SHANKAR GUPTA

ICH Q9 (R1) Adopted on 18-Jan-2023 Quality Risk Management is valuable component of effective quality system. Two primary principles of quality risk management are- 1. Risk to quality shall be based on scientific knowledge and ultimately link to protection of the patients  2. Level of efforts, formality and documentation of the quality risk management process should be commensurate with the level of risks

QMS Framework is responsible for defining the quality standards inlining with regulatory standards to ensure for consistent supply of quality medicine to the patients. Basically QMS framework design per ISO 9001:2015 standards and follow structured hierarchy - There will be three levels - Level 1- Strategic level - Policy, Manual and module - documents in this level can't be presented to HA inspections  Level 2 and Level 3- Operational level - documents in this level can be presented to HA inspections  Level 2- procedures, batch records, protocol etc Level 3- Record and reports Understanding and identifying “interested parties” is one of the foundational requirements of ISO 9001:2015, as outlined in Clause 4.2. Yet many organizations struggle with this task — not because it is difficult, but because it often feels vague or disconnected from day-to-day operations. In practice, identifying interested parties is understanding who affects or is affected by your quality management ...

 QbD is systematic approach to development and begins with predefined objective and emphasises product, process understanding and process control, based on sound science and quality risk management.  QbD enhance the assurance of product safety and effective drug supply to customer  QbD also offer promise to significantly improves manufacturing quality performance  QbD having below steps- 1. Define Target product profile (use, safety and efficacy of the product) 2. Define Target quality product profile - used by the formulator and process engineer as quantitative surrogate for the aspects of clinical safety during development. Gather relevant prior knowledge about drug substance, critical raw materials and process operation in to knowledge space. Use risk assessment to prioritise for knowledge gaps for further investigation. 3. Design formulation and identify Critical quality attributes/ Critical material attributes of final product, which required to be controlled to...

Hehe thanks for asking me that. You would also know the state of inflation today. And how hard its to catch up with that. I really have big hopes with this change and looking forward for something which can make some significant impact in my household and lifestyle. and I definitely want to see good numbers in the offer letter.

1. Have you gone through job role ? And is there anything you wanted to ask? 2. There is two different positions with different requirements and responsibilities, what you will prefer? 3. You have diverse profile, what is the reason behind? Have you worked as whatever you got opportunity - you grasped are you have changed your interest frequently? 4. What are the components in investigation? 5. Tell me examples of deviations and investigation? 6. Guideline for propylene glycol  7. Why hold time study is required  8. Overtalk 9. Sorry  10. Please 

Audit readiness Reference https://www.fdanews.com/ext/resources/files/The_Food_And_Drug_Letter/2013/Inspection-Readiness-ExecSeries.pdf https://ispe.org/initiatives/regulatory-resources/gmp/audit-checklist# Before start of audit we need to review past audits and note indication of possible problem areas and items, if any ensure that were identified for corrective actions in a previous audit. If not aware about facility learn what products being produced and how it is organised with personal and function. To have systematic audit checklist to be prepared and alongwith notebook it needs to be utilised (notebook required to make detailed entries while audit and checklist is to guide auditor). Atleast three production batches to be selected For thorough analysis to include- a) Traceability of all components or materials used in that batch. b) Documentations of raw materials or components, inprocess and finished goods testing for subject product batches. c) Warehousing and distribution reco...

US Market (Supplement): Post approval drug manufacturing supplement for NDAs/ ANDA submitted to FDA for Major or Moderate manufacturing change. Major change - If a manufacturing change is considered to be major, an applicant must submit and receive FDA approval of a prior-approval supplement (PAS) before the drug product made with the change is distributed. Moderate change- If a manufacturing change is considered to be moderate, an applicant must submit a supplement at least 30 days before the drug product is distributed (a CBE-30 supplement) or, in some cases, submit a supplement at the time of distribution (a CBE-0 supplement).  “CBE” means “changes-being-effected”. Post manufacturing supplement - 1. CBE 0 (Change being effected before 00 days): 2. CBE 30 (Change being effected before 30 days): 3. PAS (Prior approval supplement): EUROPE Market (Variation): A variation to the terms of a marketing authorization is an amendment to the contents of the docume...

Critical quality events-QP EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use - Annex 16: Certification by a Qualified Person and Batch Release Quality Event: The event occurred during manufacturing / analysis of batch / lot or event occurred during the batch / lot is in the distribution system or as a market feedback which is likely to have potential impact on finished product Qualified Person (QP): QP is the person responsible for ensuring that each individual batch has been manufactured and checked in compliance with laws in force in the Member State where certification takes place, in accordance with the requirements of the marketing authorization (MA) and with Good Manufacturing Practice (GMP) Periodic Events Notification- Quality events summary report shall be prepared on quarterly basis 1.     Incidents- Incidents which have a systemic effect: · Any validation / qualificat...

Steam In Place - Steam In Place vs Sterilize In Place- Steam in place term used to describe in situ sterilization using steam. Sterilize in place term used to describe in situ sterilization using various types of gaseous or liquid sterilizing agents including steam. Terminal sterilization = Steam under pressure - A probability of no more than one no-Sterile unit in a million (10-6) is readily achievable. Aseptic - A controlled process or condition in which the level of microbial contamination is reduced to the degree that microorganisms can be excluded from a product during processing.

Air velocity measurement As part of risk assessment this evaluation should also consider the selection of locations for the critical control points for monitoring air velocity as well as viable and non-viable particles. 1. Problem Statement- Where should airflow velocity measurements be taken with respect to a filling line or other aseptic processing areas? Recommendation Airflow velocity measurements should be taken at locations where meaningful and reproducible results can be obtained. This is typically at a distance of 6 inches from the filter face . Rationale for Recommendation The primary reason for airflow velocity measurements in unidirectional airflow areas (e.g., areas where product, product contact packaging components, and product contact surfaces are exposed) is to assure there is adequate airflow to protect the materials from external airborne contamination . Accurate measurements can be taken and changes over time detected when airflow velocities are e...

USP general chapter - 797 1. Unidirectional airflow 2. Sweeping action over and away from the product under dynamic conditions. 3. It is useful in identifying eddy currents and recirculation of air flow as a means of assessing risk of contamination in critical areas within a clean room. First air should contact critical components or products before contacting anything else. It should be free of eddy currents or deviant air that can act as a channel or reservoir for contaminants. It is important to evaluate air flow patterns to assure that these patterns do not pose a risk of distributing particles from sources such as surrounding environment, personal, operations, materials or equipment. These tests are used to demonstrate that airflow under operational conditions doesn't contribute to contamination risk. Regulatory bodies requires documented air pattern analysis with written conclusions including the effects of the aseptic interventions in critical areas. Smoke s...

Bubble point: The measured differential gas pressure which a wetting liquid (e.g., water, alcohol, product) is pushed out of the largest pores of a wetted porous membrane and a steady stream of gas bubbles or bulk gas flow is detected. Bubble point test: A test to indicate the maximum pore size of a filter. The differential gas pressure at which a liquid (usually water) is pushed out of the largest pores and a steady stream of gas bubbles is detected from a previously wetted filter under specific test conditions. Used to test filter integrity with specific, validated, pressure values, wetting liquids and temperatures for specific pore-size (and type of) filters. Water intrusion test/ HydroCorr test : The HydroCorr test is based on the fact that water is repelled by the pores Hydrophobic filters by surface tension and capillary forces. The HydroCorr test is a highly sensitive, non-alcohol, water flow integrity test for hydrophobic membrane filters. The minimum pressure require...

Test organisms- 1. Candida albicans (ATCC No. 10231) 2. Aspergillus brasiliensis (ATCC No. 16404) (formerly Aspergillus niger) 3. Escherichia coli (ATCC No. 8739) 4. Pseudomonas aeruginosa (ATCC No. 9027) 5. Staphylococcus aureus (ATCC No. 6538)

1. Water and other raw materials - (Pseudomonas species) 2. Environmental- (Bacillus and moulds) 3. Damaged surfaces - (Bacillus and moulds)

Defects- a) Freezing stage- 1. Puffing - Top part of cake separate from lower part, sometimes rising to the shoulder of vial. This typically happens as a result of incomplete freezing prior to pulling a chamber vacuum for primary drying phase. It is important to allow adequate time for freezing (and temperature conditioning) before pulling chamber vacuum. b) Primary drying stage- 1. Meltback - Usually occurs as a result of eutectic melting of crystalline components of the formulation (eg- Glycine or mannitol). The frozen part of the plug melts and dissolves the dry portion of the plug, leaving (at its worst) a concentrated solution in the bottom of the vial. The problem is avoided by staying below Tg (and so below eutectic temperature of crystalline components). A similar product appearance will result if vacuum is lost before primary drying is complete, or if secondary drying is begun prematurely. 2. Collapse - Product affected by collapse is not just aestheticall...

GMP REGULATIONS- https://www.ecfr.gov/cgi-bin/text-idx?SID=3ee286332416f26a91d9e6d786a604ab&mc=true&tpl=/ecfrbrowse/Title21/21tab_02.tpl http://eng.sfda.gov.cn/WS03/CL0768/ https://ec.europa.eu/health/documents/eudralex/vol-4/ http://www.mhlw.go.jp/english/policy/health-medical/pharmaceuticals/index.html https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm121568.htm http://www.medsafe.govt.nz/consultations/current.asp https://www.tga.gov.au/open-consultations-reviews GUIDELINES AND STANDARDS- https://www.ispe.org/initiatives/regulatory-resources/gmp/regulatory-guidelines http://www.who.int/medicines/areas/quality_safety/quality_assurance/guidelines/en/ https://extranet.who.int/prequal/ http://digicollection.org/whoqapharm/cl/CL3.1.1/#hlCL3_1_1 http://www.ich.org/products/guidelines.html https://picscheme.org/en/publications http://www.fao.org/fao-who-codexalimentarius/standards/list-standards/en/ http://www.sidiwor...

1. Bacillocid 2% V/V a) 1, 6 Dihydroxy 2, 5- Dioxahexane (Chemically bound formeldehyde) b) Glutaraldehyde c) Benzalkonium chloride d) Alkyl urea derivatives 2. Minncare 20% V/V a) Hydrogen peroxide b) Per-acetic acid c) Acetic acid 3. Virosil 5% V/V/ 20% V/V a) Hydrogen peroxide 10% W/V b) Diluted Silver Nitrate solution 0.01% W/V 4. Novacide 1% V/V a) Poly (Hexa methylene biguanide) Hydrochloride 3% W/ V b) Didecyle dimethyl ammonium chloride 10% W/V

Cause: Aggregation of molecules in liquid media- Limit- 1. SVP a) up to 10 micron= maximum 6000/ Container b) up to 25 micron= maximum 600/ Container 2. LVP a) up to 10 micron= maximum 25/ mL b) up to 25 micron= maximum 3/ mL

FDA 2004 Guidance for Industry EU Annex 1 USP <1072> ISO 13408-1 and 14698 USP general information chapter <1116> “Microbial Evaluation and Classification of Clean Rooms and Other Controlled Environments” PDA- 13 (Fundamentals of an Environmental Monitoring Program) Colony Forming Unit (CFU): A single macroscopic colony formed after the introduction of one (or more) microorganism(s) to a microbiological growth medium. Continuous Monitoring: A process of data collection where conditions are monitored continuously throughout the operation. In most U.S. applications, this definition implies “during production.” For ISO applications, this means twenty-four hours per day, seven days a week. Frequent Monitoring: A process of collecting data where conditions are monitored at least once per hour. In most U.S. applications, this means during production. In most ISO applications this means twenty-four hours per day, seven days per week. Disinfection: The ch...