w19490 IDENTIFYING THE HEALTH PRODUCTION FUNCTION
以医疗器械作用为主的药械组合产品注册审查指导原则英语

以医疗器械作用为主的药械组合产品注册审查指导原则英语Guidance Principles for the Registration Review of Medical Device-Drug Combination Products1. IntroductionMedical device-drug combination products are a category of products that combine a medical device and a drug component to achieve the intended use. The registration review of such products requires a comprehensive assessment of both the device and drug components, as well as the interaction between them. This guidance outlines the key principles and considerations for the registration review of medical device-drug combination products.2. ScopeThis guidance applies to medical device-drug combination products where the device component is the primary mode of action. The principles and considerations outlined in this guidance may also be applicable to other types of combination products, such as those where the drug component is the primary mode of action.3. Regulatory FrameworkThe registration of medical device-drug combination products is subject to the regulatory requirements for both medical devices and drugs. Applicants should ensure compliance with the relevant regulations and guidelines for each component, as well as the specific requirements for combination products.4. Product Identification and ClassificationMedical device-drug combination products should be clearly identified and classified based on the primary mode of action and the intended use. Applicants should provide a detailed description of the product, including the device and drug components, their respective functions, and the intended use of the combination product.5. Quality ConsiderationsThe quality of both the device and drug components should be thoroughly evaluated. This includes the design, manufacturing, and control of the individual components, as well as the compatibility and interactions between them. Applicants should provide comprehensive information on thequality attributes, specifications, and control strategies for the combination product.6. Nonclinical EvaluationNonclinical studies should be conducted to assess the safety and performance of the combination product. This may include studies on the device-drug interaction, the local and systemic effects of the combination, and the potential for any adverse interactions or reactions.7. Clinical EvaluationClinical studies are essential to evaluate the safety and efficacy of the combination product. Applicants should design and conduct clinical trials that assess the overall performance of the combination product, including the device and drug components, and the interaction between them.8. Risk ManagementApplicants should implement a comprehensive risk management plan to identify, assess, and mitigate the potential risks associated with the combination product. This includes the risks related to the device and drugcomponents, as well as the risks arising from the interaction between them.9. Labeling and PackagingThe labeling and packaging of the combination product should provide clear and comprehensive information to healthcare professionals and patients. This includes the instructions for use, any special handling or storage requirements, and any warnings or precautions related to the combination product.10. Postmarket SurveillanceApplicants should establish a robust postmarket surveillance system to monitor the performance and safety of the combination product after it is approved for use. This includes the collection and analysis of adverse event reports, as well as the implementation of any necessary corrective or preventive actions.中文版本:医疗器械作用为主的药械组合产品注册审查指导原则1. 引言医疗器械-药物组合产品是一类将医疗器械和药物组合在一起以实现预期用途的产品。
BinaxNOW COVID-19 Antigen Self Test产品说明书

INSTRUCTIONSINTENDED USEThe BinaxNOW™ COVID-19 Antigen Self Test is a lateral flow immunoassay intended for the qualitative detection of nucleocapsid protein antigen from SARS-CoV-2.This test is authorized for non-prescription home use with self-collected anterior nasal (nares) swab samples from individuals aged 15 years or older or adult collected anterior nasal (nares) swab samples from individuals 2 years or older. This test is authorized for individuals with symptoms of COVID-19 within the first seven days of symptom onset when tested at least twice over three days with at least 48 hours between tests, and for individuals without symptoms or other epidemiological reasons to suspect COVID-19, when tested at least three times over five days with at least 48 hours between tests.The BinaxNOW COVID-19 Antigen Self Test does not differentiate between SARS-CoV and SARS-CoV-2. Results are for the identification of SARS-CoV-2 nucleocapsid protein antigen which is generally detectablein anterior nasal (nares) swabs during the acute phase of infection. Positive results indicate the presence of viral antigens, but clinical correlation with patient history and other diagnostic information is necessary to determine infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Individuals who test positive with the BinaxNOW COVID-19 Antigen Self Test should self-isolate and seek follow-up care with their physician or healthcare provider as additional testing may be necessary.All negative results should be treated as presumptive and confirmation with a molecular assay, if necessary for patient management, may be performed. Negative results do not rule out SARS-CoV-2 infection and should not be used as the sole basis for treatment or patient management decisions, including infection control measures such as isolating from others and wearing masks. Negative results should be considered in the context of an individual’s recent exposures, history and the presence of clinical signs and symptoms consistent with COVID-19. Individuals who test negative and continue to experience COVID-like symptoms of fever, cough and/or shortness of breath may still have SARS-CoV-2 infection and should seek follow up care from their healthcare provider. Individuals should report their test result through the NAVICA app and provide all results obtained with this product to their healthcare provider in order to receive appropriate medical care. All healthcare providers will report all test results they receive from individuals who use the authorized product to relevant public health authorities in accordance with local, state, and federal requirements using appropriate LOINC and SNOMED codes, as defined by the Laboratory In Vitro Diagnostics (LIVD) Test Code Mapping for SARS-CoV-2 Tests provided by CDC. The BinaxNOW COVID-19 Antigen Self Test is intended for non-prescription self-use and/or, as applicable for an adult lay user testing another person aged 2 years or older in a non-laboratory setting. The BinaxNOW COVID-19 Antigen Self Test is only for use under the Food and Drug Administration’s Emergency Use Authorization. This product has not been FDA cleared or approved.Turn OverTEST KIT COMPONENTS OVERVIEWDo not open any parts before reading instructions.!HOW TO USE THIS TESTSerial testing should be performed in all individuals with negative results; individuals with symptoms of COVID-19and initial negative results should be tested again after 48 hours. Individuals without symptoms of COVID-19, andwith initial negative results, should be tested again after 48 hours and, if the 2nd test is also negative, a 3rd timeafter an additional 48 hours. Y ou may need to purchase additional tests to perform this serial (repeat) testing.If you test negative but continue to have symptoms of COVID-19, and both your first and second tests arenegative, you may not have COVID-19, however you should follow-up with your healthcare provider.If your test is positive, then proteins from the virus that causes COVID-19 have been found in your sample and youlikely have COVID-19.FREQUENTLY ASKED QUESTIONSWhat are the Known and Potential Risks and Benefits of this Test?Potential Risks Include:• Possible discomfort during sample collection.• Possible incorrect test results (see Results section).Potential Benefits Include:• The results, along with other information, can help your healthcare provider make informed recommendationsabout your care.• The results of this test may help limit the spread of COVID-19 to your family and others in your community.For more information on EUAs go here: https:///emergencypreparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergencyuse-authorizationWhat is the Difference Between an Antigen and Molecular Test?There are different kinds of tests for the SARS-CoV-2 virus that causes COVID-19.Molecular tests detect genetic material from the virus. Antigen tests, such as the BinaxNOW COVID-19Antigen Self Test, detect proteins from the virus. Due to the lower sensitivity of antigen tests, there is a higherchance this test will give you a false negative result when you have COVID-19 than a molecular test would.How Accurate is this Test?Clinical studies have shown that antigen tests more accurately determine whether you are infected with the virusthat causes COVID-19 when taken multiple times across several days. Repeat testing improves test accuracy.This serial testing approach is recommended to minimize the risk of incorrect results. For more information on theperformance of the test and how the performance may apply to you, please refer to the performance data in theHealthcare Provider Instructions for Use available at www.globalpointofcare.eifu.abbott.What if I Have a Positive Test Result?A positive result means that it is very likely you have COVID-19 because proteins from the virus that causesCOVID-19 were found in your sample. Y ou should self isolate from others and contact a healthcare provider formedical advice about your positive result.What if I have a Negative Test Result?A negative test result indicates that antigens from the virus that causes COVID-19 were not detected in yoursample. However, if you have symptoms of COVID-19, and your first test is negative, you should test again in48 hours since antigen tests are not as sensitive as molecular tests. If you do not have symptoms and received anegative result, you should test at least two more times with 48 hours in between tests for a total of three tests. Ifyou have a negative result, it does not rule out SARS-CoV-2 infection; you may still be infected and you may stillinfect others. It is important that you work with your healthcare provider to help you understand the next stepsyou should take.What does an Invalid Test Result mean?An invalid result means the test was not able to tell if you have COVID-19 or not. If the test is invalid, a new swabshould be used to collect a new nasal specimen and you should test again with a new test.IMPORTANTDo not use this test as the only guide to manage your illness. Consult your healthcare provider if your symptomspersist or become more severe.Individuals should provide all results obtained with this product to their healthcare provider.LIMITATIONSThe performance of this test was established based on the evaluation of a limited number of clinical specimenscollected between January, 2021, and May, 2022. The clinical performance has not been established for allcirculating variants but is anticipated to be reflective of the prevalent variants in circulation at the time andlocation of the clinical evaluation. Performance at the time of testing may vary depending on the variantscirculating, including newly emerging strains of SARSCoV-2 and their prevalence, which change over time.All COVID-19 antigen test negative results are presumptive and confirmation with a molecular assay may benecessary. If you continue to have symptoms of COVID-19, and both your first and second tests are negative,you may not have COVID-19, however you should follow-up with a healthcare provider.If the test is positive, then proteins from the virus that causes COVID-19 have been found in the sample and youlikely have COVID-19.There is a higher chance of false negative results with antigen tests than with laboratory-based molecular tests dueto the sensitivity of the test technology. This means that there is a higher chance this test will give a false negativeresult in an individual with COVID-19 as compared to a molecular test, especially in samples with low viral load.Incorrect test results may occur if a specimen is incorrectly collected or handled.This test is read visually and has not been validated for use by those with impaired vision or color-impaired vision.WARNINGS, PRECAUTIONS and SAFETY INFORMATION1. For in vitro diagnostic use.2. Wear safety mask or other face covering when collecting anterior nares swab specimen from a child oranother individual.3. Use of gloves is recommended when conducting testing.4. Keep testing kit and kit components out of the reach of children and pets before and after use.5. In the USA, this product has not been FDA cleared or approved but has been authorized by FDA under anEUA.6. This product has been authorized only for the detection of proteins from SARS-CoV-2, not for any otherviruses or pathogens.7. The emergency use of this product is only authorized for the duration of the declaration that circumstancesexist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis ofCOVID-19 under Section 564(b)(1) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.8. Incorrect test results may occur if a specimen is incorrectly collected or handled.9. Do not use if any of the test kit contents or packaging is damaged.10. Leave test card sealed in its foil pouch until just before use. Do not use if pouch is damaged or open. Onceopened, the test card should be used immediately.11. Do not dip the swab into the liquid reagent or other liquid before inserting the swab into the nose.12. Do not touch swab tip when handling the swab sample.Testing supplies are provided in each box.Test Kit Contains:Swab Test Card in Pouch Dropper BottleCOV O ID-19 AgCARDorThe NAVICA app allows you to track results for yourBinaxNOW COVID-19 tests.• Compatible smart phone includes Apple iPhone running OperationSystem (iOS): latest major version and two prior major versions(iPhone running iOS v12 or later), and Android Phones: latestmajor version and two prior major versions (Android phone runningAndroid OS v9 or later).• Download the app by scanning the QR code• Create an account• Perform a COVID-19 test (digital instructions available)• Record your result in the appAlternatively go to www.binaxnow-selftest.abbott for digitalinstructions.A positive test result means that the virus that causes COVID-19 was detected in your sample and it is verylikely you have COVID-19 and are contagious. Please contact your doctor/primary care physician or yourlocal health authority immediately and adhere to the local guidelines regarding self-isolation. There is a verysmall chance that this test can give a positive result that is wrong (a false positive result).A negative test result indicates that the virus that causes COVID-19 was not detected in your sample. Anegative result is presumptive, meaning it is not certain that you do not have COVID-19. Y ou may still haveCOVID-19 and you may still be contagious. There is a higher chance of false negative results with antigentests compared to laboratory-based tests such as PCR. If you test negative and continue to experienceCOVID-19-like symptoms, (e.g., fever, cough, and/or shortness of breath) you should seek follow up carewith your health care provider.An invalid result means this test was unable to determine whether you have COVID-19 or not. Re-test witha new swab and new test device. Please contact Technical Support at + 1 833-637-1594.For Use Under an Emergency Use Authorization (EUA) OnlyFor use with anterior nasal swab specimensFor in vitro Diagnostic Use Only13. Do not use kit past its expiration date.14. Do not mix components from different kit lots.15. All kit components are single use items. Do not use with multiple specimens. Do not reuse the used test card.16. Dispose of kit components and patient samples in household trash.17. INVALID RESULTS can occur when an insufficient volume of extraction reagent is added to the test card. Toensure delivery of adequate volume, hold bottle vertically, 1/2 inch above the swab well, and add drops slowly.18. Serial testing should be performed in individuals with negative results at least twice over three days (with48 hours between tests) for symptomatic individuals and three times over five days (with at least 48 hoursbetween tests) for asymptomatic individuals. Y ou may need to purchase additional tests to perform thisserial (repeat) testing.19. An anterior nasal swab sample can be self-collected by an individual age 15 years and older. Children age 2 to15 years should be tested by an adult.20. If you have had symptoms longer than seven days, you should consider testing at least three times over fivedays with at least 48 hours between tests.21. Do not use on anyone under 2 years of age.22. Do not read test results before 15 minutes or after 30 minutes. Results read before 15 minutes or after 30minutes may lead to a false positive, false negative, or invalid result.23. There is a higher chance of false negative results with antigen tests than with laboratory-based molecular tests.This means that there is a higher chance this test will give you a negative result when you have COVID-19.24. The Reagent Solution contains a harmful chemical (see table below). Do not ingest any kit components. Ifthe solution contacts the skin or eye, flush with copious amounts of water. If irritation persists, seek medicallegal-regulatory-and-policy-framework/emergencyuse-authorizationFor the most up to date information on COVID-19, please visit: /COVID19STORAGE and STABILITYStore kit between 35.6-86°F (2-30°C). Ensure all test components are at room temperature before use.The BinaxNOW COVID-19 Antigen Self Test is stable until the expiration date marked on the outer packagingand containers. For information about current expiration dates for at-home OTC COVID-19 diagnostic tests,visit /covid-tests.Read all instructions carefully before performing the test. Failure to follow theinstructions may result in inaccurate test results.Test Card Parts:Top HoleTopINSTRUCTIONS - START HERECarefully read instructions prior to starting test.It is recommended gloves (not provided) also be usedduring testing. See other side for important information.6 drops: False negative result may occur if more Abbott Rapid DiagnosticsTechnical SupportUS+ 1-833-637-1594*****************Abbott Diagnostics Scarborough, Inc.10 Southgate RoadScarborough, Maine 04074 USAwww.globalpointofcare.eifu.abbott© 2023 Abbott. All rights reserved.All trademarks referenced are trademarks of either theAbbott group of companies or their respective owners.IN195150WEB Rev. 6 2023/01BinaxNOW™ANTIGEN SELF TESTCOVID-193x。
ICH M5-Data Elements and Standards for drug dictionaries-Step2

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USED RAFT C ONSENSUS G UIDELINED ATAE LEMENTS AND S TANDARDS FORD RUG D ICTIONARIESM5Current Step 2 versiondated 10 May 2005At Step 2 of the ICH Process, a consensus draft text or guideline, agreed by the appropriate ICH Expert Working Group, is transmitted by the ICH Steering Committee to the regulatory authorities of the three ICH regions (the European Union, Japan and the USA) for internal and external consultation, according to national or regional procedures.M5 Document HistoryCurrent Step 2 versionD ATAE LEMENTS AND S TANDARDS FOR D RUG D ICTIONARIESDraft ICH Consensus GuidelineReleased for Consultation on 10 May 2005, at Step 2 of the ICH ProcessTABLE OF CONTENTS1.INTRODUCTION (1)1.1.Objectives of the Guideline (1)1.2Background (2)1.3Scope of the Guideline (2)2.GUIDELINE (2)2.1Medicinal Product and Term Identifiers (2)2.1.1Medicinal Product Identifier (MedID) (2)2.1.2Pharmaceutical Product Identifier (PhPID) (3)2.1.3Controlled Vocabulary Term Identifier (TermID) (4)2.2Controlled Vocabulary (4)2.2.1Background (4)2.2.2Active Ingredients Controlled Vocabulary (5)2.2.3Pharmaceutical Dose Form Controlled Vocabulary (6)2.2.4Routes of Administration Controlled Vocabulary (7)2.2.5Units and Measurements Controlled Vocabulary (9)2.3Data Elements (10)2.3.1Medicinal Product Identifier (12)2.3.2Medicinal Product Administrative Section (12)2.3.3Marketing Authorization Holder/Manufacturer/DistributorSection (14)2.3.4Marketing Authorization Section (15)2.3.5Pharmaceutical Product Section (17)2.3.6Active Ingredient(s) Section (19)2.3.7Pharmaceutical Dose Form Section (22)2.3.8Route of Administration Section (22)2.3.9Maintenance Section (23)3.GLOSSARY (25)4.REFERENCES (27)D ATAE LEMENTS AND S TANDARDS FOR D RUG D ICTIONARIES1. INTRODUCTION1.1. Objectives of the GuidelineIt is desirable for regulators and pharmaceutical industry to engage in an intensive information exchange during the drug development phase, the drug evaluation and approval phase and the post-authorization phase. The standardization of medicinal product information is regarded as one of the key elements of this information flow. However, regulators in the ICH regions and observer countries have established their own procedures and applications with standards that differ in data format, content, language and applied terminology (e.g., terminology used for active ingredients, routes of administration, pharmaceutical dose forms).Due to the lack of a common and harmonized approach, both regulators and pharmaceutical industry are confronted with the following issues:-No possibility to exchange medicinal product information between regulators and industry in a structured and efficient way;-Difficulties in ensuring data consistency and in evaluating and comparing medicinal product-related information across the ICH regions due to the lack of harmonized definitions of terminologies and data sets. This currently impairs pharmacovigilance activities in particular;-For the pharmaceutical industry, major administrative burdens and duplication of efforts requiring substantial human and financial resources to comply with and handle different regional requirements;-Lack of consistency in the use of terminology in the health care community. The objectives of this guideline are to address the issues outlined above by developing harmonized standards that build on the processes currently established in the three ICH regions and the observer countries and to support the population of existing systems/applications with fully reliable regulatory medicinal product information. More specifically, the objectives focus on the development of:-‗Unique identifiers‘ at the level of▪Medicinal products: Medicinal Product Identifiers (MedIDs);▪Pharmaceutical products: Pharmaceutical Product Identifiers (PhPIDs);▪The controlled vocabulary: Terminology Identifiers (TermIDs).-‘Controlled vocabulary’ as a standard for the electronic transmission of core sets of medicinal product information related to the following terminologies: ▪Active ingredients;▪Pharmaceutical dose forms;▪Routes of administration;▪Units and measurements.-‗Data elements’ for the electronic transmission of core sets of medicinal product information based on the following data set:▪Proprietary medicinal product name;▪Active ingredient(s);Data Elements and Standards for Drug Dictionaries▪Pharmaceutical dose form(s);▪Strength of the active ingredient(s);▪Route(s) of administration;▪Marketing authorization holder;▪Marketing authorization number;▪Country of authorization.The ‗Data elements’ have been developed for the electronic transmission of MedIDs and the related core medicinal product information.This guideline does not cover the establishment and maintenance of a drug dictionary.1.2 BackgroundThe lack of internationally harmonized standards related to core sets of medicinal product information and medicinal product terminology is hindering the scientific evaluation and comparison of product data as well as healthcare. This applies in particular to the area of pharmacovigilance, where the exchange and management of medicinal product information in expedited and periodic adverse reaction reports at the international level is a key aspect of ensuring drug safety.This document provides guidance on the harmonized standards that are being proposed by the ICH M5 EWG to facilitate the exchange and practical use of medicinal product data by regulators and pharmaceutical industry.1.3 Scope of the GuidelineThis guideline refers to approved medicinal products. Homeopathic medicinal products and investigational medicinal products are excluded from this guideline. 2. GUIDELINE2.1 Medicinal Product and Term Identifiers2.1.1 Medicinal Product Identifier (MedID)Definition:An identifier assigned to a medicinal product by the regulator of the country/territory of authorization.General Conventions:The regulators in the regions and observer countries have various processes established to identify individual medicinal products. Because medicinal product information is exchanged internationally, worldwide unique medicinal product identifiers (MedIDs) are desirable.Regulators intend to assign MedIDs as follows:▪At the ‘medicinal product level’, which means that a specific medicinal product has only one identifier for different pack sizes.For example, the medicinal product ‗TRADENAME X‘ has the same MedID related to two different presentations; a pack size of 50 tablets and a pack size of 100 tablets.Data Elements and Standards for Drug Dictionariesor▪At ‘medicinal product package level’, which means that for each package presentation of the medicinal product a different MedID is assigned.For example, the medicinal product ‗TRADENAME Y‘ has two different MedIDs for each of the two different presentations available: a MedID for the pack size of 50 tablets and a MedID for the pack size of 100 tablets. Methodology:The world-wide unique MedID is constructed as follows:▪Prefix of the country code of that region followed by▪The regionally-assigned identifier followed by▪An error detection codeThe regionally-assigned identifier refers to the medicinal product level or to the medicinal product package level. As a general rule, the MedID should accompany the exchange of the medicinal product information.Examples:EU-EU/1/2342323/001-KFR-123456-XJP-123456789-YUS-0123456789-ZCA-2323232-V2.1.2 Pharmaceutical Product Identifier (PhPID)Definition:An identifier assigned at the level of the pharmaceutical product based on the active ingredient(s), the strength(s) of the ingredient(s) and the pharmaceutical dose form. Methodology:PhPIDs represent the pharmaceutical product at four levels as defined as follows: -PhPID4 = Ingredient(s) - Strength(s) - Strength unit(s) -Pharmaceutical Dose Form-PhPID3 = Ingredient(s) - Pharmaceutical Dose Form-PhPID2 = Ingredient(s) - Strength(s) - Strength unit(s)-PhPID1 = Ingredient(s)Each PhPID is a unique, non-semantic, alphanumeric code and is derived from the ICH M5 data elements, but is not part of these data elements.Data Elements and Standards for Drug DictionariesExamples:Medicinal products with the same active ingredients, strengths and pharmaceutical dose form share a common PhPID4.Medicinal products with the same active ingredients and pharmaceutical dose form share a common PhPID3.Medicinal products with the same active ingredients and strengths share a common PhPID2.Medicinal products with the same active ingredients share a common PhPID1.2.1.3 Controlled Vocabulary Term Identifier (TermID)Definition:An identifier assigned at the level of each term of the controlled vocabulary (active ingredients, pharmaceutical dose forms, routes of administrations and units and measurements).Methodology:The TermID is a unique, non-semantic, alphanumeric code assigned for each term of the controlled vocabulary.2.2 Controlled Vocabulary2.2.1 BackgroundDifferent regulatory standard terminologies are in place in the ICH regions and observer countries, which makes it difficult to exchange this information at the international level. These terminology differences complicate specifically activities in the area of pharmacovigilance and healthcare and the management of medicinal product information.To address the identified terminology differences, the ICH M5 EWG is developing controlled vocabularies for active ingredient(s), pharmaceutical dose form(s), route(s) of administrations and unit(s) and measurement(s) using the following methodology: -Preparing an inventory of the different regulatory standard terminologies including those defined in the ICH E2B(M) guideline (version 4.4.1 includes the Post Step 4 corrections agreed by the Steering Committee on 5 February 2001);-Analyzing definitions for the different regulatory standard terminologies;-Developing a controlled vocabulary that supports good terminological practice;-Defining mapping procedures to determine unique terms and related synonym terms on the basis of the regional definitions in place;-Mapping the individual terms;-Assigning unique TermIDs.The Active Ingredients Controlled Vocabulary, the Pharmaceutical Dose Forms Controlled Vocabulary, the Routes of Administration Controlled Vocabulary and theData Elements and Standards for Drug Dictionaries Units and Measurements Controlled Vocabulary will be made available on the ICH website.2.2.2 Active Ingredients Controlled VocabularyScope:The Active Ingredients Controlled Vocabulary includes active ingredient terms related to approved medicinal products. Excluded are active ingredients related to homeopathic medicinal products and investigational medicinal products. Definitions:An active ingredient is defined as a substance that alone or in combination with one or more other ingredients produces the intended activity of a medicinal product.A substance is any matter and can be of human, animal, vegetable or chemical (natural, semi-synthetic or synthetic) origin.An active moiety is the portion of the active ingredient that is responsible for the effect.Methodology:A comprehensive list of active ingredient terms has been collected based on the standard terminologies currently used by the EMEA, FDA, MHLW and Health Canada.The active ingredient terms are limited to English language terms, with the exception of herbal active ingredients, for which the Latin language terms and/or Japanese language terms are also included.Within the list, the indication of the provenance of the term (i.e., its source) is also included.An active ingredient TermID will be assigned to each unique term.The following approach will be used for the mapping:-Chemical Abstract Service Number (CAS Number);-Reference Source for each active ingredient name (e.g., USAN, INN, JAN) that is linked to the chemical structure by the organizations;-Chemical name (e.g., following the IUPAC nomenclature).Mapping of synonyms will be performed on the level of both the active moiety and the active ingredient where applicable.Herbal substances will be mapped on the following principles:-Botanical scientific name according to the Latin binomial system (genus + species);-The author (e.g., Linnaeus, abbreviated L.) if known;-The plant parts (if known); and-The process (when applicable, and if known).Herbal preparations will be mapped on the basis of the standardized treatments (for instance extraction, distillation, expression, fractionation, purification, concentrationData Elements and Standards for Drug Dictionariesor fermentation) as described in the official Pharmacopoeias of the three regions. For extractions, the solvent will also be specified.For vaccine antigens the mapping of active substances will be based on the following principles:-Conformity with the pharmacopoeia monograph terminology for vaccine antigens in the regions;-For non-pharmacopoeia active substances, according to the formal Latin/Greek name and/or the disease being protected against.For bacteria and viruses, the strain serotype or other appropriate sub-species the designation will also be mapped with the name of each antigen, if relevant.In addition, the nature of any cellular system(s) used for production, and if relevant the use of recombinant DNA technology (including the use of the expression ‗produced in XXX cells <by recombinant DNA technology>) will be mapped, following the pattern set by the following examples:-‗produced in human diploid (MRC-5) cells‘;-‗produced in Escherichia coli cells by recombinant DNA technology‘;-‗produced in chick-embryo cells‘.The inclusion of a mention of the production process in vaccine active substance names will be mapped at the level of the following terms:-‗live, attenuated‘ (in the case of vaccines containing living micro-organisms);-‗inactivated‘ (in the case of vaccines containing killed micro-organisms). 2.2.3 Pharmaceutical Dose Form Controlled VocabularyScope:The Pharmaceutical Dose Form Controlled Vocabulary includes pharmaceutical dose form terms of standard terminologies in use by the regulators in the ICH regions and observer countries.Definitions:A Dose Form is defined as the physical manifestation [―entity‖] that contains the active and/or inactive ingredients that deliver a dose of the medicinal product. The key defining characteristics of the Dose Form can be the state of matter, delivery method, release characteristics, and the administration site or route for which the product is formulated.A Pharmaceutical Dose Form is the form in which a pharmaceutical product is presented in the medicinal product package as supplied by the marketing authorization holder/manufacturer/distributor.Methodology:A comprehensive list of Dose Form terms has been collected, which includes:-European Pharmacopoeia Standard terms;-United States Pharmacopeia (USP) terms;-Japanese Pharmacopoeia terms;-MHLW terms;-Health Canada terms.Within the list, the indication of the provenance of the term (i.e., its source) will also be included.Tasks to be undertaken include:- A term identifier will be allocated to each term (entry) in the list, enabling linkage with original dose form lists;-Each term will initially be identified as a ―dose form concept‖, pending identification of synonymy;-Synonymous terms will be identified and ―annotated‖ e.g., ―otic drops‖ and ―ear drops‖;-Terms that do not fit (for example, device terms) will be identified and annotated, as will be all terms that do not fit within the agreed definition(for example, dose forms that describe aspects of medication such asstrength or shape or indication);-Each of the ―dose form concepts‖ will be analyzed against the ag reed defining characteristics to create a logical description pattern. Thispattern will assist in the identification of unrecognized synonymy andhence will ensure that the resulting Dose Form concepts are unique andunambiguous. A description logic will enable concepts to be defined by thepattern or ―graph‖ of their relationships with other concepts;-Having analyzed all the ―dose form concepts‖, any concepts found to be sharing an identical ―set‖ of characteristics will again be reviewed;additional ―distinguishing‖ characteristics will be added as appropriate. The dose form description applies to only one concept at a time. Therefore, items that are marketed as packs containing more than one medicinal product will not themselves have a ―combination dose form‖, but each medicinal product within them will have a dose form description. This will avoid terms such as ―pessary + cream‖ or ―powder + solvent‖.2.2.4 Routes of Administration Controlled VocabularyScope:The Routes of Administration Controlled Vocabulary includes routes of administration terms of standard terminologies in use by the regulators in the ICH regions and observer countries and defined in the ICH E2B(M) guideline (version 4.4.1 includes the Post Step 4 corrections agreed by the Steering Committee on 5 February 2001).Definitions:The Route of Administration indicates the part of the body through or into which, or the way in which, the medicinal product is intended to be introduced.In some cases a medicinal product can be intended for more than one route and/or method of administration.Methodology:A comprehensive list of Route of Administration terms has been collected and includes:-European Pharmacopoeia Standard terms;-United States Pharmacopeia (USP) terms;-Health Canada terms;-MHLW terms;-ICH E2B(M) Routes of Administration List.Each term is given an identifier, a description and relationships to other terms within the terminology.Tasks undertaken include:- A term identifier is allocated to each term (entry) in the list, enabling linkage with the original route of administration term lists;-Within the list there is an indication of the provenance of the term (i.e., its source). A formal definition from the source vocabulary is included, wherenecessary.Synonymous terms are id entified and ―annotated‖ e.g., ocular use and ophthalmic use.-The route of administration terms are mapped on the basis of the same or the equivalent meaning for route of administration purposes e.g., ocular,ophthalmic. In specific cases the regional definitions were crosschecked toclarify the meaning;-An adjective is used to describe the route of administration where a suitable adjective is available, e.g., inhalational not inhalation;-The descriptor 'use' is generally not supported unless it adds a specific meaning e.g., ‗oral‘ was used instead of ‗oral use‘;-Where a prefix and a main word in the terms are concatenated, the concatenated word is hyphenated only if the ending of the prefix and thebeginning of the next word were both vowels (a, e, i, o, u);-Where a suitable ICH E2B(M) route of administration term exists, this is used as the basis for the official ICH M5 Route of AdministrationControlled Vocabulary term. Where a suitable ICH E2B(M) route ofadministration term is not available to represent the route concept, a newterm is added to the vocabulary. In either case, the above procedures areapplied;-The Routes of Administration Controlled Vocabulary presents the corresponding terms (translations) applicable in the different regions andin the E2B(M) list as follows:o MedID: e.g., 001;o ICH M5 Route of Administration Term e.g., Auricular (OTIC);o Regional Standard Terms:▪EU e.g., Auricular Use;▪FDA e.g., Auricular (OTIC);▪MHLW e.g., Otological Agent;▪Health Canada e.g., OTIC;▪E2B(M) e.g., Auricular (OTIC).-Where, within one region, two or more terms (e.g., a current term and a historic non-current term) refer to the same route of administration, these terms were specified in sequence and separated by the symbol "/". The preferred or current term is specified as the first term, e.g., ocular use/ophthalmic use for EU or unknown/unassigned for the US;- A draft translation for the ICH M5 Routes of Administration Controlled Vocabulary in Japanese has been included.2.2.5 Units and Measurements Controlled VocabularyScope:The Units and Measurements Controlled Vocabulary includes units and measurements in use by the regulators in the ICH regions and observer countries and defined in the ICH E2B(M) guideline (version 4.4.1 includes the Post Step 4 corrections agreed by the Steering Committee on 5 February 2001).General Conventions:The International System of Units (SI) and the Units and Measurements as described in the E2B(M) guideline, (version 4.4.1 includes the Post Step 4 corrections agreed by the Steering Committee on 5 February 2001) are followed in the ICH regions and observer countries. Additional, region specific units are in use specifically regarding biological and microbiological units.Methodology:A comprehensive list of Units and Measurements has been collected and includes:-International System of Units (SI);-Units and Measurements as described in the E2B(M) guideline1;-Region specific units and measurements (CA, EU, JP, US).Each unit and measurement is given an identifier, a description, a symbol and relationships to other terms within the terminology.Tasks undertaken include:- A term identifier is allocated to each unit and measurement (entry) in the list, enabling linkage with the original unit and measurement entries inthe lists;-Within the list there is an indication of the provenance of the term (i.e., its source) and a formal definition from the source vocabulary is included,where appropriate;-Synonymous entries are identified and ―annotated‖ e.g., %(v/v) and (v/v)%; 1Version 4.4.1 includes the Post Step 4 corrections agreed by the Steering Committee on 5 February 2001-The mapping of Units and Measurements is based on the International System of Units (SI) and its abbreviations and definitions. The definitionsof the SI base units refer to the NIST Special Publication 330 (SP 330);-Lower case has been used for the term description;-Exponents of symbols are not expressed in superscript format; e.g., the symbol ‗m2‘ has been used for square meters;-Some important and widely used units outside the International System have been added with regard to biological and microbiological units.Descriptions of these units and their abbreviations were added asappropriate.2.3 Data ElementsThis chapter describes the data elements for the electronic transmission of a core set of medicinal product information.The data elements as presented in this guideline refer to the consolidated core data sets of medicinal products as defined in the scope of this guideline, chapter 0.These data elements are based on the regional standards already established by these regulators to support the local data collection process and do not replace or supersede the regional standards or legal requirements for data collection between the regulators and pharmaceutical companies.As a result, a medicinal product is characterized in the frame of this guideline as follows:▪ A Medicinal Product has:o One and only one MedID;o One and only one Medicinal Product Name;o One and only one Marketing Authorization Holder;o One and only one Marketing Authorization (number);o One or more Pharmaceutical Products.▪ A Pharmaceutical Product has:o One or more Active Ingredients with a specific strength (the same active ingredient with a different strength is considered a differentpharmaceutical product);o One and only one Pharmaceutical Dose Form;o One or more possible Routes of Administration.In order to facilitate the understanding of the relationship of the data elements described in this chapter, a conceptual model is included as follows:Figure 1 - Conceptual Model of the ICH M5 MedID and Data Element SetThis conceptual model does not define the actual message specifications for the exchange format of MedIDs and the related ICH M5 data elements.The figure provides the relationship between the ICH M5 data elements and the MedID.▪All data elements are grouped as elements or attributes within a section;▪ A section defines a concept which is further described by its data elements or attributes;▪The data elements are flagged as Mandatory2 (M:) or Optional (O:);▪The data elements for which the entry is strictly controlled by a list of values(e.g., ISO Country Code 3166) or by the ICH M5 Controlled Vocabulary are initalics.There are relationships between entities, with a specific cardinality.▪The relationship with cardinality 1..1 means that, for example, a Pharmaceutical Product has precisely one pharmaceutical dose form;▪The relationship with cardinality 1..n means that, for example, a Pharmaceutical Product has one or more Active Ingredients.Each section and each element of the ICH M5 data element set is described in the following paragraphs.2The use of ‘Mandatory’ in the remainder of this document refers to technical and not legal requirements.As a general principle, it should be noted that depending on regional laws and regulations a formal marketing authorization might not be required for certain categories of medicinal products (e.g., certain OTC drugs, ‗grandfather‘ drugs). For these medicinal products the same principles apply as for ‗authorised‘ medicinal products.2.3.1 Medicinal Product Identifier2.3.1.1. Medicinal Product Identifier (MedID)User Guidance:The MedID as defined in chapter 0 of the medicinal product and as presented in the ICH M5 data element set should be provided in this field.As a general rule, the MedID should be maintained in any re-transmission of the same medicinal product information.Type:MandatoryExample:FR-123456-XEU-EU/1/2342323/001-KJP-123456789-YUS-0123456789-ZCA-2323232-V2.3.2 Medicinal Product Administrative Section2.3.2.1 Medicinal Product NameDefinition:The name assigned to a medicinal product as approved by the regulator of the country of authorization.User Guidance:The naming of a medicinal product differs in the ICH regions and observer countries.The full and complete medicinal product name as approved by the regulator of the country or territory of authorization and as appearing on the package of the medicinal product, the container or the package insert should be provided in this field.For medicinal products which do not require prior marketing authorization under regional law, the full and complete medicinal product name as appearing on the package of the medicinal product, the container or the package insert should be provided in this field.Synonyms:Proprietary Medicinal Product Name (ICH E2B(M))Name of the Medicinal ProductProduct NameType:MandatoryExamples:Lithium Carbonate liq. Paediatric Company DABC Tabs 500 Company BVinblastine Sulphate Injection Solution 10mg/mlTri-Product C ForteProduct X Oral GelBRANDX 100 U/ml Concentrate for solution for infusion-Intravenous use Vial (glass) 5 ml (100 U/ml) 1 vial2.3.2.2 Medicinal Product Short NameDefinition:The medicinal product name without the trademark or the name of the marketing authorization holder or any other descriptor (e.g., strength, dosage form, user group, route of administration).User Guidance:The name assigned to a medicinal product as approved by the regulator of the country or territory of authorization, without the trademark or the name of the marketing authorization holder or any other descriptor should be provided in this field.For medicinal products which do not require prior marketing authorization under regional law, the medicinal product name without the trademark or the name of the manufacturer/distributor or any other descriptor should be provided in this field.Synonyms:Trade NameBrand NameScientific NameCommon NameInvented NameType:Optional。
WHO偏差处理和质量风险管理-中英文对照版-2013

3) Introduction 介绍
Among the essential elements of a well established Quality Management System (QMS), deviation handling plays a key role in assuring quality in products and by contributing to continuous improvement. Manufacturers are expected to “establish processes and define appropriate controls for measurement and analysis to identify nonconformities and potential non-conformities; defining when and how corrections, corrective actions, or preventive actions should be undertaken. These actions should be commensurate with the significance or risk of the nonconformity or potential nonconformity” (7).
目的是支持在疫苗和生物制品生产过程中有效及时地实施偏差管理相关的工具。
This guidance document is in line with International Conference on Harmonization (ICH) documents like ICH Q10 Pharmaceutical Quality System, ICH Q9 Quality Risk Management, and with WHO, FDA and EU requirements. It also incorporates the experience of experts and auditors in the field.
USP药典的验证中英文对照

VALIDATION OF COMPENDIAL PROCEDURES 药典方法的验证Test procedures for assessment of the quality levels of pharmaceutical articles are subject to various requirements. According to Section 501 of the Federal Food, Drug, and Cosmetic Act, assays and specifications in monographs of the United States Pharmacopeia and the National Formulary constitute legal standards. The Current Good Manufacturing Practice regulations [21 CFR 211.194(a)] require that test methods, which are used for assessing compliance of pharmaceutical articles with established specifications, must meet proper standards of accuracy and reliability. Also, according to these regulations [21 CFR 211.194(a)(2)], users of analytical methods describedin USP–NF are not required to validate the accuracy and reliability of these methods, but merely verify their suitability under actual conditions of use. Recognizing the legal status of USP and NF standards, it is essential, therefore, that proposals for adoption of new or revised compendial analytical procedures be supported by sufficient laboratory data to document their validity.用于评估药品质量的检验方法需要满足不同的要求。
Self-Identification of Generic Drug Facilities, Sites, and Organizations

Generic Drug Facilities, Sites, and Organizations Guidance for IndustryU.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)September 2016GenericsGeneric Drug Facilities, Sites, and Organizations Guidance for IndustryAdditional copies are available from:Office of Communications,Division of Drug InformationCenter for Drug Evaluation and ResearchFood and Drug Administration10001 New Hampshire Ave., Hillandale Bldg., 4th FloorSilver Spring, MD 20993-0002Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353Email: druginfo@/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm7519 Standish Place, Rockville, MD 20855Phone: 240-276-9300/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htmU.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)September 2016GenericsTABLE OF CONTENTSI.INTRODUCTION (1)II.BACKGROUND (2)III.GDUFA SELF-IDENTIFICATION REQUIREMENTS (2)A.Who Is Required to Self-Identify? (3)B.What Information Is Required for Submission? (4)1.D-U-N-S Numbers (4)2. Facility Establishment Identifier (5)3.Additional Information (5)C.What Is the Process for Submitting Self-Identification Information? (5)D.What Is the Penalty for Failing to Self-Identify? (6)iSelf-Identification of Generic Drug Facilities, Sites, andOrganizationsGuidance for Industry1This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title page.I. INTRODUCTIONThis guidance is intended to assist human generic drug facilities, sites, and organizations by describing how to comply with the self-identification requirement contained in the Generic Drug User Fee Amendments of 2012 (Public Law 112-144, Title III), commonly referred to as GDUFA.Under GDUFA, human generic drug facilities, sites, and organizations are required to submit identification information electronically to FDA annually. FDA is issuing this guidance to help human generic drug facilities, sites, and organizations meet the self-identification requirement. Topics discussed in this guidance include:•which types of generic facilities, sites, and organizations are required to self-identify;•what information is requested;•what technical standards are to be used for electronically submitting the requested information; and•the penalty for failing to self-identify.This guidance also explains generally which types of generic facilities, sites, and organizations will be required to pay user fees.FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.1 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration.II. BACKGROUNDOn July 9, 2012, GDUFA was signed into law by the President.2 GDUFA is designed to speed the delivery of safe and effective generic drugs to the public and reduce costs to industry. GDUFA enables FDA to assess user fees to support critical and measurable enhancements to FDA’s generic drugs program. GDUFA will also significantly improve global supply chain transparency by requiring owners of facilities producing generic drug products, active pharmaceutical ingredients (API), and certain other sites and organizations that support the manufacture or approval of these products to electronically self-identify with FDA and update that information annually.Self-identification is required for two purposes. First, it is necessary to determine the universe of facilities required to pay user fees. Second, self-identification is a central component of an effort to promote global supply chain transparency. The information provided through self-identification enables quick, accurate, and reliable surveillance of generic drugs and facilitates inspections and compliance.Most facilities that self-identify are required to pay an annual facility user fee. These include facilities manufacturing, or intending to manufacture, API of human generic drugs and/or finished dosage form (FDF) human generic drugs. Other sites and organizations must self-identify, but are not required to pay the annual facility user fee. These include facilities that solely manufacture positron emission tomography (PET) drugs, or sites and organizations that only perform testing, repackaging, or relabeling operations. Please note that while repackagers are not required to pay user fees, packagers are, in most cases, FDF manufacturers and subject to facility fees.A separate system for the electronic self-identification of generic industry facilities, sites, and organizations was established for GDUFA. Entities required to register and list (under section 510 of the Federal Food, Drug, and Cosmetic Act or section 351 of the Public Health Service Act), and those required to self-identify under GDUFA submit information separately to the respective systems. Each system populates its own database to meet unique requirements and deadlines. The separate GDUFA system uses the same platform and technical standards already familiar to manufacturers required to register and list.III.GDUFA SELF-IDENTIFICATION REQUIREMENTSThe following discussion explains who is required to self-identify, what information is required for submission, and what the process is for submitting self-identification information.2 On October 5, 2012 the President signed into law the FDA User Fee Correction Act of 2012. This act amends GDUFA so that due dates for GDUFA user fees in fiscal year 2013 are not dependent on enactment of an appropriations act.A. Who Is Required to Self-Identify?The following types of generic industry facilities, sites, and organizations are required to self-identify with FDA:1. Facilities3 that manufacture, or intend to manufacture, human generic drug APIs or FDFs,or both.42. Facilities that package the FDF of a human generic drug into the primarycontainer/closure system and label the primary container/closure system.53. Sites that are identified in a generic drug submission and pursuant to a contract with theapplicant remove the drug from a primary container/closure system and subdivide thecontents into a different primary container/closure system.3 GDUFA has defined the term “facility” to identify those businesses required to pay fees and for self-identification. GDUFA defines a facility as a business or other entity under one management, either direct or indirect, at one geographic location or address, engaged in manufacturing or processing an API or an FDF. It does not include a business or other entity whose only manufacturing or processing activities are one or more of the following: repackaging, relabeling, or testing. Separate buildings within close proximity are considered to be at one geographic location or address if the activities in them are closely related to the same business enterprise; are under the supervision of the same local management; and are capable of being inspected by FDA during a single inspection. GDUFA further states that if a business entity would meet the definition of a facility but for being under multiple management, the business or entity is deemed to constitute multiple facilities, one per management entity.4 For purposes of self-identification and payment of fees, GDUFA defines API and FDF manufacturers differently from the way these categories of manufacturers have been defined historically. For example, generic drug manufacturers who mix an API when the substance is unstable or cannot be transported on its own are considered API manufacturers and not FDF manufacturers for self-identification and the payment of GDUFA fees only. GDUFA defines an FDF as:(A) a drug product in the form in which it will be administered to a patient, such as atablet, capsule, solution, or topical application;(B) a drug product in a form in which reconstitution is necessary prior to administration to a patient, such as oralsuspensions or lyophilized powders; or(C) any combination of an active pharmaceutical ingredient (as defined in the statute) with another component ofa drug product for purposes of production of a drug product described in subparagraph (A) or (B).GDUFA defines an API as:(A) a substance, or a mixture when the substance is unstable or cannot be transported on its own, intended—(i) to be used as a component of a drug; and(ii) to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the human body; or(B) a substance intended for final crystallization, purification, or salt formation, or any combination of thoseactivities, to become a substance or mixture described in subparagraph (A).5 Facilities that package the FDF of a human generic drug into the primary container/closure system and label the primary container/closure system are considered to be manufacturers, whether or not that packaging is done pursuant to a contract or by the applicant itself.4. Bioequivalence (BE)/bioavailability (BA) sites that are identified in a generic drugsubmission and conduct clinical BE/BA testing, bioanalytical testing of samples collected from clinical BE/BA testing, and/or in vitro BE testing.5.Sites that are identified in a generic drug submission and perform testing of one or moreattributes or characteristics of the FDF or the API pursuant to a contract with theapplicant to satisfy a current good manufacturing practice (CGMP) testing requirement(excludes sites that are testing for research purposes only).B.What Information Is Required for Submission?The following information is required to meet the self-identification requirement in GDUFA:1. D-U-N-S NumbersFDA requires Data Universal Numbering System (D-U-N-S) numbers for both the facility or site and the registrant owner of the facility or site if the facility or site is in a different location than the registrant owner location. A D-U-N-S number is required to uniquely identify the registrant (the owner or operator) and each physical location of the business’s facility or site (e.g., branches, divisions, and headquarters).A D-U-N-S number is a unique nine-digit sequence provided by Dun & Bradstreet. TheD-U-N-S number is specific for each site. Each distinct physical location of an entity (e.g., branch, division, and headquarter) would be assigned a different D-U-N-S number.The site-specific D-U-N-S number is a widely recognized business identification tool and serves as a useful resource for FDA in identifying and verifying certain business information submitted by a user.If no D-U-N-S number has been assigned, a business entity may obtain one at no cost directly from Dun & Bradstreet. A new number may be obtained, or an existing number verified, by phone or online. Existing facilities D-U-N-S numbers may also be verified on FDA’s current registration site for drug establishments.6Note: It takes Dun & Bradstreet approximately 30 business days to process a newD-U-N-S number and communicate it via email. A business entity may receive aD-U-N-S number in approximately 10 business days for an expedited service fee. Please note that a business entity may not request or apply for a new D-U-N-S number on behalf of another business entity due to the verification procedures used by Dun & Bradstreet. More information is available at the Dun & Bradstreet web page. See also the step-by-step instructions for obtaining a D-U-N-S number for businesses based either in the United States or abroad.6/scripts/cder/drls/default.cfm2. Facility Establishment IdentifierFacilities must also submit a Facility Establishment Identifier (FEI), a unique identifier designated by FDA to assign, monitor, and track inspections of regulated firms. 7A business entity that has previously obtained an FEI number may verify its FEI number by sending an email request to FDAGDUFAFEIRequest@.Alternatively, business entities that have not previously registered with FDA can obtain an FEI number by sending an email request to FDAGDUFAFEIRequest@. Please type “GDUFA FEI Request” in the subject line and include the following information in the body of the email:Firm NameFacility Address including City, Province, Country, and Mail CodeSize of FirmType of Operation (Manufacturer, Lab, etc.)Type of Industry: DrugsRequests for issuance of FEI numbers associated with GDUFA self-identification are typically processed within 10 to 15 business days.3. Additional InformationFDA requests the name and contact information for the registrant owner and facility information, including name, type of business operation, and contact information. Submitters are also asked to indicate whether they manufacture drugs that are not generic drugs.C.What Is the Process for Submitting Self-Identification Information?The self-identification process is similar to other FDA electronic submission standards. Self-identification files should be formatted in the same electronic messaging standard used for drug registration and listing information and for the content of labeling for abbreviated new drug applications (ANDAs). This standard, known as Health Level Seven Structured Product Labeling (SPL), allows information to be exchanged, searched, and combined with other data sources in a manner that supports health information technology initiatives to improve patient care. Providing Regulatory Submissions in Electronic Format— Drug Establishment Registration and Drug Listing8provides detailed instructions on how to submit information using SPL. FDA also offers tools and information for creating and submitting SPL files. Additional information can be found at /edrls.7 For the Agency’s policy on the assignment of FEIs, please refer to Field Management Directive (FMD) #130, Official Establishment Inventory (OEI) Development and Maintenance, which provides standardized definitions and associated procedures to facilitate consistency of data in the OEI.8 /downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072339.pdfD.What Is the Penalty for Failing to Self-Identify?Although GDUFA provides no explicit penalty for sites and organizations that fail to comply with the self-identification requirement, the failure of a site or organization to comply with the law and self-identify may raise significant concerns about that site. Such failure is a factor that may increase the likelihood of a site inspection prior to approval. FDA does not expect to give priority to completion of inspections that are required simply because sites fail to comply with self-identification requirements.More importantly, under GDUFA, if a facility fails to self-identify, all FDF or API products manufactured at the facility and all FDFs containing APIs manufactured at the facility will be deemed misbranded.9 It is a violation of federal law to ship misbranded products in interstate commerce or to import them into the United States. Such violations can result in prosecution of those responsible, injunctions, or seizures of the misbranded products. Products that are deemed misbranded because of failure of the facility to self-identify are subject to being denied entry into the United States.9 21 U.S.C. §352(aa)FDA Tracking #: 14819 FRDTS # 2013-90 Drafted: ALeboeuf/OGD 11/2/2015Reviewed: DNaik/CDER/OPQ/OS/DQIRAM/DIB 11/3/2015PLoebach/ CDER/OC/OPRO/DRLS 11/4/2015Reviewed: SLevine/OGD 03/28/16Revised: HSchwirck/OGD 04/12/16Reviewed: MNguyen/OGD 04/13/16Cleared: DBeers/OCC 09/2/16Final: ALeBoeuf/OGDP 09/09/16。
世界卫生组织儿童标准处方集

WHO Model Formulary for ChildrenBased on the Second Model List of Essential Medicines for Children 2009世界卫生组织儿童标准处方集基于2009年儿童基本用药的第二个标准目录WHO Library Cataloguing-in-Publication Data:WHO model formulary for children 2010.Based on the second model list of essential medicines for children 2009.1.Essential drugs.2.Formularies.3.Pharmaceutical preparations.4.Child.5.Drug utilization. I.World Health Organization.ISBN 978 92 4 159932 0 (NLM classification: QV 55)世界卫生组织实验室出版数据目录:世界卫生组织儿童标准处方集基于2009年儿童基本用药的第二个标准处方集1.基本药物 2.处方一览表 3.药品制备 4儿童 5.药物ISBN 978 92 4 159932 0 (美国国立医学图书馆分类:QV55)World Health Organization 2010All rights reserved. Publications of the World Health Organization can be obtained fromWHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: ******************). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the aboveaddress(fax:+41227914806;e-mail:*******************).世界卫生组织2010版权所有。
欧盟GMP附录15确认和验证中英文新版

欧盟GMP附录15确认和验证欧盟GMP附录15确认和验证ANNEX 15 附件15Qualification and Validation确认和验证Table of Contents 目录1. Qualification and Validation 确认和验证2. Planning for Validation 验证计划3. Documentation 文件4. Qualification 确认5. Process Validation 工艺验证6. Cleaning Validation 清洁验证7. Change Control 变更控制8. Revalidation 再验证9. Glossary 术语表Qualification and Validation 确认和验证Principle 原理1.This Annex describes the principles of qualification and validation which are applicable to the manufacture of medicinal products. It is a requirement of GMP that manufacturers identify what validation work is needed to prove control of the critical aspects of their particular operations. Significant changes to the facilities, the equipment and the processes, which may affect the quality of the product, should be validated. A risk assessment approach should be used to determine the scope and extent of validation.1.本附件描述了确认和验证的原理,适用于医药产品的生产者。
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We are grateful to seminar participants at ASHE, Cal State Long Beach, NBER’s Health Economics Program Meeting, RAND, Rice University, UC Riverside, and the University of Houston, and to Shin-Yi Chou and Jonathan Skinner for helpful comments. Raj Mehta and Zachary Wagner-Rubin provided excellent research assistance. We are indebted to the Agency for Healthcare Research and Quality (5R01-HS01854103) for financial support. The views expressed herein are those of the authors and do not necessarily reflect the views of the National Bureau of Economic Research. At least one co-author has disclosed a financial relationship of potential relevance for this research. Further information is available online at /papers/w19490.ack NBER working papers are circulated for discussion and comment purposes. They have not been peerreviewed or been subject to the review by the NBER Board of Directors that accompanies official NBER publications. © 2013 by John A. Romley and Neeraj Sood. All rights reserved. Short sections of text, not to exceed two paragraphs, may be quoted without explicit permission provided that full credit, including © notice, is given to the source.
NBER WORKING PAPER SERIES
IDENTIFYING THE HEALTH PRODUCTION FUNCTION: THE CASE OF HOSPITALS John A. Romley Neeraj Sood Working Paper 19490 /papers/w19490 NATIONAL BUREAU OF ECONOMIC RESEARCH 1050 Massachห้องสมุดไป่ตู้setts Avenue Cambridge, MA 02138 October 2013
Identifying the Health Production Function: The Case of Hospitals John A. Romley and Neeraj Sood NBER Working Paper No. 19490 October 2013 JEL No. D24,I1,I12 ABSTRACT Estimates of the returns to medical care may reflect not only the efficacy of more intensive care, but also unmeasured differences in patient severity or the productivity of health-care providers. We use a variety of instruments that are plausibly orthogonal to heterogeneity among providers as well as patients to analyze the intensity of care and 30-day survival among Medicare patients hospitalized for heart attack, congestive heart failure and pneumonia. We find that the intensity of care is endogenous for two out of three conditions. The elasticity of 30-day mortality with respect to care intensity increases in magnitude from -0.27 to -0.71 for pneumonia and from -0.16 to -0.33 for congestive heart failure, when we address the identification problem. This finding is consistent with the hypotheses that care intensity at hospitals tends to decrease with hospital productivity, or increase with unmeasured patient severity. John A. Romley Schaeffer Center for Health Policy and Economics University of Southern California 3335 S. Figueroa St, Unit A Los Angeles, CA 90089-7273 romley@ Neeraj Sood Schaeffer Center for Health Policy and Economics University of Southern California 3335 S. Figueroa Street, Unit A Los Angeles, CA 90089-7273 and NBER nsood@
1. Introduction Understanding the marginal product of medical care is critical to ongoing debates about the value of U.S. health care. An array of studies, based on the Dartmouth Atlas of Health Care, find that U.S. regions that spend more on medical care have similar or poorer patient outcomes than areas that spend less (Skinner 2011). This evidence has suggested to some observers that medical spending can be reduced without adversely affecting patient outcomes (Fisher, Wennberg et al. 2003). In contrast, recent studies of hospital care in health economics and other literatures have found that greater spending and intensity of care are associated with lower risk-adjusted mortality (Doyle 2005; Chandra and Staiger 2007; Card, Dobkin et al. 2009; Ong, Mangione et al. 2009; Almond, Doyle et al. 2010; Barnato, Chang et al. 2010; Kaestner and Silber 2010; Silber, Kaestner et al. 2010; Doyle 2011; Romley, Jena et al. 2011; Romley, Jena et al. 2013). These studies of the returns to hospital spending have concerned themselves with the problem of unobserved patient heterogeneity. Health or severity of illness is notoriously difficult for researchers to measure precisely, and patients or providers almost certainly observe more about health or severity of illness than a researcher does. The resulting identification problem is that the intensity of medical care is confounded with unobserved (to the researcher) health status or severity of illness. Typically, the concern is that sicker patients receive more intensive care, and so the returns to medical care are biased downward. Thus, accounting for patient selection can increase the estimated returns to medical care. One approach to dealing with this patient selection problem is to exploit discontinuities in the intensity of care (Doyle 2005; Card, Dobkin et al. 2009; Almond, Doyle et al. 2010). While this approach is compelling, its generality may be limited. Another approach is to focus on a group of patients for whom the selection problem is plausibly mild, for example, hospitalizations of out-of-state visitors with cardiac emergencies (Doyle 2011). Still another approach exploits the fact that consumers typically prefer to receive health care close to their homes, and uses distance to providers as an exogenous source of variation in intensity (McClellan, McNeil et al. 1