recreate was obvious. Now a days, drug distribution chains are becoming more complex due to multiple exports and ever-expanding generic industry competing to provide affordable medicines, especially to developed world. Therefore tackling the issue of counterfeit medicines is of paramount importance. Serialization concept was emerged which utilizes a unique random serial number to be applied on each unit of pharmaceutical product during manufacturing. This unique number can be traced back to the original source of supply [4]. Efforts in this regard were already initiated more than a decade ago where EU has initiated the serialization in 2008 (France with CIP code). The idea was to provide a digital code (2d-matrix) which will be an alphanumeric combination unique to each packaging unit describing limited product details e.g. Batch Number and expiry date. Initially it was applied only to saleable unit of packaging. However, this method was not full proof to take care of the other product related information from security perspective. With the help of GS1, many countries started adopting new format which comes with unique combination specifying each pack of the product. GS1 is an international, nonprofit organization that publishes a system of supply chain standards [5]. This has helped to regulate the practice by issuing prefix and suffix to the product code. Prefix letter is a packing level indicator digit to represent primary, secondary and tertiary packing. Suffix is a checksum character which is a last digit in the barcode used for verification. Use of GS1 in serialization was an important milestone and it helped to initiate the proper mechanism for various countries from around year 2010 onwards. Currently more than 2 million companies operating in 145 countries, designed to work together in concert. The overall serialization information available on product includes the related information like product or drug description, stock-keeping unit (SKU), lot or batch number, expiration date, date of production, along with line and plant in which it was manufactured along with GTIN (Global Trade Identification Number), is a part of serialization code [6]. Template used for some of the countries and steps followed for serializations are shown in Figure 1 and Figure 2 respectively.

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Serialization Efforts Across Globe

While many countries of the world doing good progress to control the counterfeit medicine, the other part of the world is left behind especially countries with poor healthcare system. African countries mostly depend on the institutional supplies to fulfill their medicinal requirements. Various factors like poor infrastructure, economic disparity and fragmented legal framework contribute to the prevalence of counterfeit medicines. Such substandard medicines not only result in the low efficacy but also potentially unsafe and can have fatal consequences. Data reported to WHO between 2013 and 2017 shows 42% fake drugs only from African region. In the absence of accurate data from the region, estimate shows fake drugs for pneumonia and malaria accounts for a death toll of around 250,000 children every year. On the other hand, for counterfeiter’s it may be a lucrative industry worth roughly $200bn a year. The menace is not only limited to any specific diseases like malaria but includes many others. In 2019, WHO alerted fake meningitis vaccines in Nigeria, fake hypertension drugs in Cameroon and falsified versions of the antibiotic Augmentin which were found in Uganda and Kenya [7].

An estimated 1 in 10 medical products in low- and middle-income countries are substandard or falsified. This is a major concern for countries like India and China which are major exporter of medicines. 53% of total value of seized counterfeit pharmaceuticals worldwide in 2016 belonged to India and 30% to China. To control this, Indian government has DGFT (Directorate General of Foreign Trade) guidelines in place and is under implementation. Similarly China has recently updated their guideline published by NMPA (National Medical Products Administration) [8]. Majority of the drugs from these countries are exported to mainly US and Europe. Regulatory agencies of the respective countries like USFDA and EMA have adopted certain rules and regulations to counter the falsified and counterfeit practices. While US has enacted Drug Supply Chain Security Act (DSCSA) in 2013 which outlines steps to build an electronic, interoperable system to identify and trace certain prescription drugs as they are distributed in the United States [9]. Also EU in 2011 strengthened the protection of patients and consumers by adopting a new Directive on falsified medicines for human use. Various related aspects like supply chain and good distribution practice were updated in the guidelines [10]. Serialization progress across various countries at different stages with respective timelines is depicted in the Figure 3.

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Advantages of Serialization

Serialization offers various benefits to both patient and pharmaceutical manufacturers as listed below:

Challenges Faced by Industry

While serialization is being taken up by various countries, there are many challenges need to be overcome, some of these are as below -

Conclusion

While serialization had long been pursued by industry and regulators across the nations, with the right intend to control the falsification of the lifesaving drugs, the progress has been bumpy. At least the major exporting countries like India and China have come up with their versions of serialization regulations through DGFT and NMPA respectively. Similarly, next phase of aggregation is also voluntarily taken up by many exporting manufacturers well before actual implementation target by regulatory agencies. Such controls need to be adopted at swift speed across the globe avoiding the hiccups in the process due to individual approach to the universal problem of counterfeit medicines. This marks the need for overall, unified approach involving all stakeholders and led by international common regulatory agency. This will give an extra edge in the battle to provide safe and effective medicine to the patient without being compromised in the process of worldwide distribution.