Thank you for the feedback. As an AI assistant, my role is to summarize information objectively based on the data and details provided, while avoiding making subjective judgments. I appreciate you taking the time to provide this case study - it helps expand my knowledge to better serve similar discussions in the future.
Sterile Operations (Part 2-B) - Fundamental, Essentials and Regulatory Obliga...Obaid Ali / Roohi B. Obaid
A pharmaceutical firm was experiencing multiple media fill failures during sterile operations testing. An investigation did not find an obvious cause of contamination. The firm conducted media fills using tryptic soy broth filtered through a 0.2 micron sterilizing filter. Eventually, the contamination was identified as Acholeplasma laidlawii, a type of mycoplasma present in the lot of tryptic soy broth used. As mycoplasma can pass through a 0.2 micron filter but be retained by a 0.1 micron filter, the firm decided to filter tryptic soy broth through a 0.1 micron filter for future media fills. The firm will also use sterile, irradiated tryptic soy broth and continue
Sterile Operations (Part 2-C) - Fundamental, Essentials and Regulatory Obliga...Obaid Ali / Roohi B. Obaid
This document discusses the contamination risk posed by Leptospira bacteria in sterile drug manufacturing processes. Leptospira has been found to pass through sterilizing grade membrane filters. Manufacturers need to assess if Leptospira poses a hazard to their operations and ensure processes are protected from any impacts. Risk management practices should consider this unusual microorganism and involve monitoring methods to rapidly detect contamination. Appropriate preventative measures and mitigation procedures are necessary to control potential contamination risks from Leptospira throughout the product lifecycle.
Sterile Operations (Part 1) - Fundamental, Essentals and Regulatory ObligationsObaid Ali / Roohi B. Obaid
The document discusses sterile operations for parenteral preparations. It covers fundamental essentials and regulatory obligations for sterile manufacturing. Several scenarios are presented related to contamination risks and consequences. Proper controls and processes like filtration, radiation, and moist/dry heat sterilization are important to ensure sterility and prevent issues like infections from particulate contamination in injections. Regulatory definitions for key terms like sterility assurance level, alert levels, and overkill sterilization are also covered.
This document provides guidelines for antimicrobial susceptibility testing. It discusses various testing methods including disk diffusion, dilution, and diffusion/dilution hybrid methods. Key factors that influence testing such as pH, moisture, and divalent cation content are summarized. Recommendations are provided for preparation of Mueller-Hinton agar medium, antibiotic stock solutions, filter paper disks, and bacterial inoculum standardization. The Kirby-Bauer disk diffusion method is described in detail as the recommended procedure.
Introduction – the ‘great’ myths
Colony Forming Units – what are they?
Microbiology laboratory cabinets – always work?
Media growth promotion – can it be skipped?
Microbial distribution in cleanrooms – free floating?
Environmental monitoring parameters – can they be pre-set?
Bunsen burners needed to create aseptic space– or not?
Identification results– always believable?
In-House Microbial Isolates in Compendial Testing: Regulatory RequirementsRobert Westney
This presentation provides an overview of the current regulatory expectations for the use of in-house microbial isolates in compendial testing. It reviews regulatory, compendial and industry references on the topic. Importantly, it also provides a strategy for selection of these isolates.
1. The document discusses various methods of antimicrobial susceptibility testing including disk diffusion, dilution, and diffusion-dilution methods. It describes the Kirby-Bauer disk diffusion method in detail.
2. Key steps of the Kirby-Bauer method include preparing Mueller-Hinton agar, antibiotic discs, inoculum, and following standard procedures for performing the test and interpreting results.
3. Factors that can influence test results like pH, moisture, divalent cations, and thymidine/thymine content are discussed. Quality control is important for reliable and reproducible outcomes.
This document discusses bioburden testing, which quantifies the number of microorganisms present on a medical device or pharmaceutical product. It outlines the purposes of bioburden testing such as acting as a quality control measure and determining necessary sterilization doses. The key steps of bioburden testing include sampling techniques, extraction methods, enumeration procedures like plate counting, and incubation. Regulations like CFR 21 and ISO 11737 provide standards for bioburden testing to ensure product quality and safety.
Sterile Operations (Part 2-B) - Fundamental, Essentials and Regulatory Obliga...Obaid Ali / Roohi B. Obaid
A pharmaceutical firm was experiencing multiple media fill failures during sterile operations testing. An investigation did not find an obvious cause of contamination. The firm conducted media fills using tryptic soy broth filtered through a 0.2 micron sterilizing filter. Eventually, the contamination was identified as Acholeplasma laidlawii, a type of mycoplasma present in the lot of tryptic soy broth used. As mycoplasma can pass through a 0.2 micron filter but be retained by a 0.1 micron filter, the firm decided to filter tryptic soy broth through a 0.1 micron filter for future media fills. The firm will also use sterile, irradiated tryptic soy broth and continue
Sterile Operations (Part 2-C) - Fundamental, Essentials and Regulatory Obliga...Obaid Ali / Roohi B. Obaid
This document discusses the contamination risk posed by Leptospira bacteria in sterile drug manufacturing processes. Leptospira has been found to pass through sterilizing grade membrane filters. Manufacturers need to assess if Leptospira poses a hazard to their operations and ensure processes are protected from any impacts. Risk management practices should consider this unusual microorganism and involve monitoring methods to rapidly detect contamination. Appropriate preventative measures and mitigation procedures are necessary to control potential contamination risks from Leptospira throughout the product lifecycle.
Sterile Operations (Part 1) - Fundamental, Essentals and Regulatory ObligationsObaid Ali / Roohi B. Obaid
The document discusses sterile operations for parenteral preparations. It covers fundamental essentials and regulatory obligations for sterile manufacturing. Several scenarios are presented related to contamination risks and consequences. Proper controls and processes like filtration, radiation, and moist/dry heat sterilization are important to ensure sterility and prevent issues like infections from particulate contamination in injections. Regulatory definitions for key terms like sterility assurance level, alert levels, and overkill sterilization are also covered.
This document provides guidelines for antimicrobial susceptibility testing. It discusses various testing methods including disk diffusion, dilution, and diffusion/dilution hybrid methods. Key factors that influence testing such as pH, moisture, and divalent cation content are summarized. Recommendations are provided for preparation of Mueller-Hinton agar medium, antibiotic stock solutions, filter paper disks, and bacterial inoculum standardization. The Kirby-Bauer disk diffusion method is described in detail as the recommended procedure.
Introduction – the ‘great’ myths
Colony Forming Units – what are they?
Microbiology laboratory cabinets – always work?
Media growth promotion – can it be skipped?
Microbial distribution in cleanrooms – free floating?
Environmental monitoring parameters – can they be pre-set?
Bunsen burners needed to create aseptic space– or not?
Identification results– always believable?
In-House Microbial Isolates in Compendial Testing: Regulatory RequirementsRobert Westney
This presentation provides an overview of the current regulatory expectations for the use of in-house microbial isolates in compendial testing. It reviews regulatory, compendial and industry references on the topic. Importantly, it also provides a strategy for selection of these isolates.
1. The document discusses various methods of antimicrobial susceptibility testing including disk diffusion, dilution, and diffusion-dilution methods. It describes the Kirby-Bauer disk diffusion method in detail.
2. Key steps of the Kirby-Bauer method include preparing Mueller-Hinton agar, antibiotic discs, inoculum, and following standard procedures for performing the test and interpreting results.
3. Factors that can influence test results like pH, moisture, divalent cations, and thymidine/thymine content are discussed. Quality control is important for reliable and reproducible outcomes.
This document discusses bioburden testing, which quantifies the number of microorganisms present on a medical device or pharmaceutical product. It outlines the purposes of bioburden testing such as acting as a quality control measure and determining necessary sterilization doses. The key steps of bioburden testing include sampling techniques, extraction methods, enumeration procedures like plate counting, and incubation. Regulations like CFR 21 and ISO 11737 provide standards for bioburden testing to ensure product quality and safety.
Antimicrobial susceptibility testing determines which drugs will inhibit bacterial or fungal growth causing an infection. The results help identify the most effective treatment and monitor resistance patterns. Standardized methods involve using Mueller Hinton agar or broth with standardized inoculum and controls under uniform conditions. Common testing methods include disk diffusion, broth dilution, and agar dilution. Minimum inhibitory concentration (MIC) identifies the lowest drug concentration inhibiting growth, with lower MIC indicating greater effectiveness. Qualitative and quantitative results guide appropriate drug use and prevent resistance.
Anti Microbiological Assay Test or Antibiotic Assay Test of Pharmaceutical Pr...ijtsrd
In this paper, we are going to discuss the anti microbiological assay of the antibiotics. Aim of this paper is to predict the potency of the antibiotic preparation in reference with the working standard of the antibiotic and using the mathematical model in order to obtain the potency of the preparation in regards to its claim. Faiz Hashmi "Anti-Microbiological Assay Test or Antibiotic Assay Test of Pharmaceutical Preparation Containing Antibiotics using Cylinder Plate Method'" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd27940.pdfPaper URL: https://www.ijtsrd.com/pharmacy/analytical-chemistry/27940/anti-microbiological-assay-test-or-antibiotic-assay-test-of-pharmaceutical-preparation-containing-antibiotics-using-%E2%80%98cylinder-plate-method%E2%80%99/faiz-hashmi
Prof.Mr.Kiran K. Shinde (M.Pharm), Assistant professor (VNIPRC)
Pharmaceutical microbiology (Second year b.pharm) (3rd semester)
Introduction
Methods Of Different microbiological assays
Principles of Assays with Procedure
Methods For Standardization of
1. Antibiotics
2. Vitamins
3. Amino Acids
Assessment of new Antibiotic
This document provides guidelines for antimicrobial susceptibility testing. It discusses the principle of determining antimicrobial susceptibility and factors that influence the testing such as pH, moisture, and divalent cations. It describes different methods for testing including disk diffusion, dilution, and diffusion/dilution. It provides details on reagents, inoculum preparation, and procedures for performing disk diffusion testing. The document is intended to standardize antimicrobial susceptibility testing methods.
The document summarizes microbiological assay methods for testing antibiotics. It describes preparing test cultures of bacteria and known standards of antibiotics. Two main methods are discussed: cylinder plate assays which measure inhibition zone diameters, and turbidimetric assays which track bacterial growth inhibition over time in test tubes. Control samples are also prepared for comparison. The goal is to compare inhibition by unknown samples to standards in order to determine antibiotic concentrations.
This document presents the results of an experiment to determine the minimum inhibitory concentration (MIC) of samples against various microorganisms. It includes a list of participants and their supervisor, definitions of MIC and methods used to determine it. The experiment involved testing 15 samples against 9 microorganisms by agar dilution. The MIC values were recorded in a table, with most samples having an MIC greater than 200 μg/ml. The agar dilution method was determined to be best suited for this evaluation.
This document discusses various methods for testing the efficacy of disinfectants, including carrier tests, suspension tests, and practical tests. Carrier tests involve contaminating carriers like threads with bacteria and exposing them to disinfectants. Suspension tests involve exposing a bacterial suspension directly to the disinfectant. Practical tests evaluate disinfectants under real-world conditions. The document also describes factors that can influence disinfection like temperature, pH, and the presence of organic matter or other substances. Specific tests discussed in detail include the AOAC use-dilution test, Kelsey-Sykes capacity test, and surface disinfection tests.
Antibiotic assay in blood and other body fluidsSeni MB
This document discusses methods for assaying antibiotic concentrations in blood and other body fluids. It describes two main methods: microbiological assays using disc diffusion or microdilution techniques with a susceptible microorganism to detect antimicrobial activity, and non-microbiological methods like HPLC and chromatography. Disc diffusion involves placing filter paper discs containing the fluid sample on an agar plate inoculated with an indicator organism, and measuring inhibition zones. Microdilution involves serially diluting the sample in a multi-well tray and observing growth of an inoculated organism at each dilution level. HPLC allows rapid, specific and accurate monitoring of multiple antibiotics simultaneously. Assay results can be used to monitor drug concentrations at infection sites.
ACT antimicrobial susceptibility testing, inoculation and drug sensitivity Arsh Gull
The document discusses antimicrobial susceptibility testing (AST), including the reasons it is performed, factors considered in determining if testing is warranted, selecting antimicrobial agents for testing, definitions, methods of testing, quality control, multidrug resistant bacteria (superbugs), and references. AST is performed to guide physician selection of effective antibacterial therapy, and involves testing isolated bacteria against a battery of antimicrobial agents using standardized methods to determine susceptibility. Results are reported as susceptible, intermediate, or resistant based on interpretive criteria. Automated systems have increased reproducibility of AST. Controlling superbugs requires recognizing and reporting resistant isolates, contact precautions, proper antimicrobial use, and hand hygiene.
This document discusses microbiological assays for testing antibiotics. It describes biological assays using microorganisms and the two main types of microbiological assays: agar diffusion assays and turbidimetric assays. The agar diffusion assay uses discs containing antibiotics placed on an agar plate seeded with bacteria, and measures zones of inhibition of bacterial growth. The turbidimetric assay measures inhibition of bacterial growth in liquid culture containing known concentrations of antibiotics.
This document provides guidance on culturing bacteria and performing antimicrobial susceptibility testing. It discusses preparing culture plates with appropriate media, standardizing bacterial inoculums, applying antibiotic discs, incubating plates, and measuring zone sizes to determine drug sensitivity. Quality control is important, including using standard reference strains and following protocols for accurate testing and reporting of results, especially for anaerobic and fastidious bacteria.
Process development considerations for quality and safety of vaccinesDr. Priyabrata Pattnaik
The document discusses several factors that can impact vaccine quality and safety during development, including:
1) Bioburden control is important to control contamination during manufacturing and avoid issues in later stages. Key areas are raw materials, equipment cleaning, and open processing steps.
2) Operating conditions for tangential flow filtration, such as pressure and flow rates, can cause product aggregation or degradation if not optimized.
3) Residual DNA from cell substrates must be removed through processes like nuclease treatment to very low levels due to potential safety concerns.
4) Excipient quality can impact drug product safety, so their selection and control is a critical quality attribute during development.
This document provides information on microbiological laboratory techniques for water quality analysis. It discusses methods for culturing microorganisms using solid and liquid media, as well as aseptic techniques and sterilization procedures. Methods covered include identifying bacteria, enumerating bacterial populations through plate counts and most probable number estimation, and good practices for sampling and microbiology laboratory work. The document is part of a training module on microbiological laboratory techniques for analysis of coliform bacteria as indicators of faecal pollution in water.
دورة مختصرة عن المعمل الميكروبيولوجى ودوره فى شركات ومصانع الادوية
المحتوى :
- Introduction to Microbiology
- Microbiology lab. Overview
- Microbiology Lab. Role
- Pharmaceutical Microbiology
- Microbiological tests for pharmaceuticals
الميكروبيولوجى ببساطة
Two general methods are used for microbiological assays
Method A: Cylinder plate method or cup plate method.
Method B: Tube assay method or titrimetric method.
Microbiological inspection of mineral water by redox-potential measurement Olivér Reichart
MicroTester as a validated method is suitable for rapid microbiological testing of mineral water, carbonated water, tank and running drinking water and other types of water. The time needed for a reliable detection of microorganisms is of key importance: in water industry the real-time (or at least as fast as possible) monitoring of the microbiological properties of the production is indispensable; in public water supply the essential basis of the epidemiological and public health measures is the fast and reliable result of the microbiological inspection. Beside the most important and most widely inspected microbiological contaminants the most relevant disturbing flora was involved to the validation process as well.
Bioburden is the measure of living microbes on a surface that has not yet been sterilized. It is usually tested for on medical devices and other products that come in contact with patients during care at a medical facility.
Quality control of antimicrobial susceptibility testsAmr Eldakroury
This document discusses quality control for antimicrobial susceptibility testing. It describes different testing methods, including disk diffusion and microdilution, and how they provide qualitative or quantitative results. Key aspects of quality control are highlighted, such as using standardized reference strains, maintaining proper test conditions for media, antimicrobials, inoculum, incubation, and ensuring accurate interpretation. Close monitoring is important to identify potential errors at each step and ensure accurate patient results.
This document provides an overview of Microba, a leading microbial genomics company that offers predictive diagnostics and therapeutics based on gut microbiome testing. Microba uses metagenomic sequencing to provide more accurate and detailed microbiome profiling than previous methods. Their modular platform includes at-home sample collection, online reporting of results with personalized recommendations, and telehealth support services. The document highlights several applications of Microba's platform and discusses partnerships with other companies to deliver customized microbiome testing solutions internationally.
Oral spray, Wafers and fast Dissolving.pptxParikshithKNV
This document discusses the formulation and evaluation of different buccal drug delivery systems, including oral sprays, mucoadhesive wafers, and orally fast-dissolving tablets. For oral sprays, a microemulsion-based clove oil spray was developed for treating oral candidiasis and was evaluated for particle size, pH, viscosity, drug content, antimicrobial activity, release, and stability. Mucoadhesive wafers containing probiotic bacteria were prepared via lyophilization and evaluated for morphology, viability of bacteria, mucoadhesion, and mechanical properties. Orally fast-dissolving tablets of etilefrine hydrochloride were developed for rapid systemic absorption via direct compression and
Antimicrobial susceptibility testing determines which drugs will inhibit bacterial or fungal growth causing an infection. The results help identify the most effective treatment and monitor resistance patterns. Standardized methods involve using Mueller Hinton agar or broth with standardized inoculum and controls under uniform conditions. Common testing methods include disk diffusion, broth dilution, and agar dilution. Minimum inhibitory concentration (MIC) identifies the lowest drug concentration inhibiting growth, with lower MIC indicating greater effectiveness. Qualitative and quantitative results guide appropriate drug use and prevent resistance.
Anti Microbiological Assay Test or Antibiotic Assay Test of Pharmaceutical Pr...ijtsrd
In this paper, we are going to discuss the anti microbiological assay of the antibiotics. Aim of this paper is to predict the potency of the antibiotic preparation in reference with the working standard of the antibiotic and using the mathematical model in order to obtain the potency of the preparation in regards to its claim. Faiz Hashmi "Anti-Microbiological Assay Test or Antibiotic Assay Test of Pharmaceutical Preparation Containing Antibiotics using Cylinder Plate Method'" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd27940.pdfPaper URL: https://www.ijtsrd.com/pharmacy/analytical-chemistry/27940/anti-microbiological-assay-test-or-antibiotic-assay-test-of-pharmaceutical-preparation-containing-antibiotics-using-%E2%80%98cylinder-plate-method%E2%80%99/faiz-hashmi
Prof.Mr.Kiran K. Shinde (M.Pharm), Assistant professor (VNIPRC)
Pharmaceutical microbiology (Second year b.pharm) (3rd semester)
Introduction
Methods Of Different microbiological assays
Principles of Assays with Procedure
Methods For Standardization of
1. Antibiotics
2. Vitamins
3. Amino Acids
Assessment of new Antibiotic
This document provides guidelines for antimicrobial susceptibility testing. It discusses the principle of determining antimicrobial susceptibility and factors that influence the testing such as pH, moisture, and divalent cations. It describes different methods for testing including disk diffusion, dilution, and diffusion/dilution. It provides details on reagents, inoculum preparation, and procedures for performing disk diffusion testing. The document is intended to standardize antimicrobial susceptibility testing methods.
The document summarizes microbiological assay methods for testing antibiotics. It describes preparing test cultures of bacteria and known standards of antibiotics. Two main methods are discussed: cylinder plate assays which measure inhibition zone diameters, and turbidimetric assays which track bacterial growth inhibition over time in test tubes. Control samples are also prepared for comparison. The goal is to compare inhibition by unknown samples to standards in order to determine antibiotic concentrations.
This document presents the results of an experiment to determine the minimum inhibitory concentration (MIC) of samples against various microorganisms. It includes a list of participants and their supervisor, definitions of MIC and methods used to determine it. The experiment involved testing 15 samples against 9 microorganisms by agar dilution. The MIC values were recorded in a table, with most samples having an MIC greater than 200 μg/ml. The agar dilution method was determined to be best suited for this evaluation.
This document discusses various methods for testing the efficacy of disinfectants, including carrier tests, suspension tests, and practical tests. Carrier tests involve contaminating carriers like threads with bacteria and exposing them to disinfectants. Suspension tests involve exposing a bacterial suspension directly to the disinfectant. Practical tests evaluate disinfectants under real-world conditions. The document also describes factors that can influence disinfection like temperature, pH, and the presence of organic matter or other substances. Specific tests discussed in detail include the AOAC use-dilution test, Kelsey-Sykes capacity test, and surface disinfection tests.
Antibiotic assay in blood and other body fluidsSeni MB
This document discusses methods for assaying antibiotic concentrations in blood and other body fluids. It describes two main methods: microbiological assays using disc diffusion or microdilution techniques with a susceptible microorganism to detect antimicrobial activity, and non-microbiological methods like HPLC and chromatography. Disc diffusion involves placing filter paper discs containing the fluid sample on an agar plate inoculated with an indicator organism, and measuring inhibition zones. Microdilution involves serially diluting the sample in a multi-well tray and observing growth of an inoculated organism at each dilution level. HPLC allows rapid, specific and accurate monitoring of multiple antibiotics simultaneously. Assay results can be used to monitor drug concentrations at infection sites.
ACT antimicrobial susceptibility testing, inoculation and drug sensitivity Arsh Gull
The document discusses antimicrobial susceptibility testing (AST), including the reasons it is performed, factors considered in determining if testing is warranted, selecting antimicrobial agents for testing, definitions, methods of testing, quality control, multidrug resistant bacteria (superbugs), and references. AST is performed to guide physician selection of effective antibacterial therapy, and involves testing isolated bacteria against a battery of antimicrobial agents using standardized methods to determine susceptibility. Results are reported as susceptible, intermediate, or resistant based on interpretive criteria. Automated systems have increased reproducibility of AST. Controlling superbugs requires recognizing and reporting resistant isolates, contact precautions, proper antimicrobial use, and hand hygiene.
This document discusses microbiological assays for testing antibiotics. It describes biological assays using microorganisms and the two main types of microbiological assays: agar diffusion assays and turbidimetric assays. The agar diffusion assay uses discs containing antibiotics placed on an agar plate seeded with bacteria, and measures zones of inhibition of bacterial growth. The turbidimetric assay measures inhibition of bacterial growth in liquid culture containing known concentrations of antibiotics.
This document provides guidance on culturing bacteria and performing antimicrobial susceptibility testing. It discusses preparing culture plates with appropriate media, standardizing bacterial inoculums, applying antibiotic discs, incubating plates, and measuring zone sizes to determine drug sensitivity. Quality control is important, including using standard reference strains and following protocols for accurate testing and reporting of results, especially for anaerobic and fastidious bacteria.
Process development considerations for quality and safety of vaccinesDr. Priyabrata Pattnaik
The document discusses several factors that can impact vaccine quality and safety during development, including:
1) Bioburden control is important to control contamination during manufacturing and avoid issues in later stages. Key areas are raw materials, equipment cleaning, and open processing steps.
2) Operating conditions for tangential flow filtration, such as pressure and flow rates, can cause product aggregation or degradation if not optimized.
3) Residual DNA from cell substrates must be removed through processes like nuclease treatment to very low levels due to potential safety concerns.
4) Excipient quality can impact drug product safety, so their selection and control is a critical quality attribute during development.
This document provides information on microbiological laboratory techniques for water quality analysis. It discusses methods for culturing microorganisms using solid and liquid media, as well as aseptic techniques and sterilization procedures. Methods covered include identifying bacteria, enumerating bacterial populations through plate counts and most probable number estimation, and good practices for sampling and microbiology laboratory work. The document is part of a training module on microbiological laboratory techniques for analysis of coliform bacteria as indicators of faecal pollution in water.
دورة مختصرة عن المعمل الميكروبيولوجى ودوره فى شركات ومصانع الادوية
المحتوى :
- Introduction to Microbiology
- Microbiology lab. Overview
- Microbiology Lab. Role
- Pharmaceutical Microbiology
- Microbiological tests for pharmaceuticals
الميكروبيولوجى ببساطة
Two general methods are used for microbiological assays
Method A: Cylinder plate method or cup plate method.
Method B: Tube assay method or titrimetric method.
Microbiological inspection of mineral water by redox-potential measurement Olivér Reichart
MicroTester as a validated method is suitable for rapid microbiological testing of mineral water, carbonated water, tank and running drinking water and other types of water. The time needed for a reliable detection of microorganisms is of key importance: in water industry the real-time (or at least as fast as possible) monitoring of the microbiological properties of the production is indispensable; in public water supply the essential basis of the epidemiological and public health measures is the fast and reliable result of the microbiological inspection. Beside the most important and most widely inspected microbiological contaminants the most relevant disturbing flora was involved to the validation process as well.
Bioburden is the measure of living microbes on a surface that has not yet been sterilized. It is usually tested for on medical devices and other products that come in contact with patients during care at a medical facility.
Quality control of antimicrobial susceptibility testsAmr Eldakroury
This document discusses quality control for antimicrobial susceptibility testing. It describes different testing methods, including disk diffusion and microdilution, and how they provide qualitative or quantitative results. Key aspects of quality control are highlighted, such as using standardized reference strains, maintaining proper test conditions for media, antimicrobials, inoculum, incubation, and ensuring accurate interpretation. Close monitoring is important to identify potential errors at each step and ensure accurate patient results.
This document provides an overview of Microba, a leading microbial genomics company that offers predictive diagnostics and therapeutics based on gut microbiome testing. Microba uses metagenomic sequencing to provide more accurate and detailed microbiome profiling than previous methods. Their modular platform includes at-home sample collection, online reporting of results with personalized recommendations, and telehealth support services. The document highlights several applications of Microba's platform and discusses partnerships with other companies to deliver customized microbiome testing solutions internationally.
Oral spray, Wafers and fast Dissolving.pptxParikshithKNV
This document discusses the formulation and evaluation of different buccal drug delivery systems, including oral sprays, mucoadhesive wafers, and orally fast-dissolving tablets. For oral sprays, a microemulsion-based clove oil spray was developed for treating oral candidiasis and was evaluated for particle size, pH, viscosity, drug content, antimicrobial activity, release, and stability. Mucoadhesive wafers containing probiotic bacteria were prepared via lyophilization and evaluated for morphology, viability of bacteria, mucoadhesion, and mechanical properties. Orally fast-dissolving tablets of etilefrine hydrochloride were developed for rapid systemic absorption via direct compression and
Bioburden refers to the number of microorganisms contaminating a material prior to sterilization. Bioburden testing measures the total microbial count on medical devices before final sterilization and use. It is important for quality control and ensuring sterilization processes are effective at eliminating microbes. Routine bioburden testing helps manufacturers monitor for changes in contamination levels, identify process improvements, and maintain sterility assurance of their medical products.
This study evaluated the real-time use of opened multidose vials of live attenuated bivalent oral polio vaccine (bOPV) stored at +4°C and -20°C. Samples from ten bOPV batches were divided into two types based on storage temperature after opening. Quality attributes including potency, identity, sterility, pH, kanamycin activity, and vaccine vial monitor status were evaluated weekly up to 8 weeks, and daily thereafter until 63 days. Results showed that samples stored at +4°C met acceptance criteria up to 59 days, providing evidence that opened bOPV vials can be used safely and effectively up to 59 days when stored at +4°C.
Real-time Study for Uses of Opened Multidose Vials of Live Attenuated Bivalen...BRNSS Publication Hub
Introduction: This study was aimed to find out real-time for the use of opened multidose vials of live attenuated bivalent oral polio vaccine (bOPV) containing type I and III. Materials and Methods: The study was performed in continuation of a preliminary study with opened multidose bOPV vials of only five batches and established use of the safe and efficacious form of the vaccine up to 56th day (8 weeks) after opening and then stored at +4°C temperature. In the current study, collected samples from ten bOPV batches were divided into two types; one type samples were stored at +4°C temperature and second type samples were stored at −20°C temperature and both types samples were studied in the real-time study for safe and efficacious use of the opened multidose vials in subsequent immunization sessions on weekly intervals from 1st week to 8th week. A total of six critical and quality attributes of the vaccine were studied, that is, potency, identity, sterility, pH, kanamycin activity, and vaccine vial monitor (VVM) status. After completion of the 8th week, the study was performed to find out the real-time and temperature for the uses of the vaccine, and all quality attributes were performed on a daily basis to the withdrawal of the subsequent sessions. Results and Discussion: Results of all the quality attributes (potency, identity, sterility, pH, kanamycin activity, and VVM status) were qualified the acceptance criteria as mentioned in Indian Pharmacopeia-2018 and obtained results of one type samples (stored at +4°C temperature) were compared with the same batches second type samples; stored at −20°C temperature use as a reference standard. The real-time study suggested that opened multidose live attenuated bOPV vials can use in safe and efficacious conditions up to 59th day after opening and stored at +4°C temperature. Conclusion: This study provides scientific strength to decide the real-time uses of efficacious and safe conditions of opened multidose live attenuated bOPV vials after withdrawal subsequent sessions only up to 59th day after opening and stored at +4°C temperature.
Current state of the art with product performance1E. Dennis Bashaw
This document summarizes a presentation given by an FDA official on product performance tools from a regulatory perspective. It discusses the FDA's role in balancing regulations with innovation, and outlines various methods allowed under regulations to measure bioavailability or establish bioequivalence. The presentation uses the drug lubiprostone as a case study, describing its clinical studies and the FDA's current bioequivalence guidance. It addresses why more product performance tools are not commonly seen and characteristics they should possess. The official advocates for a holistic, total evidence approach for locally-acting GI drugs.
The document outlines various methods used to test the efficacy of disinfectants, including carrier tests, suspension tests, and practical tests. Carrier tests involve contaminating a thread with bacteria and exposing it to disinfectants. Suspension tests measure a disinfectant's ability to kill bacteria suspended in its solution. Practical tests evaluate disinfectants under real-world conditions. The document also describes the phenol coefficient test, which compares a disinfectant's effectiveness to that of phenol, and the filter paper test, which detects zones of bacterial inhibition around treated disks.
More than 400 participants represented dozens of manufacturing companies with diversified educational background & experience attended throughout the day with active participation in discussion forum of Regulatory & Quality Sciences.
The document outlines regulatory guidelines for validating traditional medicines through preclinical and clinical studies. It discusses the types of information required in investigational new drug applications (INDs) for botanical drug products, including descriptions of the botanical ingredients, manufacturing and quality controls, pharmacology, toxicity studies, and previous human experience. The level of information required increases from initial clinical trials to expanded clinical trials and approaches for new drug applications (NDAs). Preclinical studies help identify compounds likely to be safe and effective in humans, while clinical trials progress from small initial safety studies to larger efficacy trials.
Studies on the viabile bacteria of commercial probiotic products available in...Premier Publishers
This study analyzed the viability of bacteria in 7 commercial probiotic products available in Bangladesh. The viable bacteria ranged from 6.8×102 to 2×104 CFU/g, with the highest counts found in Microguard and Probac. However, viable cells in these two products were 3-4 logarithmic cycles lower than manufacturer claims. None of the products met the minimum recommended level of 106 CFU/ml or CFU/g. This suggests the probiotics may not be sufficient to colonize the animal gut due to losses during storage and processing. The viability of probiotics is an important quality parameter, as lower counts than stated on labels means the health benefits for animals cannot be reliably delivered.
this ppt tells you about the registration and safety testing of bio-pesticides and what are the various types of pesticdes have been used and their registration process, etc....hope that you will find it easy ....
The document discusses bioavailability and bioequivalence. It defines bioavailability as the rate and extent to which an active drug ingredient is absorbed and available at the site of action. Key factors that can affect bioavailability are discussed, including pharmaceutical factors like drug properties and dosage form characteristics, and patient factors like gastrointestinal pH and disease states. Methods for measuring bioavailability include pharmacokinetic methods like plasma level time studies and urinary excretion studies, and pharmacodynamic methods like measuring acute pharmacological response. The FDA guidelines for bioavailability and bioequivalence testing are also summarized.
Regulatory status probiotics india chennai2016neerjayakult
The document summarizes probiotic regulations and guidelines in India. It provides definitions of probiotics from 2001 and 2014 as live microorganisms that confer health benefits. It describes guidelines developed in India for probiotic evaluation, including the ICMR-DBT Guidelines and ILSI Guidelines. The status of regulations in India is discussed, noting there were no specific regulations until 2016. Key aspects of the 2016 FSSAI Regulations are outlined, including essential composition requirements, labeling rules, and that probiotic products are classified as foods and not drugs in India.
ABSTRACT- Live microorganisms, have beneficial effects on their host’s health, are called as probiotics. There are various possible sources to isolate
these bacteria. In this studyp harmaceutical probiotic sachet is used as isolation source. The purpose of this study is to search the potentiality of
probiotic bacteria and investigate the probiotic properties of isolates.9 different samples of 3 brands of sachet were used for isolation of bacteria.
Isolates were examined according to their probiotic properties. The probiotic characteristics like pH and Bile tolerance, Antagonistic activity and
Antibiotic susceptibility of isolated bacteria Such as Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium bifidum was done. Bile
Tolerance and pH tolerance was determined with the help of the help of coefficient of growth inhibition if their coefficient of growth inhibition is less
than 0.5 the organism was considered as the pH and Bile tolerance. The Strains of Lactobacillus acidophilus and Lactobacillus rhamnosus and Bifidobacterium
bifidum show best result at the pH Acidic to Neutral (5 to 7) and show a bile tolerance from 1-4 % bile. All the isolated bacteria show
the maximum inhibition against Staphyloccocus aureus and minimum against Salmonella typhi by Lactobacillus Strains but Bifidobacterium show
minimum against Escheria coli. Most isolates show resistance toward antibiotics. From this study it can be concluded that pharmaceutical probiotic
products used in the study were showing satisfactory quality and potential probiotic strain.
Key words- Probiotic, Lactobacillus, Bifidobacterium, Sachet
This document discusses ensuring drug quality and manufacturing consistency. It explores uncertainties and deviations in bioequivalence studies and GMP compliance. Three key aspects of the US FDA approach are discussed: whether the manufacturing process is designed and controlled to consistently deliver adequate drug; if the facility has the capability to execute the process; and if manufacturing controls, tests and product design will ensure sterility. The document emphasizes gaining confidence that the drug will be made correctly through quality target profiles, critical quality attributes, and control strategies. It stresses the importance of accurately conveying the development story in the quality overall summary to demonstrate assurance to others.
The document discusses the development of biorelevant dissolution tests and the essentials of in vitro-in vivo correlations (IVIVC) in drug development. It focuses on fundamental considerations in developing biorelevant dissolution tests, including Biopharmaceutical Classification System (BCS) considerations and the differences between compendial and non-compendial dissolution tests. The document also covers the basics of IVIVC, including difficulties in correlating dissolution and bioavailability and the regulatory perspective on IVIVC.
The document discusses anti-thymocyte globulin (ATG), which is used for acute organ rejection. ATG is produced from rabbits that are inoculated with human T lymphocytes to trigger an antibody response. The antibodies produced in rabbits are then extracted, purified, and administered to patients to kill arrays of lymphocytes. Developing a process to characterize the target globulin and transferring knowledge will help establish protein production. Key challenges include maintaining clean environments and aseptic extraction, purification, and filling processes.
The document discusses establishing the OR Centre for Quality Sciences to provide consulting services to the pharmaceutical and biologics industries regarding quality, regulatory affairs, innovation, and technology. It aims to engage subject matter experts to support academia, industry, and government. The Centre will focus on shifting from a compliance to a quality culture and aligning with new regulatory expectations in a changing technological landscape with advances in areas like artificial intelligence and data sciences. It will provide training, reviews, audits, and other services to support quality systems, documentation practices, regulatory submissions, clinical trials, and more.
An article on contamination of Diethylene Glycol in Pharmaceuticals. Thanks to Dr. Ajaz S. Hussain for all teaching, sharing knowledge and supporting in professional development.
The document announces a training on demonstrating a quality management system during inspections to be held on September 30, 2023 in Kotri, Sindh. It will provide participants with techniques for showcasing compliance and procedures when regulatory audits occur. A list of attendees is included but not summarized for brevity.
The document provides tips for demonstrating a quality management system during an inspection. It advises being simple, clear, truthful, and confident when welcoming inspectors. Assign specific duties to staff and have flexibility. Listen fully to questions before responding, and don't argue - say you will look into issues. Practice mock inspections, recognize potential problems, and maintain your system daily.
The document discusses the services provided by the Centre for Quality Sciences, which include designing new and upgrading existing pharmaceutical manufacturing facilities, conducting GMP audits and training, assisting with regulatory submissions, and providing consulting services regarding quality systems, data integrity, and compliance strategies. The Centre's vision is to shift the industry towards a quality culture through knowledge sharing and facilitating discussions to develop strategic roadmaps. It aims to help companies strengthen quality compliance and sustain their quality management systems in the changing regulatory landscape.
The document discusses biomarkers, which are measurable indicators of biological states or conditions. It describes biomarkers as tools that can help facilitate medical product development. The document outlines different types, categories, and descriptions of biomarkers. It discusses how biomarkers can be qualified and approved by regulatory agencies like the FDA for specific contexts of use. The document provides examples of biomarkers that have been used for various purposes, such as assessing disease diagnosis, treatment effectiveness, and safety. It also summarizes some biomarkers that have been qualified or considered for qualification by the FDA.
1) The document discusses the evolution of ensuring drug quality from relying solely on testing to emphasizing proper manufacturing processes and controls.
2) It explains that without understanding the entire manufacturing process, one cannot say a drug is consistent in quality and purity or free of contamination.
3) Current good manufacturing practices (cGMP) help assure drug safety and efficacy by requiring facilities to control manufacturing operations through quality management systems and robust operating procedures.
The document discusses neurotoxicity and neurodegeneration in drug development. It notes that safety issues, especially related to the cardiovascular system and central nervous system, are among the most common reasons for drug development failure. Biomarkers for early detection of potential neurotoxicity could help improve success rates by facilitating safety screening earlier in the development process. The central nervous system is particularly vulnerable, as neurotoxicity is a frequent cause of failure in both pre-clinical and clinical phases of development.
Mr. Atiq ur Rahman has over 27 years of experience in pharmaceutical manufacturing and supply chain management. He has expertise in facility design, quality audits, and regulatory compliance. More recently, he has worked on data engineering, data acquisition, and applying data science concepts in pharmaceutical and other process industries. The presentation provides an overview of the industrial revolutions from Industry 1.0 to 5.0 and defines Pharma 4.0 as the convergence of people, systems, and data within a singular network powered by artificial intelligence. It discusses strategies for digital transformation and achieving digital maturity, including evaluating current technology needs and creating a roadmap with goals and timelines.
The document discusses the relationship between PIC/S and ICH and their roles in harmonizing GMP standards globally. PIC/S focuses specifically on GMP inspections and developing harmonized GMP standards and training inspectors. ICH focuses more broadly on safety, efficacy, quality and regulatory guidelines. Together they aim to promote reliance between regulatory authorities and open doors of trust through mutual recognition agreements and understanding of inspection systems. The document provides a comprehensive overview of their goals and collaboration to harmonize standards for patients worldwide.
The document discusses a presentation on quality issues observed by the FDA during inspections of pharmaceutical facilities in 2022. It notes the FDA observed deficiencies related to lack of written SOPs, insecure data, failure to investigate out of specification results, cleaning issues, and missing environmental monitoring programs. The document also presents a case study of a facility that had a significant media fill failure in November 2021 but did not initiate a recall until April 2022, exposing patients to risk. It describes poor aseptic techniques observed by FDA investigators during manufacturing operations.
The filling machine and HEPA filter located directly above the filling machine in the filling room were significantly discolored with an unknown substance. This indicates potential contamination issues that need to be investigated and addressed. Facilities should ensure machinery and equipment are properly cleaned and maintained to prevent contamination that could compromise product quality.
The document discusses the pressure of real-world evidence on pharmaceutical regulatory science. It mentions the author's experience interacting with international regulatory agencies like the FDA, EU, Health Canada, and MHRA. It lists some references on topics like continuous manufacturing and real-time dissolution prediction. The document emphasizes that improving individual parts of a system will not improve the overall system, and that a systems approach to quality is needed.
This document provides information about an upcoming training session on Good Manufacturing Practices. The session will be held on October 16th in Karachi and will run from 9:00 am to 3:00 pm. It is aimed at pharmaceutical professionals with backgrounds in pharmacy, chemistry, microbiology and related fields. Experts from the US pharmaceutical industry will discuss advancements in manufacturing technology and emerging regulatory changes. The session will include tutorials, discussions, and Q&A to help participants better understand GMP requirements and ensure quality assurance. Participants will pay Rs. 10,000 or Rs. 5,000 depending on whether they are attending as part of their job. More details and contact information are provided.
This document contains questions and answers related to pharmaceutical quality and manufacturing. It discusses topics like clean hold time, dirty hold time, contamination control strategies, particles in injections, the differences between CMC, GMP, and continuous manufacturing. It also addresses questions about PIC/S, such as whether they issue membership, if inspections by one country are accepted by others, and that GMP certificates are issued by individual regulatory authorities rather than PIC/S.
This document discusses issues that may arise with generic drugs compared to innovator drugs. Bioequivalence studies only show equivalence at a single point in time and do not guarantee equivalence over the lifetime of the drug. Manufacturing the drug involves many variables like people, equipment, materials that could result in potency and dissolution differences compared to the innovator. The document provides data that showed increased hospitalization rates for certain generics compared to the innovator drug. It emphasizes the need for consistent quality manufacturing to ensure patient safety.
The document discusses several topics related to improving drug quality including:
1) Evidence from clinical trials and real world use is key to determining drug effectiveness but quality can deteriorate after marketing authorization without a strong quality management system.
2) Errors must be eliminated through quality by design in development and operational excellence, and companies must continuously improve rather than just fixing problems.
3) Digital transformation, identifying critical quality attributes, and moving to more flexible and integrated quality systems will help address issues and improve patient outcomes.
This document appears to be a scanned receipt from a restaurant in New York City listing various food and drink items purchased, with a subtotal of $86.62 and total including tax of $97.45. The receipt details a variety of appetizers, entrees, drinks and desserts ordered for multiple guests.
This document discusses key elements of good manufacturing practices (GMP) for pharmaceutical manufacturing. It covers topics like building layout, equipment, utilities, documentation, materials, production processes, packaging, quality systems, facilities, laboratories and ensuring the safety, efficacy and quality of pharmaceutical products. The overall message is that GMP provides a foundation and framework to establish process and quality control, validate operations, continuously improve and ultimately ensure that pharmaceutical products meet their intended quality standards.
Sethurathnam Ravi: A Legacy in Finance and LeadershipAnjana Josie
Sethurathnam Ravi, also known as S Ravi, is a distinguished Chartered Accountant and former Chairman of the Bombay Stock Exchange (BSE). As the Founder and Managing Partner of Ravi Rajan & Co. LLP, he has made significant contributions to the fields of finance, banking, and corporate governance. His extensive career includes directorships in over 45 major organizations, including LIC, BHEL, and ONGC. With a passion for financial consulting and social issues, S Ravi continues to influence the industry and inspire future leaders.
Originally presented at XP2024 Bolzano
While agile has entered the post-mainstream age, possibly losing its mojo along the way, the rise of remote working is dealing a more severe blow than its industrialization.
In this talk we'll have a look to the cumulative effect of the constraints of a remote working environment and of the common countermeasures.
Employment PracticesRegulation and Multinational CorporationsRoopaTemkar
Employment PracticesRegulation and Multinational Corporations
Strategic decision making within MNCs constrained or determined by the implementation of laws and codes of practice and by pressure from political actors. Managers in MNCs have to make choices that are shaped by gvmt. intervention and the local economy.
Enriching engagement with ethical review processesstrikingabalance
New ethics review processes at the University of Bath. Presented at the 8th World Conference on Research Integrity by Filipa Vance, Head of Research Governance and Compliance at the University of Bath. June 2024, Athens
Public Speaking Tips to Help You Be A Strong Leader.pdfPinta Partners
In the realm of effective leadership, a multitude of skills come into play, but one stands out as both crucial and challenging: public speaking.
Public speaking transcends mere eloquence; it serves as the medium through which leaders articulate their vision, inspire action, and foster engagement. For leaders, refining public speaking skills is essential, elevating their ability to influence, persuade, and lead with resolute conviction. Here are some key tips to consider: https://joellandau.com/the-public-speaking-tips-to-help-you-be-a-stronger-leader/
12 steps to transform your organization into the agile org you deservePierre E. NEIS
During an organizational transformation, the shift is from the previous state to an improved one. In the realm of agility, I emphasize the significance of identifying polarities. This approach helps establish a clear understanding of your objectives. I have outlined 12 incremental actions to delineate your organizational strategy.
Org Design is a core skill to be mastered by management for any successful org change.
Org Topologies™ in its essence is a two-dimensional space with 16 distinctive boxes - atomic organizational archetypes. That space helps you to plot your current operating model by positioning individuals, departments, and teams on the map. This will give a profound understanding of the performance of your value-creating organizational ecosystem.
Ganpati Kumar Choudhary Indian Ethos PPT.pptx, The Dilemma of Green Energy Corporation
Green Energy Corporation, a leading renewable energy company, faces a dilemma: balancing profitability and sustainability. Pressure to scale rapidly has led to ethical concerns, as the company's commitment to sustainable practices is tested by the need to satisfy shareholders and maintain a competitive edge.
Specific ServPoints should be tailored for restaurants in all food service segments. Your ServPoints should be the centerpiece of brand delivery training (guest service) and align with your brand position and marketing initiatives, especially in high-labor-cost conditions.
408-784-7371
Foodservice Consulting + Design
Addiction to Winning Across Diverse Populations.pdf
Sterile Operations (Part 2-A) - Fundamental, Essentials and Regulatory Obligations
1. [Case Study (A) : 6-1]
Sterile Operations for Parenteral Preparations
Roohi B. Obaid
23 Jun 2018 at Karachi
2. An Investigation of Microbial
Contamination
(CDER-FDA Case study; Ref: John W.Metcalfe 2017)
Bulkholderiia multivorans
3. Burkholderia Cepacia Complex (BCC) 1949 … 1950
Catalase producing Lactulose non-fermenting Gram -ve
More than 20 species including B. multivorans
Plant / water Moist environment Opportunistic
Pneumonia particularly in immuno-compromised patients
12. Control of Microbiological Contamination
Regulatory
Perspective
Appropriate written procedures, designed
to prevent objectionable
microorganisms in drug product not
required to be sterile shall be established
& followed
14. Testing & Release for Distribution
Regulatory
Perspective
There shall be appropriate laboratory
testing, as necessary, of each batch of
drug product required to be free of
objectionable microorganisms
16. Field Alert / Intimations
Regulatory
Perspective
Information concerning any
bacteriological contamination,
or … one or more distributed batches of
drug product to meet specifications for it
in the application
17. Non-sterile drug is more challenging than sterile drug
Do you agree? Particularly for microbiologist
18. Non-sterile drug is more challenging than sterile drug
Do you agree? Particularly for microbiologist
Strongly
agree
1
19. Non-sterile drug is more challenging than sterile drug
Do you agree? Particularly for microbiologist
Strongly
agree
Agree
1 2
20. Non-sterile drug is more challenging than sterile drug
Do you agree? Particularly for microbiologist
Strongly
agree
Agree Neutral
1 2 3
21. Non-sterile drug is more challenging than sterile drug
Do you agree? Particularly for microbiologist
Strongly
agree
Agree DisagreeNeutral
1 2 3 4
22. Non-sterile drug is more challenging than sterile drug
Do you agree? Particularly for microbiologist
Strongly
agree
Strongly
disagree
Agree DisagreeNeutral
1 2 3 4 5
31. How was it resolved ?
How initial batches were determine to contain B. multivorans
Was it caught through USP test or any specific test
What is the concentration / ml of B. multivorans in these batches
Was test different from test performed earlier in expanded testing
32. How was it resolved ?
How initial batches were determine to contain B. multivorans
Was it caught through USP test or any specific test
What is the concentration / ml of B. multivorans in these batches
Was test different from test performed earlier in expanded testing
33. How was it resolved ?
How initial batches were determine to contain B. multivorans
Was it caught through USP test or any specific test
What is the concentration / ml of B. multivorans in these batches
Was test different from test performed earlier in expanded testing
34. How was it resolved ?
How initial batches were determine to contain B. multivorans
Was it caught through USP test or any specific test
What is the concentration / ml of B. multivorans in these batches
Was test different from test performed earlier in expanded testing
35. How was it resolved ?
How initial batches were determine to contain B. multivorans
Was it caught through USP test or any specific test
What is the concentration / ml of B. multivorans in these batches
Was test different from test performed earlier in expanded testing
36. How was it resolved ?
Is water system routinely tested for BCC
Steps of drug manufacturing process that were gone through test
What should be the plan for batches … both available & …
37. How was it resolved ?
Is water system routinely tested for BCC
Steps of drug manufacturing process that were gone through test
What should be the plan for batches … both available & …
38. How was it resolved ?
Is water system routinely tested for BCC
Steps of drug manufacturing process that were gone through test
What should be the plan for batches … both available & …
39. How was it resolved ?
Is water system routinely tested for BCC
Steps of drug manufacturing process that were gone through test
What should be the plan for batches … both available & …
40.
41. How was it resolved ?
USP <62> Bile-Tolerant Gram –ve method
Pipe in purified water system not properly sanitized/engineered
Biofilm, but it was in control during manufacturing
42.
43. Question
Do all 58 batches having valid shelf life
need to be recalled?
?
FDA Team
44. How was it resolved ?
Are all batches subject to microbiological testing at release
If so, what methodology/strategy is used
The product is preserved: are the methods suitable for use with the
subject drug product
45. How was it resolved ?
Regarding the 58 lots, they asked test methods, acceptance
criteria & data summaries from all microbiological testing
performed on the drug product at release.
They further asked data summaries demonstrating that
microbial test methods are suitable for the drug product
1
2
46. How was it resolved ?
Regarding the 58 lots, they asked test methods, acceptance
criteria & data summaries from all microbiological testing
performed on the drug product at release.
They further asked data summaries demonstrating that
microbial test methods are suitable for the drug product
1
2
47. How was it resolved ?
Regarding the 58 lots, they asked test methods, acceptance
criteria & data summaries from all microbiological testing
performed on the drug product at release.
They further asked data summaries demonstrating that
microbial test methods are suitable for the drug product
1
2
48. How was it resolved ?
They continued and asked stability protocol & data
summaries for any microbiological testing that has been
performed till time on any particular lots of 58 batches that
are under question
3
49.
50. Response
Do all 58 batches having valid shelf life
need to be recalled?
…
Firm
51. Routinely perform
microbial release
testing as per USP
<1111>
Acceptance Criteria for
Pharmaceutical Preparations &
Substance for Pharmaceutical Use
Microbiological examination of
non-sterile products
52. Routinely perform
microbial release
testing according to the
method described in
USP <61> & <62>
Enumeration Test and Test for
specified microorganisms
Microbiological examination of
non-sterile products
55. Firm has satisfactorily testing to demonstrate that the
microbiological test method are suitable for use with drug
product, including in the recovery of Bulkholderia multivorans
The microbiological release test data on the 58 batches of
drug product meet acceptance criteria and are acceptable
56. Stability data till time meets acceptance criteria and are
acceptable
Microbiological testing of drug product sample in the
stability program is routinely performed
57.
58. Rationale
Do all 58 batches having valid shelf life
need to be recalled?
…
Science
59. Firm’s Investigation
Evaluation of growth potential of the
contaminant in the drug product
The contaminant count decreases over first few days1
Day 3: Start of Log phase growth in the preserved drug2
Day 7: Counts > 10 CFU/ml of preserved drug3
5
60. Firm’s Investigation
Evaluation of growth potential of the
contaminant in the drug product
The contaminant count decreases over first few days1
Day 3: Start of Log phase growth in the preserved drug2
Day 7: Counts > 10 CFU/ml of preserved drug3
5
61. Firm’s Investigation
Evaluation of growth potential of the
contaminant in the drug product
The contaminant count decreases over first few days1
Day 3: Start of Log phase growth in the preserved drug2
Day 7: Counts > 10 CFU/ml of preserved drug3
5
62. Firm’s Investigation
Evaluation of growth potential of the
contaminant in the drug product
The contaminant count decreases over first few days1
Day 3: Start of Log phase growth in the preserved drug2
Day 7: Counts > 10 CFU/ml of preserved drug3
5
63. Firm’s Investigation
Growth Kinetic Study:
BCC in Drug Product
Performing the study provided the firm with an understanding of this
organism in this product1
May explain picking up the organism using the “expanded” testing2
Provided the firm with an avenue for Corrective Actions regarding future
micro testing of this product3
64. Firm’s Investigation
Growth Kinetic Study:
BCC in Drug Product
Performing the study provided the firm with an understanding of this
organism in this product1
May explain picking up the organism using the “expanded” testing2
Provided the firm with an avenue for Corrective Actions regarding future
micro testing of this product3
65. Firm’s Investigation
Growth Kinetic Study:
BCC in Drug Product
Performing the study provided the firm with an understanding of this
organism in this product1
May explain picking up the organism using the “expanded” testing2
Provided the firm with an avenue for Corrective Actions regarding future
micro testing of this product3
66. Firm’s Investigation
Growth Kinetic Study:
BCC in Drug Product
Performing the study provided the firm with an understanding of this
organism in this product1
May explain picking up the organism using the “expanded” testing2
Provided the firm with an avenue for Corrective Actions regarding future
micro testing of this product3
67. Firm’s Investigation Expanded Testing Sequence
Initial: 10 batches tested & 5 batches found +ve1
Next: 25 marketed batches manufactured prior to original 102
None of these batches tested +ve3
68. Firm’s Investigation Expanded Testing Sequence
Initial: 10 batches tested & 5 batches found +ve1
Next: 25 marketed batches manufactured prior to original 102
None of these batches tested +ve3
69. Firm’s Investigation Expanded Testing Sequence
Initial: 10 batches tested & 5 batches found +ve1
Next: 25 marketed batches manufactured prior to original 102
None of these batches tested +ve3
70. Firm’s Investigation Expanded Testing Sequence
Initial: 10 batches tested & 5 batches found +ve1
Next: 25 marketed batches manufactured prior to original 102
None of these batches tested +ve3
71. Firm’s Investigation Expanded Testing Sequence
Information from expanded testing of 35 batches4
Points to timeframe for biofilm formation5
Provide some assurance regarding patient safety & quality6
72. Firm’s Investigation Expanded Testing Sequence
Information from expanded testing of 35 batches4
Points to timeframe for biofilm formation5
Provide some assurance regarding patient safety & quality6
73. Firm’s Investigation Expanded Testing Sequence
Information from expanded testing of 35 batches4
Points to timeframe for biofilm formation5
Provide some assurance regarding patient safety & quality6
74. Firm’s Investigation Expanded Testing Sequence
Information from expanded testing of 35 batches4
Points to timeframe for biofilm formation5
Provide some assurance regarding patient safety & quality6
75. Firm’s Investigation Expanded Testing Sequence
Information from expanded testing of 35 batches4
Points to timeframe for biofilm formation5
Provide some assurance regarding patient safety & quality6
76.
77. Review
Do all 58 batches having valid shelf life
need to be recalled?
…
FDA
78. Reviewer acknowledges
that end product release
testing presents limitations
with regard to predicting
quality of a given product
batch
However
79. The information provided does not
suggest that a product recall of 58
batches is warranted from the
standpoint of microbiological
contamination
81. No Recall
Corrective Action followed by
Investigation
Re-engineered the bad plumbing Improved sanitization
Eyes are wide open for BCC Expanded micro testing for 12 months
Modified start time of microbiological release testing based
on growth kinetic study
82. Non-sterile drug is more challenging than sterile drug
Do you agree? Particularly for microbiologist
Strongly
agree
Strongly
disagree
Agree DisagreeNeutral
1 2 3 4 5
83. With scientific support to
present & demonstrate your
decisions driven by data
To have a question that how
would you respond when E.
coli hits the fan
You may hear any time …
please be ready …