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    Tablet Scoring - Nomenclature, Labeling, and Data For Evaluation

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    Rezaul Razib
    This document provides guidance for industry on tablet scoring, including nomenclature, labeling, and data requirements. It recommends guidelines and criteria for evaluating scored tablets, such as ensuring dosage amounts after splitting and stability of split tablets. It also provides recommended finished product testing criteria for whole and split tablets, such as weight variation and content uniformity testing. The guidance aims to ensure quality of scored solid oral dosage forms in new drug and abbreviated new drug applications.

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    Tablet Scoring - Nomenclature, Labeling, and Data For Evaluation

    Uploaded by

    Rezaul Razib
    139 views8 pages
    This document provides guidance for industry on tablet scoring, including nomenclature, labeling, and data requirements. It recommends guidelines and criteria for evaluating scored tablets, such as ensuring dosage amounts after splitting and stability of split tablets. It also provides recommended finished product testing criteria for whole and split tablets, such as weight variation and content uniformity testing. The guidance aims to ensure quality of scored solid oral dosage forms in new drug and abbreviated new drug applications.

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    Tablet Scoring_Nomenclature, Labeling, And Data for Evaluation

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    This document provides guidance for industry on tablet scoring, including nomenclature, labeling, and data requirements. It recommends guidelines and criteria for evaluating scored tablets, such as ensuring dosage amounts after splitting and stability of split tablets. It also provides recommended finished product testing criteria for whole and split tablets, such as weight variation and content uniformity testing. The guidance aims to ensure quality of scored solid oral dosage forms in new drug and abbreviated new drug applications.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    139 views8 pages

    Tablet Scoring - Nomenclature, Labeling, and Data For Evaluation

    Uploaded by

    Rezaul Razib
    This document provides guidance for industry on tablet scoring, including nomenclature, labeling, and data requirements. It recommends guidelines and criteria for evaluating scored tablets, such as ensuring dosage amounts after splitting and stability of split tablets. It also provides recommended finished product testing criteria for whole and split tablets, such as weight variation and content uniformity testing. The guidance aims to ensure quality of scored solid oral dosage forms in new drug and abbreviated new drug applications.

    Copyright:

    © All Rights Reserved
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    of 8

    Guidance for Industry

    Tablet Scoring:
    Nomenclature, Labeling, and
    Data for Evaluation

    U.S. Department of Health and Human Services


    Food and Drug Administration
    Center for Drug Evaluation and Research (CDER)
    March 2013
    CMC

    Guidance for Industry


    Tablet Scoring:
    Nomenclature, Labeling, and
    Data for Evaluation
    Additional copies are available from:
    Office of Communications
    Division of Drug Information, WO51, Room 2201
    Center for Drug Evaluation and Research
    Food and Drug Administration
    10903 New Hampshire Ave., Silver Spring, MD 20993
    Phone: 301-796-3400; Fax: 301-847-8714
    [email protected]
    http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

    U.S. Department of Health and Human Services


    Food and Drug Administration
    Center for Drug Evaluation and Research (CDER)
    March 2013
    CMC

    Contains Nonbinding Recommendations


    TABLE OF CONTENTS

    I.

    INTRODUCTION............................................................................................................. 1

    II.

    BACKGROUND ............................................................................................................... 1

    III.

    DISCUSSION .................................................................................................................... 2

    A.

    Guidelines and Criteria ................................................................................................................. 3

    B.

    Nomenclature and Product Labeling ........................................................................................... 5

    Contains Nonbinding Recommendations

    Guidance for Industry 1


    Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation
    This guidance represents the Food and Drug Administrations (FDAs) current thinking on this topic. It
    does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
    You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
    and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for
    implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate
    number listed on the title page of this guidance.

    I.

    INTRODUCTION

    This guidance provides recommendations to sponsors of new drug applications (NDAs) and
    abbreviated new drug applications (ANDAs) regarding what criteria should be met when
    evaluating and labeling tablets that have been scored. (A scoring feature facilitates the practice
    of tablet splitting. 2) Specifically, this guidance recommends:

    Guidelines to follow, data to provide, and criteria to meet and detail in an application to
    support approval of a scored tablet.

    Nomenclature and labeling for approved scored tablets.

    This guidance does not address specific finished-product release testing, where additional
    requirements may apply to scored tablets. This guidance does not describe the medical practice
    conditions under which tablet splitting is considered or recommended.
    FDAs guidance documents, including this guidance, do not establish legally enforceable
    responsibilities. Instead, guidances describe the Agencys 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.
    II.

    BACKGROUND

    The Agency has previously considered tablet scoring as an issue when determining whether a
    generic drug product is the same as the reference listed drug (RLD). 3 One characteristic of a
    1

    This guidance has been prepared by the Office of Pharmaceutical Science in the Center for Drug Evaluation and
    Research (CDER) at the Food and Drug Administration.
    2
    A score is a debossed line that runs across the planar surface of the tablet, while tablet splitting is the practice of
    breaking or cutting a higher-strength tablet into smaller portions.
    3
    See the Manual of Policies and Procedures on Scoring Configuration of Generic Drug Products (5223.2),
    November 1, 1995.

    Contains Nonbinding Recommendations


    tablet dosage form is that it may be manufactured with a score or scores. This characteristic is
    useful because the score can be used to facilitate the splitting of the tablet into fractions when
    less than a full tablet is desired for a dose. Although there are no standards or regulatory
    requirements that specifically address scoring of tablets, the Agency recognizes the need for
    consistent scoring between a generic product and its RLD.
    Consistent scoring ensures that the patient is able to adjust the dose, by splitting the tablet, in the
    same manner as the RLD. This enables the patient to switch between products made by different
    manufacturers without encountering problems related to the dose. In addition, consistent scoring
    ensures that neither the generic product nor the RLD has an advantage in the marketplace
    because one is scored and one is not.
    CDERs Drug Safety Oversight Board considered the practice of tablet splitting at its October
    2009 and November 2010 meetings. 4 During those meetings, they discussed how insurance
    companies and doctors are increasingly recommending that patients split tablets, either to adjust
    the patients dose or as a cost-saving measure. Because of this, the Agency conducted internal
    research on tablet splitting and concluded that in some cases, there are possible safety issues,
    especially when tablets are not scored or evaluated for splitting. The Agencys concerns with
    splitting a tablet included variations in the tablet content, weight, disintegration, or dissolution,
    which can affect how much drug is present in a split tablet and available for absorption. In
    addition, there may be stability issues with splitting tablets. 5, 6
    Tablet splitting also is addressed in pharmacopeial standards. The European Pharmacopeia (EP)
    currently applies accuracy of subdivision standards for scored tabletsand has at various times
    also included standards for content uniformity, weight variation, and loss of masswhile the
    United States Pharmacopeia (USP) published a Stimuli article in 2009 proposing criteria for loss
    of mass and accuracy of subdivision for split tablets. 7
    III.

    DISCUSSION

    As an outgrowth of these discussions, we are providing recommendations for application content


    regarding the scientific basis for functional scoring on solid oral dosage form products to ensure
    the quality of both NDA and ANDA scored tablet products. To accomplish this, we have
    developed consistent and meaningful criteria by which scored tablets can be evaluated and
    labeled by (1) providing a harmonized approach to chemistry, manufacturing, and controls
    (CMC) reviews of scored tablets; (2) ensuring consistency in nomenclature (e.g., score versus
    bisect) and labeling; and (3) providing information through product labeling or other means to
    healthcare providers.

    Public summaries of the Drug Safety Oversight Board meetings are available at
    www.fda.gov/AboutFDA/CentersOffices/CDER/ucm082136.htm.
    5
    Na Zhao et al., 30 November 2010, 401(1-2), Tablet Splitting: Product quality assessment of metoprolol succinate
    extended release tablets, International Journal of Pharmaceutics.
    6
    Rakhi Shah et. al., 26 August 2010, Tablet Splitting of a Narrow Therapeutic Index Drug: A Case with
    Levothyroxine Sodium, AAPS PharmSciTech.
    7
    Geoff Green et al., November-December 2009, 35(6), Pharmacopeial Standards for the Subdivision
    Characteristics of Scored Tablets, Pharmacopeial Forum.

    Contains Nonbinding Recommendations


    A. Guidelines and Criteria
    Below are guidelines and criteria by which a scored tablets characteristics will be evaluated as
    part of the review process:
    1. The dosage amount meant to be achieved after splitting the tablet should not be below
    the minimum therapeutic dose indicated on the approved labeling.
    2. The split tablet should be safe to handle and not pose risk of unintended drug
    exposure.
    3. Modified release products for which the control of drug release can be compromised
    by tablet splitting should not have a scoring feature.
    4. The split tablet, when stored in pharmacy dispensing containers (no seal/no
    desiccant), should demonstrate adequate stability for a period of 90 days at 25 C,
    plus or minus 2 C/60 percent Relative Humidity (RH), plus or minus 5 percent RH.
    5. The split tablet portions should meet the same finished-product testing requirements
    as for a whole-tablet product with equivalent strength. A risk assessment should be
    provided to justify the tests and criteria for product with the proposed functional
    scoring. The resulting data should be provided to the Agency for evaluation. The
    assessment should be undertaken on both tablets that are split nonmechanically (by
    hand) and tablets that are split mechanically (with a tablet splitter). Any
    recommended dissolution test data must be generated on a minimum of 12 individual
    split tablet portions.
    Below are the typical criteria, by dosage form, that should be assessed during
    Pharmaceutical Development (3.2.P.2.) of NDAs and ANDAs and during
    primary/exhibit stability batches and scale-up. As indicated above, a risk assessment
    should be performed to justify criteria for each product.
    New products that do not meet the criteria should not have a scoring feature or any
    reference to scoring (including language such as bisected, etc.) in the labeling.
    a. Immediate Release Solid Oral Dosage Forms

    USP General Chapter <905> Uniformity of Dosage Units - Testing for Weight
    Variation is permitted for split tablet portions intended to contain 25 mg or
    more of a drug substance that comprises 25 percent or more (by weight) of the
    split tablet portion. Otherwise, the test for Content Uniformity should be
    used. 8

    For the purpose of this guidance, each split portion of a whole tablet is considered a unit of dose and should meet
    the uniformity of dosage unit requirement.

    Contains Nonbinding Recommendations

    Tablet splitability at both ends of the proposed hardness range should be


    demonstrated by:
    1. Testing 15 tablets to ensure a loss of mass of less than 3.0 percent
    between the individual segments (30 for bisected tablets, 45 for
    trisected tablets, etc.) when compared to the whole tablet. The
    resulting data for each tablet should be provided to the Agency for
    evaluation.
    2. Confirming that the split tablet portions meet the USP Friability
    requirement. 9

    Dissolution data on split tablet portions should meet finished-product release


    requirements.

    b. Modified Release Solid Oral Dosage Forms (Using Matrix Technology)

    All above criteria under section III.A.5.a should be met.

    Dissolution should be demonstrated at both ends of the hardness range.

    Dissolution on whole versus split tablet portions should meet the similarity
    factor (f2) criteria. 10

    c. Modified Release Solid Oral Dosage Forms (Using Compressed Film Coated
    Components)

    All above criteria under sections III.A.5.a and III.A.5.b should be met.

    Dissolution profile on pre-compressed beads versus post-compressed whole


    and split tablet portions should meet similarity factor (f2) criteria to ascertain
    the integrity of beads during compression.

    See USP General Chapter <1216> Tablet Friability.


    See the guidance for industry on Dissolution Testing of Immediate Release Solid Oral Dosage Forms, August
    1997. We update guidances periodically. To make sure you have the most recent version of a guidance, check the
    FDA Drugs guidance page at
    www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

    10

    Contains Nonbinding Recommendations


    6. Scoring configuration of generic drug products should be the same as the RLD. 11

    Where the scoring configuration is protected by patent, contact the Office of


    Generic Drugs for guidance.

    For scoring configurations proposed for abbreviated applications that were


    accepted through the suitability petition process, contact the Office of Generic
    Drugs for guidance.

    7. An evaluation of the tablet splitability should be provided during the postapproval


    period for any product changes at Level 2 and Level 3 as defined in the Agencys
    Scale-up and Post-Approval Changes (SUPAC) guidances. 12
    B. Nomenclature and Product Labeling
    New products that meet the above-referenced criteria can be labeled as having functional
    scoring. Such labeling should appear in all of the following sections of the prescribing
    information 13:

    Dosage Forms and Strength section of the Highlights.


    Dosage Forms and Strength section of the Full Prescribing Information.
    How Supplied section of the Full Prescribing Information.

    For currently marketed products, manufacturers have the option to perform such an assessment
    and provide data for evaluation to the drug product application. Product labeling should be
    updated to state that it has functional scoring. In this way, the use of the term functional scoring
    in the labeling can communicate to healthcare providers that the product has been evaluated
    against the established criteria.

    11

    See the Manual of Policies and Procedures on Scoring Configuration of Generic Drug Products (5223.2),
    November 1, 1995, for information on what should happen if a change is made to the RLD.
    12
    Go to www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064979.htm for a listing
    of all SUPAC guidances.
    13
    See 21 CFR 201.57(a)(8) and 201.57(c)(4)(ii).

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