Refu to Receive for Lack of Justification of Impurity Limits
Guidance for Industry
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Rearch (CDER)
August 2016
Generics
Refu to Receive for Lack of Justification of Impurity Limits
Guidance for Industry
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Additional copies are available from:
Office of Communications
Division of Drug Information, WO51, Room 2201
Center for Drug Evaluation and Rearch
Food and Drug Administration
10903 New Hampshire Ave., Silver Spring, MD 20993-0002
Phone: 301-796-3400; Fax: 301-847-8714
druginfo@v
v/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Rearch (CDER)
August 2016
Generics
TABLE OF CONTENTS
I.INTRODUCTION (1)
II.BACKGROUND (2)
III.JUSTIFYING IMPURITY LIMITS IN DRUG SUBSTANCES AND PRODUCTS . 3
A.Refusal to Receive for Lack of Impurities Information (3)
B.Providing Justification for Impurity Limits (4)
ANDA Submissions – Refu to Receive for Lack of Justification of
Impurity Limits
Guidance for Industry1
I. INTRODUCTION
This guidance is intended to assist applicants preparing to submit to the Food and Drug Administration (FDA) original abbreviated new drug applications (ANDAs) and prior approval supplements (PASs) to ANDAs for which the applicant is eking approval of a new strength of the drug product.2 The guidance highlights deficiencies in relation to information about impurities that may cau FDA to refu to receive (RTR) an ANDA.3,4 An RTR decision indicates that FDA determined that an ANDA is not sufficiently complete to permit a substantive review.5
餐饮管理制度规章制度Typical deficiencies leading to an RTR decision include: (1) failing to provide justification for propod limits in drug substances and drug products for specified identified impurities that are above qualification thresholds; (2) failing to provide justification for propod limits for specified unidentified impurities that are above identification thresholds; and (3) proposing limits for unspecified impurities (e.g., any unknown impurity) that are above identification thresholds.
This guidance is not meant to be a comprehensive list of deficiencies in relation to impurity information that may or will lead FDA to make an RTR determination. Rather, this guidance clarifies that a failure to provide justification for propod impurity limits may lead FDA to RTR 1 This guidance has been prepared by the Office of Generic Drugs in the Center for Drug Evaluation and Rearch (CDER) at the Food and Drug Administration.
2 For purpos of this guidance, the u of the term ANDA will mean ANDAs and new-strength PAS submissions.
3 This should not be confud with a refu-to-approve determination.
4 The following types of products are currently excluded from this guidance: (1) biological/biotechnologicals; (2) peptides; (3) oligonucleotides; (4) radiopharmaceuticals; (5) fermentation products; (6) misynthetic products derived from fermentation products; (7) herbal products; (8) crude products of animal or plant origin; and (9) enantiomeric impurities. For additional information on the applicability to ANDAs, e guidances for industry ANDAs: Impurities in Drug Substances; ANDAs: Impurities in Drug Products; See also, guidances for industry
Q3A(R) Impurities in New Drug Substances (Q3A(R)); and Q3B(R2) Impurities in New Drug Product
s (Q3B(R2)).
5 21 CFR 314.101(b)(1).
an ANDA. It also makes recommendations to ensure that applicants include appropriate justification for impurities in their ANDA submissions.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The u of the word should in Agency guidances means that something is suggested or recommended, but not required.6
II. BACKGROUND
Pursuant to the enactment of the Generic Drug Ur Fee Amendments of 2012 (GDUFA),7 the Office of Generic Drugs (OGD) is tasked with a number of activities, including the development of “enhanced refusal to receive standards for ANDAs and other related submissions by the end of year 1 of the program….”8 Enhanced RTR standards are important becau the practice of submitting a
n ANDA that is not sufficiently complete to permit a substantive review, which then is “repaired” via veral cycles of applicant resubmission and FDA respon, is inherently inefficient and wasteful of resources.
FDA evaluates each submitted ANDA individually to determine whether it can be received for Agency review. FDA’s receipt of an ANDA means the Agency has made a threshold determination that the ANDA is sufficiently complete to permit a substantive review.9FDA’s regulations at 21 CFR 314.101 provide the regulatory authority by which FDA may in certain cas, and will in others, RTR an ANDA.10
Generally, FDA will not receive an ANDA for substantive review unless it contains the information required under Section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and in 21 CFR 314.101 and other regulations, for example:11
∙21 CFR 314.50
∙21 CFR 314.94捉鬼特工队
∙21 CFR 320.21
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4s店培训6 At various points this guidance notes that when FDA es a particular type of deficiency in an ANDA it will RTR the ANDA. It is important to understand that such statements do not impo legal obligations on applicants or on FDA, but are included for purpos of transparency. This means that FDA, in the normal cour, will RTR an ANDA on the grounds described in this guidance. This guidance does not preclude the possibility that an ANDA applicant may be able to demonstrate, in particular circumstances, that the regulatory requirements for receiving an ANDA have been met even when, as described in this guidance, FDA would in the normal cour find the application not sufficiently complete and RTR it.
身份证照片可以化妆吗7 Generic Drug Ur Fee Amendments of 2012 (GDUFA), Public Law 112-144, Title III.
8 See Generic Drug Ur Fee Act Program Performance Goals and Procedures (the Commitment Letter):
v/downloads/ForIndustry/UrFees/GenericDrugUrFees/UCM282505.pdf.
显卡对比9 See 21 CFR 314.101(b)(1).
10 See 21 CFR 314.101(d) -(e).
11 In certain cas, other statutes or regulations may apply.
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