QbR Frequently Asked Questions
Disclaimer: These are general answers and may not be applicable to every product. Each ANDA is reviewed individually. This document represents the Office of Generic Drugs’s (OGD’s) current thinking on these topics.
Format and Submission
How should QbR ANDAs be submitted?
OGD’s QbR was designed with the expectation that ANDA applications would be
organized according to the Common Technical Document (CTD) format, a submission
format adopted by multiple regulatory bodies including FDA. Generic firms are strongly recommended to submit their ANDAs in the CTD format (either eCTD or paper) to
facilitate implementation of the QbR. The ANDA Checklist for completeness and
profile中文acceptability of an application for filing can be found on the OGD web page:
v/cder/ogd/anda_checklist.pdf .
What is a QOS?
The Quality Overall Summary (QOS) is the part of the CTD format that provides a
summary of the CMC aspects of the application. It is an important tool to make the QbR review process more efficient.
How long should a QOS be?
OGD believes the CTD guidance1 recommendation of 40 pages to be an appropriate
compromise between level of detail and concision. The CTD guidance recommendation does not include tables and figures.
The same information should not be included in multiple locations in the QOS. Instead of repeating information, refer to the first location of the original information in the QOS by CTD section number.
Should the QOS be submitted electronically?
All applications should include an electronic QOS. For paper submissions, it is
recommended that both an electronic QOS and a paper QOS be included.
What file format should be used for the QOS?
All applications, both eCTD and paper submissions, should have an electronic QOS. The electronic QOS should be contained in one document. Do not provide separate files for
each section or question.
The electronic QOS should be provided as both a pdf and a Microsoft Word file. Microsoft Word files should be readable by Word 2003.
1 Guidance for Industry M4Q: The CTD – Quality (August 2001) v/cder/guidance/4539Q.htm
What fonts should be used in the QOS?
Because of FDA’s internal data management systems, please use only use these TrueType fonts: Times New Roman, Arial, Courier New. Times New Roman is recommended as the main text font.
Should the applicable QbR question be presented within the body of Module 2 of the relevant section, followed by sponsor's answer?
Yes, include all the QbR questions without deletion in the QOS.
Can the granularity of module 3 be used in module 2?
Yes, the granularity can be used for section and subsection headings. However, the QOS should always be submitted as a single file.
Can color be used in the QOS?
Yes, but sponsors should ensure that the QOS is legible when printed in black and white.
Colored text should not be used.
Is the QOS format available on OGD webpage and questions therein mandatory to be followed?
For an efficient review process, OGD desires all applications to be in a consistent format.
See the OGD QbR questions and example QOS:
v/cder/ogd/QbR-Quality_Overall_Summary_Outline.doc
v/cder/ogd/OGD_Model_Quality_Overall_ Summary.pdf
v/cder/ogd/OGD_Model_QOS_IR_Product.pdf
For amendments to applications, should the documentation consist of a revision of the QOS? Would new PD reports be required?
The QOS should not be updated after submission of the original ANDA. Any additional data (including any new PD reports) should be provided as a stand alone amendment.
Responses to deficiencies should be provided in electronic format as both a pdf and
Microsoft Word file.
After January 2007, what will happen to an application that does not have a QOS or contains an incomplete QOS?
OGD will contact the sponsor and ask them to provide a QOS. If the sponsor provides the QOS before the application comes up for review, OGD will use the sponsor’s QOS.
OGD’s QbR questions represent the current thinking about what information is essential to evaluate an ANDA. Reviewers will use deficiency letters to ask ANDA sponsors the
questions that are not answered in the sponsor’s QOS.
In February 2007, 75% of ANDAs submitted contained a QOS.
If a question is not applicable to a specific formulation or dosage form, should the question be deleted or unanswered?
Sponsors should never delete a QbR question, but instead answer as not applicable, with a brief justification. Please answer all parts of multi-part questions.
For sterile injectables, to what extent should sterility assurance be covered in QOS?
The current QbR was not intended to cover data recommendations for Sterility Assurance information. In the future, other summaries will cover other disciplines.
MAPP 5040.1, effective date 5/24/04, specifies location of the microbiology information in the CTD format.
Where in the CTD should an applicant provide comparative dissolution data between the generic and RLD?
The comparison between the final ANDA formulation and the RLD should be provided in
5.3.1, this comparison should be summarized in the QOS. Comparisons with other
formulations conducted during development should be included in 3.P.2.
Is it possible to submit an amendment in CTD format for a product that was already submitted in the old ANDA format?
No, all amendments to an application under review should use the same format as the
original submission.
How is a paper CTD to be paginated?
“Page numbering in the CTD format should be at the document level and not at the volume or module level. (The entire submission should never be numbered consecutively by page.) In general, all docum
ents should have page numbers. Since the page numbering is at the document level, there should only be one set of page numbers for each document.”2. For paper submission, tabs locating sections and subsections are useful.
For the ANDA submitted as in paper CTD format, can we submit the bioequivalence study report electronically? Or does the Agency require paper copy only?
The bioequivalence summary tables should always be provided in electronic format.
Will QbR lead to longer review times?
Many of the current long review times result from applications that do not completely
address all of the review issues and OGD must request additional information through the deficiency process. This iterative process will be reduced with the use of the QbR template.
Sponsors that provide a QOS that clearly and completely addresses all the questions in the QbR should find a reduction in the overall review time.
Will DMFs for the drug substance be required to be in CTD if the ANDA is in CTD format?
No. CTD format DMFs are recommended.
What should be included in 3.2.R.1.P.2, Information on Components?
COA’s for drug substance, excipients and packaging components used to produce the
exhibit batch.
2 Submitting Marketing Applications According to the ICH/CTD Format: General Considerations
v/cder/guidance/4707dft.pdf
How should an ANDA sponsor respond to deficiencies?
OGD requests that sponsors provide a copy of the response to deficiencies in electronic format as both a pdf file and a Microsoft Word file.
QUALITY OVERALL SUMMARY CONTENT QUESTIONS
2.3 Introduction to the Quality Overall Summary
What information should be provided in the introduction?
Proprietary Name of Drug Product:
Non-Proprietary Name of Drug Product:
Non-Proprietary Name of Drug Substance:
Company Name:
Dosage Form:
Strength(s):
Route of Administration:
Proposed Indication(s):
Maximum Daily Dose:
2.3.S DRUG SUBSTANCE
What if an ANDA contains two or more active ingredients?
Prepare separate 2.3.S sections of the QOS for each API. Label them 2.3.S [API 1] and
2.3.S [API 2].
What if an ANDA contains two or more suppliers of the same active ingredient?
Provide one 2.3.S section. Information that is common between suppliers should not be repeated. Information that is not common between suppliers (e.g. different manufacturing processes) should have separate sections and be labeled accordingly (drug substance,
manufacturer 1) and (drug substance, manufacturer 2).
Can information in this section be provided by reference to a DMF?
See individual questions for details. As a general overview:
•Information to be referenced to the DMF
o Drug substance structure elucidation;
o Drug substance manufacturing process and controls;
o Container/closure system used for packaging and storage of the drug
substance;
o Drug substance stability.
•Information requested from ANDA Sponsor
o Physicochemical properties;
o Adequate drug substance specification and test methods including structure confirmation;
o Impurity profile in drug substance (process impurity or degradant);
o Limits for impurity/residual solvent limits;
o Method validation/verification;
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