94 INTERNATIONAL PHARMACEUTICAL INDUSTRY Winter 2014 Volume 6 Issue 4

Manufacturing

Lawmakers and regulators around the world are demanding serialisation for drug products. It is their belief that this process, where the result is a clear identification of drug products, is a major step in the struggle against counterfeiting. While some countries have already embraced certain guidelines, others will be doing so in the coming years. Whatever their timeframe, all drug companies, along with their suppliers, are facing the challenge of implementing appropriate solutions.

Counterfeit drugs have become an enormous problem both for developing nations and the industrialised world as a whole. Counterfeit drugs jeopardise the health of patients and, in some cases, have resulted in deaths. They have also had a major negative economic impact on a global basis. According to the WHO, counterfeit drugs have cost nations an estimated $75 billion1 a year combined.

Typically, due to their high costs of development and manufacture, counterfeiters have focused on complex medications such as cytostatic and virostatic drugs, as well as antibiotics and hormones. Therefore, as a means of managing this problem, lawmakers and industry representatives have turned their attention to the tracking of these products beginning with the production line, on through to the pharmacy. The process is called ‘serialisation’, and it entails clear identification of the smallest packaging unit with a unique identification number.

While there has been some debate about this approach, it is clear that serialisation is quickly being embraced on a global basis. For every stakeholder in the supply chain, the rapid rise of serialisation means there has to be an appropriate response. And, it is essential that this solution meets the requirements as defined by official agencies while offering greater security for the patient. An economic solution is important, allowing for the optimisation of production and distribution processes. The question for companies then is ‘how can the interested parties be brought together to implement

a form of serialisation that meets future needs?’

A Variety of ChallengesThe subject of serialisation and track-and-trace has been on the industry's agenda for quite some time. Several of the major drug manufacturers have, in fact, made considerable inroads into implementing solutions. Others have waited for the regulatory standards to be in force before addressing the issue. Regardless of the approach taken, the industry as a whole is keenly aware of the need for serialisation and is working hard toward developing appropriate solutions.

However, serialisation is not a simple process. Therefore, in order for it to be effective, it is backed by some important technological transformations in both the IT and engineering areas. For those companies seeking a suitable partner and supplier, there exists a bottleneck since only a limited number of specialists are available to design and implement the required IT system, applications and plant engineering. Alternatives are difficult to find since there is some risk involved to consider suppliers unfamiliar with the industry. Packaging processes that meet stringent regulatory standards or supply chain structuring requires considerable pharmaceutical expertise.

Also complicating the issue is the fact that there exist important differences in the plants and the IT landscapes of large companies that have several locations. Each individual subsidiary usually has its own history. Thus, the plants have usually been built by a variety of suppliers and are often run by several different IT systems. The rule of thumb is the larger the company, the more extensive the challenge. Thus, the effort needed to retrofit ten lines is significantly different from the effort required for retrofitting 100 lines. Finally, the same product is often manufactured on various lines and has to go to a variety of markets that are all regulated differently.

Another set of challenges is faced by smaller or virtual companies, which usually lack in-house production facilities,

and also have to exchange serialisation data directly with officials. This entails a great deal of learning about in-line and distribution processes and packaging. And, there is also the cost factor ultimately forcing the question, “Do we make it or buy it?” It is clear: companies are facing a large number of multifaceted challenges and need to have a comprehensive knowledge of the subject.

Questions AnsweredHow then, can companies best address the tasks at hand? The first step is to get a good understanding of the extent and demands of a serialisation solution that best fits their specific needs. Those in key positions to implement serialisation, along with experts in this area, should first identify and develop the most important parameters, determine what they can put into practice themselves, and what can be outsourced to a service provider. The following questionnaire can provide some help:

• Which regulatory authorities’ serialisation rules have to be met?

• What firm guidelines do the individual agencies offer for structure and presentation?

• How should the serialisation data be shared with the regulating agencies?

• How, and in what form, should companies administer and manage the serial numbers?

• What solutions are in place to deal with the serial numbers on the manufacturing level?

• What kind of systems and transmission systems will be used in advance of the packaging line?

• How will the serialisation solution be integrated into the existing enterprise resource planning (ERP)?

• What interfaces and transfer protocols are required?

• What are the key processes demanded by warehouse management?

• How can in-process controls and quality management be integrated into the serialisation solution?

These questions are critical since they determine the tasks that a company

Implementing Serialisation

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96 INTERNATIONAL PHARMACEUTICAL INDUSTRY Winter 2014 Volume 6 Issue 4

Manufacturing

implementing serialisation has to be aware of. Each task is analysed in detail in order to produce a list of precise specifications a candidate supplier will need to meet. Clearly, companies without actual packaging lines will have to direct greater attention to a management solution. However, drug companies with their own production facilities will also have to make sure their equipment is up to the task of serialisation. Ultimately, there are two clear areas that need to be attended to. First, companies will need to implement an IT solution covering both hardware and software, and second, they will need an engineering project to retrofit the lines.

Solving the IT IssueKnowing the requirements that are expected to be met is central to implementing both hardware and software solutions. Companies that deliver products to various markets face the challenge of having to meet a variety of standards for serialisation. In such cases, the guidelines will be determined by the following:

• Code type • Serial number characteristics• Serialisation level• Reporting requirements

What is most needed is a flexible serialisation solution that can meet all regulatory requirements. Companies will have to make every effort to be sure of various aggregation depths,

as some official agencies demand aggregation from the sales packaging unit to the shipping carton, on through to the transportation pallet. Therefore, the following elements will have to be taken into account when implementing the solution:

• Integration into ERP• An IT solution for the management of

serialisation data from aggregation through sample withdrawal

• Interfaces and data transmission

The IT solution should then link order data with the corresponding serialisation data. This will allow the serial numbers to be monitored prior to delivery and generation of the subsequent data reporting, including the aggregation data. Basically there are two options to solve the IT issue: either you implement and develop an IT solution in-house, or you go with a cloud or hosted solution. Each solution has its advantages depending on your company’s IT strategy. Going with an in-house solution will take more time, but it gives your organisation more control of your data and is easier to integrate with your internal IT systems. If you have a short timeframe and don‘t have the budget for high investments upfront, a cloud solution could be the answer.

Engineering SolutionThe guidelines for serialisation demand clear identification of the smallest packaging units, i.e. the folding boxes

that the drugs are to be packaged in. Even a cursory glance at the secondary packaging such as an injectable, will reveal what system will be needed for implementation on the lines. After filling and visual inspection, the syringes are blistered and then packed into the folding boxes on the packaging line. Afterwards, the boxes are packed into shipping cartons and loaded onto pallets. Variable data are already printed onto the folding boxes, including batch numbers and expiration dates. The shipping carton and the transportation pallet also carry product information. Printing the serial numbers at the same time as the production data is recommended for serialisation.

A plant can be both retrofitted and connected to printers that can print in either number or some machine-readable form such as bar codes or 2D data matrix codes. Networked camera systems are also needed for monitoring in addition to scanners that are necessary for the in-process controls and rejects which allow for rebooking. A mobile machine might be a good start since it allows companies the flexibility to do serialisation on various lines. The fact that the machine can be qualified separately and offline also means that you are able to gain experiences without influencing your existing packaging lines. It also avoids down time and allows those in charge to collect important information on the process itself without risk of breakdowns.

Once the ‘know-how’ has been gathered and integrated, a stationary serialisation unit can be commissioned. The on-line systems will still need to be rounded off with a label printer and a camera unit for manual aggregation of the individual boxes with the shipping carton. The same principle applies to the manual aggregation of the shipping carton with the transportation pallet. The systems for each packaging line are connected via a line controller, which is controlled by means of a site server directly connected to the central IT platform.

Software and HardwareIt should be clear to the reader at this point that serialisation can only work effectively if implemented with an IT system, combined with a well-conceived engineering project. The two sides of serialisation implementation are carefully meshed with all existing integration

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98 INTERNATIONAL PHARMACEUTICAL INDUSTRY Winter 2014 Volume 6 Issue 4

systems and communicate with them as well, which requires an on-site server to control production. Integration can be performed using SAP process integration (PI) for example, with standard interfaces like EPCIS and reports using XML in EPCIS design.

The IT solution has several other tasks to perform, including recording and documenting events along the entire supply chain, and then generating full documentation as well as reports. A link-up with ERP is also vital to initiate orders and to generate, administer, and share print information and key materials, such as serial numbers. And, because the serialisation solution involves many different layers, the IT solution is important to support the work across different systems to generate and disseminate commissioning reports for the serial numbers, aggregation reports, etc. In-process controls can be used for sampling during production, while a

handheld solution could allow exception handling at the warehouse. Relabelling will then need to be completed at the warehouse as well.

Key DetailsThe official guidelines for serialisation solutions require certain fundamental elements. All sales packaging units will bear a clear set of serial numbers and other identifying features. These numbers can be in 1D linear code or 2D data matrix code, as well as the information being in text form so they can be read by humans and robots alike. The 2D data matrix code has the advantage of providing more data, i.e., expiration date and batch number, in addition to the number of folding boxes in the shipping carton. This information needs to meet the GS1 standard.

There are, of course, national differences. China, for example, demands very special guidelines, including 1D linear codes as well as aggregation with shipping boxes. For the exchange of data such as serial numbers, and reports which contain integrated photos of serialised

shipments, Chinese authorities also require a manual interface with the drug company, to enable the transition of the serial numbers and reports. South Korea follows at least for 2015 another concept, serialisation on item level. They will meet the GS1 recommendations depending on data matrix code information like GTIN, expiry date, batch/lot and serial numbers using a 2D data matrix.

Toward a Safe FutureIn summation, serialisation involves the clear tagging of the smallest packaging unit with a unique identification number. The rationale behind this new approach is to provide greater safety throughout the entire supply chain. Combatting counterfeit drugs through serialisation protects patients as well as companies whose reputation can be

adversely affected if their products are counterfeited. Serialisation combined with Track & Trace also offer potential for process optimisation, since clear mapping of distribution channels allows for easy tracking and tracing. Thanks to powerful IT systems with simple and efficient interfaces, caregivers can quickly check the origin and integrity of the drugs they are administering to patients. The fakes will be immediately identified and removed from circulation.

References1. Source: WHO http://

w w w . w h o . i n t / b u l l e t i n /volumes/88/4/10-020410/en/

Manufacturing

Alexander Ulbrich is project manager within the IT department responsible for the Serialization Project at Vetter. He began his career at Vetter in 2003 and since 2013 he is

team leader responsible for a team of SAP application consultants. Prior to Vetter, Alexander was with the technology group of Acterna (now JDSU) as system administrator member of the global Lotus Notes Core Team. After he finished his studies at the FH Reutlingen he began his working career in 1999 at Wavetek Wandel und Goltermann as a qualified engineer (FH) of Electronics.

Example of a software and hardware solution