Patient safety is at the forefront of considerations in the pharmaceutical industry, with the FDA requiring drug makers to develop and institute quality processes in manufacturing. As a result, expectations for quality from end-users is exceptionally high. It goes without saying that pharmaceutical companies should be ever-diligent to ensure that quality and compliance is a top priority. However, there must also be a balance that allows for appropriate cost management that safeguards affordability for the patient and profitability for the drug maker to ensure continued investment in bringing needed therapies to market.
To address patient and business concerns, the adoption of Quality by Design (QbD) concepts for injectable drug development has expanded within the industry in recent years. However, some manufacturers have been slow to integrate QbD for one very clear reason: cost. QbD principles require a significant up-front investment, which can understandably lead some in the industry to initially shy away. That said, the investment delivers an improved, data-driven output that provides manufacturers with superior product. QbD initiatives also lead to a process that allows stakeholders to better understand risk and how to minimize it.
Starting the QbD Process
As a first step in creating QbD initiatives, it is critical to understand the unique traits of the product at-hand. To this end, a Quality Target Product Profile (QTPP), which forms the basis for drug product formulation and process development in a QbD framework, must first be constructed. QTTP consists of a series of considerations that will uphold the highest standards. Such standards may include: the desired product performance based on the intended clinical setting, dosage strength and delivery mode, pharmacokinetic characteristics, drug product quality criteria, sterility, and the drug’s container closure system—to mention a few.
Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs) for a given product and process, respectively, are developed in support of achieving the QTPP.
The information generated to determine the CQAs and CPPs will help to:
- Develop a meaningful control strategy
- Ensure product quality throughout the product lifecycle
- Increase product and process knowledge to support decisions
- Increase transparency and understanding for regulators and industry
- Enhance information needed for identifying and evaluating potential changes
- Monitor and track critical data for continuous improvement
Assessment of attributes throughout the drug product lifecycle can reduce end-of-line rejections and facilitate overall compliance, while ensuring a reliable and adequate supply.
Understanding Total Cost of Ownership
To ensure that the QbD return on investment is maximized, it is important to understand the Total Cost of Ownership (TCO)—i.e., the analysis of price, risk, quality, service and delivery performance—in evaluating the overall cost of a product versus its benefit. Reducing end-of-line rejections is an example of how the pharmaceutical manufacturer can clearly recognize benefits from TCO. QbD can often drastically lower end-of-line rejections to very minimal rates and generate significant cost savings by enabling more product to go to market for patient use. This, in turn, reduces the probability of product shortage and helps to manage capital expenditures more effectively. The end result: more revenue is generated for the pharmaceutical or biotech company.
Container closure systems represent another area where a TCO model can support QbD initiatives. While drug packaging is often the final consideration in the drug development process, the selection of appropriate primary packaging components is critical to drug stability and the effectiveness and compliance of a commercial manufacturing process. Pharmaceutical manufacturers should seek to partner with packaging suppliers that adhere to QbD principles in the design and development of container closure systems in order to minimize risk. High-quality components and sterile packaging must be well-understood to provide significant benefit to the overall container closure or delivery system. This need is a key driver for adoption of QbD for primary packaging materials such as elastomeric stoppers used for vial closures and plungers used in pre-fillable syringe systems.
The use of components developed from a holistic QbD process helps ensure a high-quality, data-driven product that has been developed to achieve highest patient safety and lowest risk for the pharmaceutical manufacturer. At the center of a TCO analysis by the company must be hard-dollar savings coupled with the reduced financial risks associated with regulatory and quality challenges, potential loss of revenue and the long-term negative impact to brand equity. Additionally, if saved resources can be better applied to other areas of the business, the potential benefits are exponential.