CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
`214187Orig1s000
`PRODUCT QUALITY REVIEW(S)
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`C1 Approval with Post-Marketing Commitment L1 Complete Response
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`RECOMMENDATION
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`Approval
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`NDA # 214187
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`Assessment # 1
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`[Strength|150/37.5mgand200/50mgCd
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`[Applicant—sGilead
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`|USagent,ifapplicable|
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`Senmestone)
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`Assessed
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`DocumentDate
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`12/15/2020
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`1/8/2021
`1/22/2021
`1/28/2021
`2/23/2021
`3/26/2021
`4/20/2021
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`Discipline(s) Affected
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`[Quality
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`QUALITY ASSESSMENT TEAM
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`|_—Discipline__—'|_—-PrimaryAssessor|SecondaryAssessor__|
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`5/06/2021
`Laboratory(OTR)|==NA|
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`|_-Microbiology|NA
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`Biopharmaceutics
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`Process Manager
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`Lead
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`Reference ID: 4799528
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`QUALITY ASSESSMENT
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`|Environmental=|NA
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`OPQ-XOPQ-TEM-0001v07
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`Page 2
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`

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`LDSL.2)
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`QUALITY ASSESSMENT
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`For more details about the items in this template, please see the Quality
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`Assessment Data Sheet chapter of the NDA IQA Guide
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`1. RELATED/SUPPORTING DOCUMENTS
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`A. DMFs:
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`DMF # Assessment|CommentsType Holder noe
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`Referenced
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`an
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`i
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`Date
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`Completed
`Refer to DP
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`review for
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`assessment
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`of container
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`closure
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`system
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`B. OTHER DOCUMENTS: IND, RLD, RS, Approved NDA
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`OtherNAT
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`|Document Application Number Description
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`[—aacone|sen|Reon
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`NDA
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`204671
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`208341
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`18605
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`Sovaldi
`Epclusa
`Epclusa
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`2. CONSULTS
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`Biostatistics
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`Pharmacology/Toxicology
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`INA
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`Refer to pharm/tox
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`review
`CDRH
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`[NANA LT
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`|ClinicalNAT
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`EXECUTIVE SUMMARY
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`For more details about the items in this template, please see the Executive
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`Summary chapter of the NDA IQA Guide
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`OPQ-XOPQ-TEM-0001v07
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`Page 3
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`(b) (4)
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`(b) (4)
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`QUALITY ASSESSMENT
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`I.
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`RECOMMENDATIONS AND CONCLUSION ON APPROVASBILITY
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`The NDA, as amended, has provided adequate CMCinformation to
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`assurethe identity, strength, purity, and quality of the proposed drug
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`product. Therefore, this NDA is recommendedfor approval by the Office
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`of Pharmaceutical Quality (OPQ). The manufacturing and testing facilities
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`for this NDA are deemed acceptable and an overall “Approve”
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`recommendation was entered into Panorama on 04/27/2021.
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`ll.
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`SUMMARY OF QUALITY ASSESSMENTS
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`A. Product Overview
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`The proposed productis the pediatric oral pellet formulation of Epclusa
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`(sofosbuvir and velpatasvir tablets), which was approved under NDA
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`208341 in 2016. The proposed productis indicated for the treatment of
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`Hepatitis C Virus (HCV)in pediatric patients 3 years of age and older, and
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`will be available in two strengths: 200 mg/50 mg and 150 mg/37.5 mg
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`(sofosbuvir/velpatasvir). The labeling describes that the oral pellets should
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`not be chewed, and should be administered by sprinkling the pellets on
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`one or more spoonfulls of non-acidic soft food at or below room
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`temperature and taken within 15 minutes. The examplesin the labeling
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`include pudding, chocolate syrup and ice cream.
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`Proposed
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`Indication(s)
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`including Intended
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`Patient Population
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`Duration of
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`Treatment
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`Maximum Daily Dose
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`Alternative Methods
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`of Administration
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`®® in adult and pediatric
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`Treatment of
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`patients
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`12 weeks
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`400 mg/100 mg sofosbuvir/velpatasvir
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`None
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`B. Quality Assessment Overview
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`Drug Substance: Adequate
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`The drug substance information for sofosbuvir and velpatasvir are
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`referenced to Gilead’s previously approved NDA 204671 and NDA
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`208341, respectively. For sofosbuvir, the retest period is
`(j) months when
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`stored at
`()°C. For velpatasvir, the retest period is
`{@} months when
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`stored below [)°C.
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`Ph.D.
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`This NDA is recommendedfor approval from a drug substance
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`perspective. For additional details, refer to the review by Rohit Tiwari,
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`OPQ-XOPQ-TEM-0001v07
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`Page 4
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`(b) (4)
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`(b)
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`(b)
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`(b)
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`(b)
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`QUALITY ASSESSMENT
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`Drug Product: Adequate
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`Sofosbuvir/velpatasvir (SOF/VEL) oral pellets are an immediate-release,
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`® dosage form available as unit-dose packets containing
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`either 150 mg of SOF and 37.5 mg of VEL (SOF/VEL, 150/37.5 mg) or
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`200 mg of SOF and 50 mg of VEL (SOF/VEL, 200/50 mg). Velpatasvir is
`amorphous and sofosbuvir aut)aoeeeis crystalline
`on),
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`Oe)
`” XRPD data collected on SOF/VEL
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`®/pellets in the selected commercial formulation supports the
`oral
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`physical stability of both APIs after manufacturing and upon storage under
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`accelerated conditions.
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`The results from the in-use compatibility studies showedthat the oral
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`pellets are chemically stable after exposure to non-acidic soft foods for up
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`to 30 mins in chocolate pudding and ice cream, and up to 60 min in
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`chocolate syrup. This supports the proposed in-use time of 15 min at
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`room temperature after exposure to non-acidic soft foods as described in
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`current PI. Satisfactory results from 12 months of long term stability data
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`(at 30°C/75% RH) and 6 months of accelerated stability data at 40
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`°C/75% RHfor the three primary stability batches (_
`”’® scale) supports
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`the proposedshelf-life of 24 months for both strengths.
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`The applicant has submitted a claim of categorical exclusion including a
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`statement of no extraordinary circumstances. The categorical exclusion
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`cited at 21 CFR 25.31(d) and 21 CFR 25.31(b) is appropriate for this
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`application, and is acceptable.
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`This NDA is recommendedfor approval from a drug product perspective.
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`For additional details, refer to the review by Hailin (Sheena) Wang, Ph.D.
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`Labeling: Adequate
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`Labeling recommendations have been communicated to the OND PM.
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`Manufacturing: Adequate
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`(©) 4)
`In the drug product manufacturing process, Velpatasvir
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`is manufactured via the same route described for the
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`approved Epclusatablets.
`(b) (4)
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`drug product. The drug product is packaged in unit dose sachets.
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`OPQ-XOPQ-TEM-0001v07
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`Page 5
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`QUALITY ASSESSMENT
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`The manufacturing and testing facilities for this NDA are deemed
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`acceptable and an overall “Approve” recommendation was enteredinto
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`Panorama on 04/27/2021. There are no recommendations atthis time for
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`a post-approval inspection.
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`This NDA is recommendedfor approval from a Manufacturing
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`perspective. For additional details, refer to the review by Brijeshkumar
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`Vaghasia, Ph.D.
`perspective. For additional details, refer to the review by Mei Ou, Ph.D.
`Acceptable
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`Biopharmaceutics: Adequate
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`The Biopharmaceutics Review focused on the evaluation of (1) the in vitro
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`dissolution method and acceptancecriteria as a quality control (QC) test
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`for the proposed drug product, (2) the in vitro dissolution profiles of the
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`proposed drug product mixed with various soft foods, (3) the need for
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`bridging. The dissolution method and acceptancecriteria (Q= {}% in 15
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`minutes for Sofosbuvir Q = (}% in 30 minutes for Velpatasvir) are
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`acceptable as the QCtest for the proposed drug product. The dissolution
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`data are also supportive for the administration of the product in the
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`labeled soft foods. The NDA included a PK bridge between the Epclusa
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`pellets and Epclusa tablets. From a Biopharmaceutics perspective, no
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`additional bridging is needed between the pivotal clinical trial product and
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`the proposed commercial product (e.g. same formulation, manufacturing
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`process, manufacturing site, and comparable dissolution profiles).
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`This NDA is recommendedfor approval from a Biopharmaceutics
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`Microbiology(if applicable): N/A
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`C. Risk Assessment
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`From Initial Risk Identification
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`Piaberhce naliniekelee
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`can impact
`Ranking
`Mitigation
`COA
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`the CQA
`Approach
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`Assay
`Low
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`Final Risk ae
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`Evaluation Considerations/
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`Comments
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`OPQ-XOPQ-TEM-0001v07
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`Page 6
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`(b)
`(4)
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`(b)
`(4)
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`

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`Physical
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`State
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`QUALITY ASSESSMENT
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`Medium
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`®® Acceptable
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`Microbial
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`Limits
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`Acceptable
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`Acceptable
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`_ |of Content
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`Dissolution
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`Medium
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`The test
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`method and
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`acceptance
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`criteria were
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`found
`acceptable
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`Uniformity
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`Medium
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`Acceptable
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`D. List of Deficiencies for Complete Response
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`1. Overall Quality Deficiencies (Deficiencies that affect multiple sub-
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`disciplines)
`None
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`2. Drug Substance Deficiencies
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`3. Drug Product Deficiencies
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`4. Labeling Deficiencies
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`OPQ-XOPQ-TEM-0001v07
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`Page 7
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`(b) (4)
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`

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`QUALITY ASSESSMENT
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`5. ae Deficiencies
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`6. Biopharmaceutics Deficiencies
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`7. Microbiology Deficiencies
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`8. Other Deficiencies aaa such asa
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`Application Technical Lead Name and Date
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`Erika E. Englund, Ph.D. 5/21/2021
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`OPQ-XOPQ-TEM-0001v07
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`Page 8
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`

`

` QUALITY ASSESSMENT
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`APPEARSTHIS WAY ON ORIGINAL
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`OPQ-XOPQ-TEM-0001v07
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`Page 9
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`APPEARS THIS WAY ON ORIGINAL
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`

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`49 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
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`

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`QUALITY ASSESSMENT
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`CHAPTER IV: LABELING
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`For more details about the items in this template, please see Chapter IV
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`(Labeling) of the NDA IQA Guide
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`NDA 214817
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`1.0 PRESCRIBING INFORMATION
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`Assessmentof Product Quality Related Aspects of the Prescribing
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`Information:
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`1.1 HIGHLIGHTS OF PRESCRIBING INFORMATION (as revised in SD10 on
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`04/14/21)
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`Items in Proposed
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`Labeling
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`(choose “Adequate”,
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`“Inadequate”, or “N/A”)
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`Assessor’s Comments
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`(If an item is Inadequate, provide more details on
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`the issues, as appropriate)
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`ProductTitle in Highlights
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`Established name(s)!
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`Adequate
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`Dosageform “oral pellets” is consistent
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`with OPPQ’s recommendation for the
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`approved Harvoni (ledipasvir/sofosbuvir)
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`oral—————in NDA 212477 by Gilead.
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`Route(s) of administration gths Heading in Highli=
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`Adequate
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`salt, clearly state whether the
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`Summary of the dosage
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`form(s) and strength(s) in
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`metric system
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`Assess if the tablet is scored.
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`If product meets guidelines
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`and criteria for a scored
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`tablet, state “functionally
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`scored”.
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`For injectable drug products
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`for parental administration,
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`use appropriate package
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`type term (e.g., single-dose,
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`multiple-dose, single-patient-
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`use). Other package terms
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`include pharmacy bulk
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`package and imaging bulk
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`package.
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`an active ingredient that is a
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`N/A
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`eeIf the drug product contains
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`' Established name = [Drug] [Route of Administration] [Dosage Form]
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`OPQ-XOPQ-TEM-0001v07
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`Page 1
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`10 mg of drug-x) or active
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`QUALITY ASSESSMENT
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`strength is based on the
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`active moiety (e.g., Tablets:
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`1.2 FULL PRESCRIBING INFORMATION
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`issues, as appropriate)
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`1.2.1 Section 2 (DOSAGE AND ADMINISTRATION)
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`Items in Proposed
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`Assessor’s Comments
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`Labeling
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`(If an item is Inadequate, provide more details on the
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`(choose “Adequate”,
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`'TSACEAMDAUMMNSIRAUONSediGnor “N/A”)
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`|[DOSAGE AND ADMINISTRATION section——s—aeses—‘“‘“‘i;i‘i;;
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`Special instructions for
`Adequate
`Soft-food compatibility data provided in
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`product preparation (e.g.,
`3.2.P.2. supports the proposedin-use time of
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`reconstitution and resulting
`15 min after mixing with non-acid soft foods
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`concentration, dilution,
`at or below room temperature.
`compatible diluents,
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`storage conditions needed
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`to maintain the stability of
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`the reconstituted or diluted
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`product)
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`Important administration
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`instructions supported by
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`product quality information
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`(e.g., do not crush or chew
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`extended-releasetablets,
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`instructions for mixing with
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`food)
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`For parenteral products:
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`include statement:
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`“Parenteral drug products
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`mustbe inspected visually
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`for particulate matter and
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`discoloration prior to
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`administration, whenever
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`solution and container
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`permit”
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`If there is a USP
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`monograph for the drug
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`productand it contains a
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`labeling requirement,
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`ensure the labeling
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`requirement is fulfilled.
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`Note the labeling
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`requirement may be
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`Adequate
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`“Do not chew” statementis included to avoid
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`bitter aftertaste due to sofosbuvir. Mixing
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`with food is recommended and is supported
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`by product quality data.
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`OPQ-XOPQ-TEM-0001v07
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`Page 2
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`“OSHA Hazardous Drugs”.
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`QUALITY ASSESSMENT
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`applicable to another
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`section of the PI (e.g.,
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`Section 11).
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`For radioactive products,
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`include radiation dosimetry
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`for the patient and
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`healthcare practitioner(s)
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`who administer the drug
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`For hazardous products,
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`include the statement
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`“DRUG X is a hazardous
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`drug. Follow applicable
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`special handling and
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`disposal procedures.” with
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`xX numerical citation to
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`OPQ-XOPQ-TEM-0001v07
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`Page 3
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`QUALITY ASSESSMENT
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`Item
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`Assessor’s Comments
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`(If an item is Inadequate, provide more details
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`on the issues, as appropriate)
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`1.2.2 Section 3 (DOSAGE FORMS AND STRENGTHS)
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`Items in Proposed
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`Labeling
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`(choose “Adequate”,
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`“Inadequate”, or “N/A”)
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`DOSAGE FORMS AND STRENGTHS section
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`Available dosage form(s)
`Adequate
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`package.
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`Dosage form “oral pellets” is consistent
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`with OPPQ’s recommendation for the
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`approved Harvoni
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`(ledipasvir/sofosbuvir) oral pellets in
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`NDA 212477 by Gilead.
`in metric system PO
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`Strength(s)
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`If the active ingredientis a salt,
`N/A
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`apply the USP Salt Policy per FDA
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`Guidance. Clearly state whether
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`the strength is based on the active
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`moiety (e.g., Tablets: 10 mg of
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`drug-x) or active ingredient
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`(Tablets: 10 mg of drug-x
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`hydrochloride
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`A description of the identifying
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`characteristics of the dosage
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`forms, including shape, color,
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`coating, scoring, imprinting, and
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`color and clarity of the solution,
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`when applicable
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`Assessif the tablet is scored. If
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`product meets guidelines and
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`criteria for a scored tablet, state
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`“functionally
`scored’
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`For injectable drug products for
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`parental administration, use
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`appropriate package type term
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`(e.g., single-dose, multiple-dose,
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`single-patient-use). Other package
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`type terms include pharmacy bulk
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`package and imaging bulk
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`Adequate
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`The applicant accepted the
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`recommendedaddition of “film-coated”
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`to the description of the oral pellets.
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`N/A
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`N
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`/A
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`OPQ-XOPQ-TEM-0001v07
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`Page 4
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`

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`QUALITY ASSESSMENT
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`Section 11 (DESCRIPTION)
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`Items in Proposed
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`Labeling
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`(choose “Adequate”,
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`“Inadequate”, or “N/A”)
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`Assessor’s Comments
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`(If an item is Inadequate, provide more details
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`on the issues, as appropriate)
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`Item
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`/A
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`DESCRIPTION section
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`name(s
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`Dosage form(s) and route(s) of
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`administration
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`If the active ingredientis a salt,
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`apply the USP Salt Policy and
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`include the equivalency
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`statement per Salt Guidance
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`and MAPP. For example:
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`“TRADENAME contains 100 mg
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`of drug-x (equivalent to 123.7
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`List namesofall inactive
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`ingredients. Use USP/NF
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`namesin alphabetical order.
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`Avoid brand names.
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`For parenteral injectable
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`dosage forms, include the name
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`and quantities of all inactive
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`ingredients. For ingredients
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`addedto adjust the pH or make
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`isotonic, include the name and
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`statement of effect.
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`If alcohol is present, must
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`provide the amountof alcohol in
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`terms of percent volume of
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`absolute alcohol
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`Sterility statement(if applicable)
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`class
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`Chemical name, structural
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`formula, molecular weight
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`If radioactive, statement of
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`important nuclear
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`characteristics.
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`Other important chemical or
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`physical properties (Such as
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`pKa or pH)
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`N/A
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`Adequate
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`Inactive ingredients used for
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`core and film-coating of the oral pellets
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`are separately listed which are
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`consistent with information provided in
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`N
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`/A
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`N
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`/A
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`N
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`N
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`/A
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`N
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`provided for the Epclusa tablet product
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`Remains the same as previously
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`provided for the Epclusa tablet product
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`OPQ-XOPQ-TEM-0001v07
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`Page 5
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`(b) (4)
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`

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`the issues, as appropriate)
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`QUALITY ASSESSMENT
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`Items in Proposed
`
`Labeling
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`(choose “Adequate”,
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`“Inadequate”, or “N/A”)
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`Assessor’s Comments
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`(If an item is Inadequate, provide more details on
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`For oral prescription drug
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`products, include gluten
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`statement (if applicable
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`Removestatements that may
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`be misleading or promotional
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`(e.g., “synthesized and
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`developed by Drug Company
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`X,” “structurally unique
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`molecular entity”
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`If there is a USP monograph
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`for the drug product andit
`
`
`
`contains a labeling
`
`
`requirement, ensure the
`
`
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`labeling requirementis
`
`
`
`fulfilled. Note the labeling
`
`
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`requirement may be
`
`
`
`applicable to another section
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`
`
`
`
`(e.g., Section 2).
`of the PI
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`OPQ-XOPQ-TEM-0001v07
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`Page 6
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`

`

`QUALITY ASSESSMENT
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`Item
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`Assessor’s Comments
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`(If an item is Inadequate, provide more details on
`:
`:
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`the issues, as appropriate)
`
`
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`/A Special handling about the
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`1.2.4 Section 16 (HOW SUPPLIED/STORAGE AND HANDLING)
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`
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`Items in Proposed
`
`Labeling
`a
`
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`(choose “Adequate”,
`“Inadequate”, or “N/A”)
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`
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`
`
`
`HOW SUPPLIED/STORAGE AND HANDLING section
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`
`Both tablets and oral pellets are listed
`Available dosage form(s)
`Adequate
`in metric system PC
`
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`
`
`
`Strength(s)
`
`
`
`
`
`Available units (e.g., bottles
`Adequate
`
`
`
`of 100 tablets
`
`
`
`
`Identification of dosage forms
`
`
`
`
`(e.g., shape, color, coating,
`
`
`
`scoring, imprinting, and color
`
`
`
`
`
`and clarity of the solution,
`
`
`
`when applicable); Include
`
`NDC(s
`
`
`
`
`
`Assess if the tablet is scored.
`
`
`
`
`If product meets guidelines
`
`
`
`
`
`and criteria for a scored
`
`
`tablet, state “functionally
`
`scored”
`
`
`
`For injectable drug products
`
`
`
`for parental administration,
`
`
`
`use appropriate package
`
`
`
`
`type term (e.g., single-dose,
`
`multiple-dose, single-patient-
`
`
`
`
`use). Other package terms
`
`
`
`include pharmacy bulk
`
`
`
`package and imaging bulk
`
`package.
`
`
`
`
`supplied product(e.g.,
`
`
`
`protect from light,
`
`
`
`
`
`refrigerate). If there is a
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`statement to “Dispensein
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`original container,” provide
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`reason why(e.g., to protect
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`
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`from light or moisture, to
`
`
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`maintain stability, etc.). For
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`
`
`hazardous drugs, state
`
`
`
`
`
`“DRUGXis a hazardous
`
`
`
`drug. Follow applicable
`
`
`
`special handling and disposal
`
`
`
`procedures.”” with x
`
`
`
`numerical citation to “OSHA
`
`
`Hazardous Drugs.”
`
`Adequate
`
`
`
`
`
`
`
`The applicant accepted the
`
`
`
`
`
`recommendedaddition of “film-coated” to
`
`
`
`
`
`
`the description of the oral pellets.
`
`
`
`N/A
`
`
`
`N
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`
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`OPQ-XOPQ-TEM-0001v07
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`Page 7
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`
`

`

`QUALITY ASSESSMENT
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`Section 16 (HOW SUPPLIED/STORAGE AND HANDLING) (Continued)
`
`
`
`
`Assessor’s Comments
`Items in Proposed
`
`Labeling
`(If an item is Inadequate,
`
`
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`(choose “Adequate”,
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`issues, aS appropriate)
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`Adequate
`Consistent with storage
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`Storage conditions. Where applicable,
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`Latex: If product does not contain latex
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`natural rubberlatex, state: “Not made
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`with natural rubberlatex. Avoid
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`resistant packaging
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`aise
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`1.2.5 Other Sections of Labeling
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`There may be other sections of labeling that contain product-quality related
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`information. For example, there are specific required/recommended warnings for
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`certain inactive ingredients [e.g., aspartame, aluminum in large and small volume
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`parenterals, sulfites, FD&C Yellow Number5 (tartrazine), and benzyl alcohol].
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`Please notify the prescription drug review division if the product contains any of
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`Please include your comments about other sections of labeling if they contain
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`1.2.6 Manufacturing Information After Section 17 (for drug products)
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`Items in Proposed
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`Labeling
`(choose “Adequate”
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`“Inadequate”, or “N/A”)
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`Manufacturing Information After Section 17
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`Name and location of
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`business(street address,
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`city, state, and zip code) of
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`the manufacturer, distributor,
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`and/or packer
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`Assessor’s Comments
`(If an item is Inadequate, provide more details on
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`the issues, as appropriate)
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`OPQ-XOPQ-TEM-0001v07
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`Page 8
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`1 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
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`(b) (4)
`
`

`

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`Assessor’s Comments about
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`Carton Labeling
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`(If an item is Inadequate, provide more
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`details on the issues, as appropriate)
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`Thefont of the established name
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`appearsto beat least half as large
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`proprietary name. The propriety
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`name and established name
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`appear to have the same
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`prominence.
`PO
`PO
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`QUALITY ASSESSMENT
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`Items in Proposed
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`Labeling
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`(choose “Adequate”,
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`Adequate
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`Established name®, (font size and
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`prominence (21 CFR
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`201.10(g)(2))
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`Ad
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`N/A
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`Adequate
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`trength(s)
`in metric system
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`Route(s) of administration
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`If the active ingredientis a salt, include
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`the equivalency statement per Salt
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`Guidance and MAPP.
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`Net contents ((21 CFR
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`201.51(a) e.g., tablet count, volume of
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`carton labels
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`carton labels
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`carton labels
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`Not present on container labels but
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`Adequate
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`Storage conditions. If applicable,
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`include a space on the carton labeling
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`for the user to write the new beyond-
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`For injectable drug products for
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`parental administration, use appropriate
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`packagetype term (e.g., single-dose,
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`multiple-dose, single-patient-use).
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`Other package terms include pharmacy
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`bulk package and imaging bulk
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`“Not for direct infusion” statement.
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`For parenteral injectable dosage forms,
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`include the name and quantities ofall
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`active and inactive ingredients in
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`alphabetical order. For ingredients
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`addedto adjust the pH or make
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`isotonic, include the name and
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`statement of effect.
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`N/A
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`3 Established name = [Drug] [Route of Administration] [Dosage Form]
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`And others, if space is available.
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`If there is a Medication Guide, must
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`include a statement about dispensing
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`a Medication Guide to each patient.
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`No text on Ferrule and Cap overseal,
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`unless a cautionary statementis
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`required.
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`If there is a USP monograph for the
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`drug product and it contains a labeling
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`requirement, ensure the labeling
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`requirement ts fulfilled.
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`Whena drug productdiffers from the
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`relevant USP standard of strength,
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`quality, or purity, as determined by the
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`application of the tests, procedures,
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`and acceptancecriteria set forth in the
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`relevant compendium, its difference
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`shall be plainly stated on its label.
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`rep
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`QUALITY ASSESSMENT
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`If alcohol is present, must provide the
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`amountof alcohol in terms of percent
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`volume of absolute alcohol
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`Linear Bar code
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`Adequate
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`Items in Proposed
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`Labeling
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`(choose “Adequate”,
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`“Inadequate”, or “N/A”)
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`Assessor’s Comments about
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`Carton Labeling
`(If an item is Inadequate, provide more
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`details on the issues, as appropriate)
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`Assessment of Carton and Container Labeling: {Adequate}
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`The container and carton labels for both 150mg/37.5mg and 200mg/50mg
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`presentations are adequate.
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`ITEMS FOR ADDITIONAL ASSESSMENT
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`None
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`Overall Assessment and Recommendation:
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`Adequate
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`OPQ-XOPQ-TEM-0001v07
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`Page 12
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`QUALITY ASSESSMENT
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`Primary Labeling Assessor NameandDate:
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`Hailin (Sheena) Wang, Ph.D.
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`04/19/2021
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`Secondary Assessor Name and Date (and Secondary Summary, as needed):
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`ThomasF. Oliver, Ph.D.
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`9/21/2021
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`OPQ-XOPQ-TEM-0001v07
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`Page 13
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`Effective Date: April 22, 2021
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`Reference ID: 4799528
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`79 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
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`QUALITY ASSESSMENT
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`CHAPTER VI: BIOPHARMACEUTICS
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`Secondary Reviewer: Elsbeth Chikhale, Ph.D.
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`NDA:214187-ORIG-1 [505(b)(1)]
`Drug Product Name/Strength: Epclusa® (Sofosbuvir/Velpatasvir) Oral Pellets, 150
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`mg/37.5 mg and 200 mg/50 mg
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`Route of Administration: Oral
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`Proposed Indication: For the treatment of hepatitis C virus (HCV)infection in
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`pediatric patients 3 years of age and older
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`Applicant Name: Gilead Sciences, Inc.
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`Submission Date: 12/15/2020, 01/28/2021, 02/23/2021
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`Primary Reviewer: Mei Ou, Ph.D.
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`EXECUTIVE SUMMARY
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`The proposed drug product, Epclusa® (Sofosbuvir/Velpatasvir, SOF/VEL)OralPellets,
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`150 mg/37.5 mg and 200 mg/50 mg,is an immediate-release dosage form. Each
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`SOF/VELpellet is approximately 2 mm in diameter. SOF/VELpellets are packaged into
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`© packets. The 150 mg/37.5
`mgstrength contains (j) counts and the 200 mg/50 mgstrength contains ©counts of
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`SOF/VELoral pellets in each unit-dose packet. In the proposed labeling, the
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`recommendeddosagein pediatric patients 3 years
`® of age is based on
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`body weight, as 400 mg/100 mg SOF/VEL for children weighing = 30 kg, 200 mg/50
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`mg SOF/VEL for children weighing < 30 kg and = 17 kg, and 150 mg/37.5 mg
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`SOF/VEL for children weighing < 17 kg, once daily with or without food for 12 weeks.
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`The Applicant submitted this NDA 214187, as a 505(b)(1) application, based on the
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`pharmacokinetic (PK), efficacy, and safety data from Study GS-US-342-1143 entitled “A
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`Phase 2, Open-Label, Multicenter, Multi-cohort, Study to Investigate the Safety a