RAC PHARMACEUTICALS EXAM /WITH EXPLANATIONS &
QUALITY ANSWERS /A+ GRADE.
What is SPL format? - CORRECT ANSWERS -Structure Product Labeling: based on
XML language. SPL requires forms 2656, 2657, 2658 be submitted electronically in SPL
format; also required to submit official contacts name, mailing address, telephone
numbers, and email address; each registered establishments telephone number, type of
operations performed at each registered establishment; b. Foreign establishments must
follow this too
What are the goals of an NDA? - CORRECT ANSWERS -The drug is safe and effective
for its proposed use(s), The benefits of the drug outweigh the risks, The proposed
labeling is appropriate and adequate, The methods of manufacture and testing and the
controls used to maintain the drug's quality are adequate to preserve the drug's identity,
strength, quality, and purity
What is a 505(j)? - CORRECT ANSWERS -The ANDA application: generic drug
application, duplicate of reference listed drug (RLD), primary bioequivalence/CMC data;
completely relies on innovator (RLD) for safety and efficacy data; same conditions of
use/labeling as RLD; unless part of a suitability petition, must have the same as RLD for
active ingredient, route of administration, dosage form, strength; Bioequivalence
definition: rate and extent of absorption (same molar dose)= no significant difference
from RLD and an intention difference in the extent of absorption can be different from
the RLD when it's in proposed labeling; Must demonstrate bioequivalence: In vitro: in
health volunteers; pharmacokinetic study; active moiety measured normally in plasma;
In vivo: clinical comparison trial (unable to measure moiety); Inherently bioequivalent-
parenterals: injection = bioequivalent as long as excipients are the same as the RLD;
Excipients can be different for some (but not all) dosage forms; Tablets/capsules: active
moiety is same as RLD but actual excipients/binders don't have to be the same only
conform (*FYI: FDA frowns upon different excipients)
What is a 505(b)(1)? - CORRECT ANSWERS -Full tradition NDA, full reports of safety
and efficacy, typically most substantial data package, this si the foundation for
subsequent regulatory filiings
What is the required content for the NDA? - CORRECT ANSWERS -Application forms:
356(h) (application to market a new drug), 3397 (user fee cover sheet), 3331 (new drug
application field report) Index; Summary; Technical sections (at least 5 or 6): Chemistry,
manufacturing, and controls (product quality): describe the composition, manufacturer
and specifications of both the drug substance and the drug product as well as all the
manufacturing controls and stability data; Nonclinical pharmacology and toxicology: any
animal and in vitro drug studies that help to define the drug's pharmacologic properties
and address toxicity related to its administration; Human pharmacokinetics and
bioavailability; Microbiology, Clinical data: description of all clinical investigations
completed in support of the drug's efficacy and safety, as well as the study protocols
,and copies of case reports forms for each patient who died during a clinical study or did
not complete a study because of an adverse event regardless of the incident's
relationship to the study drug, Statistical, Pediatric use; Case report tabulations and
patient data; Case report forms; Financial disclosures/certification; Labeling: copies of
labeling (including package insert, carton, and container labels and Medication Guide)
should be provided in the application. Labeling must be submitted electronically in a
formal that the agency can review and process (structured product labeling (SPL)
format with an extensible markup language (XML) backbone.; Drug sample
What are the modules of the CTD? - CORRECT ANSWERS -Module 1: regional
administrative information, Module 2: Summary of Quality, Non-clinical overview, clinical
overview, non-clinical summaries, clinical summaries; Module 3: Quality, Module 4:
Non-clinical study reports, Module 5: clinical study reports
What is the intial review process when FDA receives an NDA? - CORRECT ANSWERS
-(1)Once received, FDA has 60 days to determine whether the application is sufficiently
complete to allow for a substantive review. If it is complete it will be filed on day 60, if
not FDA can "refuse to file" (RTF) and will issue a formal RTF letter by Day 60 that will
proved the reasons for the decision. FDA can also RTF sections of the NDA. If an
applicant strongly disagrees with FDA's decision to RTF an application, the applicant
has 30 days to request a meeting with FDA - following the meeting then the applicant
can request that the agency file the application "over protest". The date of filing for "over
protest" will be 60 days from the date the applicant requested the meeting. (2)For
applications that are file: FDA performs an "initial filing review" by day 60 to identify filing
review issues which are substantive deficiencies or concerns that may have significant
impact on FDA's ability to review or approve the application. (3) Then applicant will
receive the day 74 letter (mandated by PDUFA). This states the date FDA received the
application (date the review clock begins); provides the review time line and includes an
action date, when FDA will provide a decision on the application as well as dates when
the applicant can expect or receive feedback from the review division on proposed
labeling and Postmarketing requirements/commitments; also identifies the review
classification granted by FDA. (under PDUFA V "program" will also state whether the
division is considering convening an advisory committee meeting; (4)During the review
FDA may ask the applicant for additional information "solicited information" or the
applicant may submit additional information on its own initiative "unsolicited
information". If the new information constitutes an amendment FDA may determine that
an extension of the review PDUFA action
What is FDA's review process when the initial NDA has been review and no RTF was
issued? - CORRECT ANSWERS -FDA review process: (A) When the application is
validated and received it is routed to the regulatory project manager (RPM). The RMP
will ask supervisory team leaders from appropriate disciplines to assign reviewers. The
first review task is to determine from each specific discipline whether the application is
fileable. Review team is made up of clinical, pharmacology and toxicology, chemistry,
clinical pharmacology, etc. if clarification is needed the specialist can communicate to
the sponsor through an information request (IR) or advice letter (AD) these are handled
, via email, telephone or direct mail. The RPM facilitates these communications. (B) DR
letters can be issued "discipline review" after each discipline reviewed their section.
They are used sparingly (C) For some applications outside experts are needed.(D) FDA
then determines whether any bioresearch monitoring (BIMO) or current GMPs
inspections are required prior to approval. (i) Preapproval inspection: FDA can inspect
manufacturing facilities (CGMP inspection) and/or sites where the drug was tested in
nonclinical or clinical studies (BIMO inspections). They are likely to occur: (a)NMEs or
original BLAs (b) Priority reviews (c) The first application filed by an applicant (d) For-
cause inspections (ie. one clinical trial site had a significantly better trial outcome than
other sites) (e) Original or supplemental applications, if the cGMP status is unknown (ie.
more than 2 years since the domestic facility was last inspected, or the establishment is
new and has yet to be inspected by FDA or another global regulated authority. (E) FDA
will then make a determination whether postmarketing requirements or commitments
are necessary. If yes, this is communicated to the applicant to discuss and agree on
specific studies. (F) FDA also review the labeling in parallel
What is the timeline for the NDA review process? - CORRECT ANSWERS -Filing
review is 1-2 months, Day 0 is the day FDA receives the NDA, Filing day + 30 complete
application filed, Day 60 filing decision or RTF, Day 74 communicate filing review
issues, Mid-cycle review meeting : 3 months and 5 months post receipt; Mid cycle
communication 3 months and 5 months post receipt; Late cycle meeting 3 months or 2
months prior to action; Complete inspections: 2 months prior to action; between month
8-10 (roughly)PDUFA action letter
What are some postmarketing requirements and commitments? - CORRECT
ANSWERS -Approval letter will stipulate and postmarketing requirements/commitments.
(1) Postmarketing requirement: study (observational epidemiological study, animal
study or laboratory experiment) or clinical trial that the applicant must conduct after the
application is approved. (2) Postmarketing commitment: written commitment by the
applicant to FDA to provide additional information after approval of the application.
506B- reportable postmarketing commitments require annual status reports to be
submitted by the applicant.
what is the process for proprietary name review? - CORRECT ANSWERS -initiated
during the IND phase (*completion of phase 2), when submitted in IND phase FDA has
180 days to review, when submitted in NDA 90 days to review; FDA review: prosed
name's safety and promotional aspects: safety: focuses primarily on prevention of
medication errors and evaluating other products that may have similar appearance
when written out by hand; Promotional review: determine whether the name implies
being superior.
What is the process of establishment registration? - CORRECT ANSWERS -
Manufacturing facility must be registered before the marketing application can be
approved; All drug establishments (not exempt under section 510(g) and subpart B of
part 207, engage in manufacture, preparation, propagation, compounding, or
processing of a drug or drugs shall register and submit a list of every drug in
