Distribution Channel Security in Ensuring Drug Supply and Safety

• That’s Nice

Prior to the passing of the Drug Supply Chain Security Act (DSCSA), drug manufacturers were forced to comply with a patchwork quilt of drug “pedigree” laws that varied from state to state. In 2013, the Healthcare Distribution Alliance (HDA) noted that “18 states had adopted final rules regarding distributor licensing and pedigree requirements, three states had enacted legislation but rules were pending, eight states had enacted legislation, one state had proposed pedigree legislation, and 20 states had no legislation or regulations on the topic.”¹ Regardless, the industry urged action because nobody wanted to entertain the possibility of having to comply with 50 different state laws.

Seeking relief, industry groups called for unified, federal-level regulation, which became law in 2013. According to FDA, the DSCSA “outlines critical steps to build an electronic, interoperable system to identify and trace certain prescription drugs as they are distributed in the United States.” ² The FDA said the new system “will enable verification of the legitimacy of the drug product identifier down to the package level; enhance detection and notification of illegitimate products in the drug supply chain; and facilitate more efficient recalls of drug products.”

For the most part, the world’s pharmaceutical regulators have also joined the effort and are reconciling their regulations to improve the ability of the global pharmaceutical industry to create a robust, transparent supply chain that ensures the drug supply is reliable, safe and secure from counterfeiters, or any others looking to profit by exploiting gaps.

Initial FDA guidance promised “ten years after enactment, the system will facilitate the exchange of information at the individual package level about where a drug has been in the supply chain.” For drug producers that means by 2023, every vial, bottle, blister pack, combination inhaler and topical tube must be marked and coded accordingly so it can be tracked through every exchange or transaction along the supply chain and its journey to the consumer.

Serialization Is Coming ... Soon!

The FDA timeline shows the next major deadline facing drug manufacturers is the requirement to serialize all products by November 27, 2017. While the feasibility of this is debatable, there are few real technological barriers to implementing an adequate solution, whether locally or system-wide, across dispersed operations and facilties. In a June 2016 Contract Pharma article — “Is the Industry Rising to the Challenge of Serialization?” — Staffan Widengren of CDMO Recipharm noted that global pharmaceutical companies selling products at a high risk of being counterfeited have implemented a traceable, unique ID on each product pack for years.³ “In all countries, the unique information required for a pack should be printed both in human-readable format and in some form of data matrix or barcode,” said Widengren. “However, while most countries require a GS1 standard solution they can differ from country to country, such as is the case with the linear barcode required in China and the 2D matrix required in Turkey.”

Pharmaceutical companies need to be well on their way towards implementing a standard solution that includes serialization features, such as thermal printing, 2D-matrix code verification, human-readable text, brand-neutral tamper-evident labeling and the ability to create a standard file format for reporting and storing serial numbers.

There is evidence this advice is being adopted. Nice Insight’s 2016 Pharmaceutical Equipment Survey found that 49% of those interested in purchasing secondary packaging equipment were seeking to specify labels and printers. New serialization equipment and tamper-evident solutions were among leading technologies being considered for purchase as well, garnering 34% and 33%, respectively.⁴

According to the Rockwell Automation whitepaper, “Serialization: An Implementation Guide,” a serialization solution should be holistic relative to operations, and enable pharmaceutical manufacturers to comply with current regulations into the future.⁵ Rockwell’s Global Serialization Lead, Joe Whyte, said the company’s solution is built on industry standards (IEC 61131, ANSI/ISA-88, ANSI/ISA-95) and uses open network and communication protocols, as well as commercial off-the-shelf technologies. An effective solution must provide the required data links and web services to connect serialization data layers to the ERP layer and the supply chain cloud, said Whyte. Rockwell Automation identified five layers based on the enterprise and control system levels of the ISA-95 data model:

• Level 0: Printers & vision systems: serialization numbers printed & inspected
• Level 1: Unit-level controller & human-machine- interface stations: serialization & aggregation data management per station
• Level 2: Line controller: serialization & aggregation data management for the entire packaging line
• Level 3: Site server: serialization & aggregation data management for the entire facility
• Level 4: Business planning & logistics: serialization interface to enterprise resource planning & manu- facturing execution system
• Level 5: Supply chain track & trace serialization data event repository

To be effective, a serialization solution requires data input from all layers. Whyte’s paper explained standards such as GS1 for the supply chain and EtherNet/IP for manufacturing, combined with offthe-shelf programmable-logic controllers for data connectivity/data management with packaging machines, printers and marking devices and vision systems, will achieve the integration required to drive better business outcomes.

Percentage of Respondents that Indicated Interest in Secondary Packaging

Providing a high-tech electronic pedigree to all drug products, even on a unit level, can be more than just another expensive regulatory cross to bear. Serialized products allow for a much faster and more effective response to quality/safety excursions and the ability to efficiently remove products from the market well past the point of sale. In fact, industry manufacturingcentric information and control technology suppliers like Rockwell and Emerson maintain that the data generated from tracking and tracing drugs will bring tremendous opportunities for “big” data analysis and allow for much more effective decision-making related to distribution and other metrics that improve strategic performance as well as business outcomes.

Track and trace is poised to completely change the way drugs are manufactured, distributed and sold. These systems will increase transparency and, therefore, accountability of all involved in the supply chain. Track and trace technologies will become an even more critical component as drug developers respond to society’s right to a safe, reliable drug supply.

Innovation Ambition: to Be Continued

To secure an innovative future, drug developers and manufacturers are marshaling their resources and applying technology in ways that might have been unrecognizable 40 years ago. For example, drug discovery pathways are increasingly reliant on automated technology and equipment to screen millions of compounds. Investment here has proven to deliver substantial returns, as lab automation has the ability to accelerate large-scale sample analysis while maintaining the high degree of reproducibility and accuracy demanded by regulators.

Innovation in drug discovery will remain dependent on technological advances like Eve, which combines the drug screening pipeline’s three elements into a systematic, integrated process. Eve and similar technologies will be in high demand to introduce new efficiencies into compound screening, speeding hit validation and enhancing data integrity. Similarly, CADD methods will play an important role in drug innovation supporting structural-based and ligand-based de novo drug design using construction algorithms.

As knowledge of therapeutic value and market potential of compounds or molecules occurs in clinical trials, innovation is paramount in this sector as well. Trial recruitment managers are quickly learning to leverage social media. General access to the internet by consumers allows eParticipants to be active online during trial participation, which allows for a controlled and monitored trial, ultimately producing the data required to prove value.

Future innovations will also be extremely reliant on an elastic supply chain, ready to contract during market adversity or stretch to meet growth in current demand. Here the integration of flexible manufacturing capacity with the latest automation — PAT — and increasingly continuous processing techniques will have an important and lasting impact on the industry’s ability to respond to both consumers’ and regulators’ demands.

Society is demanding so much from the pharmaceutical industry in general, with the pressure to deliver being felt across all sectors of the life sciences and healthcare supply chain.

References

1. “Pharmaceutical Traceability.” Healthcare Distribution Alliance. Web.
2. “DSCSA Standards for the Interoperable Exchange of Information for Tracing of Certain Human, Finished, Prescription Drugs: How to Exchange Product Tracing Information.” Rpt. in EAS Consulting Group. Silver Spring: U.S. Food and Drug Administration. Web.
3. Widengren, Staffan. “Is the Industry Rising to the Challenge of Serialization?” Contract Pharma . 2 June 2016. Web.
4. The 2016 Nice Insight Pharmaceutical Equipment Survey.
5. Whyte, Joe. “Serialization: An implementation guide.” Rockwell Automation. Nov. 2015. Web.