Ashley Roberts

This year, Federal Drug Supply Chain Security Act (DSCSA) drug traceability requirements become mandatory. The new DSCSA requirements will be implemented in three phases over a 10-year period. Phase one, which started on Jan. 1, 2015 and will be in effect until December 2022, requires the exchange of “chain-of-ownership data.” Beginning in November 2017, the second phase will require that “pharmaceutical products be marked with a national drug code, serial number, lot number, and expiration date in machine-readable and human-readable form.” The final phase of the DSCSA requirements, starting in 2023, will require trading partners to share all data necessary to track serialized items to the product’s origin (1).

	In 2015, members of the pharmaceutical industry are implementing new equipment and systems and planning for future DSCSA deadlines. 

 spoke with Jean-Pierre Allard, global serialization program manager at Optel Vision; Chris Flori, vice-president of business innovation at ASD Healthcare, a part of AmerisourceBergen; and Tim Kearns, pharmaceutical and medical devices manager at Videojet, about the most important aspects of the 2015 and 2017 deadlines, what to consider when planning for the 2023 deadline, and what can be expected when using a cloud-based tracking system to facilitate serialization.

From your perspective, what are the most important aspects to consider when implementing equipment and systems for compliance with DSCSA 2015 and 2017 deadlines?

 One of the most important aspects to consider is to maintain maximum overall equipment effectiveness. Adding inspection and tracking equipment on a line can drop the line efficiency and affect the company profits and throughput. Floor space required by new equipment is also difficult to manage on the production line. Solution providers are challenged to offer small systems to fit on customers’ lines. Another aspect to consider when implementing printing equipment is the fact that they are subject to vibrations from adjacent machines. For example, instead of embossing the lot and expiration on cartons, one needs to add a data matrix, which can’t be embossed. Thus, the carton serialization requires the integration of printing and inspection systems on existing lines, but as the printing is done in a linear fashion as the carton moves in front of the print head, the surrounding vibrations of a cartoner machine can deteriorate the print quality. This problem leads most solution providers to provide a separate and dedicated machine for carton printing. Overall, floor space and line efficiency are crucial.

 When weighing the options available to meet the needs of manufacturers and providers, decisions should be based on what will be best for your patients and your business. From the distributor’s perspective, a key question for any equipment or system is: How can the granular data being collected be used efficiently to identify trends in treatment and adherence and to improve patient safety? The implementation of DSCSA can be seen as an opportunity to continue to focus on patient safety, both upstream with manufacturers and downstream with providers.

In general, meeting the DSCSA requirements is like a jigsaw puzzle. Make sure you have a plan, build the framework, connect the pieces that fit early in the process, don’t hesitate to solicit help, and of course, make sure you use the right pieces. Specifically, identify a team and formulate a plan, find the right equipment (e.g., high resolution, serialization-ready printers) and implement early. Be sure to work with partner companies with open communication.

What do companies need to consider now, when installing equipment and systems, to plan ahead for future compliance with final DSCSA 2023 deadlines for item-level electronic tracking?

 The main additions in 2023 are aggregation recording at the packaging line and the rework and shipping events captured in the warehouse. In order to comply with track-and-trace requirements, not only must the item level be serialized, it must be associated with its parent shipper case serial number and then up to the pallet serial number. We estimate that currently 50% of our customers will decide to go ahead with the complete compliance 2023 deadline. The reason is simple: going through a single-phase approach [adopting new equipment all at one time] provides savings of up to 25% (direct and indirect costs). Each time the equipment is changed, the packaging line can’t operate for close to two weeks to install and run all the validation tests. During this period of time, as the line is not packaging, there is an indirect cost for the manufacturer, which is a loss of profit. In terms of equipment, this means to equip the packaging line with cameras and controlled printers at the bundle, case, and possibly pallet stations. Concerning warehouse management, when implementing improvements, considerations should be made to the impacts of new serialization for the following use cases: rework, de-aggregation, heterogeneous packing, shipment, and returns.

 When making decisions today, companies need to plan for the best return on the investment in the future. Flexible, interoperable, and cloud-based systems are best positioned to remain impactful and relevant throughout the transition and into business as usual. While two-dimensional barcodes are the mandated format for product identifiers, radio-frequency identification technology can still be leveraged to obtain key benefits.  One would need to create a link between the data components, and then through the cloud, there would be ability to communicate with other systems and the option to view data as needed.

Companies must implement line-level solutions that are prepared for aggregation, set standard processes for rework, define responsibilities, and identify and address challenges early. In the early stages, it’s important for the company to define other aspects they may be trying to accomplish. For instance, besides identifying the appropriate code and code location, companies should develop an aggregation process so a plan can be started. Also, they should consider all potential products that may run on a particular line. For example, if products will be exported, do they need to plan for adherence to other countries’ regulations?

How does the use of cloud-based track and trace facilitate serialization? What are the concerns with the use of a cloud-based system and how can these be addressed?

 The main advantages are a faster implementation and the ‘full sub-contracting’ aspect (as the plant’s information technology department would have fewer responsibilities). The cloud also allows easier servicing and pre-installation testing for the packaging-line serialization solution provider. Security is the main concern, but it is becoming less of a concern because the cloud solution can be as secure as, or even more secure than, a conventional on-premise installation.

 Today’s technology captures granular data in huge volumes that must be stored appropriately while still being accessible. The cloud is an excellent option for secure storage of the data, regardless of the amount. A common concern is understanding what happens if a system goes offline and more specifically, that while offline, the data won’t be captured. Before deciding on a system, ensure it is able to capture data while offline and self-heal when back online.


	GS1 US, “Implementation Guideline: Applying GS1 Standards to U.S. Pharmaceutical Supply Chain Business Processes, R1.1” (GS1 US, Sept. 14, 2014), pp. 8, 12-14.

 When referring to this article, please cite it as A. Roberts, “Planning for the Future of Serialization,” 

Articles

Compliance with the new traceability requirements necessitates an understanding of how and when to begin implementing changes in an ever-evolving industry.

Planning for the Future of Serialization

The accuracy and ease of use provided by electronic batch records (EBR) contributed to their adoption by large pharmaceutical companies. While the cost of transitioning from paper to EBR may result in hesitancy for some manufacturers, the reduction in error and decrease in batch release time offers increases in cost savings and efficiency.

 spoke with Dennis Brandl, president of BR&L Consulting, about the advantages and disadvantages in transitioning from paper to EBR, how the integrity of data is maintained, changes in operation management, and recommendations and strategies for implementation.
	
	

: What are the primary challenges in transitioning from paper to EBR?
	
	

: One of the primary challenges is to realize that you really cannot just put your paper batch records into an electronic format. There are major advantages to electronic batch records. They allow you to improve the process that you are currently using, such as reducing the need for dual signatures or automated calculation, so that operators don’t need to sit with calculators and hand type the numbers. Just implementing the current processes you have, without streamlining and removing the unneeded checks and work, means you miss many of the advantages that you would get by implementing an electronic batch record system.

: What are the advantages in transitioning from paper records to EBR?

: Reduction in manual errors is one major advantage from transitioning to an electronic batch record. When you look at the paper records that exist on many systems, they can be stacks of paper that are inches high and the dates and times on those have to be manually entered; in an EBR, they’re automatically captured. Electronic data, which can be read directly from the equipment, can be automatically captured instead of transcribed by operators, and you can ensure that no workflow steps have been accidently skipped because somebody missed a piece of paper.

	Another major advantage is the ability to perform production releases of batches and production runs in minutes instead of weeks. An electronic system can check to make sure that there are no exceptions or errors in a batch. If there are no errors or exceptions in the batch, then you can do a production release without having to have somebody manually review, potentially hundreds of pages of a paper batch record.

: How is the integrity of electronic batch data ensured?

: The same methods that are used to ensure the integrity of financial data and transactions can be applied to electronic batch data. That means you can create copies that cannot be deleted, which might be a DVD backup. You can have robust and tested continual backup processes with offsite storage. It is extremely important to have the offsite storage simply because these are IT systems; if you lose one server room, you don’t want to lose everything. Implementation of strong network and user account security are measures used in financial data and these are the same measures that should be taken with electronic batch records. The electronic warehouses that contain this are replacing the warehouses full of paper records and doing it at a tiny fraction of the cost and space that you normally have.

: How has the operation management of data collection changed since the integration of EBR?

: The information was previously unconnected and only available through paper trails. It’s now being combined into data warehouses that combine all electronic batch records and the related data, such as lab reports, data historian graphs, and maintenance records into one place and those things are being indexed for fast searches. The ability to do these fast searches means that the time it takes you to do investigations and studies is significantly reduced. Many times today, in investigations or studies, you can spend 80% of your time simply trying to acquire the data or getting people to go look up the paper records for you. With electronic systems, you can do these online, fast, and sitting at your desk.

: What recommendations do you have for the implementation of EBR? Are there any strategies that should be considered?

: When you are implementing an electronic batch record system, it is best to start with a few major impact areas and not attempt to go completely electronic in one step. A complete EBR implementation will touch all areas of a facility, but it will impact production. In order to reduce the impact, it is best to start at one or two areas and grow the applications to cover all paper records. These may be the areas that are of particular impact to you; it might be something as simple as container management, checking if containers are sterile, and recording the container’s location. It may be material management or it may be workflows, but start with one of those major impact areas where you are currently having problems and address that. All the systems that are out there today are modular and allow you to add the extra features in place. So start small, start on the major pieces, and then grow it.

: When referring to this article, please cite it as A. Roberts, “Electronic Batch Records Offer Advantages beyond Automation,” 

Transitioning from paper records to electronic batch records decreases costs and increases efficiency.

Electronic Batch Records Offer Advantages beyond Automation

A complex and evolving set of regulations challenges drug manufacturers to understand and implement serialization requirements.

Moving Forward with Serialization

	On March 27, 2015, the White House released a 

 detailing plans to tackle antibiotic resistance and announced plans to commit $1.2 billion of Federal funding to the cause. The plan lists goals to slow the growing problem of antibiotic resistance over the next five years, reduce the rates of the most deadly superbug infections, invest in new diagnostic tools and antibiotic drugs, and improve the use of antibiotics among patients.

	The plan touches on the growing importance of regulating the antibiotics that are given to the livestock raised for human consumption, also known as food animals. Many antibiotics that are used in humans to combat bacterial infections are also used in animals for 

, FDA announced that they would be taking steps to limit the use of antibiotics in food animals that were deemed crucial to human medicine. However, the plan recommends that FDA and the Department of Agriculture “take further steps to curtail the use of medically important classes of antibiotics for growth promotion in animals raised for human consumption,” according to 

	Under the plan, the Center for Disease Control (CDC) aims to reduce the rates of the most deadly and widespread infections, hospitals will be required to implement programs to increase infection controls, including increased sanitation and reduced antibiotic use. Doctors will be required to report prescription patterns for antibiotics, especially for nonbacterial infections. The CDC will also be asked to double its screening of multidrug resistant tuberculosis carriers from other countries, moving from 500,000 screenings to one million in five years.

 also reports that the government hopes to increase two elements crucial in the fight against superbugs: to ensure two new antibiotics are available for patients, and to improve prescribing methods through the use of a diagnostic tool to help doctors determine whether a patient has a bacterial or viral infection. Few new antibiotics have been developed recently, however, FDA 

 one designed for drug-resistant bacteria, Avycaz (ceftazidime-avibactam), specifically for the treatment of complicated urinary tract infections and for the treatment of complicated intra-abdominal infections when used in combination with metronidazole. In 

, NovoBiotic, Northeastern University, and the University of Bonn announced the discovery of a new antibiotic that may prove strong in the battle to kill superbugs. With the recent 

 linked to a contaminated medical scope, the White House’s plan may help to eliminate, or at least reduce, antibiotic-resistant superbug infections.

The White House confirmed that it would release a plan to tackle the growing problem of antibiotic-resistant superbugs.

The White House Responds to Superbug Threats

	Bristol-Myers Squibb (BMS) announced on Mar. 24, 2015 that it reached an agreement to acquire an exclusive global license to Novo Nordisk’s discovery biologics research program focused on autoimmune diseases; however, the details of the agreement were not disclosed. The research program is designed to modulate the innate immune system as a therapy for autoimmune diseases.

	With the acquisition, BMS expands its immunoscience and immuno-oncology research 

. The company saw success in this area of research 

 when one of its late-stage studies for Opdivo (nivolumab) was ended early due to superior overall survival.

Bristol-Myers Squibb acquired an exclusive license for Novo Nordisk’s discovery biologics research program.

BMS Acquires Autoimmune Portfolio from Novo Nordisk

	Regeneron has received FDA approval of Eylea (afilbercept) for the treatment of diabetic retinopathy in patients with diabetic macular edema (DME). The approval came on March 25, approximately 

 after FDA granted the drug Breakthrough Therapy Designation status for this indication. This approval marks the fourth FDA indication for Eylea, which was previously approved for macular edema following central retinal vein occlusion, wet-aged macular degeneration, and diabetic macular edema. The recommended dosage of Eylea for the treatment of diabetic retinopathy in patients with DME is two milligrams every eight weeks after five initial monthly injections, however it may be dosed as frequently as two milligrams every four weeks (additional efficacy for this frequency was not determined).

	"Diabetic retinopathy coupled with DME is a serious complication of diabetes that can threaten the vision of many working-age adults. In addition to improving visual acuity in people with DME, Eylea also improves these patients' retinal vessel damage, or retinopathy. Eylea is the only treatment option for diabetic retinopathy in patients with DME that is approved for less than monthly dosing after an initial monthly dosing period,” said George D. Yancopoulos, MD, PhD, chief scientific officer of Regeneron and president of Regeneron Laboratories, in a press release.

, FDA granted Genentech approval of Lucentis (ranibizumab injection 0.3 mg) for the treatment of diabetic retinopathy in patients with DME. Lucentis was approved for the treatment of wet age-related macular degeneration in 2006, DME in 2012, and has been used to treat macular edema following retinal vein occlusion since 2010. 

FDA has approved another indication for Eylea, a treatment for diabetic retinopathy in patients with diabetic macular edema.