The critical elements of cutting-edge quality programmes
It takes more than Quality by Design (QbD), fostering a culture of quality and measuring quality to meet the drug packaging standards that 21st century pharmaceutical and biopharmaceutical companies demand. It takes all three —working in harmony — facilitated by the best available technology.
What do they demand? Zero defects, which is a manufacturing principle that some industries have attempted to adopt at various times during the last seven decades (its peak, perhaps, coming with the Six Sigma philosophy of the 1980s and 1990s). Although some companies remain true to Six Sigma, others have moved on to other quality programmes.
Whatever a manufacturing company calls it, the principle remains the same: achieving as close to zero defects as possible by the continuous improvement of processes. It involves machine operators, operator training programmes and the automation of inspection processes — along with a strong, quality focused culture — to achieve the highest possible quality standards.
Most industries strive to live up to this principle, but it’s especially crucial in the pharmaceutical industry, wherein potential product defects can cause direct harm to patients, many of them living with chronic disease diagnoses and a subset who have multiple comorbidities. In addition to leveraging the latest technologies, remaining mindful of the end user and their challenges is an essential part of establishing a culture of quality and achieving zero defects.
To ensure the highest quality, pharmaceutical packaging and delivery companies are adopting QbD concepts in the design and production of packaging components, resulting in improved, data-driven output — along with superior product and process understanding that minimises risk — and enhanced drug product quality, safety and efficacy.
Employing QbD for drug packaging and delivery systems during the early stages of drug development can help to mitigate quality risks and better position the drug manufacturer to meet regulatory requirements throughout the drug’s lifecycle. Although it’s not easy to meet these challenges, pharmaceutical manufacturers can benefit from early investment in high quality components for drug packaging and delivery systems.
As a first step in incorporating QbD approaches, it is critical to understand the unique traits of a given drug product. For example, with many inherently sensitive biologics coming on the market, the compatibility of packaging components with injectable drugs and their delivery systems is being closely scrutinised.
To this end, developing a Quality Target Product Profile (QTPP) forms the basis for drug product formulation and process development in a QbD framework. The QTTP consists of a series of considerations that will uphold the highest standards for patient safety. Such standards may include the desired product performance, based on the setting in which a drug product is administered, dosage strength and delivery mode, pharmacokinetic characteristics, drug product quality criteria, sterility and the drug’s container closure system, to mention just a few.
As a first step in incorporating QbD approaches, it is critical to understand the unique traits of a given drug product
Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs) for a given product and process, respectively, are developed to support the QTPP. CQAs and CPPs can help to establish a meaningful control strategy and ensure product quality throughout the product lifecycle, as well as monitor and track critical data for continuous improvement.
A cutting-edge quality programme that achieves the highest standards begins with designing processes with appropriate controls to ensure that these high standards can be met. For instance, automating inspections to check every single unit — whether it’s a vial or a prefilled syringe — at every step of the process, when possible, will ensure that quality thresholds are met.
In the last 5–10 years, camera-based component inspection has replaced human inspection, giving manufacturers and their customers the capacity to detect what they couldn’t previously see. By having the ability to take a more precise, data-driven approach in the analysis of every rejected piece, the industry has been able to improve processes and work more collaboratively with suppliers to do an effective root cause analysis and mitigate quality issues.
To ensure that product quality goes beyond leveraging technology, it should be rooted in a true culture of quality. It takes an environment in which employees not only follow appropriate guidelines, but also feel personally responsible for maintaining quality. For pharmaceutical delivery system manufacturers, this means making sure that all employees understand the patient’s point of view, and the critical role they play in ensuring those patients’ safety.
If you don’t have measurable data, you can’t tell if you’re improving the quality of your products
That internal commitment can take many different forms. At West Pharmaceutical Services, every employee takes annual training, which includes three modules. The first shows who our customers are (global pharmaceutical and biopharmaceutical companies) and the needed injectable therapies they provide to patients around the world. The second module shows how our products are used by customers, what matters to them and how defects could impact the finished drug delivery system. The third comprises education about particulates and best practices regarding how to control them in a manufacturing space.
Beyond that, each employee develops their knowledge and skills into a customised knowledge base for their role — and that can include technical education on sterilisation procedures and cleanroom practices to more general work skills such as oral and written communication skills, knowledge of industry standards and trends in pharmaceuticals and product manufacturing, among other topics.
Continuous information sharing across a global enterprise is also critical. For example, if an employee participates in a gemba walk — in which employees make personal observations about potential risks for contamination in the place the work is done — that information can be entered into a shared knowledge management system for other facilities to analyse those risk factors in their own manufacturing processes. When employees are engaged in the culture of quality at a company, the focus on improving quality and operational metrics becomes a collaborative — and more successful — effort.
If you don’t have measurable data, you can’t tell if you’re improving the quality of your products. Creating metrics on which to gauge quality improvement programmes offers needed benchmarks from which a platform for continuous improvement can be launched. For international manufacturing concerns, regulations governing quality come into play as well. Groups such as the International Conference on Harmonisation of Technical Requirements for Registration for Pharmaceuticals for Human Use (ICH) — now in its 26th year — offers guidance on how to meet differing quality requirements across borders.
The ICH, led by European, Japanese, Canadian and US regulatory authorities, sets procedures and standards in the realms of pharmaceutical development, risk management and quality. Its guidance has the strength of law in many countries. Measurables come into play here, because those laws mandate continuous improvement. Setting key performance indicators and determining your output quality against them — and then striving to reduce any imperfections — makes the measurement process fundamental to achieving zero defects.
It takes more than just machines to get from ‘almost perfect’ to true zero defects. It takes people to act on quality data and a collaborative effort to improve manufacturing processes and employ QbD principles to ensure a high-quality, data-driven product. For a drug product to be successful, the patient must be the focus of both pharmaceutical manufacturers and suppliers of packaging solutions.
In the past, companies might have developed products separately and tried to match finished medications with packaging choices that had been developed without a specific drug product in mind. Today, drug containment systems need to be considered early in the drug development process to truly develop a product with the patient in mind.
With pharmaceutical companies and their manufacturing partners working together in this way, the highest quality standards for purity, usability and efficacy can be achieved, and therapies can be utilised with the best possible outcomes.