RAC, Regulatory Affairs, RAC 14

Reporting Period? IND SAE Fatal or Life Threatening

"7 calendar days, by phone or facsimile, followed by a written report within 8 additional calendar days"

Reporting Period? Postmarket, NDA foreign or domestic serious or unexpected SAE

"within 15 days following receipt of the information. Adtl info in 15 days"

Study types eligible for SPA?

1. animal carcinogenicity protocols 2. final product stability protocols 3. clinical protocols for Phase 3 trials

PDUFA date

10 months

Type A - When is brief due?

14 Days

Type A Meeting time to FDA response

14 days from request

Reporting Period? IND SAE all other

15 calendar days, in writing

Type B Meeting time to FDA response

21 days from request

Type C Meeting time to FDA response

21 days from request

Type B - When is brief due?

28 Days

Type C- When is brief due?

28 Days

Type A - When will meeting occur?

30 days from request

Reporting Period ? All Blood and HCT/P Problems

45 calendar days of Fatal/Life threateneing/Disabling/Surgical Intervention and hospitalization

AKA: New NDA

505(b)(1)

AKA: NDA Submission with no right of reference

505(b)(2)

Pathway: No right of Reference to Original NDA=

505(b)(2)

Your company wishes to seek approval of a combination of individually approved anti-hypertensive and anti-diabetic drugs. However, there is no Reference Listed Drug (RLD) for the proposed combination. Which of the following regulatory pathways is most applicable?

505(b)(2)

Which of the following is the best regulatory pathway for drugs containing similar active ingredients as a previously approved drug for a new indication

505(b)(2) NDA

A company has a new oral drug, GOODDRUG, it wishes to market in the US. Studies on intravenous GOODDRUG have been conducted by several academic centers demonstrating safety and efficacy and have been published in peer-reviewed journals. The most-appropriate method to gain approval would be by filing a:

505(b)2

AKA: ANDA

505(j)

When are advisory committee meeting materials due?

55 days out

PDUFA Priority Review Clock

6 Months

Prority Review Benefit(s)

6 month review clock (instead of 10)

How long does FDA have to review an RFD

60 days (combination product)

When is an NDA annual report due?

60 days after the anniversary date of U.S. approval of the application. NDA

Type B - When will meeting occur?

60 days from request

Orphan exclusivity period

7 Years

Type C - When will meeting occur?

75 days from request

How long after proprietary name submission does FDA provided a tentative acceptance or non acceptance letter?

90 days

What is the minimum initial IND submission

A clinical study protocol and one completed 1572

Pathway: Same as RLD

ANDA (CMC, Fasted and Fed BE, Crossover)

Which FDA expedited program for serious conditions allows approval without demonstration of efficacy.

Accelerated Approval

Company X has conducted clinical studies to support drug A's safety and effectiveness. Company X is planning to develop a new drug A dosage formulation and route of administration. This new formulation will rely on previously conducted clinical studies to support drug A's safety and effectiveness. Which of the following should be submitted by Company X?

An NDA containing full reports of investigations of safety and effectiveness

A manufacturer changes the size and shape of a container for a nonsterile solid dosage form drug already approved by FDA. What would be the most appropriate postapproval vehicle for this potential action?

Annual Report.

Type C Meetings

Any other product development or guidance meeting not included as Type A or Type B

Accelerated Approval Benefits

Approval based on surrogate endpoint

Your company is making a change to a specification to comply with an official compendium of an NDA product. How should this change be reported?

As an update in the next Annual Report

21 CFR 600s

Biologics

How should an NDA holder report a change to aseptic processing filtration parameters (including flow rate, pressure, time or volume, but not filter material or pore size rating).

Changes Being Effected in 30-Days

Mechanisms to Amend an OTC Drug Monograph

Citizen Petition Citizen Petition Time and Extent Application (TEA)

A company manufactures a combination internal analgesic product, regulated under a tentative final monograph. An Advisory Committee meeting is being planned to discuss potentially lowering either the maximum daily dose of one of the internal analgesic active ingredients, or limiting the single dosage unit. This will impact your product, and you plan to provide safety and efficacy data to FDA to support the currently existing dosing regimen for your product. How, as the regulatory professional, do you communicate with FDA regarding this topic?

Citizen's Petition

A deficiency letter may be issued to a company during a Biologics License Application (BLA) review for which of the following?

Clinical testing did not include enough subjects

What type of communication will FDA send an applicant when the review division concludes an NDA or ANDA cannot be approved in its present form and certain additional information or clarifications are needed?

Complete response letter

Which of the following IDE reports needs to be sent to FDA on a biannual basis?

Current Investigator List

Type A Meeting Types

Dispute Resolution Clinical Hold SPA

Hatch-Waxman Act of 1984

Encouraged the creation of both generic and new medications by streamlining the process for generic drug approval and by extending patent licenses.

An important consideration in developing 505(b)(2) products as compared to ANDA products is:

Extended market exclusivity of 505(b)(2) products.

Act creating Fast Track?

FDAMA 1997

What act exempted orphan drugs from user fees?

FDAMA 1997

What act created breakthrough therapy designation?

FDASIA 2012

The drug substance manufacturing plant proposes widening a critical in-process test limit associated with the final intermediate manufacturing process. What will need to be done for the plant to implement the change?

File a Prior Approval Supplement and wait for agency approval before implementation

21 CFR 1271

Human Cell and Tissue Products

21 CFR 300s

Human Drugs

21 CFR 1270

Human Tissues for Transplant

An investigator wishing to begin a clinical investigation using xenotransplantation must submit the following:

IND

What is the benefit of an abbreviated IDE

IRB review only, NSR

Post-market Field Alert Criteria

Labeling Mistaken or Swapped, Bacterial Contamination, Chemical/Deterioration, Batch Spec Failure

21 CFR 200s

Labeling, CGMPs, Controlled Substances

4. A sponsor is interested in having a pre-IND meeting with FDA. When must the meeting package be submitted to the appropriate FDA review division to ensure that the reviewers have sufficient time to review the material prior to the meeting?

No later than 30 days before the scheduled date of the formal meeting

An Investigational New Drug Application (IND) goes to the "Inactive Status" when:

No subjects are entered into clinical trials for a period of two years or the IND is on clinical hold for one year.

eCTD Module 4

Nonclinical Study Reports

Type B Meeting Types

Pre-IND EOP1 EOP2 Pre-NDa or BLA

Pivotal Study Enrollment change - what kind of supplement

Prior Approval

Significant risk, narrow subgroup - what kind of supplement

Prior Approval

An applicant wants to manufacture an approved tablet at a site that currently produces capsules and has a satisfactory GMP inspection for capsule production. What type of submission would be required for this change?

Prior Approval Supplement is required because the manufacturing process is different.

FDA's Office of Generic Drugs (OGD) remains committed to the "first-in, first-reviewed" review order for original Abbreviated New Drug Applications (ANDAs), amendments and supplements unless there is specific reason to expedite an application. Which of the following is NOT specific reason to grant expedited review?

Products that show evidence of safety and effectiveness in a new subpopulation

21 CFR 0-99

Protection of Human Subjects

Orphan Drug Act of 1983

Provides incentives to promote research, approval, and marketing of drugs needed for the treatment of rare diseases.

eCTD Module 2

Quality Overall Summary Nonclinical Overview Nonclinical Summary Clinical Overview Clinical Summary

How long does a sponsor provide Periodic Adverse Drug Experience Reports?

Quarterly for first three years, then annually thereafter

After product approval, ADEs that do not meet the 15-day reporting requirements should be reported by the company:

Quarterly for three years after application approval, annually thereafter, unless alternative reporting is required by FDA.

Company X is planning to conduct a clinical investigation for its new oral suspension for a reconstituted drug product. What information related to expiration dating is Company X required to include in the investigational drug product labeling?

Reconstituted drug product expiration information is required

eCTD Module 1

Regional Admin Information

A pharmaceutical company received approval of a drug that contains a boxed warning on its labeling. What type(s) of advertisements are NOT permitted?

Reminder advertisements

FDAAA 2007

Required registration clinicaltrials.gov FDAAA reauthorized a number of key programs, including PDUFA, MDUFMA and PREA

Fast Track Benefits

Rolling Review Extra Communication

A physician reports to a manufacturer a patient was hospitalized with acute sepsis after treatment with an approved device. This side effect is not listed in the package insert. The manufacturer must report this event to FDA no later than:

Serious injury must be reported within 30 days; see 21 CFR 803.50(a)

Reporting Period? Field Alert Reports

Submit a FAR within 3 days of being aware of a significant issue, phone and report

Pathway: Similar to RLD, Same Labeling

Suitability Petition

Citizen's petition

The Citizen Petition (CP) Process can be used to request FDA to amend an OTC drug monograph at any phase of its development and after publication of a final monograph.

Once an Investigational New Drug (IND) is in effect, an amendment can be submitted for all the following EXCEPT:

The sponsor intends to conduct a clinical investigation with an exception from Informed Consent for emergency research

Prescription drug user fee act of 1992

This act states that manufacturers must pay a user fee along with each drug that is marketed, facility that manufacturers drugs, and each app from approval.The money is used to hire drug reviewers and facilitate the drug approval process.

Circumstance leading to fast track but not priority review.

Treats serious disease but isn't a significant improvement compared to marketed product.

Recall Class III

Where a product is not likely to cause adverse effects

Pediatric Research Equity Act of 2003

act that authorizes the FDA to require research of pediatric uses for new drugs

Items on OTC medicine label

active ingredient purpose uses warnings dosage instructions inactive ingredients

Food and Drug Administration Modernization Act of 1997

additional authority for monitoring the progress of drug and biologic postmarketing studies The law codified the expedited review policy for certain medical devices, amended and clarified the humanitarian device provisions of SMDA FDA to recognize international or other national standards Agreement Meetings and Determination Meetings

21 CFR 601 Subpart H

animal rule

eCTD Module 5

clinical study reports

Kefauver-Harris Amendments of 1962

efficacy as well as safety informed consent for research subjects FDA regulates advertising of rx drugs established GMP Drug advertising from FTC to FDA

Administrative Procedure Act

federal law enacted in 1946, "notice and comment rulemaking"

1906: The Pure Food and Drug Act (PFDA)

interstate commerce labeling

Recall Class II

product may cause temporary or medically reversible adverse health consequences, or where the probability of serious adverse health consequences is remote

eCTD Module 3

quality

1912 Pure Food and Drug Act

revised in 1912, stated that a drug was misbranded if its label contained a "false and fraudulent" statement regarding "curative or therapeutic effect."

Breakthrough Designation Criteria

serious life threatening preliminary evidence suggests superiority

Fast Track Criteria

superior effectiveness avoid serious side effects improve diagnosis of serious disease decrease toxicity

Recall Class I

where this is a strong likelihood that the product may cause serious adverse effects or death

Durham-Humphrey Amendment of 1951

• Created a distinction between "OTC" and "Legend Drugs". • Legend Drugs can only be dispensed with a valid Prescription.. • Required Legend Drugs to carry the statement: "Caution: Federal law prohibits dispensing without a prescription.". • Most people refer to Legend drugs simply as "Prescription Drugs". • The emphasis on this act was to insure safety thru qualified medical supervision.