Patient safety
Future quality standards for pharmaceutical packaging

The packaging is an integral part of a medicine product, and it does more than just protect and stabilize the contents. It also provides information and simplifies application. Drug packaging is also an important part of the production process. Stringent quality standards apply from raw material acquisition right through to distribution.

Increased life expectancy, high expectations relating to personal health care and advances in medical technology have all stimulated growth in the pharmaceutical market. More than 180 million packages of medicine cross the counter annually in Switzerland, accounting for ten percent of total expenditure on health care. The average household spends about 1.5% of income on medication, which is about the same as the amount that it spends on cosmetics and telephone calls. During recent years, the ICH (International Conference on Harmonization) has brought about much closer alignment of cGMP norms between the US, European and Japanese economic regions. Compliance with these norms is mandatory in the pharmaceutical industry. Harmonization formed the basis for a number of MRAs, which set down guidelines for mutual recognition of inspections by official bodies. But what will quality standards look like in the future? If you look specifically at pharmaceutical packaging, you can identify several trends which are discussed in more detail below.

Regulatory requirements have evolved rapidly
Regulatory requirements relating to patient safety, drug effectiveness and the development and production of drugs have evolved very rapidly on the past few decades. GxP standards and national guidelines will continue to drive the quality requirements which apply to drugs and pharmaceutical packaging, albeit in harmonized form. Some aspects are already very concrete:
Improved flow of information
Global electronic databases will enable the authorities to efficiently manage information on active ingredients and products as well as production and the country-specific use of the ingredients and products.
Batch release
Annex 16 of the EU GMP Guide has been in effect since 2002. It defines the requirements that must be fulfilled before a batch of medicinal products can be released. These requirements were deemed to be necessary because the authorities recognized that the drug production process and the packaging can encompass highly complex acquisition and manufacturing steps which are distributed across a number of different companies. The qualified person, who has ultimate responsibility for release, must have sufficient information about the process flow and be able to evaluate the information properly.
Electronic Batch Recording
Paperless documentation is based on Electronic Batch Recording (EBR), which guarantees compliance with the FDA requirements defined in 21 CFR Part 11 relating to electronic signatures and records. Controlling operator data access, recording all activity, events and process changes and the use of electronic signatures made it possible to take a quantum leap forward in documentation. This creates an opportunity to greatly increase the efficiency of batch documentation for packaging, and it will lead to a paradigm shift in the production process. Rather than being primarily responsible for documentation, personnel will be used to evaluate unexpected events and take appropriate corrective action.
Child safety
Drugs must be supplied in child-proof packaging which meets US and EU requirements. This can be difficult to achieve with some types of packaging. Stick packs are currently popular in the pharmaceutical market, but technology to provide safe opening aids has not yet been developed.
Process Analytical Technology
There is widespread discussion of the FDA PAT initiative among experts. Although the focus is on methods relating to analytical chemistry and NIR spectroscopy, PAT is seen as a system which is designed to increase understanding and control of the production process. The goal is to use state-of-the-art measurement technology to monitor and control processes in real time. If you follow this logic further, you can apply this methodology to the packaging process where numerous control parameters have to be regulated and analyzed.
Traceability and protection against counterfeiting
As the supply chain becomes more complex, the task of ensuring traceability and preventing counterfeiting poses an even greater challenge for support systems. Stringent quality control all along the process and logistics chain, from the packaging step to the wholesaler, is crucial. The risks are primarily the result of insufficient transparency as products flow through the sales channels. RFID can be used as a quality assurance tool to significantly improve the level of control. The application of Good Distribution Practices during distribution, warehousing, re-packaging and re-labeling will have a key role to play in the future.
The problem of pharmaceutical counterfeiting continues to grow. Experts estimate that this problem is currently costing the industry significantly more than $10 billion a year, which is 5% of pharmaceutical market volume. This is not merely a financial issue. It also puts patient welfare at risk. The importance of counterfeit-proof packaging will continue to increase in the pharmaceutical industry. There are three different aspects to consider:
the use of special features to safeguard the packaging,
tamper proofing,
Electronic Article Surveillance (EAS).
There is a wide range of engineering solutions including DNA tagging with color recognition, holograms, thermosensitive and UV fluorescent substances on cover foil for blister packaging and RFID technology using microchips (on labels or directly integrated into the packaging). These techniques can be used on primary and secondary packaging. However, to ensure complete security coverage, identical features must be used to protect the product’s primary packing, the patient information leaflet and the secondary packaging. The packaging industry can benefit from the experience of the industry which produces financial documents.
Automation and process control
Automation systems are still very important in the process industry, and this is particularly true for the pharmaceutical industry. However, this raises other issues for plant operators. MES, Manufacturing Execution Systems, are increasingly becoming the hubs in the pharmaceutical manufacturing environment. They support complex operations and link distributed process control systems to higher-level ERP systems. This presents a challenge to quality systems which are designed to monitor the processes. ERP and MES systems will enhance the level of integration in pharmaceutical packaging production. Process control systems that record and analyze process data in addition to providing graphic-based process control will provide vital quality assurance functionality.
Integral quality systems
Mounting cost pressure will increasingly force manufacturers to enter into strategic alliances which are able to handle cost-intensive production steps and technologies. Appropriate control measures will be required to manage these complex networks. The cGMP approach taken by the FDA in its 21st century initiative is to implement science-based risk management and integrated quality systems. The intention is to move on to a risk-based approach. Instead of asking what could possibly happen, the goal will be to identify risks and then to minimize them. CAPA will play a key role in this context in the years to come.
CAPA stands for “corrective action preventive action”. It describes a tool for achieving integrated, comprehensive fault management. The goal is to develop an effective methodology for handling quality defects, faults and other deviations and preventing fault situations. The CAPA approach provides a good indicator for corporate quality management, and it has proven its effectiveness in the medication industry. Adoption of the CAPA approach to the management of pharmaceutical and packaging technology is advisable, because it establishes an overall process that encompasses failure detection, analysis and correction, which are often viewed as sub-processes.
The challenge facing manufacturers is to manage the “golden triangle” of quality/safety, delivery schedule and cost and to find the right balance of parameters.
Interpack, the world’s largest packaging technology show, is the place to be if you want to see the latest trends in the industry. The trade fair will take place in Duesseldorf from April 21st–27th, 2005.