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    The Top 15 Pharmaceutical Deficiencies Cited by FDA in 2014 Posted 08 December 2014 By Alexander Gaffney, RAC The US Food and Drug Administration (FDA) has released data on the observations it makes during inspections of pharmaceutical facilities, indicating the most common issues faced by pharmaceutical companies. Total 483s Issued Declines for First Time in Six Years In its most recent report, FY 2014 Inspectional Observation Summaries, FDA said it issued 645 Form 483s—forms indicating areas of noncompliance at a facility—to pharmaceutical companies in fiscal year 2014. The number of 473s issued (645) marked the second consecutive year FDA has issued fewer pharmaceutical 483s than the year prior, and the 2014 total (645) is 19% less than its 2012 high water mark (787 inspections). Number of 483s Issued by FDA by Year - Pharmaceutical The Top 15 Pharmaceutical Deficiencies in FDA's 483 Reports FDA's inspections also noted common deficiencies by pharmaceutical manufacturers. Regulatory Citation Short Description Long Description Frequency 21 CFR 211.22(d) Procedures not in writing, fully followed The responsibilities and procedures applicable to the quality control unit are not [in writing] [fully followed]. 145 21 CFR 211.160(b) Scientifically sound laboratory controls Laboratory controls do not include the establishment of scientifically sound and appropriate [specifications] [standards] [sampling plans] [test procedures] designed to assure that [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] conform to appropriate standards of identity, strength, quality and purity. 109 21 CFR 211.192 Investigations of discrepancies, failures There is a failure to thoroughly review [any unexplained discrepancy] [the failure of a batch or any of its components to meet any of its specifications] whether or not the batch has been already distributed. 94 21 CFR 211.100(a) Absence of Written Procedures There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. 87 21 CFR 211.67(b) Written procedures not established/followed Written procedures are not [established] [followed] for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. 72 21 CFR 211.113(b) Procedures for sterile drug products Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not [established] [written] [followed]. 72 21 CFR 211.165(a) Testing and release for distribution Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the [final specifications] [identity and strength of each active ingredient] prior to release. 64 21 CFR 211.67(a) Cleaning / Sanitizing / Maintenance Equipment and utensils are not [cleaned] [maintained] [sanitized] at appropriate intervals to prevent [malfunctions] [contamination] that would alter the safety, identity, strength, quality or purity of the drug product. 63 21 CFR 211.68(a) Calibration/Inspection/Checking not done Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance. 54 21 CFR 211.166(a) Lack of written stability program There is no written testing program designed to assess the stability characteristics of drug products. 51 21 CFR 211.110(a) Control procedures to monitor and validate performance Control procedures are not established which [monitor the output] [validate the performance] of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. " 51 21 CFR 211.198(a) Complaint Handling P

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    The Top 15 Pharmaceutical Deficiencies Cited by FDA in 2014 Posted 08 December 2014 By Alexander Gaffney, RAC The US Food and Drug Administration (FDA) has released data on the observations it makes during inspections of pharmaceutical facilities, indicating the most common issues faced by pharmaceutical companies. Total 483s Issued Declines for First Time in Six Years In its most recent report, FY 2014 Inspectional Observation Summaries, FDA said it issued 645 Form 483s—forms indicating areas of noncompliance at a facility—to pharmaceutical companies in fiscal year 2014. The number of 473s issued (645) marked the second consecutive year FDA has issued fewer pharmaceutical 483s than the year prior, and the 2014 total (645) is 19% less than its 2012 high water mark (787 inspections). Number of 483s Issued by FDA by Year - Pharmaceutical The Top 15 Pharmaceutical Deficiencies in FDA's 483 Reports FDA's inspections also noted common deficiencies by pharmaceutical manufacturers. Regulatory Citation Short Description Long Description Frequency 21 CFR 211.22(d) Procedures not in writing, fully followed The responsibilities and procedures applicable to the quality control unit are not [in writing] [fully followed]. 145 21 CFR 211.160(b) Scientifically sound laboratory controls Laboratory controls do not include the establishment of scientifically sound and appropriate [specifications] [standards] [sampling plans] [test procedures] designed to assure that [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] conform to appropriate standards of identity, strength, quality and purity. 109 21 CFR 211.192 Investigations of discrepancies, failures There is a failure to thoroughly review [any unexplained discrepancy] [the failure of a batch or any of its components to meet any of its specifications] whether or not the batch has been already distributed. 94 21 CFR 211.100(a) Absence of Written Procedures There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. 87 21 CFR 211.67(b) Written procedures not established/followed Written procedures are not [established] [followed] for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. 72 21 CFR 211.113(b) Procedures for sterile drug products Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not [established] [written] [followed]. 72 21 CFR 211.165(a) Testing and release for distribution Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the [final specifications] [identity and strength of each active ingredient] prior to release. 64 21 CFR 211.67(a) Cleaning / Sanitizing / Maintenance Equipment and utensils are not [cleaned] [maintained] [sanitized] at appropriate intervals to prevent [malfunctions] [contamination] that would alter the safety, identity, strength, quality or purity of the drug product. 63 21 CFR 211.68(a) Calibration/Inspection/Checking not done Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance. 54 21 CFR 211.166(a) Lack of written stability program There is no written testing program designed to assess the stability characteristics of drug products. 51 21 CFR 211.110(a) Control procedures to monitor and validate performance Control procedures are not established which [monitor the output] [validate the performance] of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. " 51 21 CFR 211.198(a) Complaint Handling P

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    12 Ansichten31 Seiten

    稳定性

    Hochgeladen von

    windli2014
    The Top 15 Pharmaceutical Deficiencies Cited by FDA in 2014 Posted 08 December 2014 By Alexander Gaffney, RAC The US Food and Drug Administration (FDA) has released data on the observations it makes during inspections of pharmaceutical facilities, indicating the most common issues faced by pharmaceutical companies. Total 483s Issued Declines for First Time in Six Years In its most recent report, FY 2014 Inspectional Observation Summaries, FDA said it issued 645 Form 483s—forms indicating areas of noncompliance at a facility—to pharmaceutical companies in fiscal year 2014. The number of 473s issued (645) marked the second consecutive year FDA has issued fewer pharmaceutical 483s than the year prior, and the 2014 total (645) is 19% less than its 2012 high water mark (787 inspections). Number of 483s Issued by FDA by Year - Pharmaceutical The Top 15 Pharmaceutical Deficiencies in FDA's 483 Reports FDA's inspections also noted common deficiencies by pharmaceutical manufacturers. Regulatory Citation Short Description Long Description Frequency 21 CFR 211.22(d) Procedures not in writing, fully followed The responsibilities and procedures applicable to the quality control unit are not [in writing] [fully followed]. 145 21 CFR 211.160(b) Scientifically sound laboratory controls Laboratory controls do not include the establishment of scientifically sound and appropriate [specifications] [standards] [sampling plans] [test procedures] designed to assure that [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] conform to appropriate standards of identity, strength, quality and purity. 109 21 CFR 211.192 Investigations of discrepancies, failures There is a failure to thoroughly review [any unexplained discrepancy] [the failure of a batch or any of its components to meet any of its specifications] whether or not the batch has been already distributed. 94 21 CFR 211.100(a) Absence of Written Procedures There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. 87 21 CFR 211.67(b) Written procedures not established/followed Written procedures are not [established] [followed] for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. 72 21 CFR 211.113(b) Procedures for sterile drug products Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not [established] [written] [followed]. 72 21 CFR 211.165(a) Testing and release for distribution Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the [final specifications] [identity and strength of each active ingredient] prior to release. 64 21 CFR 211.67(a) Cleaning / Sanitizing / Maintenance Equipment and utensils are not [cleaned] [maintained] [sanitized] at appropriate intervals to prevent [malfunctions] [contamination] that would alter the safety, identity, strength, quality or purity of the drug product. 63 21 CFR 211.68(a) Calibration/Inspection/Checking not done Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance. 54 21 CFR 211.166(a) Lack of written stability program There is no written testing program designed to assess the stability characteristics of drug products. 51 21 CFR 211.110(a) Control procedures to monitor and validate performance Control procedures are not established which [monitor the output] [validate the performance] of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. " 51 21 CFR 211.198(a) Complaint Handling P

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    von 31

    2

    NDA/ANDANew Drug Application/Abbreviated New


    Drug ApplicationNCENew Chemical Entity
    INDInvestigational New Drug Application
    Variation Application

    1
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    10 5060
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    1.2106Luxhr 200whr/m2
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    53 12
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    23

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    1.Accelerated testing

    2.Intermediate testing
    25
    30/65%RH

    3.Long-term testing

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    /

    24

    5.Bracketing

    6.Matrixing

    7.Climatic zones
    W.Grimm Drugs Made in Germany,
    28:196-202, 1985 and 29:39-47. 1986

    25
    4
    21 45%RH
    25 60%RH
    30 35%RH
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    B 30 75%RH
    ICH
    199310
    25 2
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    Q1A/R2
    252/60%RH5%RH252/60%RH5%RH
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    8.Pilot scale batch

    9.Primary batch

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    32

    26
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    10.Production batch

    11.Commitment batch

    12.Container closure system


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    13.Impermeable container

    14.Semi-permeable container

    27

    LDPELVPs

    15.Expiration dating period


    16.Expiration date

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    20111102013110
    17.Re-test period
    /

    18.Re-test date

    28

    22011
    1102013110
    19.Specification-Release

    20. Specification-Shelf
    life

    21. [ Stress testing drug


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    22.[ Stress testingdrug product]


    23.Mass balance

    29

    100%
    24.Supporting data


    1.ICH Q1A(R2):Stability Testing of New Drug Substances and
    Products
    2.ICH Q1B:Photostability Testing of New Drug Substances and
    Products
    3.ICH Q1C:Stability Testing of New Dosage Forms
    4.ICH Q1DBracketing and Matrixing Designs for Stability
    Testing of New Drug Substances and Products
    5.ICH Q1EEvaluation for Stability Data
    6.ICH Q5C Stability Testing of Biotechnological/ Biotechnological
    Products
    7.ICH Q6A:Specifications: Test Procedures and Acceptance
    Criteria for New Drug Substances and New Drug Products: Chemical
    Substances
    8.ICH Q6B:Specifications: Test Procedures and Acceptance

    30
    Criteria for New Drug Substances and New Drug Products:
    Biotechnological/Biological Products
    9.FDA (June 2013), Guidance for Industry ANDAs:Stability
    Testing of Drug Substances and Products

    31

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