WHAT IS QUALITY BY DESIGN?
“You can’t test quality into drug products” has been heard for decades – so what’s new?
- It’s a culture – incorporates quality principles as well as strong compliance function,
- Incorporates risk assessment and management,
- Refocuses attention and resources on what’s important to the customer, i.e., the patients, health professionals, payors and distribution chain,
- Systematic approach to development,
- Begins with predefined objectives,
- Emphasizes product and process understanding and process control,
- Based on sound science and quality risk management.
- Continuous improvement is a hallmark of quality by design
ICH Q8 Pharmaceutical Development focuses on the content of the Module 3.2.P.2 of the Common Technical Document (CTD) and promotes the concept of QbD. It supports knowledge gained through the lifecycle of a product and using scientific approaches and quality risk management principles. Within the scope of Q8 Pharmaceutical Development, an important step in the QbD approach to the development of drug products requires a distinction between critical and non-critical product attributes and process parameters. Additionally, the quality target product profile (QTTP) is defined as a summary of the quality characteristics or attributes of a product that ideally will be achieved and is related to quality, safety and efficacy, considering e.g., the route of administration, dosage form, bioavailability, strength, and stability.
ICH Q9 Quality Risk Management defines risk and offers a systematic approach to quality risk management via describing how to conduct risk assessments and to manage the risks defined providing guidance on the principles and some of the tools of quality risk management. It can be a guide as a resource document that is independent of, yet supporting, other ICH Quality documents and complementing existing quality practices, requirements, standards, and guidelines within the pharmaceutical industry and regulatory framework.
The ICH guideline Q10 describes a model for an effective pharmaceutical quality system that is based on International Standards Organization (ISO) quality concepts, includes applicable GMP regulations and complements ICH Q8 and ICH Q9, and is applicable for a lifecycle of a product. This guideline focuses on regulating the quality management systems of drug manufacturers; whereby any changes to manufacturing processes would be managed by appropriate change control procedures have been developed.
If the principles described in the ICH Q8, Q9 and Q10 guidance documents are implemented together in a holistic manner, then an effective system that emphasizes a harmonized science and risk-based approach to product development and maintenance is in place. This provides an even greater (quality) assurance that the patient will receive product that meets the critical quality attributes (CQA).
OVERVIEW OF QbD:
An approach to designing product and processes to supply product to meet patient needs at desired quality levels without reliance on release testing.
- Build in quality versus test in quality.
- Scientific-based knowledge of the products and processes
- Identify, understand, and control CQA’s (Critical Quality Attributes) and CPP’s (Critical Process Parameters)
- QRM (Quality Risk Management) approach (risk assessment, risk control, and risk review)
- Design Space (DS) to identify acceptable limits of operation via DOE (Design of Experiments)
- Control Strategy to ensure production is maintained within the DS
- Use advanced statistical tools and technology such as PAT (Process Analytical Technology). This can extend to real-time release (RTR)
SYSTEM COMPARISON: TRADITIONAL VERSUS QbD
ADVANTAGES OF QbD:
- Better innovation due to the ability to improve processes without resubmission to the FDA when remaining in the Design Space
- More efficient technology transfer to manufacturing
- Less batch failures
- Greater regulator confidence of robust products
- Risk-based approach and identification
- Innovative process validation approaches
- Less intense regulatory oversight and less post-approval submissions
- For the consumer, greater drug consistency
- More drug availability and less recall
- Improved yields, lower cost, less investigations, reduced testing, etc.