QBD IN PHARMACEUTICAL DEVELOPMENT

M.PHARM 2ND SEM CAD

1. MANOJ R DEPT OF PHARMACEUTICS NANDHA COLLEGE OF PHARMACY

2. ⦿ The suitability of either a drug substance or a drug product for its intended use. This term includes such attributes as the identity, strength and purity. QUALITY

3. ⦿ It is a syst e m a tic a p p ro a ch t o d e vel o p m e nt that begins with pre-defined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. QUALITY BY DESIGN

4. QUAL IT Y B Y D ESIGN ME A N S - d e sig n i n g and developing formulations and manufacturing processes to ensure a predefined quality. Q U AL I T Y BY DESIGN R E QUIRE S - understanding how formulation and manufacturing process variables influence product quality. QUALITY BY DESIGN ENSURES- Product quality with effective control strategy. SIGIFICANCE OF QbD

5. KEY ASPECTS OF QbD

6. ⦿ Active ph a rmaceu t ical in g red i en t s ⦿ Mat e rials includ i ng excipi e nts ⦿ Analytics ⦿ Sim p le dosa g e forms ⦿ Advanced drug d elivery s y stems ⦿ De v ices ⦿ Com b in a ti o n p rod u cts QbD APPROACH USED FOR

7. Benefits for Industry: Better understanding of the process. Less batch failure. More efficient and effective control of change. Return on investment / cost savings Reduction of post-approval submissions. More efficient technology transfer to manufacturing Risk-based approach and identification. Innovative process validation approaches ADVANTAGES OF QbD

8. Target Product Profile Critical Quality A ttributes LINK Mas and Pps To CQAS Establish Design Space Establish Control Strategy Risk Management STEPS IN QbD APPROACH

9. ⦿ The t a r g et pr o d u ct pr o fi l e (TPP) ha s been defined as a “prospective and dynamic summary of the quality characteristics of a drug product that ideally will be achieved to ensure that the desired quality, and thus the safety and efficacy, of a drug product is realized”. 1. TARGET PRODUCT PROFILE

10. ⦿ 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. ⦿ C Q As are g e n e ral l y associat e d with th e - Drug substance Excipients intermediates (in-process materials) Drug product 2.CRITICAL QUALITY A TTRIBUTES

11. MATERIAL: Raw materials, starting materials, reagents solvents process aids, in t erm e di a tes, AP I s, p a c k a g ing and labelling materials, ICH Q7A A TTRIB U T E : A p h y s ical, che m ical, biological or microbiological property or characteristic 3a. M A TERIAL A TTRIB U T E

12. ⦿ M A TERIAL A TTRIB U T E : Can be an excipient CQA, raw material CQA, starting material CQA, drug substance CQA etc A material attribute can be quantified Typically fixed Can sometimes be changed during further processing (e.g.PSD-milling) Example of material attributes:PSD, impurity profile,porosity, specific volume, moisture level, sterility.

13. ⦿ 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 (Q8R2). ⦿ CPPs have a direct impact on the CQAs. 3b. PROCESS PARAMETER

14. ⦿ A pr o c e ss p a ram e ter (PP) can be measured and controlled (adjusted) Exam p les of CPPs for sma l l mol e cul e : t e m p er a t u re, a d d i ti o n ra t e, c o o l i n g ra t e , rotation speed Exam p les of CPPs for large mol e cul e : temperatue , pH, agitatiom , dissolved oxygen, medium constituents, feed type and rate.

15. ⦿ The m u l ti d i m ensio n al com bi n a ti o n a n d interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. ⦿ Regul a tory fl e xi b il i ty- working with i n the design space is not considered a change ⦿ De s ign sp a ce i s pr o p o s e d b y t h e a p pl i cant and is subject to regulatory assessment and approval. 4. DESIGN SPACE

16. DESIGN SPACE DETERMINATION FIRS T -PRINCIP L ES APPROACH : Combination of experimental data and mechanistic knowledge of chemistry, physics and engineering to model and predict performance. NO N-MECHANISTIC/ E M PIR I CAL APPROACH : Statistically designed experiments (does) linear and multiple-linear regression

17. ⦿ SCAL E -UP CORREL A TIONS Translate operating conditions between different scales or pieces of equipment ⦿ RISK ANA L YSIS Determine significance of effects

18. ⦿ A PLANNED SET OF C O NT R OLS Derived from current product and process understanding. That a s sur e s p roc e ss p e rfor m a n ce a nd product quality. ⦿ THE CONT R OLS CAN INCLU D E Parameters and attributes related to Drug substance Drug product materials Components, facility 5. CONTROL STRATEGY

19. Equipment operating conditions In-process controls Finished product specifications The associated methods and frequency of monitoring and control (ICH 10)

20. ⦿ RISK : Risk is defined as the combination of the probability of occurrence of harm and the severity of that harm. ⦿ RISK ASS E SSMEN T : A syste m a tic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards. 6. RISK ASSESSMENT

21. ⦿ ICH G u i d e l i n e Q 8 -Ph a rm a ceu t ical Development, http://www.ich.org (10 NOV 2005) ⦿ U .S . F o o d a nd D r ug A d m i n i stra t i o n Guidance for Industry. PAT- A Framework for Innovative. REFERENCES

22. THANKS