FDA has taken initiatives to enrol the sound scientific principles that involve prior identification of the loop poles in the manufacturing and operating procedures that provide hindrance in the development of safe, efficacious and effective product with better therapeutic value. Hence the concept of Quality by Design has been originated which is the combination of ICH guidelines ICH Q8 (Pharmaceutical Development), Q9 (Quality Risk Management) and Q10 (Pharmaceutical Quality System). Q8 addresses collection of necessary knowledge, and Q9 addresses applying the collected knowledge to manage risk. Q10 addresses the need for systems to maintain the process, the facility and, ultimately, product quality throughout the product lifecycle. Implementation of these three concepts defines QbD – a modern systematic approach for the pharmaceutical product development as it involves predefined objectives, involves product and process understanding, monitoring all the critical steps based on sound science and quality risk management. It means designing and developing formulations and manufacturing processes to ensure predefined product quality objectives. Therefore it is a concept that follows quality should not be tested but should be built into the product.
The scope of QbD is vast and can be applied to any process or a step of process, analytical method, dosage form whether generic or new chemical entity to fulfil the objectives cited. Due to its importance and success in pharmaceutical fields, the concept is also shifting to other fields. It’s because all the fields focus on cost, quality and timelines.
Earlier when formulations were developed there used to be flaws that lead to delayed marketing and recalls of the products were more often. Traditional aspect had minimal approaches for the development of formulations whereas when it comes to QBD it is more enhanced and detailed approach.
A) TRADITIONAL APPROACH:
B) QUALITY BY DESIGN APPROACH:
ESSENTIAL ELEMENTS IN QUALITY BY DESIGN:
The basics of QbD remain same for any dosage form. QbD can be described as a four stage process addressing both design and control. The stages are:
The Active Pharmaceutical Ingredient’s (API) chemical and physical characteristics and Drug Product (DP) performance targets are identified.
- Target Product Profile (TPP): It is actually expresses overall intent of the drug development program. The physicochemical properties play an important role in defining the targeted drug product. The selection of which type of formulation and process depends on the physicochemical properties of the drug substance.
- The other point of consideration is the already available dosage forms of the drug substance if it’s a new dosage form or a new chemical entity and its posology, route of administration, contraindications, adverse affects etc. It is necessary to keep the TPP up to date as knowledge of drug substance increases with time.
- The type of excipient chosen, their characteristic and concentration which can increase the drug product’s performance should also be considered.
2) DESIGN SELECTION:
The API manufacturing process and the DP formulation and manufacturing process are selected to achieve the design intent for the product.
- When target product profile has been studied there is need to design formulation and process. This includes what kind of formulation will be suitable for the defined target product profile and which processes will justify the formulation to be prepared.
3) CONTROL DEFINITION:
- The largest contributors to Critical quality attribute (CQA) and Critical process parameter (CPP) variability are established and controls are defined to ensure process performance expectations are met.
- It is important to define drug product CQA’s. The next step is the identification of the API and excipient CQA’s and CPP’s which have drug product CQA’S.The design space is defined through these CQA’s and CPP’s.
- A CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. CQA’s are generally associated with the drug substance, excipients, intermediates (in-process materials) and drug product.
- A CPP is a process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality.
- Once the CQA’s and CPP’s are defined risk assessment is done. Risk assessment is a valuable science based process that help in identifying which material attributes and process parameters will eventually have an effect on CQA’s.
- Then design space is constructed which is a multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality.
4) CONTROL VERIFICATION:
The performance of the API and DP processes in manufacturing are measured to verify that the controls are effective and the product performance acceptable. A control strategy is designed to ensure that a product of required quality will be produced consistently. The source of variability should be identified, appropriately understood and then subsequently controlled. Once identified with their nature of impact it is helpful in reducing the need for end product testing.