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    VAL 195 Maximum Safe Carry Over (MSCO) Determination

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    Sameh Mostafa

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    VAL 195 Maximum Safe Carry Over (MSCO) Determination

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    Sameh Mostafa
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    19 views5 pages

    VAL 195 Maximum Safe Carry Over (MSCO) Determination

    Uploaded by

    Sameh Mostafa

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
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    of 5

    Standard Operating Procedure

    Title: Maximum Safe Carry-Over (MSCO) Determination

    Department Validation/Technical Services Document no VAL-195


    Prepared by: Date: Supersedes:
    Checked by: Date: Date Issued:
    Approved by: Date: Review Date:

    A PURPOSE
    The purpose of this document is to instruct the user on the operations required in order to conduct a
    Maximum Safe Carry-Over Determination (MSCO) for a piece of equipment or product equipment
    grouping.

    B SCOPE
    The scope of this SOP is limited to instructing the user on how to conduct a MSCO determination,
    following documented risk assessment of the materials and products to be processed on a piece of
    equipment or product equipment train.

    C RESPONSIBILITITY
    1 The Validation Engineer and/or Supervisor is responsible for obtaining true, compliant data for
    conducting a Maximum Allowable Carry Over (MACO). They are responsible for following the
    calculation process as defined in this SOP and for review of the MACO calculations generated by
    peers.
    2 The Quality Assurance Manager(s) and/or Quality Manager are responsible for review of the
    MACO calculations and formal acceptance of the indicated results for reference in future studies.

    D PROCESS SPECIFIC INFORMATION

    1. Regulations

    Regulatory References which govern the actions outlined in this SOP are contained below.

    1.1 PIC/S Guide to Good Manufacturing Practice (GMP) - 15 January 2009, PE 009-8.

    1.1.1 Guide to Good Manufacturing Practice for Medicinal Products - Part II, Chapter 12:
    Section 12.7

    1.1.2 Guide to Good Manufacturing Practice for Medicinal Products Annexes, Annex 15:
    Qualification and Validation, Clauses 36 - 42
    2. Guidelines
    The guidelines utilized for reference for this SOP are included below

    2.1 Guideline on setting health based exposure limits for use in risk identification in the
    manufacture of different medicinal products in shared facilities (EMA, 2014)

    2.2 ICH Topic Q3C (R4) Impurities: Guideline for Residual Solvents (EMA, 2009)

    E. BACKGROUND AND CALCULATION INFORMATION

    1. Guideline for MSCO Calculation


    1.1 The MSCO calculation is derived from the European Medicines Agency (EMA) guidelines for
    compliance with European Union (EU) GMP regulations regarding cleaning validation. This is
    required for product which is exported to regions governed by EU GMP regulations. The
    previous term utilized for calculating residue limits “Maximum Allowable Carry-Over” (MACO)
    has been replaced with Maximum Safe Carry-Over, owing to the derivation of the value from
    the Permitted Daily Exposure calculations.

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    Standard Operating Procedure
    Title: Maximum Safe Carry-Over (MSCO) Determination

    𝑚𝑔
    𝑘𝑔
    𝐿𝐷 𝑇𝑎𝑟𝑔𝑒𝑡 𝐴𝑛𝑖𝑚𝑎𝑙 𝑊𝑒𝑖𝑔ℎ𝑡 𝑒. 𝑔. 50𝑘𝑔 𝑓𝑜𝑟 𝑆ℎ𝑒𝑒𝑝
    𝑑𝑎𝑦
    𝑁𝑂𝐴𝐸𝐿 𝑓𝑟𝑜𝑚 𝐿𝐷
    2000
    6.2.1 It should be noted that this formula (adapted from the “guidance on aspects of cleaning
    validation inactive pharmaceutical ingredient plants” (APIC, 2000)) should only be
    utilized where toxicological data has not been found available.
    1.3 The use of this equation in place of toxicological assessment data should be considered
    based on the risk of the target species.
    1.4 As an additional alternative, the Low Observed Adverse Effect Level (LOAEL) may be utilized
    to calculate the NOAEL. The LOAEL can be obtained from the Minimum Therapeutic Dose
    value (reported in appropriate scientific literature). If the LOAEL is utilized in the PDE
    calculation, then an F5 factor of 10 must be used (refer to section 2 for greater detail).
    2. F – Value Assumptions for PDE
    The assumptions for the F-values chosen for calculations are indicated in the sections below.
    Select the appropriate F – values corresponding to the toxicological data/NOAEL/LOAEL
    source as described in section F1. Each F-value selection should be justified as per the
    guidance below or based on the risk of the target species.
    2.1 The F1 Factor is for extrapolation of data between (animal) species.
     F1 = 5 for extrapolation from rats to humans
     F1 = 12 for extrapolation from mice to humans
     F1 = 2 for extrapolation from dogs to humans
     F1 = 2.5 for extrapolation from rabbits to humans
     F1 = 3 for extrapolation from monkeys to humans
     F1 = 10 for extrapolation from other animals to humans
    2.2 The F2 factor is nominally a factor of 10 to account for variability between individuals
     A factor of 10 is generally given for all organic solvents, and 10 is typically used
    consistently in guidelines.
    2.3 The F3 factor is a variable factor to account for toxicity studies of short-term exposure
     F3 = 1 for studies that last at least one half lifetime (1 year for rodents or rabbits; 7
    years for cats, dogs and monkeys).
     F3 = 1 for reproductive studies in which the whole period of organogenesis is covered.
     F3 = 2 for a 6-month study in rodents, or a 3.5-year study in non-rodents.
     F3 = 5 for a 3-month study in rodents, or a 2-year study in non-rodents.
     F3 = 10 for studies of a shorter duration. In all cases, the higher factor has been used
    for study durations between the time points, e.g., a factor of 2 for a 9-month rodent
    study.
    2.4 F4 is a factor that may be applied in cases of severe toxicity, e.g., non-genotoxic
    carcinogenicity, neurotoxicity or teratogenicity. In studies of reproductive toxicity, the following
    factors are used:
     F4 = 1 for fetal toxicity associated with maternal toxicity
     F4 = 5 for fetal toxicity without maternal toxicity F4 = 5 for a teratogenic effect with
    maternal toxicity

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    Appendix A: Biologicals Area Cleaning Validation New or Changed Product,
    Process and Equipment Assessment

    1. Introduction

    This form is to be utilised for recording new product details and/ new process details that may have impact
    on the applicability of existing cleaning procedures on the biological production area.

    2. Purpose and Scope

    This form will be utilised for assessment of new product/process and equipment risk in both blending and
    antigen production areas. The form will guide the user to supply appropriate product and equipment
    information so that the impact of the new product material components and process can be assessed in
    regards to existing or future cleaning validation documentation.

    3. New or Modified Product/Process Material

    Product Name:

    Product Type (Circle): Vaccine / Sterile Pharmaceutical / Antigen (Bacterin) / Antigen (Toxoid)

    Is the product aqueous or non- aqueous? (Circle): Aqueous / Non - Aqueous

    Instruction Component Description Component


    Concentration

    1.

    List the Active 2.


    Pharmaceutical 3.
    Ingredients (APIs)
    that are of a biological 4.
    origin. 5.
    6.
    1.

    List the Active 2.


    Pharmaceutical 3.
    Ingredients (APIs)
    that are of a chemical 4.
    origin. 5.
    6.
    Attach the Product Formulation Sheet or the Finished
    Product Specification containing the product component Sign/Date
    specifications
    Attach Solubility Data for all APIs (typically available in
    Sign/Date
    the raw material MSDS

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    Appendix A: Biologicals Area Cleaning Validation New or Changed Product,
    Process and Equipment Assessment

    4. Enter all product contact equipment in the process list below, in order from commencement of
    manufacture to the completion.

    4.1 MEDIA PREPARATION EQUIPMENT

    4.1.1

    4.1.2

    4.1.3

    4.1.4

    4.1.5

    4.1.6

    4.1.7

    4.1.8

    4.1.9

    4.1.10

    4.2 ANTIGEN AREA EQUIPMENT

    4.2.1

    4.2.2

    4.2.3

    4.2.4

    4.2.5

    4.2.6

    4.2.7

    4.2.8

    4.2.9

    4.2.10

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    Appendix A: Biologicals Area Cleaning Validation New or Changed Product,
    Process and Equipment Assessment

    5. Cleaning Validation Review

    (To be completed by a Validation Representative)

    1. Are there new APIs? Circle Yes / No


    1.1. If Yes, update PVA-SOP-023b section 5.1, then continue to 2
    1.2. If No, continue to (2)
    2. Update PVA-SOP-023b sections 5.1.4 onwards
    2.1. If the product is to be blended and filled in production area 3, update sections 5.1.4-5.5
    2.2. If the product is to be manufactured and contained in the antigen area update section 6
    3. If applicable, check that PVA-SOP-009 Appendix 1 has been updated with the new product details.
    3.1. Verify if it is current (Yes / No )
    3.2. If No, Update the Appendix with the new product details, if Yes, no further action is required

    Review Completed By (Name):

    Sign / Date:

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