Mauricio Jungbauer is the marketing and sales manager for PacOnline at Spirit GmbH

Mauricio K.E. Jungbauer

				There have been numerous automation and computing developments in many areas of pharmaceutical packaging. For many years, document management systems (DMSs), workflow systems and complex artwork tools have been used. The new generation of computer-supported artwork management, however, is a combination of these single applications. Data, which have so far been stored on different systems within the company, have to be brought together and combined in a single, centralized system. Only such a system will fulfil the requirements for electronic, validated processes for artwork documents, thereby ensuring paperless, automated documentation of the artwork process (21 CFR Part 11). Similar to the workings of an enterprise resource planning system, this all- encompassing approach will bring many advantages  vis Ã  vis  companies not yet working with this level of automation within the artwork process.

Introducing new computerized systems for use in pharmaceutical processes is expensive, because of the fact that such systems must be validated. Companies must compare the advantages of the system with the associated costs. Artwork creation is an area that has, traditionally, operated with computerized systems. However, the programs used merely represent tools that are not included in any electronically based working processes. An integrated artwork management system (AMS) offers a great number of possibilities for process control and automated artwork generation in the field of pharmaceutical packaging artwork. 			

There are many benefits that automated artwork generation can bring to the pharmaceutical industry. For example, legal requirements often force pharma manufacturers to make changes at short notice. Additionally, marketing departments require rapid changes to react to fluctuations in market conditions. And, in the field of generics, lead times in the introduction of new products is of paramount importance; although pharmaceutical companies have little influence on the time taken for product registration, they do need to have their artwork completed as early as possible. Even a few weeks can be decisive. 			

Lead times in the preparation of artwork is dependent on available resources. Employees are frequently overloaded as the number of changes is constantly growing. Service providers may be able to alleviate the situation, but are themselves frequently overloaded too. Communication and documentation place a further burden and this results in lead times becoming even longer. To remain efficient in this time-critical process, packaging artwork has, as a rule, strict design regulations. By means of this harmonization, employees are able to concentrate on the key aspects that are of importance for medicine packaging artwork. Consequently, the packaging of a particular manufacturer is very similar and only differs in the text element. The text itself is also subject to frequent changes.

The specialized text is usually written by text editors, and is then processed into the artwork by other departments. Many companies rely on service providers to layout the documents. During this phase, communication is based on e-mails to exchange information and there may be more than 10 drafts of a text before a document is finally approved. As final approval for printing is always required, there is the need for a printed and signed-off document. This results in documents having to be posted and distributed amongst departments, which in turn leads to accumulating documentation.  

 The key to the efficient operation of the artwork process is the correct combination of information, processes and users. Some companies are already using computer-based systems, which only cover some areas.  

 A central problem for companies and service providers is handling the large number of artwork documents, particularly with reference to the importance of quality assurance (QA) and traceability. DMSs help to manage the 'flood' of documents, but do not safeguard the data as they only administer the files.  

 Some companies already use content management systems (CMSs) or text editing systems for the storage and care of documentation. With artwork documents it is important that information can be retrieved, which can be controlled by such systems.  

 The control of information distribution and processing is of utmost importance. Workflow systems are, however, still rare. The reason for this is that these systems can control time lines, but not the flow of individual information. This is done by different systems and is, therefore, not a controlled part of the workflow. This poses a basic problem for the validation of an artwork system.

The required information for artwork production is brought together by a graphic designer. This process has been computer-supported for many years; however, the tools used offer no possibility of administering each piece of information. They are reduced to the purpose of producing the artwork itself. 			

A weakness of multiple sets of data is that they are not incorporated into a single computerized system. A workflow system knows nothing about the file content and the artwork tool has no correlation to the running processes. Only if these individual operations are brought together is there the possibility of automating the artwork process and, consequently, artwork generation. An AMS can support these processes electronically whilst taking into account the requirements of EU and US regulators. A web-based system can combine the separate systems and functionalities of document management, process control and artwork generation to a central operational platform.  

For users in the pharmaceutical industry, automated artwork generation allows all tasks resulting from the process to be completed by a single working platform; this includes defining the contents right through to the automated generation of artwork documents. This is possible as all data relevant to the creation of artwork are available within the system.  			

The data are used by the user and brought into correlation when defining a piece of artwork. Thus, an abstract data model can be created for a specific artwork containing all information such as type, origin, validity and content. To obtain a ready for print file, technical specifications, layout information and contents are required from these data.  

Artwork requires that technical parameters for the production of the packaging are available. In the case of automated artwork generation, die-cut (norms), size and production codes have to be defined. A layout can then be created. 			

Layout templates are defined according to the company's corporate identity (CI) guidelines. The position and size of contents for the artwork are defined in placeholders. As the relationship between the technical specifications and the placeholders is dynamic, a change in the artwork's technical specification will result in the correctly adapted position of the placeholders in the new version.  			

The placeholders defined in the layout template are linked to the content, which are also stored within the system. This ensures, particularly for text, enhanced security. As the texts are stored only once, errors in transferring these onto the artwork document are minimized.  			

Graphic content is uploaded into the system and, just as the text, are subject to strict rules. Changes to the contents of a version are, therefore, neither deliberately nor inadvertently possible.  

A further advantage of automated artwork generation is that barcodes can be created automatically by the system. Classical artwork creation basically uses the same amount of information required for creating the artwork file. As a rule, this information is stored in folders and forwarded to the employee responsible. The transfer of this information into an electronic data model now makes it possible for artworks to be created automatically with the help of a powerful graphics engine. Only by integrating all the information into a central database is it possible to apply the process of artwork generation within the scope of other running processes.  

An automated AMS can provide information such as use and period of validity, which gives users total control over the entire artwork process. The system gives rise to two major advantages: 					

As the documents are totally protected during the development process, the system can be validated and replace printed documentation.

The second advantage is in the workflow functionalities. An artwork document can be proofed online, meaning that several proof readers, irrespective of location, can add their comments to the document. All comments can be stored and documented centrally. Paper copies are not required.

When the artwork is ready to go to the printer, the system ensures that only the correct and validated version is sent. 

Automated artwork generation has many advantages for pharmaceutical companies: 									

QA in terms of traceability and error-free.

Fewer resources are needed for the creation of artwork documents.

The required qualification for the remaining work is much easier and more productive.

It is easier to maintain consistency in packaging creation.

Lead times for artwork files are reduced to a few minutes.

Document management and content management are an integral part of the system.

The artwork is available globally within seconds at any time for proofing and other purposes.

				The impact of IT systems in pharmaceutical companies is growing constantly, and this is demonstrated by computerized AMSs. 

Articles

This article examines automated artwork generation, which enables pharma companies to generate validated artwork for their products' packaging. Automated artwork generation is based on a complete set of data stored in an artwork management system. It enables the dynamic assembly of artwork documents, accelerates traditional processes and significantly reduces costs.

Automated artwork generation

Only a small number of information technology (IT) projects are completed entirely successfully; approximately a third are cancelled and more than half significantly exceed deadlines and budgets (Figure 1). This is often because software suppliers have little or no experience of the validation required for the programs. However, validated software is important because good IT projects can help to reduce costs. 	

Pharmaceutical manufacturing process quality is governed by the requirements of the European Union's (EU's) EU-GMP Guideline, which covers implementing both hardware and software systems in production areas. The area concerning computer systems is described in Annex 11 "Computerized Systems," part of which requires that computer systems are validated from an early stage.	

Figure 1:  The success and failure of IT projects.			

The principle of Annex 11 is that "when a computerized system replaces a manual operation, there should be no resultant decrease in product quality or quality assurance. Consideration should be given to the risk of losing aspects of the previous system, which could result from reducing the involvement of operators." Additionally, it is essential that there is close co-operation between key personnel and those involved in implementing the system.				

Annex 11 details how personnel responsible for computerized systems must be appropriately trained to manage and use such systems. This includes ensuring that relevant expertise is available to advise on aspects of design, validation, installation and operation of computerized systems. 	

According to the annex guidelines, the system requirements can be summarized as follows:	

The system should be in a stable environment, eliminating interference from extraneous factors.

There must be a detailed written description of the system, which needs to be kept up to date.

A computerized system should be thoroughly tested before it is used. If a manual system is replaced, the two should be run in parallel for a time as part of the testing and validation procedure.

Data should only be entered or amended by authorized persons, and suitable methods of 

preventing unauthorized entry must be in place. When critical data are entered manually, there should be an additional check on the accuracy of the record; this may be done by a second operator or by validated electronic means.

It should be possible to obtain clear printed copies of electronically stored data. Data should be regularly backed up and stored at a separate, secure location. 

A procedure should be established to record and analyse system errors, and to enable corrective action to be taken.

Generally, it is the company using the computerized systems that must ensure validation and compliance with Annex 11 requirements. It also has to ensure that its supplier works in accordance to the requirements. 	

Annex 11 devotes only a brief paragraph to the complex subject of validation. It offers little definitive advice to those implementing computerized systems, and leaves much scope for interpretation. However, it does contain an important statement, which frequently causes problems: "Validation should be considered as part of the complete life cycle of a computer system." Often, the responsible personnel are not aware of this and assume that validation is a single process that takes place at the end of the development phase.	

Figure 2:  Each phase must be validated throughout the project life cycle.						

Validation, however, is a continuous process that includes stages such as planning, specifying, programming, testing, commissioning, documenting, operation, monitoring and modifying. Each stage must be validated to comply with Annex 11 requirements. It is essential that if a system is modified, all stages must be validated again (Figure 2). For example, if a user requirement specification (URS) document is not validated at every stage, it cannot be compared with the completed computerized system. More work will be required to bring the URS up to date.	

If each stage is validated, the result is a comprehensive document. The relationship between the effort needed to produce the documentation and the actual system development work is frequently misjudged - the ratio is approximately 8:1 (Figure 3).	

Producing the large amounts of documentation that validation requires is often avoided. Because developers do not primarily associate documentation with functionality, there is no immediate association with system quality. Developers often do not understand the importance of validation documentation until further into the project, by which time it is far more difficult to produce. Inexperienced vendors underestimate the amount of documentation required to validate systems and often just provide general unified modelling language (UML) diagrams and comments. The fact that validation requires extensive documentation must be made clear from the outset, because the quality of a system decreases without this documentation (Figure 4).	

Figure 3:  The relationship between documentation and system development and Figure 4:  Quality decreases without documentation.			

Successful validation is based on a quality assurance (QA) system that encompasses all the departments involved in an IT project. Standard operating procedures (SOPs) must be provided for the work, and only by working to the SOPs will the implemented system achieve the required validation and quality.				

If quality is to be maintained, this principle has to be adhered to. If, for example, a URS is produced according to a particular SOP then all further work on the document must be performed according to the same SOP. It is also important to maintain traceablity during the life cycle of the system. This procedure leads to complete documentation and is a requirement for successful audits.	

Computerized systems are often produced by external providers. 	

To save time and money at a later stage, it is important that the vendor has experience of validation and works according to QA procedures. Although companies should ensure that the vendor is working according to the required guidelines, both sides must be aware of the requirements of computer system development. Only a system developed according to these guidelines will be successfully validated after implementation.	

Many projects fail because of the difficulties addressed earlier in this article. Computerized systems can bring significant cost benefits if they are implemented into processes that, traditionally, have not been automated. For example, during the course of a packaging project, work was produced by a number of people in different areas. The work had to be checked by a second person after all alterations had been made and so the document was sent to proofreaders. Problems arose when a number of copies of the document were circulated, resulting in many copies of the same document being proofed. Because all of the copies were editable, inadvertent changes were being made, resulting in a number of documents with differing content; the whole process, therefore, did not conform to EU-GMP guidelines. It also allowed the possibility of the wrong document being released.				

A validated process would require that a uniquely identifiable document is proofed. Because digitally produced documents are frequently still processed manually, the system does not comply with validation guidelines and QA requirements. Many companies still use manual processes because, until recently, appropriate computerized systems have not been available.	

Implementing a computerized system can eliminate the risks of human error inherent in manual systems. The system makes it possible to locate the document to be proofed from a central store. In place of the document, the system provides a non-editable version to the proofreader, which only allows correction notes to be attached, eliminating the possibility of inadvertent changes. The system allows all proofreaders to check the relevant document from one location and add their annotations to this single document. 	

Manual systems are still used for many processes, despite not conforming to the EU guidelines. However, these systems are increasingly being replaced with validated computer systems. The pharmaceutical industry can benefit from the significant time and cost savings to be gained by implementing computerized systems.  	

When implementing computerized systems, it is important that both purchasers and vendors ensure that each stage of the process (from planning through operation to modifying) is properly validated. This article looks at some of the issues that arise when switching from traditional document-based procedures, and at the benefits that computerized systems can bring.