High demand in the pharmaceutical industry is a constant
Manufacturers both large and small must look to optimise their production lines to ensure production quotas are met in a timely, profitable and, above all, safe manner.
Larger producers running single product batches seek outstanding reliability and accuracy in checkweighing, whereas smaller contract packagers — who are likely servicing multiple clients — need the flexibility to effect quick changeovers to keep throughput to a maximum.
As manufacturers need to remain certified to produce pharmaceutical products, compliance is also critical. Products entering the supply chain that do not meet the required standard threaten patient safety, retailer confidence and in the worst case scenario a company’s ability to continue production.
All are damaging to profit margins to varying degrees and the risks can be mitigated with a well executed product inspection programme.
Automation is a given in these environments and it is universally recognised that checkweighers play an instrumental role in day-to-day production.
A checkweigher’s main function in a pharmaceutical environment is to check the package for missing components such as the leaflet or complete blisters. This is a vital part of the package, as a box of tablets for example will not be considered safe or compliant without it.
End of line applications are also commonplace, where systems are used to check the completeness of secondary and tertiary packaging, ensuring that what is sent into the supply chain is exactly what is expected.
Checkweighers automatically inspect 100% of products on the line, which is highly recommended compared with random off-line sampling, as the latter gives a sample size that is now considered to be of little statistical significance.
Downtime is the enemy of any manufacturer; therefore identifying areas that affect this directly is important when looking at Overall Equipment Effectiveness (OEE).
System set-up is one such area that can be optimised, and checkweighing features such as digital position control help to verify this is done correctly — otherwise the batch cannot be run at all.
Running a batch with incorrect inputs can be very costly to correct because of the wastage involved. Also, should these products enter the supply chain, it could have significant consequences, both in terms of consumer safety and brand reputation.
Another feature that increases OEE is in-process-testing. The test procedure, to be followed step by step, is normally written down on a separate instruction document and the results are manually entered on separate documents.
Such testing procedures are very labour intensive, cause operational downtime and rely heavily on the operator consistently testing for reliable results.
In-process tests significantly reduce the risk of errors during test procedures and are highly flexible — so are able to adapt to customers' specific requirements.
They are easy to operate, generate automatic reports for each test scenario, and – most importantly of all – require no shutdown of production.
In-process tests are done with the help of special screen prompts, which guide the operator through the complete procedure and automatically record the results, which can then be saved and printed.
Clear guidance during testing reduces labour time and possible operator errors and manufacturers benefit from more consistent, reliable results and higher operational uptime. In-process tests enable several configurable test scenarios.
In addition, there is an easy to operate, intuitive Graphical User Interface (GUI), which helps the user to make changes easily. Mettler-Toledo also offers ProdX, a product inspection data management software application, which can significantly increase OEE as it enables nearly all processes on the line to be monitored from a central point.
Pharmaceutical checkweighers in particular are designed to meet the regulatory requirements of the pharmaceutical industry.
First of all, GMP offers a broad guidance, although GMP regulations are not prescriptive instructions but consist of guidelines based on general principles.
These include, for example, the validation of processes, record keeping, operator training or prevention of cross-contamination. It is always up to the manufacturer to design the production process and quality programmes in accordance with GMP principles, to interpret the guidelines and asseses process risks accurately.
Mettler-Toledo, to maintain process safety, offers equipment qualification, which is a huge benefit to users as it reduces the qualification and validation time to comply with FDA or cGMP (current good manufacturing practice) requirements. Equipment qualification comprises all aspects of design, installation, operational and performance qualification.
Minimising changeover downtime is critical. Advanced checkweighing systems offer useful features such as digital positioning control.
Owing to a plausibility check, the system does not allow users to enter false parameters. Users are immediatley alerted if settings are entered incorrectly and the system will not start if the parameters are wrong — another factor that influences the usability of the GUI also helps users to save time and therefore minimise changeover times — key factors when looking to increase productivity.
Statistical Process Control (SPC), in addition, is possible via software functions that can be utilised to predict issues on the line. SPC measures and refers to industry standard values of process capability CP and CPK.
Standalone or integrated systems allow users access to the statistical data needed to understand, document and control profitability and production efficiency. This way, early detection of problems can be achieved ahead of any major issues that may have a significant impact on uptime.
The ability to monitor performance is directly linked to OEE, and the net effect of reduced machine downtime is that higher production levels can be achieved using the same amount of resources. This leads to a faster return on investment with regard to capital purchases such as checkweighers.
Individual boxes, for blister packs of pills for example, are lightweight; therefore the load cell of a checkweigher has to be very precise.
The checkweigher helps to check for product completeness, to reject falsely produced products and ensure the safety of the processes comply with FDA requirements. Another demand is the legal compliance with CFR 21 Part 11, which describes the way access to information is managed and changes made to the checkweigher.
Everything has to be traceable and logged. This is integrated into the audit trail feature that the pharmaceutical checkweigher offers and a local audit trail operates completely automatically in the background and usually requires no user intervention.
Another useful feature is the domain login server, which enables the manufacturer to use accounts, passwords and rules issued and administered by the company's IT department for the checkweighers.
Operators, maintenance personnel, supervisors and quality managers can use their normal network login name and password for tasks at the checkweigher just as they would with a network PC. This is not an FDA requirement but is a very valuable addition to the system.
A challenge for pharmaceutical manufacturers will be the European Falsified Medicine Directive (EU FMD). Depending on how many products the manufacturer has, how they are produced and whether they are produced using internally owned facilities or with external partners, there really isn’t a great deal of time left before implementation.
Manufacturers generally deal with multiple facilities, which will all have to be enhanced with hardened serialisation software to comply with these regulations.
Overall serialisation is the key to success here, and the EU FMD will require a unique serialisation number on every salable unit of drug product intended for dispensation to a patient.
So, for instance, a batch of 60 boxes of blister pack pills will have 60 different identifiers, not just one at the lot level. During production, every aggregation level will have to be integrated into the serialisation process and can be supported by checkweighing technology.
Added value can be generated either by checkweighers with integrated serialisation functionality, tamper evident sealing or aggregation solutions for the secondary and tertiary packaging at the end of the line.
If a pharmaceutical manufacturer works together with contract packagers, which is quite common in Europe, it should keep in mind that those contractors may not be ready for serialisation when it needs them to be.
In addition to upcoming regulatory requirements, the US Drug Supply Chain Security Act (DSCSA) is in development for the pharmaceutical industry, which is to be applied in three phases for the US market up until 2023.
The first phase is to ensure lot traceability, followed by unique serialisation and last, but not least, a combination of the two. Like the EU FMD, this act will involve an increase in work, and systems such as checkweighers will be instrumental in helping manufacturers to remain both compliant and profitable as the regulatory landscape continues to evolve.