Guidance For Industry Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation with Regulatory Requirement for Other Regulated Market.«TABLE OF CONTENTS, > INTRODUCTION > BACKGROUND > DISCUSSION 1. Guidelines and Criteria 2. Nomenclature and Product Labeling > AS PER EUROPEAN PHARMACOPEIA > HEALTH CANADA REQUIREMENT > QUESTION & ANSWERS FOR SCORING AS PER GUIDANCE > REFERENCES|. 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. > Specifically, this guidance recommends: > Guidelines to follow, data to provide, and criteria to meet J and detail in an application to support approval of a scored \ tablet. Nomenclature and labeling for approved scored tablets.vee DEEINITION ay » Ascore 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. Unscored tablet Scored tabletIl. BACKGROUND > Why is it required ? When determining whether a generic drug product is the same as the reference listed drug (RLD), i.e. One characteristic of a tablet dosage form is that it may be manufactured with a score or scores. (Quality target Product Profile) 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. 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. , “ib it.Sake bse Quty 5222 Pht Dene Suc aa [ecarae | tee [ee eae Seti feat sp nth dy Tn devises Vent Serial |" Vtryn eid epi om ly, sia atic ey ie icajamte | |store pcr sone sia cpr ci empeceiaed cn oa etek Se seein cinema eestor - |snfgrsin_|Ueomnt 58 cigars ial act ni Sa ea apenas TaN tiaiy [amines | [IRresdmnmgeinntncimet ota cco mt sso messes es ncteenign | sur [ssc megmetermat dbenendcp tan sin | Sat cpa aes ae Poe ae ie pmereatis | og (tran anbe nctnan 5 nr aera ares a Raa eerie ntl | to [pena meade aCe ra god =F fess aia nace a sivas | hina ina ii: Onin cr hen COA cating Sey, rn ve an mci aware —_[ Dean ties ena penance pe Dl Se tUR oy Soe. Swe | cee de peers dredges ep Feet, aes GAs lng cme ote ioe ee(ele BACKGROUND > The Agency’s concerns ? ‘Agency concluded that in some cases, there are possible safety issues, especially when tablets are not scored or evaluated for splitting. Splitting tablet included variations in the i. Tablet content (Content Uniformity), 4. Weight (Weight Variation), si, 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.4) 2 2 IIL DISCUSSION Criteria for functional scoring on solid oral dosage form products to ensure the quality of both NDA and ANDA scored tablet products can be evaluated and labeled by: Providing a harmonized approach to chemistry, manufacturing, and controls (CMC) reviews of scored tablets. Ensuring consistency in nomenclature (e.g., score versus bisect) and labeling. Providing information through product labeling or other means to healthcare providers.veil A Guidelines and Coterias, Below are guidelines and criteria by which a scored tablet’s characteristics will be evaluated as part of the review process: ‘The dosage amount meant to be achieved after splitting the tablet should nat be below the minimam therapeutic dose indicated on the approved labeling. ‘The split tablet shoud he safe to handle and not pose risk of unintended drug expire Modified release products for which the contral of drug release can be compromised by tablet splitting should not have a scoring feature. ‘The split tablet, when stored in pharmacy dispensing containers (no seal/no desiccant), should demonstrate adequate stability fora period of 90 days at 25°C, plus or minus 2° C/60 percent Relative Humidity (RK, plus or minus 5 percent RH. ‘The split tablet portions should meet the same finshed-product testing requirements as for a whole-tablet product with equivalent strength. Arisk assessment should be provided to justify the tests and criteria for product with the proposed functional coring 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 minim of 12 Individua Spit tablet portions.‘y Wethod 3 Incest nteneeingesition | age edn theta downer nasaUSP General chapter <905> Uniformity of Dosage Units “Tablet stability at both ends ‘of the proposed hardness range should be demonstrated by [Tablets spt ronmechanicaly (by hard) and pl mechani (with 3 {able splitter Dissolution Ill. A. Guidelines and Criteria Below are typical criteria: Here each spit portion of a whole tablet is considered Uni of dove and should meet the uniformity of dosage unit requirement. “Testing for Weight Variation permitted for split tablet portions intended to contain 25 mor mare ofa Sng Substance that comprises 25 percent or more (by weieht) of the split tablet portion. Otherwise, the test for Content Uniformity shoul be used, 1. Testing 15 tablets to ensure a loss of mass of less than 3.0 percent between the iniveual segments (30 for bisected tablets, 45 fr tnsected tablets, et.) when compared wo use whale tablet, The cesulteg data for teach tablet should be provided to the agency for valuation 2. Confirming thatthe sit tablet portions meet the USP Frinbility requirement «NAT 16/¥) Dissclution data on split tablet partons should meet fished: product release recuireents, Allertera same as under section TiLA.S.a should be met. Allerteria same asunder section LAS should be met. 1. Dissolution should be demonstrated at both ends of thehardness range 2. Disaiution on wile versus spit tablet portions should meet the silty factor 2) catera, All above critena under sections TILA.S.a and IN-A.S.b should be met Allabove enter under sections MAS. and Il AS sul be met. Dissolution profile on pre-comtpressed beads verse pot-conpresed whole land spit tablet portions should meet simanty factor (f2) criteria to ascertain the integrity of beads during ‘comptesion._ IIL. A. Guidelines and Criteria _ Scoring configuration of generic drug products should be the same as the RLD. 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. 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 Agency’s Scale-up and Post-Approval Changes (SUPAC) guidances.Ill. 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 “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. Functional scoring used in the labeling can communicate to healthcare providers that the product has been evaluated against the established criteria.> Same as for “US-FDA Guidance For Industry Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation” > Refer to “Quality (Chemistry and Manufacturing) Guidance: New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs), Page no. 46 - 47”QUESTION & ANSWERS FOR SCORING AS PER GUIDANCE 023: How many batches of drug product should be tested for split-portions of scored tablets? A23: In general, one batch testing for each scored strength on the split tablets will sulice, as recommended in the guidance for industy, Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation. Reference: Guidance for Industry ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers, May 2014 , Page no. 15 8. Scoring and Conditions of Use Q29: Will FDA RTR an ANDA containing « statement that the score mark is non- funetional? ‘The scoring configuration of a generic drug product generally should be the same as the RLD to demonstrate that the test product can be administered in a manner consistent with the dosing recommendations of the RLD. An applicant should include a comparison of the test product to the RLD for any proposed scoring configuration of the generic drug product. FDA will RTR an ANDA that contains as justification an applicant's statements that the score mark is non-functional when the RLD labeling contains dosing recommendations consistent with the dose delivery enabled by the score mark. Reference: ANDA Submissions - Refuse-to-Receive Standards: Questions and Answers Guidance for Industry, DRAFT GUIDANCE , October 2017 , Page no. 17es REFERENCES ey) Guidance for Industry Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation, March 2013, Page no. 1 - 5 ‘Quality by Design for ANDAs: An Example for Immediate-Release Dosage Forms, Page no. 10-11 Quality (Chemistry and Manufacturing) Guidance: New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs), Page no. 46 - 47 Guidance for Industry ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers, May 2014 , Page no. 15 ANDA Submissions - Refuse-to-Receive Standards: Questions and Answers Guidance for Industry. DRAFT GUIDANCE , October 2017 , Page no. 17Thanks for your attention...!!! Any Queries ??"Our Werk Is The Presentation Of Our Capabilities"