From Terminal Sterlization to Aseptic Manufacturing of Perentral Products: Gut Sound of Regulatory Sciences
•
3 likes•1,580 views
For a discussion forum among selected manufacturing leadership of sterile drug product
Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Viewers also liked
Viewers also liked (20)
Similar to From Terminal Sterlization to Aseptic Manufacturing of Perentral Products: Gut Sound of Regulatory Sciences
Similar to From Terminal Sterlization to Aseptic Manufacturing of Perentral Products: Gut Sound of Regulatory Sciences (20)
More from Obaid Ali / Roohi B. Obaid
More from Obaid Ali / Roohi B. Obaid (20)
Recently uploaded
Recently uploaded (20)
From Terminal Sterlization to Aseptic Manufacturing of Perentral Products: Gut Sound of Regulatory Sciences
- 1. From Terminal Sterilization to Aseptic Manufacturing of Parenteral Products Gut Sound of Regulatory Sciences Obaid Ali R.Ph., M. Phil., Ph. D. Civil Services Officer 02 June 2016 Arena, Karachi
- 3. Mr. Sultan Jawa (MD, Irza Pharma, Lahore) Last Sunday & Mr. Masroor Hassan (Production Manager, Hudson Pharma, Karachi) Yesterday May Allah give them eternal success
- 4. Not the view of DRAP Current judgment of speaker No obligation on DRAP Regulatory experience It has nothing to do with any specific commercial product or organization It is just a knowledge sharing exercise nothing more than that D I S C L A I M E R
- 5. Machines are fast, accurate and dumb People are slow, sloppy and brilliant Albert Einstein Opening Message
- 6. P A R E N T E R A L S IV IM IG SC . . .
- 7. When life is everything Risk
- 9. Good Luck Cannot swim itself Cannot move itself
- 10. Good Luck Sensitive to heat Sensitive to radiation Sensitive to chemicals
- 15. Way to kill Approach to kill
- 16. When calculated risk is the only option Each and every caution is indispensible
- 17. If something has not happened yet, it will likely not happen Design may be flawed, but there is no evidence that there is a problem If something has not been identified by inspector, it is ok Passing the media fill assures process control Lets correct, it is misconception
- 18. Sterility test has not yet failed but reason of pass is not defendable We are complying and it is enough, no matter what you are referring Traditional approach is a good approach Insulin was filled in an area under exhaust fans in history Lets correct, it is misconception
- 20. Towards stringent control, not otherwise
- 21. Compendial requirements are the minimum standards
- 22. Where we have an option to choose
- 23. Aseptic processing proven safe but not sterile IncreasedseparationofPersonnel Increased confidence in Sterility Assurance Manual aseptic fill Conventional aseptic fill Barrier System Open RABS Closed RABS Open Gloved Isolator Closed Glove Isolator Glove-less Isolator
- 25. Freedom from Road Blocks Come out from traditional approach of intellectual block Be proactive in using technical knowledge Live safe and keep moving forward
- 26. What happens if there is fire ? Alarm React Glass breaking Etc. etc.
- 27. Have a Fundamental Stroke …. “ Leadership is essential to establish and maintain a company wide commitment to quality and for the performance of the Pharmaceutical Quality System” ICH Q10
- 28. So have an overview “ An effective risk management program aids in the careful control of process, reducing the risk of contamination as well as wasted efforts in controlling insignificant risk” Risk management of Aseptic Processing, Ed White, 2009
- 30. Detection sensitivity (n = 20 samples) Microorganism Concentration Probability of one Sterility test positive (+) 1.0 1.0 0.1 0.88 0.01 0.18 0.001 0.02 10-6 1.9x10-5 18% of time, not 82% of time
- 31. Sterility is very difficult to prove Microorganisms are not homogenously distributed over all units Sample Size % Contamination 0.1 1 5 10 15 10 0.01 0.09 0.40 0.66 0.80 20 0.02 0.18 0.65 0.89 0.96 50 0.05 0.34 0.92 0.99 100 0.09 0.63 0.99 300 0.26 0.95 3000 0.95
- 32. Take an area as an example of challenge
- 33. • Protects body from pathogens • Prevents loss of moisture • Body temperature regulation 2m2 • Considerable diversity in species • Variation b/w different locations on body • Variation b/w individuals Diversity • Average person sheds 1 billion skin cells/ day • 10% have micro-organisms on them30 million Human Skin Go in clean rooms They touch, shed, do things wrong sometimes
- 34. ORAL CAVITY High population High diversity SKIN Variable population Low diversity URETHRA/VAGINA High population Low diversity GUT High population High diversity People Ecology
- 35. Others that contribute a lot
- 36. Clean room requirements are demanding when stringent particulate control and aseptic conditions are required during manufacturing This requirement applies in particular to filling lines located in HEPA filtered UDAF. In such cases, turbulent regions and wakes can play critical roles by causing an accumulation of contaminants Bengt & Berit, 2004 Just for the sake of reference
- 37. Just for the sake of reference Engineers design and install Validation department executes validation Production department performs production Maintenance department performs maintenance Quality Control performs tests Quality Assurance reviews and approves
- 38. Just for the sake of reference Microorganisms unique to your facility and operation Personnel and material flow Air flow pattern evaluations Observation of aseptic filling operation Environmental monitoring sample site selection
- 40. Diclofenac Sodium Injection Innovator uses terminal sterilization
- 41. Diclofenac Sodium Injection Innovator uses terminal sterilization Generic ????????
- 42. A Is it consistent with science to opt aseptic filling ? 1 2 3 4 5 6 7 8 9 10 Yes No
- 43. B Is impurity not the subject of interest ? 1 2 3 4 5 6 7 8 9 10 Yes No
- 44. C Should impurity be included in release specifications ? 1 2 3 4 5 6 7 8 9 10 Yes No
- 45. D
- 46. Lets be honest Risk management encourages proactive rather than reactive, management of product processing and is a means to end itself Quality Risk Management for Aseptic Processing PDA Technical Report No. 22, Vol. 62, No. S-1, 2008
- 47. Lets be honest Rigorous thinking is involved with logical, systematic and science based approaches to improve the effectiveness and efficiency of decision making Quality Risk Management for Aseptic Processing PDA Technical Report No. 22, Vol. 62, No. S-1, 2008
- 48. Lets be honest The goal of Quality Risk Management program should be to better understand the process and improve the process, thereby assuring patient safety Quality Risk Management for Aseptic Processing PDA Technical Report No. 22, Vol. 62, No. S-1, 2008
- 49. Become wise and proactive Don’t wait for any human tragedy Read the wall ….
- 50. Good ideas are not adopted automatically. They must be driven into practice with courageous patience Admiral H.G. Rickover Closing Message