1. Pre-requisite

However, the setting up of an EBR requires a number of prerequisites that are necessary to successful project implementation. They can be categorized as follows:

Human

• A change in the mindset of all players (operatives, quality, management, process advisers, IT, maintenance). The EBR entails a way of operating which in the first instance is generally perceived as involving a loss of time and increased constraints as the actions being eliminated are habitual and automatic. In particular, definition of Masters necessitates more tricky construction (or is perceived to be more difficult) than on paper. It is just the opposite, however, as in the end the EBR saves production time, avoids data integrity deviations and loss of raw data, etc. In addition, dematerialization of the Paper Record may result in loss of the more global understanding of all production steps. This must be offset by providing the right support to ensure that users fully understand how to find their way around the tool.
• Training of operational and quality staff who will have to use the production MES on release of the batch record. This training must also be accompanied by the provision of information to support teams (HSE, Management, Maintenance …). The handling of a significant non-negligible volume of documentation is to be taken into account.

Process

• Having a manufacturing process that is as fixed as possible and avoiding constant requests for changes and corrections. This can generate excess cost and especially a loss of confidence on the part of users.
• Incorporating key process control data, CQA (Critical Quality Attributes) and CPP (Critical Process Parameters), particularly by ensuring the participation of product quality and operational SME (Subject Matter Experts), process advisers, and operatives in working groups to define processes. These key data must be linked, by secure configuration, to validated tolerances to allow the system to generate an alert when a threshold is exceeded.
• Standardization of the batch record to incorporate the review by exception which allows a production record review assisted by qualified computerized systems. Only deviations generated by the computerized systems are reviewed by operational and quality staff.

Financial

• The installation of an MES has a cost and therefore to obtain a significant return on investment (ROI) in terms of data integrity, industrial performance, batch record review, a business case must be established to, if needed, prioritize certain processes that are more appropriate for transition to EBR.
• A high demand for expertise and uncommon skills, at the crossroads between production, quality, and IT, should also be anticipated. Generally, these resources are service providers that can be called on by several customers for the same need. Staffing of these resources is vital to the successful execution of the project.

Technical

• A dedicated infrastructure that can support the MES and allow it to be accessed at any time without stoppages which would hinder production. This infrastructure must have one or more redundant servers to guarantee data availability. A qualification campaign is to be anticipated for these installations.
• A choice of solution in line with the various players on the market. Generally, the choice depends on the complexity of the process and the budget allocated. There are several publishers of MES which are more or less flexible depending on process complexity. A case by case study or indeed a group strategy must be researched before installing the EBR.
• The possibility of interfacing with other IS (ERP, SCADA, LIMS) or not. The production record contains data from several IS, for example graphs in SCADA, laboratory results in LIMS and raw material consumption in ERP. Communication between the different IS will allow optimization of the review by exception and management of production in real time.
• Enabling the maintainability and future development of the EBR by having individuals with appropriate skills. A production record is not fixed in time, it may evolve in line with the various associated changes. Because of this, this record must be maintained by a team and allow for changes associated with process changes.

An EBR is a multi-faceted tool: it can serve at once as a traceability tool, a user guidance tool, a tolerance monitoring tool, a step sequencing control tool. Each of these facets requires specific questions to be raised by the final user. These questions, if they are not asked and answered collectively by the parties that use the system, risk leading to difficulties (use-related or financial) when the system is used.

2. Checkpoints

In our experience, we recommend anticipating the following key points:

2.1 Data selection to be performed

The first prerequisite in the world of EBRs is the data items that you want to record. The first instinct might well be to take all current data falling within the framework of its activity, implement them in the system and leave them there without any prior judgement as to whether they will finally be used or not when the system is operated. Each data item recorded in the EBR will be the subject of specification, technical modification and finally qualification. Each excess unnecessary data item will represent a dual cost to the EBR: on its creation then when it is used.

The first step before trying to implement an EBR therefore consists in rationalising the information necessary to the goal attached to use of the system. If the goal is to create traceability for all activities that concern the batch record, then the data used currently must be sorted against those that really need to be tracked. If the goal is additionally to conduct a review by exception, then an analysis must be carried out of all parameters to be checked by the system and a rationale attached to each test.

In sum, everything that is unnecessary to the goal set in the context of EBR implementation should not be there.

2.2 Maintenance that may be very costly

A computerized system in a GxP environment requires a high level of testing when changes are made. Each modification is subject to change management, evaluations of potential impacts and finally qualification (see: qualification of IS (GMP Annex 11 (§2), FDA 21 CFR Part 820 (§820.70i), FDA 21 CFR Part 211 (§211.68a/b)). All these steps have a cost, sometimes high, that should be taken into account when an EBR is being implemented. The right balance between necessary testing and “convenience” testing when installing an EBR must therefore be found in order not to give rise to spiralling costs and maintenance requirements throughout the lifetime of the EBR.

2.3 A system that detects

In most EBR installations, the system is used both for traceability and detection of the exceedance of tolerances, deadlines, of the order of activities, etc. These events do not necessarily all have the same impact on the manufacture of the product of interest. A method of ranking the events detected by the system must therefore be found, without which each event will be analysed in the same way: either in a manner that is too advanced (which leads to a significant waste of energy), or in a way that is not sufficiently thorough (which may lead to quality system faults). These rules should therefore be fixed and then system user needs specified accordingly.

Finally, not all scenarios can be imagined when the EBR is designed. Production will put the theory into practice, and this will be placed under sustained observation via the EBR.

Numerous events not previously captured will be passed on and will therefore need to be evaluated in the context of using the EBR. A high level of event detection activity must therefore be expected during installation. This significant volumetry should be weighed by an appropriate event management process that is thought through carefully before use.

3. Conclusion

In conclusion, installation of an EBR has tangible benefits described below:

• Shorter review or release times as the system controls production from the start and warns if tolerance is exceeded. This benefit will be ensured by the review by exception.
• Enhanced compliance with the data integrity imperative, which is ensured by testing of the system that is qualified on installation. There is a guarantee of the reliability and traceability of recorded data.
• Process operations are governed by instructions as well as by the computerized system which also guides this. This allows operational performance to be made reliable. Access rights management is set up on installation, which allows actions associated with the process or the review to be controlled in line with training carried out.
• Fewer anomalies associated with raw data. The digitalization of the batch record will allow avoidance of the loss of raw data or indeed cross-contamination between two batches.

Intangible benefits also result from its dematerialization, as the batch record will not have a physical flow and can be released without the obligation to be physically on site. This will boost flexibility and avoid the obstacles associated with a physical presence. In addition, this dematerialization will open the door to the future and to new technologies such as “big data” or “business intelligence” to create provisional data on equipment for example.

The installation of an EBR procures multiple tangible and intangible benefits in the medium and long terms but does require a high level of investment at the start of the project.