The document discusses quality assurance (QA) and quality control (QC) in the pharmaceutical industry. It defines QA as the organized arrangements to ensure products meet quality requirements for intended use. GMP is part of QA focused on consistently manufacturing products to a quality appropriate for intended use. QC is the part of GMP concerned with sampling, specifications, testing, documentation, and release procedures to ensure necessary tests are performed and products meet quality standards before release. The document emphasizes that QA is company-based while QC is laboratory-based and operational. It provides guidelines for establishing acceptance criteria for various quality attributes like impurities, degradation products, particle size, and polymorphism in drug substances and drug products.
Through this Guidance you are able to understand the basics requirements of Table scoring, agencies recommendations and data to be generated on split tablets.
Comparison of stability testing requirements of ich with otherJun Brown
Stability plays an important role in the drug development process. Present work aims to compare the stability
testing (ST) requirements of International Conference on Harmonization (ICH) with other international regulatory
agencies like World Health Organization (WHO), Association of South East Asian Nations (ASEAN) and
European Agency for Evaluation of Medicinal and Health Products (EMEA). ICH guidelines describe stability
testing requirements for new drug substance and drug product. WHO guidelines describe stability testing
requirements for both new and existing Active pharmaceutical ingredients (APIs) and addresses information
to be submitted in original and subsequent applications for marketing authorization of their related Finished
pharmaceutical products (FPP) for human use. ST requirements for WHO are similar, except for the parameters
like selection of batches and storage conditions. WHO guidelines have an additional requirement for long term
storage condition (general case) and accelerated storage conditions (substance/product intended to be stored
in refrigerator). ASEAN guideline mainly focuses on the requirements for stability testing of drug products along
with new chemical entities (NCE’s). The differences were observed in stress testing, selection of batches and
real time storage conditions. EMEA guidelines discussed here are an extension of the note for guidance on
stability testing requirements for new active substance and related products. It sets out the stability testing
requirements for existing active substance and related finished product. The minimum time period to be covered
by data at the time of submission during long term storage conditions differs from ICH guidelines.
A presentation on regulatory guidelines for photostability testingzaartab
This document provides guidelines for photostability testing of drug substances and products according to ICH regulations. It discusses the purpose of photostability testing to evaluate a drug's sensitivity to light and ensure stability. Testing involves exposing samples to light sources and analyzing degradation over time. For drug substances, forced degradation tests evaluate photosensitivity while confirmatory tests provide handling and packaging information. For drug products, sequential tests progress until adequate light protection is demonstrated. The goal is to identify necessary precautions and ensure stability through appropriate packaging and labeling.
The document discusses issues with the Drug Regulatory Authority of Pakistan's (DRAP) recommendations for batch sizes in product development and stability studies, which contradict international regulatory science norms. Specifically, DRAP recommends a batch size of only 2,500 tablets for lab-scale trials and stability testing every 1-2 weeks, rather than the accepted standards of at least 25% of pilot-scale batch size and testing every 3-6 months. The author argues this approach is not supported by any scientific reference and could compromise drug quality, safety and efficacy. The document advocates for DRAP to align its practices with international guidelines from organizations like the International Council for Harmonization to strengthen regulatory systems in Pakistan and better serve patients and industry.
This document provides an overview of the ICH Q1A(R2) guideline for stability testing of new drug substances and products. The guideline defines the stability data package required for drug registration in major regions. It addresses testing timelines and conditions for long term, intermediate, and accelerated studies on at least three batches of drug substance and product. The goal is to establish a re-test period or shelf life and recommended storage conditions. Specifications must cover attributes susceptible to change that could impact quality, safety or efficacy. The guideline provides detailed recommendations for testing frequency, storage conditions, and evaluation of results.
Impurity profiling and degradent characterization {presented by shameer m.pha...ShameerAbid
these slides discuss
Impurity profiling
Degradation characterization
Stability testing & Accelerated stability testing (ICH)
Evaluation of the test (shelf life)
analytical method development
ICH vs USP definition
methods for identification
method for the isolation of the impurity
factors affecting the degradation of formulation
What is degradation characterization
general protocol of degradation conditions used for drug substance and drug product
Degradation conditions
Stress testing
Container closure system
Through this Guidance you are able to understand the basics requirements of Table scoring, agencies recommendations and data to be generated on split tablets.
Comparison of stability testing requirements of ich with otherJun Brown
Stability plays an important role in the drug development process. Present work aims to compare the stability
testing (ST) requirements of International Conference on Harmonization (ICH) with other international regulatory
agencies like World Health Organization (WHO), Association of South East Asian Nations (ASEAN) and
European Agency for Evaluation of Medicinal and Health Products (EMEA). ICH guidelines describe stability
testing requirements for new drug substance and drug product. WHO guidelines describe stability testing
requirements for both new and existing Active pharmaceutical ingredients (APIs) and addresses information
to be submitted in original and subsequent applications for marketing authorization of their related Finished
pharmaceutical products (FPP) for human use. ST requirements for WHO are similar, except for the parameters
like selection of batches and storage conditions. WHO guidelines have an additional requirement for long term
storage condition (general case) and accelerated storage conditions (substance/product intended to be stored
in refrigerator). ASEAN guideline mainly focuses on the requirements for stability testing of drug products along
with new chemical entities (NCE’s). The differences were observed in stress testing, selection of batches and
real time storage conditions. EMEA guidelines discussed here are an extension of the note for guidance on
stability testing requirements for new active substance and related products. It sets out the stability testing
requirements for existing active substance and related finished product. The minimum time period to be covered
by data at the time of submission during long term storage conditions differs from ICH guidelines.
A presentation on regulatory guidelines for photostability testingzaartab
This document provides guidelines for photostability testing of drug substances and products according to ICH regulations. It discusses the purpose of photostability testing to evaluate a drug's sensitivity to light and ensure stability. Testing involves exposing samples to light sources and analyzing degradation over time. For drug substances, forced degradation tests evaluate photosensitivity while confirmatory tests provide handling and packaging information. For drug products, sequential tests progress until adequate light protection is demonstrated. The goal is to identify necessary precautions and ensure stability through appropriate packaging and labeling.
The document discusses issues with the Drug Regulatory Authority of Pakistan's (DRAP) recommendations for batch sizes in product development and stability studies, which contradict international regulatory science norms. Specifically, DRAP recommends a batch size of only 2,500 tablets for lab-scale trials and stability testing every 1-2 weeks, rather than the accepted standards of at least 25% of pilot-scale batch size and testing every 3-6 months. The author argues this approach is not supported by any scientific reference and could compromise drug quality, safety and efficacy. The document advocates for DRAP to align its practices with international guidelines from organizations like the International Council for Harmonization to strengthen regulatory systems in Pakistan and better serve patients and industry.
This document provides an overview of the ICH Q1A(R2) guideline for stability testing of new drug substances and products. The guideline defines the stability data package required for drug registration in major regions. It addresses testing timelines and conditions for long term, intermediate, and accelerated studies on at least three batches of drug substance and product. The goal is to establish a re-test period or shelf life and recommended storage conditions. Specifications must cover attributes susceptible to change that could impact quality, safety or efficacy. The guideline provides detailed recommendations for testing frequency, storage conditions, and evaluation of results.
Impurity profiling and degradent characterization {presented by shameer m.pha...ShameerAbid
these slides discuss
Impurity profiling
Degradation characterization
Stability testing & Accelerated stability testing (ICH)
Evaluation of the test (shelf life)
analytical method development
ICH vs USP definition
methods for identification
method for the isolation of the impurity
factors affecting the degradation of formulation
What is degradation characterization
general protocol of degradation conditions used for drug substance and drug product
Degradation conditions
Stress testing
Container closure system
Testing of drugs can verify that they meet specifications but cannot guarantee their quality, safety, or efficacy. Quality must be built into the manufacturing process through good manufacturing practices (GMP) rather than relying solely on testing. GMP ensures proper design, monitoring, and control of production to reduce risks that testing cannot detect. National regulations and international guidelines on current GMP provide systems to assure identity, strength, purity and quality of drugs. While testing is required, it alone is insufficient to ensure quality given its limitations, so GMP is critical to building quality into every step of design and manufacturing.
The document provides an overview of stability testing during product development. It discusses the importance of stability testing to ensure product quality and safety over the shelf life. Various methods of stability testing are described, including real-time, accelerated, and retained sample testing. Guidelines for stability testing from ICH, WHO, and other agencies are also covered. The document outlines the key aspects of a stability testing protocol, including batches, containers, storage conditions, sampling plan, test parameters, and acceptance criteria. It provides details on conducting, recording, and presenting stability testing data.
Stability testing is used to provide evidence of how the quality of a drug substance or product varies over time under environmental conditions like temperature, humidity, and light. Guidelines provide recommendations on conducting stability tests including storing samples under long-term, intermediate, and accelerated conditions and specifying the testing frequency. Stability tests evaluate attributes of the drug substance or product that may change during storage. The results are used to establish a retest period to ensure the stated quality of the substance or product through the expiration date.
This document discusses guidelines for stability testing of pharmaceuticals according to the International Conference on Harmonization (ICH). It describes the ICH guidelines for stability testing, including stability protocols, reports, and studies. The key points covered include stability testing procedures, factors affecting drug stability, types of stability studies, and organizations that regulate stability guidelines such as the ICH.
This document provides an overview of ICH guidelines for stability studies. It discusses guidelines Q1A-Q1F which provide recommendations for conducting stability testing of new drug substances and products. The guidelines address objectives, scope, general principles and recommendations for testing parameters, storage conditions, batch selection, specification setting and evaluation of stability data. Bracketing and matrixing designs are also covered as approaches to reduce the number of stability test samples required.
Generic Drugs; Comparative Dissolution Profile & Discriminative Method for Di...Obaid Ali / Roohi B. Obaid
The document discusses generic drugs and dissolution testing. It notes that some generic products pass dissolution testing using their own methods but fail comparative dissolution testing against innovator products in different pH mediums. Proper dissolution method development is important to demonstrate a method's ability to detect manufacturing variations. The document emphasizes that generic drugs should show similar dissolution profiles to innovator products in different pH environments to help ensure similar clinical responses. It also stresses the importance of methods being able to discriminate between formulations and catch impacts of manufacturing changes.
This document summarizes guidelines for stability testing according to ICH guidelines. The key points are:
1) ICH guidelines are most commonly accepted and provide information on stability testing in the EU, Japan, and US. Stability testing aims to provide evidence of how quality varies over time under different conditions.
2) The objectives of ICH are more economical use of resources, eliminating delays in global development and availability of medicines, and maintaining safeguards for quality, safety, and efficacy.
3) Stability topics covered by ICH include testing, validation, impurities, specifications, and manufacturing. This summary focuses on stability testing guidelines for new drug substances and products.
The document discusses stability studies of pharmaceuticals. It begins with an introduction defining stability studies and their purpose to ensure drug efficacy, safety and quality over the shelf life. It then outlines the key stages of stability studies including stress testing, international stability guidelines, and development of stability indicating assay methods (SIAMs). SIAMs are validated quantitative methods that can detect changes in drugs and products over time. The document concludes with two case studies demonstrating the development and validation of SIAMs for pharmaceutical combinations using HPLC and HPTLC methods.
The document discusses planning and reporting of stability studies for pharmaceutical products. It provides definitions of key terms from ICH guidelines related to stability testing of active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs). Specifically, it defines terms like re-test date, shelf life, formal stability studies, stress testing, primary and commitment batches, and more. It also discusses requirements for stability protocols and reports, including details of batches tested, storage conditions, analytical methods used, and results. Forced degradation studies aim to identify potential degradation pathways and validate stability-indicating methods.
This document provides guidelines for stability studies of drug products, including objectives, scope, design considerations, testing parameters, storage conditions, evaluation, and reporting requirements. Key aspects covered include testing at least three primary batches of new chemical entities and two batches of generics, analyzing physical, chemical, and microbiological attributes, storing products under various conditions like room temperature and refrigeration, evaluating data at multiple time points, and committing to a shelf life. The guidelines aim to ensure drug products maintain quality, safety and efficacy throughout their proposed shelf life.
Q1A(R2): STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTSBhaumik Bavishi
The document provides guidelines for submitting stability data for drug substances and drug products as part of a registration application. It outlines the objectives, scope, and general principles of stability testing. Guidelines are given for conducting long-term, accelerated, and intermediate stability studies under various storage conditions. Specifications, testing frequency, number of batches, and container closure systems are also addressed. A commitment to continuing stability studies is recommended if the available data does not cover the proposed shelf life period.
The document discusses ICH stability testing guidelines for drug substances and products, outlining the types of studies required including long term, intermediate, and accelerated studies under various storage conditions. Key aspects that are evaluated include physical, chemical, and microbial changes that may occur over time and factors that influence stability such as temperature, humidity, and light exposure. The purpose of stability testing is to establish a product's shelf life and ensure it remains safe and effective when stored as recommended.
This document provides guidance on bracketing and matrixing study designs for stability testing of new drug substances and products. Bracketing involves testing only samples on the extremes of certain design factors, like strength or container size, at all time points. Matrixing involves testing a subset of all possible samples at each time point. The guideline outlines when and how bracketing and matrixing can be applied, including design examples. Any reduced design must be justified and have the ability to adequately predict shelf life or retest period. All factor combinations should be tested at initial, final, and 12-month time points.
The document discusses the objectives and guidelines of the International Council for Harmonization (ICH) for stability testing of pharmaceutical products. It provides an overview of the key ICH guidelines for stability testing (Q1A-Q1F) and describes the principles of stability testing including establishing re-test periods and shelf lives. It also discusses the different types of stability testing, protocols, study designs like bracketing and matrixing, and key parameters for evaluation.
Stability Indicating HPLC Method Development A Reviewijtsrd
High performance liquid chromatography HPLC is an essential analytical tool for evaluating drug stability. HPLC methods must be able to isolate, detect, and quantify drug related degradation products that may form during storage or production, and identify drug related impurities that may form during synthesis. .. This article describes strategies and challenges for designing HPLC methods to demonstrate drug stability. It will deepen our understanding of drugs and medicinal chemistry and demonstrate advances in stability that reflect an analytical approach. Several important chromatographic parameters were investigated to improve the detection of potentially related degradants. It is necessary to find suitable solvent and mobile phase samples that provide sufficient stability and compatibility with each component and potential impurities and degradants. This method should be carefully considered as it has the ability to distinguish between primary and secondary decomposers. The study of forced destruction of chemicals and new drugs is essential for the development and characterization of these immobilization methods. Practical guidance is provided at each stage of drug development to develop a forced disposal protocol and avoid common issues that might impede data interpretation. Suraj Nagwanshi | Smita Aher | Rishikesh Bachhav "Stability Indicating HPLC Method Development - A Review" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd46310.pdf Paper URL: https://www.ijtsrd.com/pharmacy/other/46310/stability-indicating-hplc-method-development--a-review/suraj-nagwanshi
Bracketing and Matrixing Methods for Stability analysisSarath Chandra
This document discusses bracketing and matrixing designs for stability testing of new drug substances and products according to ICH Q1D guidelines. Bracketing design involves testing only the extremes of design factors like strength or container size, assuming stability of intermediates is represented by extremes. Matrixing design involves testing selected combinations of factors at each time point rather than all combinations at all time points. Both designs provide reduced testing compared to full design testing all samples at all time points, but require justification and carry potential risks of underestimating shelf life if variability is high.
The ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) brings together regulatory authorities and pharmaceutical industry representatives from Europe, Japan and the US to discuss scientific and technical issues around ensuring safety, quality and efficacy of medicines. The objectives of ICH include increasing international harmonization of technical requirements and developing pharmaceuticals in an efficient manner while promoting public health. ICH guidelines cover quality, safety, efficacy and multidisciplinary topics with the goal of international harmonization.
The document provides guidelines for specifications of new drug substances and products. It discusses setting specifications based on development data and stability studies. Universal tests for drug substances include identification, assay, impurities. For products, additional tests depend on dosage form and may include dissolution, uniformity, sterility. The guidelines provide concepts for justifying specifications and periodic testing. They apply principles for biotech products, addressing characterization, analytical validation, process controls, and linking specifications to manufacturing and clinical data.
Testing of drugs can verify that they meet specifications but cannot guarantee their quality, safety, or efficacy. Quality must be built into the manufacturing process through good manufacturing practices (GMP) rather than relying solely on testing. GMP ensures proper design, monitoring, and control of production to reduce risks that testing cannot detect. National regulations and international guidelines on current GMP provide systems to assure identity, strength, purity and quality of drugs. While testing is required, it alone is insufficient to ensure quality given its limitations, so GMP is critical to building quality into every step of design and manufacturing.
The document provides an overview of stability testing during product development. It discusses the importance of stability testing to ensure product quality and safety over the shelf life. Various methods of stability testing are described, including real-time, accelerated, and retained sample testing. Guidelines for stability testing from ICH, WHO, and other agencies are also covered. The document outlines the key aspects of a stability testing protocol, including batches, containers, storage conditions, sampling plan, test parameters, and acceptance criteria. It provides details on conducting, recording, and presenting stability testing data.
Stability testing is used to provide evidence of how the quality of a drug substance or product varies over time under environmental conditions like temperature, humidity, and light. Guidelines provide recommendations on conducting stability tests including storing samples under long-term, intermediate, and accelerated conditions and specifying the testing frequency. Stability tests evaluate attributes of the drug substance or product that may change during storage. The results are used to establish a retest period to ensure the stated quality of the substance or product through the expiration date.
This document discusses guidelines for stability testing of pharmaceuticals according to the International Conference on Harmonization (ICH). It describes the ICH guidelines for stability testing, including stability protocols, reports, and studies. The key points covered include stability testing procedures, factors affecting drug stability, types of stability studies, and organizations that regulate stability guidelines such as the ICH.
This document provides an overview of ICH guidelines for stability studies. It discusses guidelines Q1A-Q1F which provide recommendations for conducting stability testing of new drug substances and products. The guidelines address objectives, scope, general principles and recommendations for testing parameters, storage conditions, batch selection, specification setting and evaluation of stability data. Bracketing and matrixing designs are also covered as approaches to reduce the number of stability test samples required.
Generic Drugs; Comparative Dissolution Profile & Discriminative Method for Di...Obaid Ali / Roohi B. Obaid
The document discusses generic drugs and dissolution testing. It notes that some generic products pass dissolution testing using their own methods but fail comparative dissolution testing against innovator products in different pH mediums. Proper dissolution method development is important to demonstrate a method's ability to detect manufacturing variations. The document emphasizes that generic drugs should show similar dissolution profiles to innovator products in different pH environments to help ensure similar clinical responses. It also stresses the importance of methods being able to discriminate between formulations and catch impacts of manufacturing changes.
This document summarizes guidelines for stability testing according to ICH guidelines. The key points are:
1) ICH guidelines are most commonly accepted and provide information on stability testing in the EU, Japan, and US. Stability testing aims to provide evidence of how quality varies over time under different conditions.
2) The objectives of ICH are more economical use of resources, eliminating delays in global development and availability of medicines, and maintaining safeguards for quality, safety, and efficacy.
3) Stability topics covered by ICH include testing, validation, impurities, specifications, and manufacturing. This summary focuses on stability testing guidelines for new drug substances and products.
The document discusses stability studies of pharmaceuticals. It begins with an introduction defining stability studies and their purpose to ensure drug efficacy, safety and quality over the shelf life. It then outlines the key stages of stability studies including stress testing, international stability guidelines, and development of stability indicating assay methods (SIAMs). SIAMs are validated quantitative methods that can detect changes in drugs and products over time. The document concludes with two case studies demonstrating the development and validation of SIAMs for pharmaceutical combinations using HPLC and HPTLC methods.
The document discusses planning and reporting of stability studies for pharmaceutical products. It provides definitions of key terms from ICH guidelines related to stability testing of active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs). Specifically, it defines terms like re-test date, shelf life, formal stability studies, stress testing, primary and commitment batches, and more. It also discusses requirements for stability protocols and reports, including details of batches tested, storage conditions, analytical methods used, and results. Forced degradation studies aim to identify potential degradation pathways and validate stability-indicating methods.
This document provides guidelines for stability studies of drug products, including objectives, scope, design considerations, testing parameters, storage conditions, evaluation, and reporting requirements. Key aspects covered include testing at least three primary batches of new chemical entities and two batches of generics, analyzing physical, chemical, and microbiological attributes, storing products under various conditions like room temperature and refrigeration, evaluating data at multiple time points, and committing to a shelf life. The guidelines aim to ensure drug products maintain quality, safety and efficacy throughout their proposed shelf life.
Q1A(R2): STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTSBhaumik Bavishi
The document provides guidelines for submitting stability data for drug substances and drug products as part of a registration application. It outlines the objectives, scope, and general principles of stability testing. Guidelines are given for conducting long-term, accelerated, and intermediate stability studies under various storage conditions. Specifications, testing frequency, number of batches, and container closure systems are also addressed. A commitment to continuing stability studies is recommended if the available data does not cover the proposed shelf life period.
The document discusses ICH stability testing guidelines for drug substances and products, outlining the types of studies required including long term, intermediate, and accelerated studies under various storage conditions. Key aspects that are evaluated include physical, chemical, and microbial changes that may occur over time and factors that influence stability such as temperature, humidity, and light exposure. The purpose of stability testing is to establish a product's shelf life and ensure it remains safe and effective when stored as recommended.
This document provides guidance on bracketing and matrixing study designs for stability testing of new drug substances and products. Bracketing involves testing only samples on the extremes of certain design factors, like strength or container size, at all time points. Matrixing involves testing a subset of all possible samples at each time point. The guideline outlines when and how bracketing and matrixing can be applied, including design examples. Any reduced design must be justified and have the ability to adequately predict shelf life or retest period. All factor combinations should be tested at initial, final, and 12-month time points.
The document discusses the objectives and guidelines of the International Council for Harmonization (ICH) for stability testing of pharmaceutical products. It provides an overview of the key ICH guidelines for stability testing (Q1A-Q1F) and describes the principles of stability testing including establishing re-test periods and shelf lives. It also discusses the different types of stability testing, protocols, study designs like bracketing and matrixing, and key parameters for evaluation.
Stability Indicating HPLC Method Development A Reviewijtsrd
High performance liquid chromatography HPLC is an essential analytical tool for evaluating drug stability. HPLC methods must be able to isolate, detect, and quantify drug related degradation products that may form during storage or production, and identify drug related impurities that may form during synthesis. .. This article describes strategies and challenges for designing HPLC methods to demonstrate drug stability. It will deepen our understanding of drugs and medicinal chemistry and demonstrate advances in stability that reflect an analytical approach. Several important chromatographic parameters were investigated to improve the detection of potentially related degradants. It is necessary to find suitable solvent and mobile phase samples that provide sufficient stability and compatibility with each component and potential impurities and degradants. This method should be carefully considered as it has the ability to distinguish between primary and secondary decomposers. The study of forced destruction of chemicals and new drugs is essential for the development and characterization of these immobilization methods. Practical guidance is provided at each stage of drug development to develop a forced disposal protocol and avoid common issues that might impede data interpretation. Suraj Nagwanshi | Smita Aher | Rishikesh Bachhav "Stability Indicating HPLC Method Development - A Review" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd46310.pdf Paper URL: https://www.ijtsrd.com/pharmacy/other/46310/stability-indicating-hplc-method-development--a-review/suraj-nagwanshi
Bracketing and Matrixing Methods for Stability analysisSarath Chandra
This document discusses bracketing and matrixing designs for stability testing of new drug substances and products according to ICH Q1D guidelines. Bracketing design involves testing only the extremes of design factors like strength or container size, assuming stability of intermediates is represented by extremes. Matrixing design involves testing selected combinations of factors at each time point rather than all combinations at all time points. Both designs provide reduced testing compared to full design testing all samples at all time points, but require justification and carry potential risks of underestimating shelf life if variability is high.
The ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) brings together regulatory authorities and pharmaceutical industry representatives from Europe, Japan and the US to discuss scientific and technical issues around ensuring safety, quality and efficacy of medicines. The objectives of ICH include increasing international harmonization of technical requirements and developing pharmaceuticals in an efficient manner while promoting public health. ICH guidelines cover quality, safety, efficacy and multidisciplinary topics with the goal of international harmonization.
The document provides guidelines for specifications of new drug substances and products. It discusses setting specifications based on development data and stability studies. Universal tests for drug substances include identification, assay, impurities. For products, additional tests depend on dosage form and may include dissolution, uniformity, sterility. The guidelines provide concepts for justifying specifications and periodic testing. They apply principles for biotech products, addressing characterization, analytical validation, process controls, and linking specifications to manufacturing and clinical data.
ICH Guideline Stability Testing of New Drug Substances and Product Q1A(R2).pptxTrishala Bhatt
This presentation outlines the ICH Guideline for Stability Testing of New Drug Substances and Products, Q1A(R2). It serves as a comprehensive framework for ensuring the stability of new pharmaceuticals, with a focus on the requirements for registration applications within the EC, Japan, and the United States. The guideline emphasizes a balance between a standardized approach and the flexibility to adapt to specific scientific considerations and characteristics of the materials under evaluation.
This document provides an overview of pharmaceutical product development. It discusses the objectives of product development which include designing quality products and manufacturing processes to consistently deliver intended performance. It also covers regulations related to preformulation, formulation development, stability assessment, and quality control testing of different dosage forms. The document outlines guidelines from organizations like ICH and WHO for various stages of product development.
stability The ability of a pharmaceutical product to retain its chemical, physical, microbiological and biopharmaceutical properties within specified limits throughout its shelf-life.Why is stability of a drug important?
Drug stability affects the safety and efficacy of the drug product; degradation impurities may cause a loss of efficacy and generate possible adverse effects. Therefore, achieving the chemical and physical stability of drugs is essential to ensure their quality and safety.Common factors that affect this stability include temperature, light, pH, oxidation and enzymatic degradation. Special considerations are also required when dealing with chiral molecules, deuterated internal standards and large biomolecules.
This document discusses concepts related to bioequivalence studies for generic drugs, including:
- Generic drugs must be pharmaceutically equivalent and bioequivalent to the reference brand name drug to be considered substitutable.
- Bioequivalence studies evaluate the rate and extent of absorption of the generic drug compared to the brand name drug and ensure the generic drug performs in the same manner.
- Acceptance criteria for bioequivalence studies specify that the 90% confidence intervals for AUC and Cmax of the generic must fall within 80-125% of the reference drug.
- Special study designs may be needed for certain drugs based on their pharmacokinetic properties or ability to be measured in plasma.
1) The document provides guidance on in vitro and in vivo evaluation of drug products, including characterization of the drug substance and product through physicochemical properties and dissolution testing.
2) It outlines the types of pharmacokinetic and pharmacodynamic studies that should be conducted to understand how the drug substance and product properties relate to clinical performance.
3) The document emphasizes that in vivo studies are generally needed to demonstrate bioequivalence, but in some cases in vitro studies may suffice, such as for BCS Class I drugs with rapid dissolution.
ICH guidelines on impurities in new drug products.pptxDivya Pushp
This document provides a summary of a presentation on ICH guidelines for impurities in new drug products. The guidelines provide guidance for registration applications on reporting and qualifying degradation products and impurities. Key points include: analytical procedures must be validated for detecting degradation products; batches used in development and commercial processes must be compared; degradation products above certain thresholds must be identified, reported, and qualified; and specifications for degradation products should be based on batches from the commercial process. The guidelines do not apply to certain product types like biologics but provide direction on identifying, analyzing, reporting, and qualifying degradation products found in new small molecule drug products.
CMC, post approval regulatory affairs, etcJayeshRajput7
this document covers points such as CMC, post approval regulatory affairs, regulation for combination products, and medical devices, common technical document (CTD) and electronic common technical document (eCTD) format, industry and FDA liasion, ICH guidelines of ICH Q,S,E,M, regulatory requirements of EU, MHRA, TGA and ROW countries.
3. Section-IN PROCESS QUALITY CONTROL and QUALITY CONTROL.pdfosos24
This document discusses quality control in the pharmaceutical industry. It defines quality control and explains that it is essential to ensure pharmaceutical products are safe, pure, and effective. It describes various in-process quality control tests done at different stages of production for tablets, capsules, syrups, semisolids, and injectables. These tests evaluate attributes like drug content, hardness, dissolution, and sterility. Finally, it compares quality control tests for tablets specified in British, Indian, and US pharmacopeias.
In process & finished products quality control test for pharmaceuticalsSuraj Ghorpade
This document discusses in-process quality control (IPQC) and finished product quality control (FPQC) for pharmaceutical products. It defines IPQC and outlines its objectives to optimize processes, monitor operations, and inspect raw materials, equipment, environment and more. Key IPQC tests are described including physical/chemical tests (identity, quality, purity, potency), biological/microbiological tests. Specific IPQC parameters and checks are provided for tablets, including tests for size/shape, color, thickness, assay, dissolution and more. Acceptance criteria are defined according to pharmacopeial standards. The importance of IPQC for ensuring quality products is emphasized.
Stability testing of herbal products involves subjecting samples to various conditions like heat, light, and humidity to determine shelf life and ensure quality over time. Key aspects of stability testing include establishing acceptance criteria and storage conditions, conducting both accelerated and long-term real-time tests, and developing a protocol that specifies test attributes, analytical methods, sampling plans, and evaluation procedures. Challenges with testing herbal products relate to their complex compositions, but can be addressed through marker analyses and fingerprinting techniques. Proper stability testing is important for determining appropriate packaging, storage, and expiry dates.
Forced degradation studies for drug substances and drug products a regulator...Veeprho Laboratories
Introduction –
Various regulatory guidance are available which provides useful definitions and general comments about degradation studies. However, guidance concerning the scope, timing, degradation condition and best practices for degradation studies is very general. Various issues related to stress testing are addressed in numerous guidance documents but not always in the context of stress testing. Therefore, stress-testing conditions should be realistic and not excessive.
The forced degradation studies are also expected -
1. Structure elucidation of possible degradation path-ways.
2. Identification of degradation products that may be spontaneously generated during drug storage and during use.
3. To facilitate improvements in the manufacturing process and formulations in parallel with accelerated pharmaceutical stability studies.
Formulation development of pharmaceutical drugSriramPraveen5
The document discusses the importance of formulation development in the pharmaceutical industry. It outlines key steps in the formulation development process, including excipient compatibility studies, formulation optimization, evaluation, and stability testing. Proper formulation is crucial for ensuring patient safety and therapeutic efficacy. The summary discusses formulation development as a critical aspect of drug discovery that can enhance patient outcomes through improved drug delivery and compliance.
The FDA regulates food, drugs, medical devices and other products. It oversees the drug approval process which involves preclinical testing in animals, followed by Phase I-III clinical trials in humans to test safety, efficacy and side effects. If approved, the drug can be marketed and is monitored for side effects. The document outlines the drug approval process and regulations around generic drugs, biologics, manufacturing and product changes.
This document provides an overview of stability indicating method development. It defines key terms like stability, shelf-life, and stability indicating method. It describes the types of stability studies including accelerated and real-time. The main objectives and climatic zones for stability testing are outlined. Forced degradation studies and the approach to developing a stability indicating method through stress testing, method development/optimization, identification of degradation products, and validation are summarized. Critical issues like the need for stress testing and achieving mass balance are also discussed.
Similar to Qualityassurancecontrolinpharmaindustry (20)
This document discusses RNA molecule structure prediction and the assumptions made, including that the most likely structure is similar to the most stable energetically, and that the energy of any position is only influenced by local sequence and structure. It also mentions complementary interactions of secondary structures and circle plots of base pairs.
This document discusses several topics related to proteins including the titration curve of glycine, CLUSTALW scoring scheme for protein sequence alignment, formation of peptide bonds, structural hierarchy of proteins, protein sequencing, alpha-helix and beta conformations, and hydropathy plots for analyzing protein sequences.
This document discusses the primary, secondary, tertiary, and quaternary structure of proteins. It begins by describing the important biological functions of proteins and the general structures of globular and fibrous proteins. It then discusses the structures of amino acids and how peptide bonds link amino acids into polypeptide chains. The levels of protein structure are introduced, including the alpha helix and beta sheet secondary structures, tertiary folding of polypeptide chains, and arrangement of subunits in quaternary structure. Common protein domains and motifs are also illustrated.
This document discusses protein structure, classification, prediction, and visualization. It covers secondary structure elements like alpha helices and beta sheets, as well as tertiary and quaternary structure. It describes protein structure databases like the Protein Data Bank and tools for visualizing protein structures. Different amino acid properties that influence secondary structure are also discussed.
This document provides information on various computational tools and methods for protein identification, characterization, and structure prediction. It discusses tools that use amino acid composition, sequence alignment, peptide mass fingerprinting, and physico-chemical properties to identify proteins. It also describes methods such as Chou-Fasman, GOR, and neural networks that predict protein secondary structure and properties based on amino acid order, propensities, and probabilities.
Structurally variable regions like loops, insertions and deletions can complicate protein structure modeling. The structure of an equivalent length segment from a homologous protein provides a guide for modeling missing regions, though the chosen segment may not always fit properly. De novo prediction involves using rotamer libraries of common amino acid conformations to predict side chain positions. Model validation checks the stereochemical accuracy, packing quality, and folding reliability of the predicted structure.
This document discusses important parameters for designing successful PCR primers. Key factors include primer length, melting temperature (Tm), specificity, and GC content. Primer length determines specificity, annealing temperature and time. For primers between 18-24 bases targeting a 50°C annealing temperature, the calculated Tm should be around 55°C. Both primers should have similar Tms. Other considerations include avoiding intra-primer complementarity beyond 3 base pairs and maintaining a GC content between 45-55%.
This document discusses phylogenetic studies and the construction of phylogenetic trees. It notes that fossil records are unreliable, so phylogenetic trees are primarily based on molecular sequencing data and morphological data. There are several assumptions made in phylogenetic analysis, including that sequences are homologous, phylogenetic divergence is bifurcating, and each position in a sequence evolved independently. The document outlines different types of phylogenetic trees, steps in phylogenetic analysis like choosing molecular markers and tree building methods, and criteria for assessing the reliability of phylogenetic trees.
Multiple sequence alignment is used to determine evolutionary relationships and structural relationships between sequences. It provides information on the most similar regions between sequences and can predict specific probes. Multiple sequence alignment extends pairwise sequence alignment through dynamic programming to align three or more sequences simultaneously. Popular multiple sequence alignment programs like CLUSTALW use progressive alignment methods that first align closely related sequences, then progressively align more distantly related sequences.
Homology modeling is a technique used to generate a three-dimensional structural model of a protein from its amino acid sequence. Modeller is a popular software program used for homology modeling that automates model building from a sequence-structure alignment using a known protein structure as a template. Homology modeling is useful for predicting protein structure and function when experimental structures are not available.
Homology modeling is a technique used to predict the 3D structure of a protein based on the alignment of its amino acid sequence to known protein structures. It relies on the observation that structure is more conserved than sequence during evolution. The key steps in homology modeling include: 1) identifying a template structure through sequence alignment tools like BLAST, 2) correcting any errors in the initial alignment, 3) generating the protein backbone based on the template structure, 4) modeling any loops or missing regions, 5) adding side chains, 6) optimizing the model structure energetically, and 7) validating that the final model matches the template structure and has correct stereochemistry. Homology modeling is useful for applications like structure-based drug design
This document discusses different methods for genome sequencing and assembly, including restriction enzyme fingerprinting, marker sequences, and hybridization assays. It focuses on using marker sequences like sequence-tagged sites (STS), expressed sequence tags (ESTs), untranslated regions (UTRs), and single nucleotide polymorphisms (SNPs) to map genomes. Large-insert cloning vectors like BACs and PACs can be used with restriction enzyme fingerprinting and FPC software to assemble contigs and map genomes at a large scale. Marker sequences provide a dense set of physical markers to build accurate physical maps of genomes.
This document discusses gene identification and genome annotation. It describes how gene finding in eukaryotes is difficult due to smaller percentages of genes in genomes like humans, and larger intron sizes. It covers open reading frames, complications with introns, and the use of six-frame translation to find protein coding sequences. Software tools for structural and functional annotation are outlined, including identifying genes through homology searching and ab initio prediction using hidden Markov models. The accuracy challenges of ab initio prediction are also summarized.
This document discusses genome analysis and sequencing. It provides background on identifying genes and studying disease processes through genome sequencing. It also describes goals of identifying gene function through experiments and challenges like gene prediction and repetitive sequences. Specific projects aimed at tracking human genetic variations and the first bacterial genome sequencing are summarized. Criteria for selecting early genomes to sequence are outlined. Key differences between prokaryotic and eukaryotic genomes are noted, including the presence of chromosomes, repeats, introns and heterochromatin/euchromatin. Different types of repetitive sequences like satellites, minisatellites and microsatellites are defined. Transposable elements in eukaryotes are also briefly introduced.
FASTA is a program for rapidly aligning protein and DNA sequences. It searches for matching k-tuples or sequence words and builds a local alignment based on these matches. It identifies the 10 best matching regions through k-tuple screening, joins nearby matches, and finds the highest density regions. It generates longer regions of identity and recalculates scores, with INITN and OPT scores used to rank database matches. Sensitivity refers to the ability to locate distantly related family members with limited similarity.
Drug design involves inventing new pharmaceutical drugs based on knowledge of biological targets, with classes of medications defined by their chemical properties, routes of administration, effects on biological systems, and therapeutic effects. The Anatomical Therapeutic Chemical classification system categorizes drugs into groups such as antipyretics, analgesics, antimalarial drugs, antibiotics, and antiseptics based on their medical use. Strategies for drug design include ligand-based and structure-based approaches.
Molecular descriptors are numerical values that characterize molecular properties and structures. They can represent physicochemical properties or values derived from algorithmic techniques applied to molecular structures. Descriptors vary in complexity and computational requirements. Some are based on experimental data while others are algorithmic constructs. Two-dimensional (2D) descriptors are calculated from 2D structures and include counts, physicochemical properties, and topological indices. Three-dimensional (3D) descriptors encode spatial relationships and include fragment screens and pharmacophore keys.
Biological data is widely distributed over the web and can be retrieved using search engines like Google or data retrieval tools. Dedicated data retrieval tools for molecular biologists include Entrez, DBGET, and SRS which allow text searching of linked databases and sequence searching. Entrez, developed by NCBI, integrates information from databases including GenBank, PubMed, and OMIM. DBGET covers databases like GenBank, EMBL, and PDB. SRS, developed by EBI, integrates over 80 molecular biology databases.
BLAST is a program that compares nucleotide or protein sequences to sequence databases and calculates the statistical significance of matches. It performs sequence similarity searches using either FASTA or BLAST algorithms. The BLAST process involves filtering sequences, preparing a list of words, evaluating matches using BLOSUM62, organizing high-scoring words into a search tree, scanning databases for matches, extending alignments, identifying statistically significant matches, and calculating expect values for alignments.
This document provides information about several nucleotide and protein sequence databases including:
- INSDC (International Nucleotide Sequence Database Collaboration) which includes GenBank, EMBL, and DDBJ.
- GenBank which contains over 80 billion nucleotide bases from 76 million sequences and doubles in size every 18 months. The top species represented are human, mouse, rat, cattle, and maize.
- EMBL and DDBJ which are similar to GenBank in content and format but maintained by different collaborations. Secondary databases like UniProt, PROSITE and PRINTS/BLOCKS provide additional annotation and analysis of sequences.
3. QA
It is the sum total of the
organized arrangements
with the objective of
ensuring that products
will be of the quality
required for their
intended use
4. GMP
Is that part of Quality
Assurance aimed at
ensuring that products
are consistently
manufactured to a quality
appropriate to their
intended use
5. QC
Is that part of GMP
concerned with sampling,
specification & testing,
documentation & release
procedures which ensure
that the necessary &
relevant tests are
performed & the product is
released for use only after
ascertaining it’s quality
6. QQAA aanndd QQCC
• QC is that part of GMP
which is concerned with
sampling,
specifications, testing
and with in the
organization,
documentation,and
release procedures
which ensure that the
necessary and relevant
tests are carried out
• QA is the sum total of
organized
arrangements made
with the object of
ensuring that product
will be of the Quality
required by their
intended use.
7. QQAA aanndd QQCC
• Operational
laboratory
techniques and
activities used to
fulfill the
requirement of
Quality
• All those planned
or systematic
actions necessary
to provide
adequate
confidence that a
product will satisfy
the requirements
for quality
9. ESTABLISHING ACCEPTANCE CRITERION FOR A SPECIFIED IMPURITY IN A
Determine impurity level in
relevant batches1
Acceptance criterion = A or
B
(as appropriate)
Is
impurity also
a
degradation
product?
Is
A or B
greater than the
qualified
level?
Acceptance criterion = qualified
level
or establish new qualified level2
Estimate maximum increase in impurity
at retest date using data from relevant
accelerated and long-term stability
studies
Determine maximum likely level as:
A + increase in degradation product at
appropriate storage conditions.
(Let this = B)
YES
YES
NO
NO
NEW
DRUG SUBSTANCE
1 Relevant batches are those from development, pilot and scale-up studies.
2 Refer to ICH Guideline on Impurities in New Drug Substances
Definition: upper confidence limit = three times the standard deviation of batch analysis data
Determine mean + upper
confidence
limit for the impurity (Let this = A)
10. ESTABLISHING ACCEPTANCE CRITERION FOR A DEGRADATION PRODUCT IN A
Does
degradation
occur during product
manufacture?
NEW DRUG PRODUCT
Estimate maximum increase in
degradation product at shelf life using
data from relevant accelerated and
long-term stability studies.
(Let this = D)
Determine maximum likely level as
drug substance acceptance criterion2.
((A or B) + C + D)
Is
maximum
likely level greater
than the
qualified
level?
Estimate maximum increase in degradation
product during manufacture from relevant
batches1. (Let this = C)
Acceptance criterion = maximum likely level.
Acceptance criterion = qualified
level
or establish new qualified level3
or new storage conditions
or reduce shelf life.
NO
NO
YES
YES
1 Relevant batches are those from development, pilot and scale-up studies.
2 Refer to Decision Tree 1 for information regarding A and B.
3 Refer to ICH Guideline on Impurities in New Drug Products.
11. SETTING ACCEPTANCE CRITERIA FOR DRUG SUBSTANCE PARTICLE SIZE
Is the drug product a solid
dosage form or liquid
containing undissolved
drug substance?
No drug substance particle
size acceptance criterion
required for solution dosage
forms.
1. Is the particle size critical to dissolution,
solubility, or bioavailability?
2. Is the particle size critical to drug product
processability?
3. Is the particle size critical to drug product stability?
4. Is the particle size critical to drug product
content uniformity?
5. Is particle size critical for maintaining
product appearance?
Set Acceptance Criterion
No Acceptance Criterion
Required
If YES to any
If NO to all
NO
YES
DISTRIBUTION
12. INVESTIGATING THE NEED TO SET ACCEPTANCE CRITERIA FOR
POLYMORPHISM
IN DRUG SUBSTANCES AND DRUG PRODUCTS
Drug Substance
1.
Can
Conduct polymorphism
screen on drug substance. No further action
2.
NO
different polymorphs
be formed?
YES
GO TO
Characterize the forms:
e.g., - X-ray Powder
Diffraction
- DSC /
Thermoanalysis
- Microscopy
- Spectroscopy
13. INVESTIGATING THE NEED TO SET ACCEPTANCE CRITERIA FOR
POLYMORPHISM
IN DRUG SUBSTANCES AND DRUG PRODUCTS
2.
GO TO 3.
NO
NO
Do the
forms have
different properties?
(solubility, stability,
melting point)
YES
Is drug
product safety,
performance or
efficacy affected?
No further test or
acceptance criterion
for drug substance
YES
Set acceptance criterion
for polymorph content
in drug substance
14. INVESTIGATING THE NEED TO SET ACCEPTANCE CRITERIA FOR
POLYMORPHISM
IN DRUG SUBSTANCES AND DRUG PRODUCTS
Drug Product - Solid Dosage Form or Liquid Containing Undissolved Drug Substance
Undertake the following processes only if technically possible
to measure polymorph content in the drug product.
3.
YES
Does
drug product
performance testing
provide adequate control if
polymorph ratio changes
(e.g., dissolution)?
NO
NO
YES
Establish acceptance criteria
for the relevant performance
test(s).
Monitor polymorph form during
stability of drug product.
No need to set acceptance criteria
for polymorph change in drug
product.
Does a
change occur
which could
affect
safety or
efficacy?
Establish acceptance criteria
which are consistent with
safety and/or efficacy.
15. ESTABLISHING IDENTITY, ASSAY AND ENANTIOMERIC IMPURITY PROCEDURES
FOR CHIRAL NEW DRUG SUBSTANCES AND NEW DRUG PRODUCTS CONTAINING
CHIRAL DRUG SUBSTANCES
YES
AND RACEMIC
Consider the need for
verifying chiral identity in
drug substance release
and/or acceptance
testing.
Is the new
drug substance
chiral1?
Chiral identity, assay
and impurity
procedures
are not needed.
NO
YES
AND ONE ENANTIOMER
Needed for drug substance specification:2
-chiral identity3
-chiral assay4
-enantiomeric impurity5
Needed for drug product specification6:
-chiral assay4
-enantiomeric impurity5
1 Chiral substances of natural origin are not addressed in this Guideline.
2 As with other impurities arising in and from raw materials used in drug substance synthesis, control of chiral quality could be established alternatively
by applying limits to appropriate starting materials or intermediates when justified from developmental studies. This essentially will be the case when
there are multiple chiral centers (e.g., three or more), or when control at a step prior to production of the final drug substance is desirable.
3 A chiral assay or an enantiomeric impurity procedure may be acceptable in lieu of a chiral identity procedure.
4 An achiral assay combined with a method for controlling the opposite enantiomer is acceptable in lieu of a chiral assay.
5 The level of the opposite enantiomer of the drug substance may be derived from chiral assay data or from a separate procedure.
6 Stereospecific testing of drug product may not be necessary if racemization has been demonstrated to be insignificant during drug product
manufacture and during storage of the finished dosage form.
16. MICROBIOLOGICAL QUALITY AATTTTRRIIBBUUTTEESS OOFF DDRRUUGGSS
SSUUBBSSTTAANNCCEE AANNDD EEXXCCIIPPIIEENNTTSS
Is the drug
substances/excipient
Capable of supporting microbial
Growth or viability
Is the drug substances/excipient
Sterile?
NO
Does drug
substances/excipient
Synthesis/processing involve
Steps which inherently
Reduce microorganisms?
NO
Establish microbial limit acceptance
Criteria
As per the harmonized pharmacopoeial
monograph
Are monitoring
Microorganism/indicator levels
Consistently below acceptance criteria
Levels?
Test lots on a skip-lot basis for
Microbial limits and freedom from
Compendial indicator organisms.
Test each lot for microbial limits
and freedom from compendial
indicator organisms.
Provide supporting data. Microbial
Limits acceptance criteria and
testing
May not be necessary
No further microbial limits testing or
Acceptance criteria are necessary
Establish microbial limit acceptance
criteria
As per the harmonized pharmacopeial
monograph
Does scientific evidence demonstrate that
Reducation steps result in microorganism levels
<acceptance criteria limits (and the absence of
Compendial indicator organisms)
In the drug substance/excipient?
Provide supporting data.
Microbial limits acceptace
Criteria and testing
May not be necessary
YES
YES
YES
YES
YES NO
NO
NO
17. SETTING ACCEPTANCE CRITERIA FOR DRUG PRODUCT DISSOLUTION
1.
What type of drug release acceptance criteria are appropriate?
Is the dosage
form designed to produce
modified release?
YES Establish drug release acceptance criteria.
Extended release: multiple time points
Delayed release: two stages, parallel
or sequential
NO
Is drug solubility
at 37 ± 0.5°C high throughout
the physiological pH range?
(Dose/ solubility < 250 mL
(pH 1.2 - 6.8))
NO
NO
Continued on next page.
Generally single-point dissolution
acceptance criteria with a lower limit
are acceptable.
YES
Is dosage form
dissolution rapid?
(Dissolution > 80% in 15 minutes
at pH 1.2, 4.0, and 6.8)
Has a relationship been
determined between disintegration
and dissolution?
Generally disintegration acceptance
criteria with an upper time
limit are acceptable.
YES
YES
NO
18. SETTING ACCEPTANCE CRITERIA FOR DRUG PRODUCT DISSOLUTION
2. What specific test conditions and acceptance criteria are appropriate? [immediate release]
Does
dissolution significantly
affect bioavailability?
(e.g., have relevant developmental
batches exhibited unacceptable
bioavailability?)
Attempt to develop test conditions and acceptance
criteria which can distinguish batches
with unacceptable bioavailability.
YES
NO
YES
NO
YES
NO
Do changes in
formulation or
manufacturing variables
affect dissolution?
(Use appropriate ranges.
Evaluate dissolution
within pH 1.2 - 6.8)
Are these changes controlled
by another procedure and acceptance
criterion?
Adopt appropriate test conditions
and acceptance criteria without
regard to discriminating power, to
pass clinically acceptable batches. Adopt test conditions and acceptance criteria
which can distinguish these changes.
Generally, single point acceptance criteria
are acceptable.
19. SETTING ACCEPTANCE CRITERIA FOR DRUG PRODUCT DISSOLUTION
3.
What are appropriate acceptance ranges? [extended release]
YES
NO
NO
YES
YES
NO
YES
NO
Are bioavailability
data available for batches
with different drug release rates?
Is drug release independent of
in vitro test conditions?
Can an in vitro / in vivo
relationship be established?
(Modify in vitro test
conditions
if appropriate.)
Use all available stability, clinical, and
bioavailability data to establish
appropriate acceptance ranges.
Use the in vitro / in vivo
correlation, along with
appropriate batch data, to
establish acceptance ranges.
Are acceptance
ranges >20% of the
labeled content?
Provide appropriate
bioavailability data
to validate the
acceptance ranges.
Finalize acceptance
ranges.
20. MICROBIOLOGICAL ATTRIBUTES OOFF NNOONN--SSTTEERRIILLEE
DDRRUUGGSS PPRROODDUUCCTTSS
Does the drug product contain
Antimicrobial preservatives or possess
Inherent antimicrobial
activity
Is the drug product a dry dosage form
(e.g. solid oral or dry powder)?
Does scientific evidence demonstrate
Growth inhibitory properties of the
Drug product?
Microbial limits acceptance criteria and testing
May not be necessary
Establish preservative chemical acceptance criteria and
Perform preservative effectiveness validation of product
Containing less than or equal to the minimum specifie
Preservative concentration, or demonstrate the inherent
Antimicrobial activity of the drug product.
Establish microbial limit acceptance criteria
As per the harmonized pharmacopoeia
Monograph.
Perform microbial limits testing on a
Lot-by-lot basis.
Do production lots consistently meet
Microbial limits acceptance criteria?
Perform skip-lot testing for microbial
Limits, or provide scientific justification for
no routine microbial limits testing.
No
No
No
No
YES
YES
YES
YES
21. ICH Harmonised TTrriippaarrttiittee GGuuiiddeelliinnee
• Stability Testing of New Drug Substances and Products
• Stability Testing: Photostability Testing of New Drug
Substances and Products
• Stability Testing for New Dosage Forms
• Bracketing and Matrixing Designs for Stability Testing of
New Drug Substances and Products
• Evaluation for Stability Data
• Stability Data Package for Registration Applications in
Climatic Zones III and IV
• Validation of Analytical Procedures: Text and Methodology
• Impurities In New Drug Substances
22. ICH Harmonised TTrriippaarrttiittee GGuuiiddeelliinnee
• Impurities in New Drug Products
• Impurities: Guideline for Residual Solvents
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Microbiological
Examination of Non-Sterile Products: Microbial
Enumerations Tests
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Microbiological
Examination of Non-Sterile Products: Test for
Specified Micro-Organisms
23. ICH Harmonised TTrriippaarrttiittee GGuuiiddeelliinnee
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Microbiological
Examination of Non-Sterile Products: Acceptance
Criteria for Pharmaceutical Preparations and
Substances for Pharmaceutical Use
• Evaluation and Recommendation of Pharmacopoeial Texts
for Use in the ICH Regions on Residue on
Ignition/Sulphated Ash
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Test for
Extractable Volume of Parenteral Preparations
24. ICH Harmonised TTrriippaarrttiittee GGuuiiddeelliinnee
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Test for
Particulate Contamination: Sub-Visible Particles
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Disintegration
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Uniformity of
Dosage Units
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Region on Dissolution Test
25. ICH Harmonised TTrriippaarrttiittee GGuuiiddeelliinnee
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Sterility Test
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions onTablet Friability
• Evaluation and Recommendation of Pharmacopoeial
Texts for Use in the ICH Regions on Polyacrylamide
Gel Electrophoresis
• Viral Safety Evaluation of Biotechnology Products
Derived from Cell Lines of Human or Animal Origin
26. ICH Harmonised TTrriippaarrttiittee GGuuiiddeelliinnee
• Quality of Biotechnological Products: Analysis of the
Expression Construct in Cells used for Production of r-DNA
Derived Protein Products
• Quality of Biotechnological Products: Stability Testing of
Biotechnological/Biological Products
• Derivation and Characterisation of Cell Substrates Used for
Production of Biotechnological/Biological Products
• Comparability of Biotechnological/Biological Products
Subject to Changes in their Manufacturing Process
• Specifications: Test Procedures and Acceptance Criteria for
New Drug Substances and New Drug Products: Chemical
Substances
27. ICH Harmonised TTrriippaarrttiittee GGuuiiddeelliinnee
• Specifications: Test Procedures and Acceptance
Criteria for Biotechnological/Biological Products
• Good Manufacturing Practice Guide for Active
Pharmaceutical Ingredients
• Pharmaceutical Development
• Quality Risk Management
• Pharmaceutical Quality System
• Quality Implementation Working Group
29. HHooww ttoo wwrriittee SSttaannddaarrdd OOppeerraattiinngg
PPrroocceedduurree
• SOP describes standard SOP format
that you can use immediately for
your quality procedure.
• SOP has instructions on how to write
a formal operating procedure for
your systems which your people can
follow everyday.
30. AAllll DDooccuummeennttss--CCllaassssiiffiiccaattiioonnss,,
DDeeffiinniittiioonn aanndd AApppprroovvaall MMaattrriixx
• In this SOP you will find all type of quality
and Technical/Master file documents to
build up a good quality management
system for your manufacturing sites,
definition of documents, their
classification, approval requirements and
retention requirements.
• This procedure has schematic diagrams for
your understanding of how different types
of documents are prepared and stored in a
typical documentation.
31. Quality DDooccuummeennttaattiioonn MMaannaaggeemmeenntt
aanndd CChhaannggee CCoonnttrrooll
• This SOP describes how to generate new
quality documents or change control of
existing documents, review of quality
documents, satellite file management, role
of document author, approver, document
control officer and satellite file
administrator.
• In this SOP you will also find numbering
systems of different quality documents like
audit files, SOP’s, forms, manuals, training
files, QA agreements, project files etc and
their effective archiving system.
32. Documentation RRuullee ffoorr GGMMPP
DDooccuummeennttss
• This SOP describes the principles to
be followed in GMP documents, entry
of data and information, signature
requirements and correction
technique of incorrectly entered data
or information.
33. Quality DDooccuummeennttaattiioonn--CCoonnttrrooll,,
TTrraacckkiinngg aanndd DDiissttrriibbuuttiioonn
• In this SOP you will find mainly the role of
document control officer during the initiation,
creation, circulation and approval of new quality
related documents.
• It also describes the procedure of modification
and review of existing document using a
documentation database.
• Management of existing and superseded
documents is also a art of this procedure.
• You will see all the forms referred during the
instruction are attached at the end of the
procedure.
34. PPrreeppaarraattiioonn,, MMaaiinntteennaannccee aanndd
CChhaannggee CCoonnttrrooll ooff MMaasstteerr DDooccuummeennttss
• This SOP particularly focused on the management
of master file documents like specifications,
control methods, raw materials, finished goods
and packaging specification and test reports,
formulation, stability files etc required to
generate during the product registration in the
market.
• This SOP gives instruction on their creation,
change control, numbering system, approval
requirements and maintenance in a simple
master file database.
• You will see all the forms referred during the
instruction are attached at the end of the
procedure.
35. DDeevviiaattiioonn RReeppoorrtt SSyysstteemm
• It is a regulatory requirement to capture all sorts
of deviations evolves in your systems in order to
maintain the continuous improvement to your
processes and systems.
• This SOP describes how to categorize the
deviations between production, audit, quality
improvements, technical deviations, customer
complaints and environmental, health and safety
deviations.
• It describes the management responsibilities of
initiating deviation, capture data, analysis,
investigation, determination of assignable causes,
generation of management report and initiatives
to be taken on corrective and preventative
actions.
36. SShheellff LLiiffee ooff PPrroodduucctt
• This simple SOP describes the
meaning of shelf life and provides on
how to interpret shelf lives and
storage conditions for your raw
materials from the Certificate of
Analysis, determining expiry date for
your finished products by use of raw
material date of manufacturing and
their shelf lives.
37. VVeennddoorr SSeelleeccttiioonn aanndd EEvvaalluuaattiioonn
• This SOP describes the procedure to be
followed during the vendor assessment
and vendor evaluation for purchasing of
raw materials, critical and non critical
packaging components, laboratory
supplies, engineering supplies and
imported finished goods from the vendor.
• These instructions are essential for
approving prospective vendor.
38. VVeennddoorr CCeerrttiiffiiccaattiioonn
• This procedure aim to describe the process
by which a vendor may be certified to
supply materials or services.
• This procedure applies to vendors that
supply a material or service to be used at
any stage of manufacture by operations.
• Here you will get the roles of each
department in the process to certify an
approved vendor.
39. PPrroodduucctt CCoommppllaaiinntt PPrroocceedduurree
• This procedure covers the receipt, logging,
evaluation, investigation and reporting system of
all complaints received from customers for the
marketed products.
• This SOP contains step by step instruction to be
followed in the customer complaint management
like numbering of complaint, registration,
evaluation of complaints, determination of
assignable cause for the complaint deviation,
implementation of corrective and preventive
actions, trending of complaints and handling of
counterfeit products.
40. AAnnnnuuaall PPrroodduucctt RReevviieeww
• This procedure provides a guideline
to annual product review which is
required to be performed for each
product produced for the commercial
market to evaluate data, trends and
to identify any preventative or
corrective action that would lead to
product quality improvements and
report them to management.
41. RReewwoorrkk PPrroocceedduurree
• This SOP contains the step by step instruction to
be followed when the rework of an in-process or
completed finished good is required.
• This SOP covers the reworks of in-process
manufactured goods where new batch number is
introduced for the reworked part and rework of
manufactured finished good keeping the same
batch number.
• This SOP also describes how to create rework
protocols for each individual case.
42. AAuutthhoorriizzeedd PPeerrssoonn
• This simple procedure describes the
accreditation, accountabilities and
responsibilities of an Authorized
person, responsible for release of
finished goods for sale.
43. PPrroodduucctt IIddeennttiiffiiccaattiioonn aanndd
TTrraacceeaabbiilliittyy
• The purpose of this SOP is to define the
method used for the identification of all
contributing materials that could affect
product quality and to ensure their full
traceability.
• Here you will find instruction on all the
records and documents used for the
identification and traceability of incoming
raw materials and out going finished
goods.
44. AAuuddiittss
• This SOP describes the process of
planning, performing, reporting and
follow-up of different audits for your
systems like Internal Quality audit, Vendor
audit, Environmental Health and Safety
(EHS) audit, EHS workplace inspection,
Housekeeping audit.
• This SOP also describes the process to be
followed by manufacturing personnel
during an audit from a Regulatory
authority.
45. Example-Checklist ffoorr BBaattcchh DDooccuummeennttaattiioonn
• This SOP describes the identification of all
documentation relevant to a production
process in the form of “Batch
Documentation Checklists” and to ensure
their collection by completion of the
checklists by Authorized Persons.
• This procedure is based on an example of
tablet packaging process described in the
‘Manufacturing’ category.
46. Evaluation ooff BBaattcchh DDooccuummeennttaattiioonn
aanndd RReelleeaassee ffoorr SSaallee
• This procedure describes the process of
collection, evaluation and record of batch
related document generated during the
production of a batch before an authorized
person can release the batch for sale.
• This procedure is based on an example of
tablet packaging process described in the
‘Manufacturing’ category.
47. GGMMPP TTrraaiinniinngg
• This SOP describes how to design
and deliver GMP related training for
your manufacturing staffs, training
assessment design, recording of
assessment and preparation of
training reports.
48. How ttoo WWrriittee TTrraaiinniinngg MMaatteerriiaallss
• This simple SOP contains instructions
on how to write training materials,
identification of training
requirements, available resources,
preparation of training aid checklists
for your manufacturing staffs.
49. HHoouussee KKeeeeppiinngg AAuuddiitt PPrroocceedduurree
• This SOP describes the requirements, checklists
and reporting procedure on housekeeping audits.
• Individual checklist forms are attached at end of
the procedure for different areas like process,
laboratory, engineering stores, warehouses.
• This procedure also describes the handling of
non-compliance found during the housekeeping
audits.
50. Management and CCoonnttrrooll ooff CCoonnttrraacctt WWoorrkk
• The procedure describes the
management and control of contract
work provided by the contractors for
packaging and finished products for
your company as well as control of
contract works done by your
company on behalf of others.
51. Criteria for Sourcing ooff RRMM,, CCrriittiiccaall
PPaacckkaaggiinngg CCoommppoonneennttss aanndd IImmppoorrtteedd
FFiinniisshhiinngg GGooooddss
• The purpose of this SOP is to describe the process
for approval of an external vendor/manufacturer
supplying products to your company.
• It covers raw materials (including bulk products
for subsidiaries and contract manufacturers),
critical packaging components in contact with
product and imported finished goods.
• The SOP also references affiliated documentation
detailing the scope of active materials used and
the approved manufacturers of these materials.
52. Quality CCoonncceerrnn IInnvveessttiiggaattiioonn
PPrroocceessss
• This procedure contains instruction to be followed
when conducting Investigations and to raise and
assess Deviation Report when an investigation or
incident Investigation occurs.
• This procedure is to be used in conjunction with
SOP, which covers the approval and follow-up
activities associated with a Deviation Report.
• Here you will find collection of information for an
incident or a deviation, steps to be followed for a
cross functional investigation, reporting and
implementing of the outcomes of investigation.
54. RReetteesstt DDaattiinngg ooff RRaaww MMaatteerriiaallss
• The purpose of this procedure is to
describe how to run the expired stock
report; to describe how to define the
requirements for the retesting and
assignment of storage period for active
ingredients, excipients and raw materials;
to instruct retesting procedure and to
determine the status of a finished goods
batch with a shorter shelf life.
55. Calibration PPoolliicciieess ffoorr LLaabboorraattoorryy
IInnssttrruummeennttss
• This SOP describes the calibration polices
of laboratory instruments/equipments.
• It describes labeling and security
requirements of laboratory
instruments/equipments.
• This SOP also describes the investigational
steps to be required in the case of failed
calibration
56. Archiving LLaabboorraattoorryy DDooccuummeennttaattiioonn
• This procedure describes retention and
disposal procedures of laboratory
documentation, general laboratory
documentation system that includes
handling of rejected raw material and
finished product reports, finished goods
certificate of analysis, finished goods
register, raw material certificate of
analysis, register, trend cards, procedure
for long term document retention.
57. MMaannaaggeemmeenntt ooff RReeffeerreennccee
SSuubbssttaanncceess
• This SOP describes the ordering
referencing, storing, coding, use and
general register maintenance of primary
and impurity reference substances,
primary reagent reference solutions,
secondary raw material reference
substance, assay testing procedure of
secondary raw material reference
substance, use of secondary raw material
reference substance in the laboratory
routine analysis, determination of expiry
date and re-test date of reference
substances.
58. LLaabboorraattoorryy WWoorrkkbbooookk
• This SOP describes types of laboratory
workbooks, general and GMP requirements
of using workbooks, analytical data entry
in the workbook, formatting of laboratory
workbooks for routine testing,
experiments and trials, workbook
retention policy, instruction on data entry
for incomplete experiments and additional
data.
59. Creation ooff CCeerrttiiffiiccaattee ooff AAnnaallyyssiiss
• The purpose of this procedure is to
define the content and format of a
Certificate of Analysis (C/A) and
Certificate of Manufacture (C/M) and
to provide guidance for issuing a
Certificate of Analysis or Certificate
of Manufacture and to locate the
appropriate data required for this
task.
60. MMaannaaggiinngg AAnnaallyyttiiccaall RReeaaggeennttss
• This procedure identifies the need for all
analytical reagents and solutions prepared
from the reagents, to have an assigned
expiry date and storage conditions
recorded on the label.
• Here you will find the procedure for
purchase and management of analytical
reagents and laboratory prepared
reagents.
61. LLaabboorraattoorryy WWaassttee MMaannaaggeemmeenntt
• This simple procedure describes how
to dispose off laboratory generated
wastes of toxic, explosive, flammable,
corrosive, oxidizing and biologically
damaging natures.
62. RReetteennttiioonn SSaammpplleess--LLaabboorraattoorryy
• The purpose of this SOP is to
describe the finished good and raw
material sample retention
procedures, products manufacture
and/or received onsite and/or
chemically tested by the laboratory.
63. LLaabboorraattoorryy SSuupppplliieerr AApppprroovvaall
• In this simple SOP you will find the
procedure for approving laboratory
suppliers and criteria for the
purchase of equipment,
instrumentation, consumables,
durables and glassware for the
laboratory.
64. Laboratory RReessuullttss--OOuutt ooff SSppeecciiffiiccaattiioonn
IInnvveessttiiggaattiioonn
• This procedure describes the actions to be taken
by an analyst in the event the result of a test
does not conform to raw material/components or
finished products specifications for physical and
chemical tests.
• An out of specification (OOS) result does not
necessarily mean the batch under investigation
fails and shall be rejected.
• The OOS result shall be investigated and the
findings of the investigation, including re-test
results shall be interpreted to evaluate the batch
and reach a decision regarding release or
rejection.
65. RRaaww MMaatteerriiaallss--LLaabboorraattoorryy TTeessttiinngg
aanndd DDooccuummeennttaattiioonn
• This SOP describes the procedure for
sampling, location, pre-testing,
testing and documentation of all raw
materials and components subject to
test, out of specification results,
microbiological tests and release
procedure for passed raw materials
and components.
66. Finished GGooooddss--LLaabboorraattoorryy TTeessttiinngg aanndd
DDooccuummeennttaattiioonn
• This SOP describes the procedure for
sampling, location, pre-testing,
testing and documentation of all
finished products subject to test,
reagents and standards to be used
for analysis, management of out of
specification results, microbiological
tests and release procedure for
passed finished goods.
67. PPrreeppaarraattiioonn aanndd MMaaiinntteennaannccee ooff
SSttaabbiilliittyy PPrroottooccoollss ((PPhhaarrmmaacceeuuttiiccaallss))
• This procedure describes the preparation and
management of stability protocols for marketed
products.
• This procedure is applicable to all protocols for
stability studies on commercial products.
• The responsibility of the commercial Site stability
manager for creating and maintaining protocols
that are required for studies that came as a result
of validation or process deviation.
68. Stability aanndd TTrriiaall TTeessttiinngg PPrroocceedduurree
((PPhhaarrmmaacceeuuttiiccaallss))
• To describes the steps necessary to ensure the
effective control of stability and trial testing
programs of new and existing products.
• This procedure is focused on setting up of
stability programs, testing, reporting, general
sampling procedure for stability programs, data
generation and analysis, annual maintenance of
stability, new product stability procedure,
procedure for in-house trials, reporting and
interpretation of trials and conclusion of the trail
program.