Quality by Design

A presentation covering QbD inclusive of its definition, goals, advantages, QTTP, Risk Assessment Methods, Design of experiment, Life Cycle Management, etc.,

1. QUALITY BY DESIGN By:- Lalit M.Pharm (Quality Assurance) Delhi Institute Of Pharmaceutical Science And Research

2. Quality By Design :- Quality by Design ( QbD ) refers to a new approach to product development that could increase efficiencies, provide regulatory relief and flexibility, and offer important business benefits throughout the product life cycle. QBD is defined in ICH Q8 guideline as “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management”.

3. Goals Of QBD :- To achieve meaningful product quality specifications that are based on clinical performance. To increase process capability and reduce product variability and defects by enhancing product and process design, understanding, and control.

4. Advantages Of QBD :- Higher level of assurance of drug product quality. Offers cost savings and efficiency for the pharmaceutical industry. Increases efficiency of pharmaceutical manufacturing processes and reduces manufacturing costs and product rejects. It facilitates innovation for unmet medical needs. Makes the scale-up, validation and commercialization transparent, rational and predictable

5. Q uality Target Product Profile (QTPP) Necessary Elements Quality characteristics: sterility, purity etc. (including specific safety-related impurities where necessary) Pharmacokinetic characteristics: dissolution etc. Therapeutic effect Target patient population: neonate, adult etc., clinical diagnosis Shelf life: temperature, light conditions etc. Desired Elements Dosage form: liquid for injection, solid tablet etc. Route of administration: oral, IV, IM, SC Clinical setting: self or clinic administration Primary/secondary packaging: glass or plastic vial/syringe; blister packaging etc

6. The QTPP Leads to Critical Quality Attribute (CQA) Definition Critical Quality Attribute (ICH Q8): “A property or characteristic that when controlled within a defined limit, range, or distribution ensures the desired product quality.” Potential CQAs are derived from the QTPP and guide product and process development. CQAs are identified by quality risk management and experimentation to determine the effect of variation on product quality. The CQA list can be dynamic and may be updated based on product and process knowledge.

7. Process Performance Qualification Verification that the defined CS consistently delivers the desired product quality PPQ is a significant product milestone Provides proof the process is well controlled Establishes an initial baseline for future process evaluation PPQ is a dynamic part of the validation concept

8. Risk assessment method Quality risk management (QRM) FDA defines QRM as a systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product lifecycle. The goal of QRM is therefore to identify risks within a process or event, analyzing the significance of these risks, and take appropriate measures to mitigate such risks if deemed unacceptable.

9. Various methods for determination of risk There are various method for determination of risk are as follows :- Failure mode effect analysis Failure mode effect and criticality analysis Decision tree analysis Hazards analysis & critical control point Hazard operability analysis Preliminary hazard analysis Risk ranking & filtering

10. Design Of Experiment DOE is an efficient procedure for planning experiments so that the data obtained can be analyzed to yield valid and objective conclusions. A structured, organized method for determine the relationship between factors affecting a process and the output of that process is known as “Design of experiment”.

11. Application Of DOE DOE is used to :- Determine the causes of variation in the response Find conditions under which the optimal (maximum or minimum) response is achieved To compare responses at different levels of controlled variables To develop a model for predicting response.

12. Control Strategy Control strategy is defined as “a planned set of controls, derived from current product and process understanding that assures process performance and product quality”. The control strategy in the QbD paradigm is established via risk assessment that takes into account the criticality of the CQA and process capability.

13. Life Cycle Management According to Elaine Morefield (Deputy Director USFDA) it includes continuous improvement of method performance and the design space allows flexibility for continuous improvement in analytical method can be done without prior regulatory approval because of design space made previously.