The Next Great Serial: Pharmaceutical Security

A patient recently diagnosed with a chronic illness is prescribed a medication. The physician trusts this drug and, as a result, the patient assumes that it will help him/her manage the condition. Though neither party may give much thought to how the medication was produced or how it made its way to the pharmacy, odds are it changed hands several times. How can the patient be sure the medication he/she is going to take is exactly what the doctor ordered?

Every year, substandard, spurious, falsely-labeled, falsified and counterfeit (SSFFC) drugs work their way into the market and, eventually, into the homes and hands of patients treating everything from routine illnesses to chronic conditions. Estimating the size of the counterfeit market is difficult, with numbers ranging from $75 to $200 billion, but these products potentially account for up to 50% of the drugs sold in low-income countries.¹ Most of these products come from outside the United States, with 97% of the counterfeit drugs seized at the US border in 2015 arriving from four countries: China, Hong Kong, India and Singapore.² For trained scientists or researchers within a given pharmaceutical company, spotting these products may be fairly simple due to a variety of factors, including often overlooked misspellings, brand color inconsistencies and, most importantly, lot or batch numbers.³ However, by the time a counterfeit reaches the research lab for investigation, the drug it contains has likely already been sold around the world.

As the global supply chain grows larger and more complex, with multiple outsourcing partners for everything from clinical trials to API production to secondary packaging, these counterfeiting efforts are becoming increasingly sophisticated and difficult to prevent. Medications are often transported between suppliers, partners and customers-according to a recent report from TrackLink Inc., 57% of pharmaceutical company respondents had more than 500 customers, with 26% reporting over 10,000 customers - and every change of hands presents an opportunity for tampering and counterfeit.⁴ Title II of the Drug Quality and Security Act (DQSA) of 2013, the Drug Supply Chain Security Act (DSCSA), aims to address this problem head-on. Now, with the first required wave of serialization under the DSCSA expected to hit manufacturers in November of this year, implementation planning for a compliant global labeling system (GLS) should already be well underway as initial implementation is less than half the battle.

New Standards For Drug Security

In 2013, the World Health Organization (WHO) launched a global surveillance program to try and better understand the movement of SSFFC drugs. When the larger DQSA became a law that same year, it set into motion sweeping changes to improve the industry in the United States. More specifically, the DSCSA detailed plans for establishing an electronic track and trace system for prescription drugs distributed throughout the US. Over the course of a 10-year rollout, these regulations will require the implementation and use of an interoperable system that must function between nearly every single party in the entire pharmaceutical supply chain, including product manufacture, packaging design, logistics, distribution and dispensing.⁵

Over the implementation period, the goal of the DQSA is simple enough: Ease verification of legitimacy, improve detection of counterfeit products and enhance/streamline the recall process.⁵ There is obviously considerable overlap between these three objectives but, simple as they are on paper, the logistics of making this possible is incredibly complex. In part, these complications are due to issues regarding the volume and quality of the drug/label data that may currently be on file with a manufacturer or pharmaceutical company. These data issues often have nothing to do with serialization itself - including old logo information, lingering labels for old parts, obsolete brands, old fonts etc. - but can contribute to significant delays when transitioning to a complaint GLS.⁶ Cleaning this data takes time and requires the involvement of nearly every department, including regulatory, brand management, QA, marketing and legal, as changes to master data must be documented and verified to guarantee integrity.⁶

These housekeeping issues aside, the real challenge for the industry arguably rests in a lack of preparation. Though there is a broad agreement that these requirements are necessary to improve supply chain safety, many pharmaceutical companies and contract development and manufacturing partners (CDMOs) have taken a casual approach to the impending deadlines. However, with serialization becoming compulsory in November, processes should be under development now and must be collaborative throughout the supply chain to ensure smooth implementation and communication between global systems. Fortunately, many pharmaceutical companies are recognizing the value of collaboration and are proactively involving CDMOs in the serialization/ labeling requirements planning and implementation process rather than simply handing down requirements.⁷

As many CDMOs already have advanced track and trace systems that analyze customers and regulations within a detailed serialization infrastructure, they are well positioned to lead this charge. By developing or enhancing serialization/regulatory expertise and working to ensure easy data management throughout the process in advance of customer engagement, manufacturing partners looking to stand out and offer additional value to their customers can take effective leadership roles. Despite the potential advantages, however, many CDMOs remain unprepared, choosing instead to wait for their customers to make the move, but this is a dangerous game to play.⁷ With numerous customers and supply partners coming from and selling to even more numerous markets, waiting will result in a build up of requirements, many of which are likely to be based on disparate systems and potentially counterproductive requirements.⁷

This process becomes even more complicated when the requirements of DSCSA are paired with existing or pending serialization requirements in countries such as Turkey, Brazil, China, and Taiwan and the pending Falsified Medicines Directive (FMD) Safety Features Delegated Regulation, scheduled for early 2019 implementation, in the European Union (EU).⁸

Regardless, even with all systems in place, ensuring the infrastructure can handle this vast amount of data for both storage and distribution on a demanding day-to-day basis is a separate challenge entirely.

From Serialization to Success

Every facet of the DSCSA and other serialization requirements rely on one thing: Data. From case and pallet identification to lot and batch numbers, every identifier involved in the process must be scanned, keyed, stored and/or communicated between systems, companies, countries and regulatory bodies. To ensure proper system functionality and round-the-clock availability, multiple facets of communication have to be established, evaluated and validated. From the regulatory standpoint, the system must be compliant with FDA 21 CFR Part 11, Electronic Records; Electronic Signatures, but data delivery is crucial.⁶

Internally, the system should be owned by the data owners, but administered by IT.⁶ For manufacturers, this implementation requires touch-points throughout the organization, including interactions with work orders (for lot/ batch numbers), product-specific algorithms for expiration dates, and basic brand information.⁶ Under the DSCSA, this information, along with shipping specifics as the goods change hands, form what is called transaction information (TI); as the goods progress, this information becomes part of the larger transactions history (TH) and the transaction statement (TS) that the transferring company must supply when the product moves.⁹ This master data - comprised of as many as 30 unique fields for products, partners and companies - is often challenging to manage on a global scale and risks straining compliance systems and breaking down entirely if varying assumptions are not vetted early on to ensure a mutual understanding/agreement from all parties.⁷ In other words, a reliable and globally available serialization system involves more than putting a barcode on a box.

Currently, two main serialization models have emerged. The “pedigree” model in the US requires authentication at every change in custody but, with no real traceability within an organization (e.g. between distribution centers), tampering is still possible; the “authentication model” in the EU requires item level traceability and national/regional registration, but does not prevent a counterfeit from hitting shelves before the real product.⁹ Neither system is perfect but both are working toward a safer tomorrow. Even the most welldefined network with robust data management (including both storage and request-response), proper scale and the flexibility required to change and evolve with these requirements may not be impervious to malicious intent, but that does not mean serialization and traceability should be dismissed, ignored or viewed as ineffective. As long as counterfeiting remains a threat to patient health and brand reputation, serialization will remain as a frontline defense for patients and pharmaceutical companies alike.

References

1. International Trade Administration. “2016 Top Markets Report Pharmaceuticals.” United States Department of Commerce. 2016. Web.
2. Brennan, Zachary. "USTR: 97% of Counterfeit Drugs in US Shipped From Four Countries.” Regulatory Affairs Professionals Society. 2 May 2016. Web.
3. Moran, Barbera. “Cracking Down on Counterfeit Drugs.” PBS. 20 Aug 2013. Web.
4. “2016 Global Drug Supply, Safety and Traceability Report.” TraceLink Inc. 2016. Web.
5. Food and Drug Administration. “Drug Supply Chain Security Act (DSCSA): Title II of the Drug Quality and Security Act of 2013.” U.S. Department of Health and Human Services, 18 Jan 2017. Web.
6. Heckert, Chris and Drey, Phil. “PRISYM ID - Mind the Gap! Labeling Experts share the 7 Steps of building a Global Labeling System and reducing the Validation effort.” Business Review Webinars. 26 Jan 2017. Web.
7. Shanley, Agney. "Tracking Pharma’s Serialization Efforts.” Pharmaceutical Technology. 4 May 2016. Web.
8. Widengren, Staffan. “Is the Industry Rising to the Challenge of Serialization?.” Contract Pharma. 2 Jun 2016. Web.
9. Chatterjee, Bikash. "Serialization and the Drug Quality & Security Act.” Pharmaceutical Manufacturing. 20 Jan 2015. Web.