SHANKAR GUPTA

Limits for Microbial Environmental Monitoring-

Sterilizing filtration is the process of removing all microorganisms excluding viruses from the solution, without adversely affecting the product quality. It is suitable sterilization method (aseptic process) for heat sensitive drug products . 1. Porcelain filter cartridges- Discontinued 2. Asbestos cellulose layers- - Discontinued 3. Membrane filters Pseudomonas diminuta (currently reclassified as Brevundimonas diminuta)= 0.3x0.6-0.8 µm registered with American Type Culture Collection ATCC No.: 19146. Use of this organism leads to several advantage - 1. Non-pathogenic to human. 2. Can be consistently cultured under controlled condition to to yield very small , mono-dispersed cells with narrow size distribution. 3. A process stream isolate, it is therefore a realistic potential problem organism. The disadvantages of B. diminuta are- 1. Not viable in many pharmaceutical formulations. 2. May not be the smallest bacterium potentially encountere d in all formulations, ...

E1. Line clearance activities at different processing stage- - Dispensing - Manufacturing - Decartoning, Vial washing and depyrogenation - Unit preparation area LC - Filling/ sealing assembly - EDMC - Visual inspection etc 2. In- process quality assurance checks - Area monitoring - Filled weight - Visual inspection and sealing quality check - Seal integrity check or Leak test - Machine speed and nitrogen flow rate - Interventions monitoring - Aseptic area practice monitoring 3. Aseptic Media Fill Simulation Study 4. Internal audit 5. SOP revision and it's training 6. Sampling at different processing stage 7. Offline NVPC monitoring and it's quarterly trending Limit - 8. Protocol preparation and its approval 9. Batch record review and it's compliance 10. Oversight on online activity - Assembling procedures & its flow - Manufacturing procedures & its flow 11. AQL Limit for manual visual inspection - Critical - Major - Minor- Limit...

The following Methodology techniques may be employed as necessary to facilitate the determination of the root cause- A. 5 Why analysis B. Cause and Effect analysis - Ishikawa or ‘fishbone’ diagram C. Fault Tree Analysis D. Any other suitable tool(s)

Parenteral Drug Association - Technical Report No.: 4, Design Concepts for the validation of Water for Injection System. Parenteral Drug Association - Technical Report No.:13 Rev 2, Fundamentals of an Environmental Monitoring Program. Water for Pharmaceutical Purposes USP <1231>. Alert level:  are levels or ranges that when exceeded, indicate that the process may have drifted from its normal operating condition. Alert level constitutes a warning, necessary investigation has to be done, may not require a corrective action. Action level:  are levels or ranges that, when exceeded, indicate that the process has drifted from its normal operating range. Exceeding an action level, necessary investigation shall be performed and Corrective Action and Preventive Action (CAPA) shall be taken as appropriate. PRETREATED/ POTABLE/DRINKING WATER GENERATION AND DISTRIBUTION SYSTEM (NEW SYSTEM) =  Feed water for purified water system Pre-treated water from ...

Interventions are aseptic processing manipulation necessary for batch processing aseptically. Interventions are categoriesed- 1.Based on requirements 1.1. Corrective A) Open Door B) Closed Door 1.2. Inherent A) Open Door B) Closed Door 2.Based on impact 2.1. Critical 2.2. Major 2.2. Minor Inherent interventions (Routine interventions) Inherent (routine) close door: Example: Addition of rubber stoppers Inherent (routine) open door: Example: Initial filling parts assembly etc. Corrective interventions (Non routine interventions) Corrective (non routine) close door: Example: Clearing of vial jam from infeed turn table, clearing of seal jam in chute by forceps,etc. Corrective (non routine) open door: Example: Glove port glove fixation for cRAB, sealing roller head / sealing die adjustment, etc. Critical intervention: Directly pose risk of contamination to the product or zone of sterilized product/container closure exposure. Major interven...

Guidelines- 1. PDA Technical report No.: 29 (Revised- 2012)- Points to be considered for Cleaning Validation. Cleaning Validation Study necessary to validate cleaning process to be used before start of batch execution, and it gives- Assurance that the established cleaning process is effective and it prevents the carryover of previous product/ cleaning agents in subsequent batch. It Limits potential carryover to an acceptable level. Controls potential carryover of the products, intermediate, and impurity.  Quality of the next product does not compromised with the waste of previous product.  TRF (Total Risk Factor) - Decides the selection of worst case molecule (Marker compound) for validation of cleaning process. TRF components are Toxicity (OEB), Solubility, Potency (Minimum therapeutic dose), and other factors as cytotoxicity. OEB and Solubility are the major component and shall be added as multiplier of 6. Potency and other factors (if any) shall ...

Guidelines - 1. PDA Technical report No.: 22- "Process Simulation Testing for Aseptically Filled Products". 2. PDA Technical report No.: 44- "Quality Risk Management for Aseptic Processes". 2. PIC'S (Pharmaceutical inspection convention or Pharmaceutical inspection co-operation scheme) 3. USFDA Guidance to industry (Sep/2004)- "Guidance for Industry, Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice, September 2004" 4. European guideline to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use, Annex 1: Manufacture of Sterile Medicinal Products, (corrected version) November 2008. Aseptic Media fill Simulation Study necessary to- *Qualify the process line *Qualify the personal *Qualify the container- closure system Media fills may be used to: 1. Support new or revised aseptic processes are operating under the desired state of control. 2. Periodically confirm the aseptic pr...

Steam Quality (Pure Steam) for Pharmaceutical use shall be ensured by- 1. Test for Level Non- Condensable Gases (Oxygen, Carbon di-oxide, Nitrogen, Ammonia, and some halogenated hydrocarbon gases etc). Limit= Should not be more than 3.5 %. 2. Dryness Value Test or Moisture Level in Steam 0.90- For porous Loads 0.95- For Metal Loads Excess moisture in steam will cause dumping of Loads.  Less moisture cause raising of superheat value.  Value for porous Load= Value for Non-porous Load= 3. Super heat value of steam at expansion tube. 25 degree Celsius