Shared Flashcard Set

Details

Title

RAC Exam 2018

Description

Studying for RAC exam

Total Cards

230

Subject

Health Care

Level

Professional

Created

04/05/2018

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Term

Your company is licensed as a biological IVD (in vitro diagnostic) manufacturer. To expand manufacturing capabilities quickly, company management is considering using a contractor to manufacture the active ingredient for one IVD. You have been asked for regulatory advice on the best way to accomplish this while minimizing the impact on the final product labeling and the customer. What do you recommend?

Definition

Recommend contracting with another manufacturer to manufacture the product under your license. This represents the least disruption to both your facility and the product labeling since the contractor would be operating under your license. Your license must be amended to include the contract manufacturer and qulaity/regulatory oversight must be maintained through the quality agreement/contract with the contractor. Under the scenarios in answers 1 (using another manufacturer licensed to manufacture and intermediate product you then process into the final product) and 3 (participating with another licensed IVD manufacturer currently manufacturing this product and have it perform some of the manufacturing steps), your labeling will have to indicate the new manufacturer. Answer 4 (entering into a short supply agreement with an unlicensed facility to receive a partially manufactured product), is not appropriate since short supply agreements are to be used only in specific circumstances not part of this scenario.

Term

Company ABC has requested orphan drug designation for its product. the product currently is in clinical trials for a rare blood disease with a prevalence of approximately 100,000 individuals. The product previously was approved for anotehr indication for which the prevalence is approx. one million individuals. Would the company be eligible for orphan drug designation for the rare blood disease and why?

Definition

Yes, ODD can be granted because it is for a different indication than the indication currently marketed.

- a sponsor may request ODD for a previously unapproved drug or a new orphan indication for an already marketed drug. Also, a sponsor of a drug otherwise the same as an already approved orphan drug, may seek and obtain ODD for the subsequent drug to treat a rare disease or condition if it can present a plausible hypothesis that its drug may be clinically superior to the first drug.

Term

The manufacturer of an approved prostate-specific antigen (PSA) test developed a new automated analyzer to perform total PSA testing. there were no changes to the test's indications for use or technology and no new clinical data were required. only analytical testing was performed to demonstrate the new analyzer did not alter the assay's performance. what kind of PMA supplement to the approved premarket application will be required for this change?

Definition

180-day supplement.

this is a significant change to the PMA device and will require a 180-day supplement.

180-day supplement: a supplement to an approved premarket application or premarket report under section 515 that is not a panel-track supplement and requests a significant change in components, materials, design, specification, software, color additives, or labeling.

The guidance states automation is subject to 30 days notice. However this is in reference to the manufacturing processes, by and large, and not an automation that potentially could have a design or performance indication, which this change will have as it is automating the test analysis, itself. further, the key of the word 'total' implies the initial test was more specific and 'total PSA testing' is more comprehensive and thus further implies a design difference.

Term

In a company's originally approved application for drug product Y, the finished product specification for a noncompendial impurity had an acceptance criterion of 0.1%. in a subsequent annual report, this noncompendial impurity's acceptance criterion was tightened to 0.08%. Now, the company wants to relax the specification back to 0.1%. What reporting category is appropriate for this change?

Definition

Prior Approval Supplement

Prior approval is required for relaxing a noncompendial impurity's release specification limit. (Relaxing or deleting specifications to comply with USP is reportable in a Changes Being Effected-30 supplement).

Term

An NDA holder wants to extend the drug product shelf life from 2 to 3 years. What is the best course of action to pursue?

Definition

Present 3 years of real-time stability data on 3 consecutive batches following an approved stability protocol in the NDA Annual Report.

- Data from stability studies should be provided on at least 3 consecutive batches of the drug product. An extension of an expiration dating period based on full shelf life data on production batches obtained under a protocol approved in the application.

In the absence of an approved/agreed stability protocol with FDA, if the sponsor chose to provide real time stability data on 3 batches, the change should be submitted as a prior approval supplement (PAS).

Term

A special control for a medical device may include

Definition

- a black box warning included in the package insert of a new medical device

special controls may include special labeling requirements, mandatory performance standards and postmarket surveillance.

Class II devices are those for which General Controls alone are insufficient to assure safety adn effectiveness, and existing methods are available to provide such assurances. In addition to complying with General Controls, Class II devices are also subject to Special Controls.

Term

General Controls Examples

Definition

General controls include:
- establishment registration of companies which are required to register, such as mfrs, distributors, repackagers, and relabelers
- medical device listing with FDA of devices to be marketed
- manufacturing devices in accordance with GMPs
- labeling devices in accordance with labeling regulations
- submission of a premarket notification (510k) before marketing device.

Term

Special Controls Examples

Definition

- special labeling requirements
- mandatory performance standards
- postmarket surveillance

Term

How are labeling changes reported for approved NDAs?

Definition

- Depending on the type of change, labeling changes are either reported in the annual report or in a supplement.
- labeling and promotional material must be submitted during the preapproval period.
- fees may be waived if the designated drug is for orphan products
- NDAs may be submitted in the traditional format on paper or electronically.

Term

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?

Definition

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

Term

What are some examples of changes considered to have a substantial potential (major changes; Prior Approval Supplement) to have an adverse effect on a drug product's identity, strength, quality, purity, or potency, because all of these factors relate to the safety or effectiveness of the drug product?

Definition

- A move to a different manufacturing site for
1) the manufacture, processing, or primary packaging of drug products when the primary packaging components control the dose delivered to the patient of the formulation modifies the rate or extent of the drug's availability; or
2) the manufacture or processing of in-process materials with modified-release characteristics.

Examples of these drug product types include the modified-release solid oral dosage forms, transdermal systems, liposomal drug products, depot drug products, oral and nasal metered-dose inhalers, dry powder inhalers, and nasal spray pumps.

- Changes that may affect the dose's controlled (or modified) release, metering, or other characteristics (e.g. particle size) delivered to the patient.

- Any fundamental change in the manufacturing process or technology the applicant currently uses.

Term

While reviewing complaint files for a drug-eluting stent, a single entity combination product, it was noticed an adverse event had occurred and a patient was hospitalized for two additional days. Such an AE was a foreseeable event and the stent's mechanical features contributed to the occurrence. As a regulatory professional, your decision regarding the AE Reporting would be:

Definition

Report to FDA in Form 3500A (MDR) within 30 days of becoming aware of the event.

For a combination product, the lead center assignment is based on the combination product's primary mode of action (PMOA). In this stent, the device has the PMOA, so it follows MDR reporting requirements.

30-day reporting timeframe for serious AEs for medical devices.

- Answers (1) report to FDA in a 15 day alert report and (2) no action is needed as ADE reporting is required only for serious and unexpected AEs; this ADE is expected so no reporting is needed; Are postmarket reporting requirements for DRUGS.

Answer (4) (report to FDA within 7 calendar days of becoming aware of the AE) - is an IND reporting requirement.

Term

A mfring process requires purified water to produce several finished class I exempt and Class II 510(k) medical devices. Quality control tests the water monthly. Since results consistently have been within specifications, the product is sent to distributors before QC results are final. Over the past 6 months, quality test results have been getting closer to the specification limit. Internal review determines QC testing now should take place weekly. How should this information be provided to FDA?

Definition

This information does not need to be submitted.

Each mfr shall establish and maintain procedures for changes to a specification, method, process, or procedure. Such changes shall be verified or, where appropriate, validated according to 820.75 before implementation and these activities shall be documented. Changes shall be approved in accordance with 820.40.

Term

When a finished medical device's quality deteriorates over time, each mfr shall establish and maintain a product storage and handling system including all of the following except:

a. separate areas for release and quarantine products
b. Procedures for controlling stock used for shipping supplies
c. Environmentally controlled areas for products with shelf life
d. procedures for rotation of stock.

Definition

Answer is b. Procedures for controlling stock used for shipping purposes.

There are no storage and handling requirements for shipping supplies.

Each mfr shall establish and maintain procedures for the control of storage areas and stock rooms for product to prevent mix-ups, damage, deterioration, contamination, or other adverse effects pending use or distribution and to ensure that no obsolete, rejected, or deteriorated product is used or distributed. When the quality or product deteriorates over time, it shall be stored in a manner to facilitate proper stock rotation, and its condition shall be assessed as appropriate.

- each mfr shall establish and maintain procedures that describe the methods for authorizing receipt from and dispatch to storage areas and stock rooms.

Term

Postapproval pharmacovigilance for an adverse drug experience is (mandatory and/or voluntary) for (product license holder and/or healthcare professionals)?

Definition

Mandatory for product license holder.
Voluntary for healthcare professionals.

Term

A company revised a 10-page Form FDA-483. The regulatory professional prepared a detailed response assuring the FDA District Office corrective action had been taken for each observation. What else should also be done?

Definition

The company should re-audit its corrective actions to ensure adequate implementation before the letter is sent.

The Form FDA-483 is a letter from the regulatory professional that states that the corrective action has already taken place. The firm may be subject to inspection at any time; therefore, these corrections should be reviewed.

Term

FDA Form-483

Definition

Form FDA 483, "Inspectional Observations," is a form used by the FDA to document and communicate concerns discovered during these inspections. Also referred to as "Form 483" or merely "483", it states thereon that it

"...lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance"

A recipient of a 483 should respond to the FDA, addressing each item, indicating agreement and either providing a timeline for correction or requesting clarification of what the FDA requires.[4] This response must be submitted within 15 business days regardless of the number of observations, as of September 2009.

Term

A company decides to add an additional quality control test during in-process testing of its marketed Class II device. The appropriate submission to send to FDA for this change is:

Definition

Special PMA Supplement - Changes being effected.

The special PMA Suppelment is used when the changes enhances or increases the device's safety.

Term

If a device failure is occurring with greater than expected frequency and investigation of the problem implicates improper use by the end user, which of the following should occur?

Definition

The labeling needs to be revised.

- The labeling should provide appropriate information for proper use of the product.

Term

You have been assigned as the reg. representative for a marketed OTC cough and cold product, regulated by a final monograph. Your product is for adult use only and contains 0.7% ethanol in the final product. While assessing the product, you notice the alcohol content is not provided on the product labeling. The product is currently in distribution centers and on store shelves. Your product is in what state and what is the appropriate course of action?

Definition

Misbranded product - voluntary recall to correct the labeling.

The final monograph published declares that for any product intended for oral ingestion, the ethanol content must be stated on the principal display panel. As the product contains ethanol, but does not carry this statement on the PDP, the product is deemed to be misbranded.

Term

Which of the following is NOT an example of an annual reportable change for a marketed product?
- Deletion of a specification for drug substance
- a change in specification made to comply with an official compendium
- an editorial change to a label
- tightening of acceptance criteria

Definition

Answer- deletion of a specification for drug substance.

- This type of change requires a PAS (changes to ingredients need a PAS)

Term

For validated processes and systems, the possibility of revalidation should be considered for all of the following except:

a. when the manufacturer tightens the specification for container closure torque
b. whenever there are changes in packaging, formulation, equipment, or processes which could impact product effectiveness or product characteristics
c. when a change is made in raw material supplier
d. based on the procedures in the change control standard operating procedures.

Definition

Answer: all except (a) when the manufacturer tightens the specification for container closure torque.

Term

What FDA notification method would be required for a postapproval change described as "a change in technical grade" of a release-controlling agent?

Definition

Prior approval supplement - this type of changes is classified as level 2 (one that could affect the product's formulation quality and performance significantly). Thus, this change should be described in a PAS and contain a minimum of 3 month's accelerated stability data and multipoint dissolution studies (or IVIV correlation), with long term first production batch stability data to follow in the Annual Report. Certain products (i.e. those with a narrow therapeutic range) could require bioequivalence documentation and/or stability data on 3 batches instead of one in the PAS.

Term

A mfr is closing its current approve drug manufacturing facility. The mfr asked regulatory to examine its 2 other facilities and develop an appropriate regulatory strategy. Facility A: large one, built near existing facility, new electronics to monitor the mfring process, new isolated mfring areas and new equipment. will open 1 month before the current facility closes. this process will be the first process moved to the new building. Facility B: a smaller facility 100 miles away, that has been mfring several approved drug products for the same therapeutic purpose for the past 15 years. Which is the most accurate analysis/recommendation?

Definition

Facility B has been mfring approved drug products for the same therapeutic purpose for the past 15 years and has been inspected by FDA. Moving the mfring process to facility B would be a moderate change that could be filed in a CBE-30.

- FDA needs to be notified when a mfring process is moved to a new facility.

Facility A has not yet been inspected by FDA and would result in a major change of the approved NDA. would require a PAS before drug product manufactured in this location could be placed onto the market.

Term

A handling and storage system for medical devices must always include:

Definition

procedures for inspection, processing, and rotation of stock.

- a medical device handling and storage system must have procedures that describe the methods for authorizing receipt from and dispatch to storage areas and stock rooms.

Term

A key pharmaceutical product parameter has a specification range of 90-100. Which of the following postmarketing specification changes would require FDA notification?

a. 89-100
b. 90-99
c. 95 +/- 5
d. 95-100

Definition

Answer is a (89-100) because it makes the range wider. Relaxing acceptance criterion is an example of a major or moderate change that would need a PAS or CBE-30, respectively (FDA needs to be notified).

Term

What are required by FDA to support product postapproval stability requirements?

Definition

- A status report is to be included in any chemistry, manufacturing, and controls studies the applicant has agreed to perform and for all product stability studies.
- sample size and test intervals based on statistical criteria for each attribute examined to assure valid estimates of stability.
-storage conditions for samples retained for testing
- reliable, meaningful, ,and specific test methods
- testing of the drug product in the same container-closure system as that in which the drug product is marketed.
- testing of drug products for reconstitution at the same time of dispensing (as directed in the labeling) as well as after they are reconstituted.

-- an adequate number of batches of each drug product need to be tested to determine the expiration date and a record of such data shall be maintained.
- accelerated studies, combined with basic stability information on the components, drug products, and container-closure system may be used to support tentative expiration dates provided full shelf life studies are not available and are being conducted. Where data from accelerated studies are used to project a tentative expiration date that is beyond a date supported y actual shelf life studies, there must be stability studies conducted, including drug product testing at appropriate intervals, until the tentative expiration date is verified or the appropriate expiration date determined.

Term

When a mfr is performing design validation activities, which element is NOT included as a requirement under QSR's device design validation section?

1. conformance to defined user needs and intended uses
2. testing production units under actual or simulated use conditions
3. software validation and risk analysis, where appropriate
4. translation of device design into production specifications

Definition

Answer: 4: translation of device design into production specifications.

Answers 1-3 are 'device validation' activities. Answer 4 is a 'design transfer' activity. Design transfer relates to establishing procedures to ensure the device design is translated correctly into production specifications. Conformance to defined user needs and intended uses (answer 1), testing under actual or simulated conditions (answer 2), and software validation and risk analysis (answer 3) are all design validation activities.

Term

What is a Special Protocol Assessment Meeting used for?

Definition

Used for trials in which the proposed study design or endpoints are unusual, or for studies that involve an indication or disease for which the FDA has not previously approved a drug or biologic.

Term

What is a Type A meeting used for?

Definition

Used generally for dispute resolution; also used if a sponsor wants a meeting after receiving comments from FDA on the Special Protocol Assessment.

necessary for otherwise stalled product development program to proceed or to address an important safety issue.
- discuss clinical holds

Dispute resolution meetings as described in the Code of Federal Regulations (CFR), and in the Guidance for Industry Formal Dispute Resolution: Appeals Above the Division Level
Meetings to discuss clinical holds in which development is stalled and a new path forward should be discussed
Special protocol assessment meetings that are requested by sponsors or applicants after receipt of FDA evaluation of protocols under the special protocol assessment procedures
Post-action meetings requested by the sponsor within 3 months after an FDA regulatory action other than an approval

Term

What is a Type B meeting used for?

Definition

Pre-investigational new drug application (pre-IND) meetings
Certain end-of-phase 1 meetings for Subpart E or Subpart H or similar products
End-of-phase 2 and pre-phase 3 meetings
Pre-new drug application (pre-NDA) pre-biologics license application (pre-BLA) meetings
Meetings regarding risk evaluation and mitigation strategies (REMS) or post-marketing requirements that occur outside the context of the review of a marketing application
Post-action meetings requested by the sponsor 3 months or more after an FDA regulatory action other than an approval
Meetings held to discuss the overall development program for products granted Breakthrough Therapy designation status.

Term

What is a Type C meeting used for?

Definition

General drug development questions

Any meeting other than a type A or type B regarding the development and review of a product.

A written response to questions posed in pre-IND or Type C meeting requests may be requested by the sponsor
FDA may determine that a written response would be the most appropriate means for responding to a meeting request
FDA shall notify the requester of the date it intends to send the written response
FDA shall provide this notification within the specified time frame for responding to the meeting request

Term

What is a Pre-NDA meeting used for?

Definition

happens later, after you would need to discuss the phase 3 trial design.

Term

Is the meeting held to discuss the overall development program for products granted "Breakthrough Therapy" designation status a new Type B meeting?

Definition

Yes

Term

When is the earliest I can request a drug development (A, B, C) meeting?

Definition

Generally, the earliest a meeting can be requested to be held is the day after the response goal; 14 days for Type A meetings and 21 days for Type B and C meetings.

Term

When should the sponsor submit Type A meeting package?

When should the sponsor submit the Type B and Type C meeting package?

Definition

Type A: Submit meeting package along with meeting request
Type B and C: Submit meeting package at least 1 month before formal meeting

Term

Meeting packages should include the following:

Definition

- Product name and application number (if applicable)
- Chemical name and structure
- Proposed indication
- Dosage form, route of administration, and dosing regimen (frequency and duration)
- An updated list of sponsor or applicant attendees, affiliations, and titles
- A background section that includes:
--A brief history of the development program
--The events leading up to the meeting
--The status of product development
--A brief statement summarizing the purpose of the meeting.
--A proposed agenda.
--A list of the final questions for discussion grouped by discipline and with a brief summary for each question to explain the need or context for the question.
--Data to support discussion organized by discipline and question.

Term

Your company recently had a successful End-of-Phase 2 meeting for a novel drug and would like your regulatory advice on designing the pivotal Phase 3 study. The clinical compound team wants to use a primary endpoint and unusual design never utilized before in the therapeutic area you are studying. Which type of meeting would be the best for getting FDA alignment with your pivotal phase 3 study?

Definition

Request a special protocol assessment meeting

Term

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. The 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?

- a 505(b)(2) app'n
- an NDA containing full reports of investigations of safety and effectiveness
- a 505(j) application
- an efficacy supplement

Definition

answer is: an NDA (new drug application) containing full reports of safety and efficacy

the applicant conducted the clinical studies. a new dosage formulation and route of administration will require an NDA.

Term

505(b)(2) application:

Definition

The 505(b)(2) regulatory pathway is another type of NDA submission that can be used to obtain the approval of a new drug. This type of submission differs from the 505(b)(1) NDA in that the product in question contains similar active ingredients to a previously approved drug. As such, the data included in the submission can rely, at least partially, on the Agency’s findings of safety and effectiveness related to another product. Sponsors taking advantage of the 505(b)(2) regulatory pathway can experience a shorter drug development program that requires less resources than the 505(b)(1) regulatory pathway.

Term

505(j) application (ANDA):

Definition

An Abbreviated New Drug Application (ANDA) is an application for a U.S. generic drug approval for an existing licensed medication or approved drug.

The ANDA is submitted to FDA's Center for Drug Evaluation and Research, Office of Generic Drugs, which provides for the review and ultimate approval of a generic drug product. Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the American public. Electronic submissions of ANDAs have grown by 70% since November 2008.[1] The Section IV challenge has been credited with suppressing new drug innovation.[2]

A generic drug product is one that is comparable to a patented drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use. All approved products, both innovator and generic, are listed in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).

Generic drug applications are termed "abbreviated" because (in comparison with a New Drug Application) they are generally not required to include preclinical (animal and in vitro) and clinical (human) trial data to establish safety and effectiveness. Instead, generic applicants must scientifically demonstrate that their product is bioequivalent (i.e., performs in the same manner as the innovator drug). One way scientists demonstrate bioequivalence is to measure the time it takes the generic drug to reach the bloodstream in 24 to 36 healthy volunteers. This gives them the rate of absorption, or bioavailability, of the generic drug, which they can then compare to that of the innovator drug. The generic version must deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the innovator drug. In cases of topically active drugs, the bioequivalence of a drug can be demonstrated by comparing drugs dissolution or transdermal drug absorption is compared with the innovator drug. In cases of systemically active drugs, active drug blood concentration of that drug is compared with the innovator drug.

Using bioequivalence as the basis for approving generic copies of drug products was established by the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act. This Act expedites the availability of less costly generic drugs by permitting FDA to approve applications to market generic versions of brand-name drugs without conducting costly and duplicative clinical trials. At the same time, the brand-name companies can apply for up to five additional years longer patent protection for the new medicines they developed to make up for time lost while their products were going through FDA's approval process. Brand-name drugs are subject to the same bioequivalence tests as generics upon reformulation.

Term

505(b)(1) application:

Definition

The 505(b)(1) regulatory pathway is the traditional New Drug Application (NDA). This pathway is used to obtain the approval of a new drug whose active ingredients have not previously been approved. As you can imagine, this type of submission requires extensive research including both clinical and nonclinical studies to prove the product’s safety and efficacy for the indication being sought. Because of the substantial amount of research and data that is required, 505(b)(1) NDA submissions can take many years to complete, and require a significant amount of resources to get approved.

Term

Common Technical Document modules

Definition

Module 1:9 107 Administrative information;
108 • Module 2: CTD Summaries;
109 • Module 3: Quality;
110 • Module 4: Nonclinical study reports; and
111 • Module 5: Clinical study reports.

Term

A company has submitted its NDA for review. When must additional safety information be submitted to FDA in a safety update report to avoid triggering an extension of the review clock?

Definition

Four months after the initial NDA submission (120 day safety update)
- applicant needs to update pending application with new safety information learned about the drug that may reasonably affect the statement of contraindications, warnings, precautions, and adverse reactions in the draft labeling.
- The applicant is required to submit these 'safety update reports' (1) 4 months after the initial submission, (2) following receipt of an approvable letter, and (3) at other times as requested by FDA.

Term

The difference between advertising and professional labeling for prescription drugs is:

Definition

Advertising must be accompanied by a brief summary and professional labeling must be accompanied by a package insert.

Term

Which of the following does NOT describe requirements for reserve samples?

- a reserve sample representative of one lot of shipped product per year must be retained
- the reserve sample should be at lest twice the amount required for all tests required to determine whether the active ingredient meets established specs except for sterility and pyrogen testing
- any evidence of reserve sample deterioration should be investigated and documented.

Definition

A does NOT describe requirements for reserve samples (A: a reserve sample representative of one lot of shipped product per year must be retained).

A reserve sample representative of each lot of each shipment of each active ingredient shall be retained - NOT one lot of shipped product per year.

Term

All of the following are considered raw data in a preclinical study except:
- final pathology report
- records of quarantine and animal receipt
- animal data entered into the animal chart
- computer printout derived from data transferred to computer media from lab data sheets

Definition

NOT raw data: - computer printout derived from data transferred to computer media from lab data sheets

Term

during the open-label extension phase of a clinical trial for NEWDRUG, some new and different adverse events occurred that could affect final labeling. NEWDRUG's NDA was submitted 6 weeks ago. What is the best way to notify FDA of these events?

Definition

- Four month update.

Term

Company ABC is planning to move its mfring process to a new clinical mfring site. the product is a biologic and currently in a phase 2 clinical study. once the manufacturing site is validated, it will produce material for the planned phase 3 pivotal study. what sort of comparability data would be required for the mfring site change?

Definition

Analytical data and a nonclinical toxicology study.

- to prove that two processes are comparable, bioanalytical data, stability studies, and a nonclinical toxicology study are suggested, prior to starting phase 3 studies at the new manufacturing site.

Term

A special control for a medical device may include

Definition

Class II devices are those for which general controls alone are insufficient to ensure safety and effectiveness, and existing methods are available to provide such assurances. in addition to complying with general controls, Class II devices are also subject to special controls.

Special controls may include:
- special labeling requirements
- mandatory performance standards
- postmarket surveillance

Term

A general control for a medical device may include:

Definition

- establishment registration of companies which are required to register, such as manufacturers, distributors, repackagers, and relabelers
- medical device listing with FDA of devices to be marketed
- mfring devices in accordance with GMP
- labeling devices in accordance with labeling regs
- submission of a premarket notification (510(k)) before marketing a device.

Term

With regard to NDA app'ns, all of the following are true EXCEPT:

a. labeling and promotional material must be submitted during the preapproval period
b. labeling changes are reported in the quarterly report to an approved NDA
c. Fees may be waived if the designated drug is for orphan products
d. NDAs may be submitted in the traditional format on paper or electronically

Definition

Answer: Labeling changes are reported in the quarterly report to an approved NDA

This is NOT something that happens; labeling changes are reported in either the Annual report or an a supplement.

Term

FDA may refuse to file a PMA for all of the following EXCEPT:

a. the app'n does not contain all of the information required by Section 515(c)... of the FD&C act.
b. the PMA contains a false statement of material fact
c. Major or minor deficiencies are identified with the clinical data after substantive FDA review.
d. the PMA is not accompanied by a statement of either certification or disclosure as required by 21CFR54 Financial Disclosure by Clinical Investigators

Definition

answer - C: major or minor deficiencies are noted after substantive FDA review - the FDA cannot refuse to file the PMA, because the substantive review only occurs once FDA has determined that the submission will not be refused.

Term

How long is market exclusivity from competitor product marketing app'n approval for an orphan drug?

Definition

7 years.
-orphan drug exclusivity prevents FDA from approving an app'n for the same drug for the same condition for 7 years.

- New chemical entity (NCE): 5 years exclusivity (but not for ANDA/generics)
- Pediatric exclusivity: extends all other exclusivity by 6 months.
- Paragraph IV (non-infringement of patent) exclusivity provides 180 day exclusivity to any 'first applicant' if all other conditions are met.

Term

FDA has issued a Complete Response Letter to a company. The company views many of the deficiencies as minor. The regulatory professional should meet with the team to:

Definition

Devise a strategy for responding to all deficiencies identified by FDA.

Term

Definition

Term

Definition

Term

Definition

Term

Definition

Term

An NDA holder wants to extend the drug product shelf life from 2 to 3 years. What is the best course of action to pursue?

Definition

Term

A special control for a medical device may include

Definition

Term

General Controls Examples

Definition

Term

Special Controls Examples

Definition

- special labeling requirements
- mandatory performance standards
- postmarket surveillance

Term

How are labeling changes reported for approved NDAs?

Definition

Term

Definition

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

Term

Definition

Term

Definition

Term

Definition

Term

Definition

Term

Postapproval pharmacovigilance for an adverse drug experience is (mandatory and/or voluntary) for (product license holder and/or healthcare professionals)?

Definition

Mandatory for product license holder.
Voluntary for healthcare professionals.

Term

Definition

Term

FDA Form-483

Definition

Term

A company decides to add an additional quality control test during in-process testing of its marketed Class II device. The appropriate submission to send to FDA for this change is:

Definition

Special PMA Supplement - Changes being effected.

The special PMA Suppelment is used when the changes enhances or increases the device's safety.

Term

If a device failure is occurring with greater than expected frequency and investigation of the problem implicates improper use by the end user, which of the following should occur?

Definition

The labeling needs to be revised.

- The labeling should provide appropriate information for proper use of the product.

Term

Definition

Term

Definition

Answer- deletion of a specification for drug substance.

- This type of change requires a PAS (changes to ingredients need a PAS)

Term

Devices under IDEs are EXEMPT from cGMP regs except for design control requirements.

Definition

IDE applications
- study protocols must be reviewed and approved by IRB
- IND/IDE goes into effect 30 days after FDA receives the app'n, unless FDA says otherwise
- App'n must include environmental impact statement

Term

INDs must be compliant with cGMP for finished pharmaceuticals. (the production of the drug is exempt from needing to be in compliance with cGMP)

Definition

Phase 1 investigational drugs should be mfred with the application of some (not full) cGMP.

Term

If classification (class I, II, III) of device is unclear, regulatory professional should submit what?

Definition

513(g) request for information
- is used to ask FDA to determine a device's classification (I, II, III) and applicable requirements under FDC act.

Term

Minor manufacturing changes to an FDA-approved device. Company currently conducting a clinical study for a new indication for the device. Correct submission type?

Definition

IDE 5-day notice.
-During the conduct of a clinical study for a device, if minor mfring changes are made, these changes can be reported to FDA in an IDE 5-day notice.

Term

3-year exclusivity criteria?

Definition

- active moiety must have been the subject of an approved application (NDA, BLA, 505(b)(2), or a supplement to any app'n mentioned) must contain new clinical trial data essential to support the new app'ns approval, and the applicant must conduct the clinical trials.

Term

Company is developing demineralized bone matrix (DBM) product intended as a bone void filler. The product consists of DBM manurfacutred from human allograft bone and a polymer gel to improve DBM handling and containment in the bone defect. The DBM product must comply with the following regs:

Definition

21 CFR 1271 and 820
DBM alone, not combined with another component, is an HCT/P that meets 4 criteria for being regulated SOLELY under PHS act section 361.

However, FDA has determined that the addition of certain components of DBM, such as polymer gels or calcium phosphates, meets the def'n of a device since they are intended to affect the body's structure or function by assisting in filling bone voids. THese DBM products are therefore regulated as devices by CDRH (510k clearance) and must comply with 21CFR820 QSR.
Also, the product also needs to comply with the requirements of 21CFR1271 HCT/P due to the human tissue component.

Human tissue component - 21CFR1271
Devices because they include polymer - 21CFR820 (QSR)

Term

505(b)(2) NDA app'ns are NOT appropriate regulatory submission for the approval to market a New Chemical Entity when the sponsor has a right of reference to all applicable published studies.

Definition

A 505(b)(2) app'n means an application submitted under 505(b)(1) of the act for a drug for which the investigations described in Section 505(b)(1)(A) of the act and relied upon by the applicant for approval of the application were NOT conducted by or for the applicant and for which the applicant has NOT obtained a right of reference or use from the person by or for whom the investigations were conducted.

Term

A class II device with electrical components was subjected to extensive standardized testing such as the IEC series. The tests were conducted by a 3rd party. WHich route of submission is the most suitable for this device?

Definition

Abbreviated 510(k) - when FDA has recognized relevant consensus standards applicable to the device. Abbrev. 510(k) will include a declaration of conformity to the standard, and the declaration should eliminate the need to review actual test data for those aspects of the device addressed by the standards. The review is more efficient.

Term

What scenarios should use a Special 510(k)?

Definition

If a new 510(k) is needed for the modification and if the modification does not affect the intended use of the device or alter the fundamental scientific technology of the device, then summary information that results from the design control process can serve as the basis for clearing the application along with the required elements of a 510(k) found in 21 CFR 807.87.

- Modifications to the indications for use of the device or any labeling change that affects the intended use of the device will not be accepted as a Special 510(k).

Term

Autologous cellular therapy product under development. FDA says it'll be regulated as HCT/P. Based on this info, which regulatory requirements will your company need to be in compliant while mfring this product?

Definition

All Subparts of 21 CFR 1271 except Subpart C (donor eligibility)

21CFR1271 is the regulatory requirements for HCT/Ps. Donor eligibility isn't required because the product is autologous.

Term

What's the deal with the Medicare and Medicaid Patient Protection Act of 1987?

Definition

This law made it illegal for physicians reimburse by federally funded programs to prescribe or recommend a patient use a particular mfr's medical products when the doctor receives payment from that manufacturer.

Term

MDR complaint regarding a common failure mode of an implantable screw. No AE were reported in the complaint. Your firm has initiated a Class I recall for this implantable screw due to safety issues associated with this failure mode. As a regulatory prof, your decision is to -

Definition

The complaint is reportable; an MDR will be filed with FDA within 30 days.
- when a recall is initiated for a particular product failure mode, such failure mode automatically is MDR-reportable to FDA.

Also, while the complaint did not report an AE, the mfr should evaluate the potential to cause an AE if the failure mode were to re-occur.

Term

New drug to used in combo w/a light device for the early detection of bladder cancer. You are asked to develop reg strategy. What's the first step?

Definition

Make a preliminary internal company determination of the combination product's primary mode of action.

- first, the company does a preliminary assessment of the primary mode of action;
- then, the company should request designation with FDA OCP if deemed necessary when the product's classification or FDA center to which it should be assigned is unclear or in dispute.

Term

Senior mgmt asked for justification for Fast Track status for investigational new cancer drug. What are some things about fast track drug justification?

Definition

Preliminary evidence indicates the new drug may decrease clinically significant toxicity of available treatment.

Drug treats a serious disease.

preliminary evidence shows that new drug has potential for superior effectiveness compared to available treatment.

But fast track status does NOT comprise or alter the standards for the drug's safety and effectiveness.

Term

A sponsor may request orphan drug designation of a

Definition

- a previously unapproved drug
OR
- a new orphan indication for an already marketed drug

Term

A clinical trial sponsor is assembling a clinical eval plan for a NCE to include in an IND submission. Which of the following NCE studies does NOT need to be included by the sponsor in the clinical trial registry at www.clinicaltrials.gov?

Definition

Phase 1
Phase 2
Phase 3
Phase 4

Phase 1 trials for drugs do NOT need to be registered with clinicaltrials.gov.
Also, for devices, small feasibility studies are not required to register with clinicaltrials.gov

Term

An IND for a life-threatening disease for which no suitable alternative drugs are available. Which type of IND application would be most suitable for this type of investigation?

Definition

Treatment IND
- treatment INDs are issued as a means of providing eligible subjects with investigational drugs or biologics for the treatment of serious and life-threatening illnesses for which there are no suitable alternative treatments.

Term

Which document required by the QSR tracks each device's mfr by unit, lot, and batch?

Definition

Device history record.

- device history record includes completed reports for each batch, lot or unit, and demonstrates the device is manufactured according to its specifications in the device master record (DMR)

Term

A company using a clinical research organization (CRO) to develop the protocol and monitor the clinical investigators for the company's clinical trial. The regulatory professional may interact with the CRO in which of the following situations?

Definition

Making presentations tot he reviewing division at FDA. - Since regulatory professionals normalyy are not involved in such activities like making presenations to IRBs, witnessing and signing patient consent forms, an arranging for FDA to observe treatment of subjects, only answer 2 is correct (presenting to FDA).

Term

The final authority for ensuring an IND informed consent form's adequacy resides with ...

Definition

the IRB (the FORM itself needs to be adequate, and that is up to the IRB.)

- IRBs have the final authority for ensuring the adequacy of the info in the informed consent document.

Term

A company has promising results from a preclinical mouse study of a biologic agent indicating that the agent is effective against a lab-developed strain of pathogen considered to be a potential bioterrorism agennt. Infection by the agent is known to cause irreversible morbidity and death. At this point, how should the company proceed?

Definition

Submit an IND to start clinical safety trials in humans for approval of the product under the Animal Rule.

- Because the drug's target (the biothreat) causes irreversible morbidity and death, clinical efficacy studies in humans are not ethical. This eliminates choices 1, 2, and 3. Approval under the animal rule requires clinical safety data (to be completed in healthy volunteers).

in other words, the animal rule lets us rely on animal preclinical data for efficacy, when that evaluation wouldn't be ethical. (someone would be sick and need help).

Term

Financial disclosure by investigators carrying out the clinical study is required during the period of the study and for 1 year following its completion if they have -

Definition

been a prior employee of the sponsor company and own stock worth more than $50k.

Term

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

Definition

File a PAS and wait for agency approval before implementation.

- widening acceptance criteria for an in process test performed on the final intermediate would be classified as a PAS.

Term

during a clinical study which is NOT the role of the sponsor?

Definition

Sponsor is NOT supposed to obtain informed consent; the INVESTIGATOR is responsible for obtaining informed consent.

- the SPONSOR is in charge of 'control distribution of drugs'; 'monitor studies', and 'submit IND/Protocol to FDA if required'

Term

The responsibilities of the investigator of a clinical study include all of the following EXCEPT:

Definition

INVESTIGATOR does not - dispose of unused study medication; instead, the SPONSOR is required to dispose of the unused study medication in a well-documented way.

Term

The investigator is responsible for controlling the study medication during the study, but the sponsor is required to dispose of the unused medication in a well-documented way.

Definition

the investigator also:
- ensures compliant IRB reviews and approves study
- provides current and updated financial disclosure information
- obtains informed consent

Term

What is included in the Device Master Record?

Definition

Labeling specifications; A Device Master Record is a compilation of all the instructions, drawings and other records, that must be used to produce a product.

Term

A drug clinical trial subject involved in car accident ends up with surgery, ruptured spleen, requires hospitalization. What should be done?

Definition

No expedited reporting is required and subject can continue the study when recovered.

Term

When can a notice of Intent to Revoke License be issued by CBER?

Definition

- Unable to gain access to mfring facility
- licensed products no longer safe and effective for intended use
- mfr fails to conform to applicable standards to ensure product safety, potency, and purity.

Failure to report serious AE is a Postapproval reporting issue.

Term

Removal of a distributed product involved in a minor violation that would be subject to legal action by FDA is known as:

Definition

Product recall.

Term

What is stock recovery?

Definition

a firm's removal or correction of a product that has not been marketed or that has not left the direct control of the firm. (the product is located on premises owned by, or under control of, the firm and no portion of the lot has been released for sale or use.

Term

What is market withdrawal?

Definition

A firm's removal of correction of a distributed product which involves a minor violation that would NOT be subject to legal action by FDA or which involves no violation (normal stock rotation practices, routine equipment adjustments and repairs, etc.)

Term

What is a product recall?

Definition

A firm's removal or correction of a marketed product that the FDA considers to be in violation of the laws it administers and against which the FDA would initiate legal action (seizure). Recall does not include market withdrawal or stock recovery.

Term

US medical device company wants to sell Class III product in Australia, where it has approval.The product doesn't have approval in US yet. Product is mfred in accordance w us QSR. What does mfr need to do in order to sell in australia?

Definition

Send a simple notification to FDA and obtain 802 certificate of exportability from FDA (if requested by australia)

Term

in most cases, a biological product mfr should retain samples for a minimum of what amount of time beyond the exp date?

Definition

6 months.
- mfrs should retain for a period of at least 6 months after the exp date, unless a different time period is specified in additional standards, a quantity of representative material of each lot of each product, sufficient for examination and testing for safety and potentcy, except Whole Blood, Cryoprecipitated AHF, Platelets, RBCs, Plasma, and source plasma and allergenic products prepared by physician's prescription.

Term

An NDA holder wants to extend the drug product shelf life from 2 to 3 years. What is the best course of action to pursue?

Definition

Present 3 years of real time stability data on 3 consecutive batches following an approved stability protocol in the NDA annual report.

- an extension of an expiration dateing period based on full shelf life data on production batches obtained under a protocol approvied in the application.

in the absence of an approved/agreed upon stability protocol with FDA, if the sponsor chose to provide real time stability data on 3 batches, the change should be submitted as a PAS.

Term

a defective product was released into distribution and has caused patient injuries. the pts were treated in a local hospital for reversible medical consequences as a result of the defective product. what type of recall classification would be assigned to this product?

Definition

Class II recall - exposure to this product may cause temporary or medically reversible adverse health consequences.

Term

How often should the investigator of an IND's CV be updated -

Definition

it does not need to be updated. (CV is not required)

Term

new blood pressure medicine NOSTRESS, clinical trials are completed and demonstrate similar safety and efficacy to drugs currently on the market. Clinical data are ready for submission to FDA. Chemistry, mfring, and controls data are not ready, but will be in 2 months. What is the fastest NDA filing method?

Definition

Wait until CMC data are ready to submit.

- rolling review and fast track are ONLY for drugs treating serious disease and meeting an unmet medical need;
- the 4 month safety report is for clinical safety only.

Term

What is form FDA 482 used for?

Definition

FDA may conduct an inspection of your operation for a variety of reasons, such as a routinely scheduled investigation, a survey, or a response to a reported problem. The investigator will present credentials and "Notice of Inspection" (FDA Form 482) upon arriving at your plant.

Term

What is form FDA 483 used for?

Definition

An FDA Form 483 is issued to firm management at the conclusion of an inspection when an investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts.

This form with the eponymous number 483 is used by the executing Inspector (FDA Investigator) to document the deficiencies he found. It is issued at the end of the inspection and should be answered officially. This response is expected within 15 working days after its issuance. Only then it is guaranteed that the statement will be taken into account in a possible Warning Letter (see below). Sometime, in the case of reasonable compliance, no 483 is issued.

Term

What is form FDA 1572 used for?

Definition

The Statement of Investigator, Form FDA 1572 (1572), is an agreement signed by the
investigator to provide certain information to the sponsor and assure that he/she will
comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic.

Term

What is an EIC (establishment investigation report) used for?

Definition

The EIR is also created by the Inspector in addition to the form 483. This should be done within 30 working days. The EIR is then examined by the responsible Center or District Office of the FDA, issuing the following statuses:

NAI: No Action Indicated - there were no objectionable items found during the inspection
VAI: Voluntary Action Indicated - objectionable items were found, but no action is required on the part of the authority. All of the company's actions are on a voluntary basis.
OAI: Official Action Indicated - objectionable items were found and further regulatory measures will be derived (e.g. Warning Letter).
The EIR is forwarded to the inspected company. As part of the so-called 'Freedom of Information Act' it can also be requested by other companies, though. But experience has shown that the disclosure of a foreign EIR may take some time.

Term

The Quality System Regulation calls for finished device mfrs to carry out all of the following EXCEPT:

- quality audits conducted by individuals who do not have direct responsibility for the operation being audited.
- annual audits of operations
- documenting the dates and results of quality audits and re-audits
- having findings reviewed by management responsible for the matters audited

Definition

Answer: QSR does not call for finished device mfrs to carry out annual audits of operations.

- FDA recommends periodic audits and does not specify a time.

Term

a deficiency letter may be issued to a company during a BLA review for which of the following?

Definition

Clinical testing did not include enough test subjects.

- a drug master file is optional in a BLA and pertinent info regarding facilities and processing can be incorporated directly into the BLA.

Term

An NDA containing full reports of investigations of safety and effectiveness is required for...

Definition

among other things, a new dosage formulation and route of administration will require a new NDA.

Term

a company received FDA approval to market a new drug. when must the drug sponsor submit labeling content in a structured product labeling (SPL) format using FDA's automated drug registration and listing system?

Definition

ASAP, but no later than 14 days from the date of the FDA approval letter.

Term

Company Z selected a proprietary name for its new molecular entity, currently in development. The NDA will be submitted in 6 months. All of the following are relevant to the proprietary name EXCEPT:

Definition

TRUE:
- the request for proprietary name approval may be submitted WITH the NDA
- the request for the proprietary name approval may be submitted PRIOR to the NDA
- FDA will communicate to the applicant a tentative acceptance or non-acceptance of the proposed proprietary name submitted with the NDA within 90 days of the receipt of the complete submission.

NOT TRUE:
- The proprietary submission package may be submitted up to 1 month after the NDA submission;
----the request for proprietary name approval must be submitted NO LATER THAN THE NDA. Companies have the option of submitting a proprietary name request PRIOR to NDA submission under the IND.
------FDA needs to communicate IND proprietary name acceptance or non-acceptance within 180 days of the receipt of the complete submission; and within 90 days of the receipt of the complete submission for an NDA/BLA.

Term

A 505(b)(2) NDA is not an appropriate regulatory submission for the approval to market a:

new chemical entity when the sponsor has a right of reference to all acceptable published studies.

Definition

A 505(b)(2) NDA is an app'n where approval of the new drug relies on data that, at least in part, are not developed by the applicant.

A 505(b)(2) application means an application submistted under section 505(b)(1) of the act for a drug for which the investigations described in Section 505(b)(1)(A) of the act and relied upon by the applicant for approval of the app'n were note conducted by or for the applicant AND for which the applicant has NOT obtained a right of reference or use from the person by or for whom the investigations were conducted.

Term

How many days does FDA have to review an abbreviated 510(k)?

Definition

90 days.

Special 510(k)s and abbreviated 510(k)s are alternate approaches to the traditional 510(k), with the goal of streamlining application evaluation, the special 510(k) review clock is 30 days.

The review clock for the abbreviated 510(k is 90 days.

Term

A sponsor intends to submit a special protocol assessment (SPA) request for a clinical trial that will form the primary basis of an NDA efficacy claim. Which of the following are TRUE?

Definition

TRUE: A sponsor can submit a revised protocol while the agency is reviewing an earlier version of the same protocol.

FDA can communicate w/the sponsor regarding the protocol before issuing a SPA letter. In such cases, the sponsor can choose to submit a revised protocol. If a sponsor submits a revised protocol, for any reason, while the agency is reviewing an earlier version of the same protocol, FDA usually will not respond to the questions posed about the earlier version of the protocol and will consider the original request withdrawn. THe FDA will consider a request for a SPA of a revised protocol to be a new request and will act on the revised protocol within 45 days.

Term

A Special Protocol Assessment (SPA) is an advanced declaration from the Food and Drug Administration that an uncompleted Phase III trial's design, clinical endpoints, and statistical analyses are acceptable for FDA approval. The purpose of a SPA is to allow a company to run or initiate a clinical trial of an experimental drug without fear that the FDA will object to the trial design itself, in the event that the company subsequently applies for product approval.

Three types of protocols related to PDUFA products are eligible for this special protocol assessment under the PDUFA goals:[1]

animal carcinogenicity protocols,
final product stability protocols,
clinical protocols for phase 3 trials whose data will form the primary basis for an efficacy claim if the trials had been the subject of discussion at an end-of-phase 2/pre-phase 3 meeting with the review division, or in some cases, if the division agrees to such a review because the division is aware of the developmental context in which the protocol is being reviewed and the questions are being answered.
The clinical protocols for phase 3 trials can relate to efficacy claims that will be part of an original new drug application (NDA) or Biologic License Application (BLA) or that will be part of an efficacy supplement to an approved NDA or BLA.

Definition

Term

Product currently available by Rx only that comes in several different strengths. Due to the nature of the symptoms the lower doses treat, the drug is a candidate for a partial switch to an OTC med. What type of marketing app'n would need to be filed to support the partial switch of the product?

Definition

NDA

- because the drug is not a candidate for FULL switch to OTC, the product in an OTC status is considered to be a 'new drug'.; so a new NDA under section 505(b)(1) must be submitted.

Term

A special 510(k) must contain all of the following components except:

- proposed labeling
- design controls activity summary
- 510(k) summary or 510(k) statement
- Summary of safety and effectiveness data

Definition

NOT NEEDED for special 510(k): Summary of safety an effectiveness data.

Term

Which of hte following is NOT required in a BLA but is required in a NDA?

Definition

Field copy certification is NOT required for a BLA.

Field copy certification applies only to NDA products; while other sections (User fee cover sheet, chemistry section, and debarment certification) are required for both BLAs and NDAs.

Term

IND for a new investigational drug's use on subjects with a life-threatening disease for which no suitable alternative drugs are available. Which type of IND is most suitable?

Definition

Treatment IND - these are issued as a means of providing eligible subjects with investigational drugs or biologics for the treatment of serious and life-threatening illnesses for which there are no suitable alternative treatments.

-

Term

Investigator IND

Definition

An Investigator IND is submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. A physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population.

Term

Treatment IND

Definition

Treatment IND is submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.

Term

Emergency USE IND

Definition

Emergency Use IND allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with 21CFR , Sec. 312.23 or Sec. 312.20. It is also used for patients who do not meet the criteria of an existing study protocol, or if an approved study protocol does not exist.

Term

A product has a drug, biologic, and device components. Product classification hasn't been classified previously by FDA. What is the most appropriate reg pathway?

Definition

A request for designation (RFD) should be sent to the office of combination products (OCP) at FDA to determine primary mode of action and assign the center with primary jurisdiction.

An unclassified combination product should be evaluate by OCP through the RFD process to determine the primary mode of action.

an RFD is also referred to as an applican't sletter of request. It is a written submission to OCP. RFD's generally request a determination of (1) the regulatory identity or classification of a product as a drug, device, biological product, or combination product.

Term

Once an IND is in effect, an amendment cannot be made when the sponsor indends to conduct a clinical investigation with an exception from informed consent for emergency research.

Definition

whenever a sponsor intends to conduct a clinical investigation with an exception from informed consent for emergency research, the sponsor shall submit a SEPARATE IND to FDA for the investigation.

Term

Under 21cFR 314.80: postmarketing safety reports must be submitted to FDA for:

- 15 day alert reports: Serious and unexpected adverse experiences from all sources (domestic and foreign)

- Periodic adverse events reports: Domestic spontaneous adverse events that are:
---serious and expected
---non-serious and unexpected
---non-serious and expected
---quarterly for the first 3 years, then annually.

Definition

Drug Postmarketing safety reporting requirements

Term

All of the following are types of WHAT?

- death
- life-threatening adverse experience
- inpatient hospitalization - new or prolonged
- persistent/significant disability/incapacity
- congenital birth defect
- something that may jeopardize the patient and require intervention to prevent a serious outcome.

Definition

Serious Adverse Event (drug)

Term

Medical device reporting

Definition

mfrs are required to report death or serious injury resulting from their device. (30 days)

- must also report when they become aware that their device has malfunctioned and would be likely to cause or contribute to a death or serious injury if malfxn were to recur. (30 days)

Importers: required to report to FDA and mfr when they learn that a device may have caused or contributed to death or serious injury.

User facility (hospital) - must report a suspected medical device-related death to FDA AND the mfr. Must report medical device-related serious injury to MFR, or to FDA if mfr is unknown.

User facilities must also submit annual reports by Jan 1 of each year. (Form 3419 annual user facility report)

Term

Which is NOT TRUE regarding post-approval pharmacovigilance of a drug?

A. It is intended to detect all medically important AEs and uncommon safety risks in the 'real world' of clinical practice.

B. Health professionals report all adverse drug reactions associated with the use of a marketed drug

C. Adverse effects from products in the same pharmacological class as the marketed drug must be considered along with those for the marketed drug

D. Serious and unexpected adverse drug reactions in patients treated with the product outside the US need to be reported within within 15 days after initial notification.

Definition

Answer: B.

Term

The marketing dept. has designed a journal advertisement that mentions leadership in a particular therapeutic area and includes on the name of the company's approved prescription drug products. Which of the following should be included in the advertisement to be in compliance with regulations?

A. Full prescribing info
B. A brief summary of the prescribing info
C. all the available names of the drug product and the established name of each of the active ingredients in the drug product
D. A complete listing of adverse events

Definition

Answer: C.

Term

What additional FDA clearances are required to export a drug approved by FDA when the drug will be used for its approved use?

A. Certificate of Free Sale
B. Customs Tax Stamps
C. No clearance required
D. FDA receipt for sample Form-484

Definition

Answer: C.

Term

Which activity is regulated by FDA?

A. Advertising of OTC drug?
B. Advertising of a toothpaste that does not contain fluoride
C. Refuse entry of an imported drug into US
D. Placement of substances on a Class IV narcotic drug schedule

Definition

Answer: D.

FDA places substances on the Class IV narcotics drug schedule

Term

WRT drug product distribution procedures, a distributor is required to do all of the following EXCEPT:

A. establish a system whereby the oldest approved drug is distributed last
B. Establish written procedures describing the distribution of drug products
C. Establish a system whereby the oldest approved stock of a drug is distributed first
D. Establish a system by which the distribution of each lot can readily be tracked and the lot recalled if necessary

Definition

Answer: A.

Term

Because of reported dispensing errors due to the similarity of proprietary drug names, one of the companies involved has decided to quickly and voluntarily notify physicians and others responsible for providing patient care about the issue via a 'Dispensing Error Alert'. In this approach, the company is NOT required to:

A. use first class mail and number 10 white envelopes
B. Use appropriate language on the outside of the mailing envelope that indicates the nature of the alert
C. notify FDA of its action prior to disseminating the dispensing alert notification.
D. Include its name and address in the upper left hand corner of the envelope

Definition

Answer C.

Term

Establishment registration

Definition

Manufacturers (both domestic and foreign) and initial distributors (importers) of medical devices must register their establishments with the FDA. All establishment registrations must be submitted electronically unless a waiver has been granted by FDA. All registration information must be verified annually between October 1st and December 31st of each year. In addition to registration, foreign manufacturers must also designate a U.S. Agent. Beginning October 1, 2007, most establishments are required to pay an establishment registration fee.

Term

Medical device listing

Definition

Manufacturers must list their devices with the FDA. Establishments required to list their devices include:

manufacturers,
contract manufacturers that commercially distribute the device,
contract sterilizers that commercially distribute the device,
repackagers and relabelers,
specification developers,
reprocessors single-use devices,
remanufacturer
manufacturers of accessories and components sold directly to the end user
U.S. manufacturers of "export only" devices

Term

Premarket notification (510K)

Definition

If your device requires the submission of a Premarket Notification 510(k), you cannot commercially distribute the device until you receive a letter of substantial equivalence from FDA authorizing you to do so. A 510(k) must demonstrate that the device is substantially equivalent to one legally in commercial distribution in the United States: (1) before May 28, 1976; or (2) to a device that has been determined by FDA to be substantially equivalent.

Premarket Notification 510(k)
On October 26, 2002 the Medical Device User Fee and Modernization Act of 2002 became law. It authorizes FDA to charge a fee for medical device Premarket Notifcation 510(k) reviews. A small business may pay a reduced fee. The application fee applies to Traditional, Abbreviated, and Special 510(k)s. The payment of a premarket review fee is not related in any way to FDA's final decision on a submission.

510(k) Review Fees
Most Class I devices and some Class II devices are exempt from the Premarket Notification 510(k) submission. A list of exempt devices is located at:

510(k) Exempt Devices
If you plan to send a 510(k) application to FDA for a Class I or Class II device, you may find 510(k) review by an Accredited Persons beneficial. FDA accredited 12 organizations to conduct a primary review of 670 types of devices. By law, FDA must issue a final determination within 30 days after receiving a recommendation from an Accredited Person. Please note that 510(k) review by an Accredited Person is exempt from any FDA fee; however, the third-party may charge a fee for its review.

Term

Premarket Approval (PMA)

Definition

Premarket Approval (PMA) - 21 CFR Part 814
Product requiring PMAs are Class III devices are high risk devices that pose a significant risk of illness or injury, or devices found not substantially equivalent to Class I and II predicate through the 510(k) process. The PMA process is more involved and includes the submission of clinical data to support claims made for the device.

Premarket Approval
Beginning fiscal year 2003 (October 1, 2002 through September 30, 2003), medical device user fees apply to original PMAs and certain types of PMA supplements. Small businesses are eligible for reduced or waived fees.

Term

IDE for clinical studies

Definition

An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification 510(k) submission to FDA. Clinical studies with devices of significant risk must be approved by FDA and by an Institutional Review Board (IRB) before the study can begin. Studies with devices of nonsignificant risk must be approved by the IRB only before the study can begin.

Term

Quality system regulation

Definition

The quality system regulation includes requirements related to the methods used in and the facilities and controls used for: designing, purchasing, manufacturing, packaging, labeling, storing, installing and servicing of medical devices. Manufacturing facilities undergo FDA inspections to assure compliance with the QS requirements.

Term

Labeling requirements

Definition

Labeling includes labels on the device as well as descriptive and informational literature that accompanies the device.

Term

medical device reporting

Definition

Incidents in which a device may have caused or contributed to a death or serious injury must to be reported to FDA under the Medical Device Reporting program. In addition, certain malfunctions must also be reported. The MDR regulation is a mechanism for FDA and manufacturers to identify and monitor significant adverse events involving medical devices. The goals of the regulation are to detect and correct problems in a timely manner.

Term

General labeling requirements for medical devices

Definition

- name and place of business of mfr, packer, or distributor
- intended use
- adequate directions
-

Term

FDA's website for IDE

Definition

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/default.htm

Term

Data requirements for PMA application

Definition

Technical Sections: The technical sections containing data and information should allow FDA to determine whether to approve or disapprove the application. These sections are usually divided into non-clinical laboratory studies and clinical investigations.

Non-clinical Laboratory Studies Section: Non-clinical laboratory studies section includes information on microbiology, toxicology, immunology, biocompatibility, stress, wear, shelf life, and other laboratory or animal tests. Non-clinical studies for safety evaluation must be conducted in compliance with 21CFR Part 58 (Good Laboratory Practice for Nonclinical Laboratory Studies). To assist you in determining the appropriate preclinical bench studies for your device, refer to the applicable guidance documents and standards identified in the Product Classification database for your device. You may also seek input from the review branch via the Pre-Submission Program.

Clinical Investigations Section: Clinical investigations section includes study protocols, safety and effectiveness data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, tabulations of data from all individual subjects, results of statistical analyses, and any other information from the clinical investigations. Any investigation conducted under an Investigational Device Exemption (IDE) must be identified as such.

Like other scientific reports, FDA has observed problems with study designs, study conduct, data analyses, presentations, and conclusions. Investigators should always consult all applicable FDA guidance documents, industry standards, and recommended practices. Numerous device-specific FDA guidance documents that describe data requirements are available. Study protocols should include all applicable elements described in the device-specific guidance documents.

Term

Who is Required to Submit a 510(k)?

The FD&C Act and the 510(k) regulation (21 CFR 807) do not specify who must submit a 510(k). Instead, they specify which actions, such as introducing a device to the U.S. market, require a 510(k) submission.

Definition

The following four categories of parties must submit a 510(k) to the FDA:

Domestic manufacturers introducing a device to the U.S. market;

Finished device manufacturers must submit a 510(k) if they manufacture a device according to their own specifications and market it in the U.S. Accessories to finished devices that are sold to the end user are also considered finished devices. However, manufacturers of device components are not required to submit a 510(k) unless such components are promoted for sale to an end user as replacement parts. Contract manufacturers, those firms that manufacture devices under contract according to someone else’s specifications, are not required to submit a 510(k).
Specification developers introducing a device to the U.S. market;

A specification developer develops the specifications for a finished device, but has the device manufactured under contract by another firm or entity. The specification developer submits the 510(k), not the contract manufacturer.
Repackers or relabelers who make labeling changes or whose operations significantly affect the device.

Repackagers or relabelers may be required to submit a 510(k) if they significantly change the labeling or otherwise affect any condition of the device. Significant labeling changes may include modification of manuals, such as adding a new intended use, deleting or adding warnings, contraindications, etc. Operations, such as sterilization, could alter the condition of the device. However, most repackagers or relabelers are not required to submit a 510(k).
Foreign manufacturers/exporters or U.S. representatives of foreign manufacturers/exporters introducing a device to the U.S. market.
Please note that all manufacturers (including specification developers) of Class II and III devices and select Class I devices are required to follow design controls (21 CFR 820.30) during the development of their device. The holder of a 510(k) must have design control documentation available for FDA review during a site inspection. In addition, any changes to the device specifications or manufacturing processes must be made in accordance

Term

When a 510(k) is Required

Definition

A 510(k) is required when:

Unless exempt, introducing a device into commercial distribution (marketing) for the first time. After May 28, 1976 (effective date of the Medical Device Amendments to the Act), anyone who wants to sell a device in the U.S. is required to make a 510(k) submission at least 90 days prior to offering the device for sale, even though it may have been under development or clinical investigation before that date. If your device was not marketed by your firm before May 28, 1976, a 510(k) is required.
There is a change or modification to a legally marketed device and that change could significantly affect its safety or effectiveness. The burden is on the 510(k) holder to decide whether or not a modification could significantly affect safety or effectiveness of the device. Any modifications must be made in accordance with the Quality System regulation, 21 CFR 820, and recorded in the device master record and change control records. It is recommended that the justification for submitting or not submitting a new 510(k) be recorded in the change control records.

A new 510(k) submission is required for changes or modifications to an existing device, where the modifications could significantly affect the safety or effectiveness of the device or the device is to be marketed for a new or different intended use.

Term

When a 510(k) is NOT Required

Definition

The following are examples of when a 510(k) is not required.

You sell unfinished devices to another firm for further processing or sell components to be used in the assembling of devices by other firms. However, if your components are to be sold directly to end users as replacement parts, a 510(k) is required.
Your device is not being marketed or commercially distributed. You do not need a 510(k) to develop, evaluate, or test a device. This includes clinical evaluation. Please note that if you perform clinical trials with your device, you are subject to the Investigational Device Exemption (IDE) regulation (21 CFR 812).
You distribute another firm's domestically manufactured device. You may place a label on the device, "Distributed by ABC Firm" or "Manufactured for ABC Firm," (21 CFR 801.1) and sell it to end users without submission of a 510(k).
In most cases, if you are a repackager or a relabeler and the existing labeling or condition of the device is not significantly changed. The labeling should be consistent with the labeling submitted in the 510(k) with the same indications for use and warnings and contraindications.
Your device was legally in commercial distribution before May 28, 1976 and has not been significantly changed or modified in design, components, method of manufacture, or intended use. These devices are "grandfathered" and you have Preamendment Status documentation to prove this.
The device is made outside the U.S. and you are an importer of the foreign made medical device. A 510(k) is not required if a 510(k) has been submitted by the foreign manufacturer and received marketing clearance. Once the foreign manufacturer has received 510(k) clearance for the device, the foreign manufacturer may export his device to any U.S. importer.
Your device is exempted from 510(k) by regulation (21 CFR 862-892). That is, certain Class I or II devices can be marketed for the first time without having to submit a 510(k). A list of the Class I and II exempted devices can be found on Medical Device Exemptions 510(k) and GMP Requirements. However, if the device exceeds the limitations of exemptions in .9 of the device classification regulation chapters (e.g., 21 CFR 862.9, 21 CFR 864.9), such as the device has a different intended use or operates using a different fundamental scientific technology than a legally marketed device in that generic type of device, or the device is a reprocessed single-use device, then a 510(k) must be submitted to market the new device.

Term

Some examples of items discussed in a Type B meeting are:

Definition

- Pre-IND
- Certain End-of-Phase 1 meetings
- End-of-Phase 2
- Pre-BLA

Term

Phase 2 clinical trials are being planned for a novel cancer drug. All of the following are appropriate factors in this phase of the study EXCEPT:

a. enrollment of cancer pts
b. enrollment of healthy subjects
c. study of one or more indications
d. collection of efficacy data

Definition

Answer: b. Enrollment of healthy subjects is NOT appropriate for a Phase 2 clinical trial.

Phase 2 includes controlled clinical studies conducted to evaluate drug's effectiveness for a particular indication/indications in pts w/the disease or condition under study, to determine the common short-term side effects and risks associated w/the drug. Phase 2 studies typically well-controlled, closely monitored and usually conducted in a few hundred pts.

Term

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
Request a Type A meeting with FDA
Request a Type B meeting with FDA
Request a Type C meeting with FDA

Definition

No official meeting request will be submitted to a product subject to a monograph, since there is no NDA or IND upon which to base the meeting request.

Term

A physician reports to a mfr a pt was hospitalized w acute sepsis after treatment w an approved device. This side effect is not listed in the pkg insert. The mfr must report this even to FDA no later than...

Definition

30 calendar days after receipt or becoming aware of info.

Term

The supplier of the active drug substance for a company's OTC monograph drug product informs the company it will be moving its drug substance production from the current plant to a new mfring facility in another state in 6 months. The supplier states all mfring processes will remain the same and the specs will not change. the company intends to qualify the change suitably. How should the company report the change to FDA?

Definition

The change would be reported during the annual drug listing process.

- monograph drugs are NOT subject to annual reports or preapproval supplements. An active drug substance supplier is not prescribed by regulation (so a monograph change is not warranted). However the mfing API drug establishment number will change and this must be updated with FDA as part of the annual drug listing process.

Term

FOIA allows a mfr to:

Definition

Obtain public documents on another mfr's product.

Term

During a QSIT audit of a medical device mfr, it is important for the company to clearly identify what the FDA inspector is requesting and thoroughly review all documentation before presenting the documentation to the FDA inspector.

Definition

An FDA inspector can request and receive the audit schedule information to establish the company has an internal audit program. However, a company is not obligated to
provide internal audit report summaries. In this case, the internal audit summary was provided by the company in error, not at the request of the inspector. It is important for a
company to provide only information an inspector requests. The inspector can use any information provided to him or her to identify deficiencies in a company’s quality system, even if it was not requested.

Term

A blood center has discovered a unit of packed red blood cells for commercial use previously shipped to a local hospital was stored inappropriately for four days during the
manufacturing process. The blood center should:

Definition

Recall the blood product and initiate a blood product deviation report to CBER within 45 calendar days of discovery of the deviation

Term

Distribution records for drug products must reference or contain:

Definition

- Name and address of the consignee (buyer)
- name and strength of the product
- description of the dosage form
- date and quantity shipped
- lot or control number of the drug product.

--for compressed medical gas products, distribution records are not required to contain lot or control numbers

Term

Which is NOT required for compliance under 21CFR Part 11 (electronic records and electronic signatures)?

a. Manually generated, time-stamped audit trails to record the date and time of operator entries and actions that create, modify, or delete electronic records
b. validation of systems to ensure accuracy, reliability, consistent intended performance and the ability to discern invalid or altered records.
c. authority checks to ensure that only authorized ppl can use the system, e-sign a record, access the operation or computer system input or output device, alter a record, or perform the operation at hand.
d. establishment of, and adherence to, written policies holding individuals accountable for actions initiated under their e-signatures, in order to deter record and signature falsification.

Definition

A.NOT REQUIRED: Manually generated, time-stamped audit trails to record the date and time of operator entries and actions that create, modify, or delete electronic records

Term

During the open-label extension phase of a clinical trial for NEWDRUG, some new and different adverse events occurred that could affect final labeling. NEWDRUG’s NDA
was submitted six weeks ago. What is the best way to notify FDA of these adverse events?

Definition

Four-month update

- Section 505(i) requires an NDA update four months after the initial submission—entitled “safety update report” by the code—which would affect the draft labeling’s
contraindication, warnings, precautions and adverse reactions sections.

Term

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?

a. Products to respond to current and anticipated public health emergencies
b. Products that show evidence of safety and effectiveness in a new subpopulation
c. Products for which a nationwide shortage has been identified
d. First generic products for which there are no blocking patents or exclusivities on the Reference Listed Drug (RLD)

Definition

NOT SPECIFIED: Products that show evidence of safety and effectiveness in a new subpopulation.

Prioritization of Review for ANDA is granted under four major categories: :
1) Submissions containing patent certifications pursuant to 21 CFR 314.94(a)(12
2) Submissions related to drug shortage
3) Supplements for which expedited review is requested under 21 CFR 314.70(b)(4)
Under 21 CFR 314.70(b)(4), an applicant “may ask FDA to expedite its review of a supplement for public health reasons or if a delay in making the change described in [the
supplement] would impose an extraordinary hardship on the applicant.” For purposes of expedited review, “extraordinary hardship on the applicant” will be interpreted to
include the following:
Catastrophic events such as explosion, fire or storm damage to manufacturing facilities. Events that could not have been reasonably foreseen by the applicant, and for
which the applicant could not have planned. Examples include:
Abrupt discontinuation of supply of an active ingredient, packaging material or container closure system
Relocation of a facility or change in an existing facility because of a catastrophic event. (In the absence of a catastrophic event, the applicant should contact OGD
early in the planning stage of a contemplated relocation or change.)

Term

The following biological products are regulated by CBER EXCEPT:

- Immunizing toxoids

- monoclonal abs for in vitro use

- monoclonal abs for in vivo use

- infusion of animal sourced cells into a human

Definition

answer: CBER does NOT regulate monoclonal antibodies for in vivo use.

- monoclonal antibodies for in vivo use were transferred to CDER's OND in 2003.

Term

An API mfr developed a validated process to mfr an active ingredient used in generic drug products. The API mfr is collaborating w/3 different generic mfrs who are planning to submit an ANDA for another generic version of the drug. The API mfr submitted a Drug Master File (DMF) to FDA to describe the API's chemistry, mfring, and controls. Which of the following is NOT true regarding DMF?

- The API mfr can authorize FDA to reference the DMF in the ANDAs of the 3 generic mfrs

- Although the DMF is submitted to FDA, it is never approved or disapproved

- the API mfr submits a Type II DMF for the active ingredient

- The API mfr must update the DMF only when the submitted info changes or is no longer accurate

Definition

Answer: NOT TRUE: - The API mfr must update the DMF only when the submitted info changes or is no longer accurate

Rationale: The holder needs to also provide an ANNUAL report on the anniversary date of the original submission.

Term

Your company's commercial product is mfred by a third-party mfr (TPM). The mfring site undercharges one of the excipients. Without contacting your company, the TPM decides to rework the batch and now would like the product to be released upon completion of the investigation. Your technical team contacts you for regulatory advice on whether the lot can be released upon approval of the investigation. As a regulatory professional. as a first step you:

Definition

Correct first step: assess whether the rework steps are within the regulatory filing and whether there is a potential regulatory impact.

Product release and disposition is a quality responsibility, not regulatory. The reg. prof. is responsible for reviewing the event and assessing whether the additional steps performed in the mfring process are allowed within the regulatory filing. The team may decide to include the rework procedure; however, additional data might be needed for the submission.

Term

A US medical contract mfr has customers for whom it mfrs medical device components (parts) and finished medical devices. To date, all medical products produced are either parts for Class II devices or are class III finished medical devices. The new business manager contacts the regulatory manager to assess the impact of possible new business involving a class III device. What is the first question the regulatory manager should ask to begin to assess the impact of Class III on plant operations?

Definition

Is it a COMPONENT, or is it a FINISHED DEVICE that would be manufactured?

- because:the regulation doesn't apply to mfrs of components of finished devices. QSR is mandatory for finished devices.

The QSR applies to finished device mfrs that intend to distribute medical devices commercially.

Term

NDA Priority Review

Definition

drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.

Term

Special protocol assessment

Definition

applies to a phase 3 study; must be requested before study initiation.

SPA is an advanced declaration from FDA that an uncompleted Phase III trial's design, clinical endpoints, and stats analyses are acceptable for FDA approval.

three types of protocols related to PDUFA products are eligible for this special protocol assessment:
- animal carcinogenicity protocols
- final product stability protocols
- clinical protocols for phase III trials whose data will form the primary basis for an efficacy claim (does it work) if the trials had been the subject of discussion at an end-of-phase 2/phase 3 meeting.

Term

Fast track designation

Definition

designation by the United States Food and Drug Administration (FDA) of an investigational drug for expedited review to facilitate development of drugs which treat a serious or life-threatening condition and fill an unmet medical need.

Term

Subpart H - accelerated approval of new drugs for serious or life-threatening illness

Definition

FDA may grant marketing approval for a new drug product on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity.

Term

If an AE for an investigational drug in a phase 3 trial is Grade 4 (Life threatening/serious), report as a serious and unexpected AE associated with the investigational drug within how many days?

Definition

by phone or fax within 7 days; followed by a written report within 8 additional days.

- for drugs, the reporting criteria is serious and unexpected.
- for devices, the reporting criteria is serious. (not unexpected)

Term

During a clinical study, which is NOT the role of the sponsor?
- control distribution of drugs
- monitor studies
- obtain informed consent
- submit ind/protocol to FDA if required

Definition

The sponsor is NOT responsible for obtaining informed consent. The investigator is responsible for obtaining informed consent.

Term

to begin a clinical trial using xenotranslplantation, you must submit a

Definition

IND (even though the approved products are regulated by CBER); FDA determines if the product should be submitted as an IND or IDE.

Term

A drug master file may be used for any of the following purposes EXCEPT:

- supplemental info on the drug product or substance
- supplemental info for any type of submission to the agency
- FDA approval of the drug master file
- inforporation by reference of all or part of any drug master file's contents to support a submission when the holder has authorized the incorporation in writing.

Definition

The Drug Master File may NOT be used for FDA approval of the drug master file.

- FDA does not approve or disapprove the DMR - it only reviews them as supplemental information

Term

When used in promotion the established name of a drug product should be;

Definition

printed in letters at least half as large as the letters of the proprietary name or designation with which it is joined.

Term

A defective product was released into distribution and has cause pt injuries. The pts were treated in a local hospital for reversible medical consequences as a result of the defective product. What type of recall classification would be assigned to this product?

Definition

Class II - temporary or medically reversible adverse health consequences.

Term

A company wants to modify its legally marketed device in a way that doesn't affefct the device's intended use or alter its fundamental scientific technology. If the modified device's design outputs meet the design input requirements, this change would best be filed as a:

Definition

Special 510(k): for a special 510(k), the change should not affect intended use, alter the fundamental scientific technology of the device.

Term

A handling and storage system for medical devices must always include:

Definition

procedures for inspection, processing, and rotation of stock.

Term

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

Definition

Annual report: this change would have minimal potential to have an adverse effect on a drug product's identity, strength, purity, quality, or potency.

Term

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

Definition

30 calendar days of being aware.

serious injury must be reported by MFR within 30 days, expected OR unexpected.

Term

A drug company's phase 3 trials will conclude in 6 months- stats team members have questions about pooling the studies for the eCTD module 2 stats analysis. What is the best course of action?

Definition

Submit a meeting request for a type B meeting.
- type B meetings include pre-NDA mtgs

Term

when multiple facilities are involved in a class III device design, assembly, or processing, the PMA holder should NOT

Definition

submit quality system information only for the facility involved in the DESIGN of the device - the PMA holder SHOULD submit applicable quality system info for EACH facility in separate volumes, clearly identifying the facilities to which they apply.

Term

during a review of the production records for Batch 1 of drug product X, it was discovered that the theoretical yield exceeded the max % established in the master production and control records by 1.5%. The batch has not been distributed. As a reg. prof. you should recommend the investigation:

Definition

be extended to other drug products that may have been associated with the discrepancy.

- any unexplained discrepancy (including a % of theoretical yield exceeding the max % established in master production and control records) or the failure of a batch or any of its components to meet any of its specs shal be investigated thoroughly, whether or not the batch has been distributed already.

Term

Citizen petition

Definition

a way to request an amendment or repeal of conditions covered by an existing proposed or final OTC drug monograph. Accompanying data must demonstrate general safety and effectiveness. No User Fee.

Term

Efficacy supplement:

Definition

submitted to an approved NDA for a prescription product if the sponsor plans to switch the drug product covered under the NDA to OTC marketing status in its entirety without a change in the dosage form or route of admin.
- An NDA 505(b)(1) should be submitted if the sponsor is proposing to convert some but not all of the approved prescription indications to OTC marketing status.
- An original NDA (505(b)(2) or 505(b)(2)) needs to be submitted if the sponsor plans to market either a new product OTC whose active substance, indication, or dosage form has never previously been marketed OTC.

Term

accelerated approval

Definition

In some cases, the approval of a new drug is expedited. Accelerated Approval can be applied to promising therapies that treat a serious or life-threatening condition and provide therapeutic benefit over available therapies. This approach allows for the approval of a drug that demonstrates an effect on a “surrogate endpoint” that is reasonably likely to predict clinical benefit, or on a clinical endpoint that occurs earlier but may not be as robust as the standard endpoint used for approval. This approval pathway is especially useful when the drug is meant to treat a disease whose course is long, and an extended period of time is needed to measure its effect. After the drug enters the market, the drug maker is required to conduct post-marketing clinical trials to verify and describe the drug’s benefit. If further trials fail to verify the predicted clinical benefit, FDA may withdraw approval.

Term

PMA amendment

Definition

adds info or modifies pending application. - resets 180d clock for a major addition// includes voluntary and requested information

Term

PMA supplement

Definition

changes or modifies PMA approved device (180d)

Term

special PMA supplement - changes being effected

Definition

limited supplement changes can be made during the application review period

Term

30-day notice (PMA)

Definition

for changes in manufacturing that affect S&E (could lead to 135-day supplement if more information is needed)

Term

Periodic PMA Reports

Definition

post-approval changes that don't affect S&E, submitted after approval letter, in annual report or as indicated by FDA

Term

Requirements for IDE (devices)

Definition

Informed consent
IRB review + approval of protocol
GCP
no user fees

Term

What types of investigations are EXEMPT from IDE?

Definition

IVDs for lab research/ custom devices/devices shipped for animal research / consumer preference testing/ vet use only

Term

IDE SPONSOR Responsibilities

Definition

- select investigators
- control distribution
- monitor studies
- ensure investigator receives IRB approval
- submit IDE to FDA if required
- ensure FDA and IRB(s) are informed of significant new investigator information

Term

IDE SPONSOR Records

Definition

- Significant/nonsignificant risk decision
- correspondence
- device shipment and disposition
- investigator agreements
- Financial disclosure
- adverse events
- investigator list
- IRB list and other records

Term

IDE SPONSOR Reports

Definition

- evaluation of unanticipated AEs (10days)
- withdrawal of IRB or FDA approval
- current investigator list
- progress reports, at least annually
- recall and device disposition
- informed consent
- final report (for sig risk - tell FDA within 30 d of completion and send final report within 6 months) (for nonsig risk, submit final report within 6 months)
- sig. risk determination

Term

IDE IRB Responsibilities

Definition

- review and approve studies and informed consent
- protect safety and welfare of subjects
- determine sig or non-sig risk of device

Term

IDE INVESTIGATOR Responsibilities

Definition

- Get IRB approval before study
- conduct study per agreement
- follow protocol and FDA regs
- control and supervise device use
- obtain informed consent

Term

IDE INVESTIGATOR Records

Definition

- correspondence
- device receipt/use/disposition
- subject records
- Informed consent
- Adverse events
- Device exposure date/times
- Protocol and other records

Term

IDE INVESTIGATOR Reports

Definition

- Unanticipated AE (10d)
- Withdrawal of IRB approval
- progress reports at least annually
- deviations from investigational plan
- informed consent
- final report due to sponsor and IRB within 3 months of study end.

- retain records for the LATER of 2y after study is over OR when records are no longer needed to support a PMA

Term

DEVICES AE Reporting (Postmarket)

Definition

MDR: info suggestive that a device may have caused or contributed to death or ser. inj. OR a malfxn has occurred that would cause or contribute to death/ser. inj. if it were to recur.
- MFR Has 5 days to report even that needed remedial action
- MFR has 30 days after becoming aware of a reportable event to report it to FDA
- USER FACILITY: death needs to be reported within 10 days
- Serious injury needs to be reported to the MFR if known or FDA if MFR is unknown within 10 days
- deaths and serious injuries need to be reported in annual report with 3500A form

Term

DEVICES QSR

Definition

- general provisions
- Qsystem requirements (mgmt. responsibilities, personnel)
- design controls
- document controls
- purchasing controls
- identification and traceability
- production and process controls (process validation)
- acceptance activities
- nonconforming product
- corrective and preventive action
- labeling and packaging controls
- handling, storage, distribution, and installation
- Records (DMR, DHR, Qsystem record, complaint files)
- servicing
- stats techniques

Term

DEVICES - complaint files

Definition

written procedures required for receiving, reviewing, evaluation of complaints by a designated unit.
- determining whether an MDR reportable event has occurred.
- Review and investigate service reports to identify MDR event
- complaint retention - time equal to device's design and expected life or at least 2 years.
- Complaint must be available during GMP inspection

Term

DEVICES - FDA inspections

Definition

TYPES OF INSPECTIONS:
- GMP/QSR compliance
- GLP compliance
- GCP compliance

FDA may not inspect sales data, financial, personnel info, internal audit files, research

INSPECTIONAL OBSERVATIONS
- issued to MGMT at the end of the inspection when conditions may be in violation of the FD&C act./regs.
-- receipt of form 483: mfr has 15 days to respond with corrective action plan!!!

EIR Establishment Inspection Report: review of inspection findings/evidence.
- NAI (no action indicated)
- OAI (official action indicated)
- VAI (voluntary action indicated)

Term

DEVICES: Lot and Batch Release requirements

Definition

Review activities required in DEVICE MASTER RECORD to ensure they are complete and signed off.
- Date of finished device acceptance by a designated person
- sterile devices need sterility test results review before release.

Term

DEVICES - retention of product samples

Definition

no requirement except for where required by company procedures or GLP

Term

DEVICES - Import/Export requirements

Definition

import for domestic distribution - foreing establishments must meet applicable US medical device regs (reg+listing, QSR mfring/MDR/510(k)/PMA)
- must designate US agent and communicate with FDA

- EXPORT: devices cleared as legal in the US may be exported anywhere.

- All devices NOT CLEARED in US must: follow the other country's rules
-- class III /no PMA devices required FDA approval to export.

---alternate (section 802)for Class II devices with no PMA - does not require FDA approval for export - only requires simple notification with restrictions.

- requests for export permit letters and simple notifications can be submitted via CECATS.

Term

DEVICES: FDA enforcement options

Definition

Form 483:
- withdrawal of approval
- criminal actions vs. investigator
- disqualified investigator
- inspections
- warning letters
- adverse publicity
- recalls (mandatory/voluntary)
- alert list
- import alert
- civil money penalty
- policy investigation and enforcement(3rd party)
- injunctions/seizures/criminal
- request to state agencies to take action

Term

DEVICES: Field corrections/recalls

Definition

CLass I-II (Most->least serious), assigned by FDA.
- Mandatory reports/corrections/removals required for any firm-initiated removal/correction conducted to:
---Reduce risk to health posed by device
---remedy a violation of the FD&C act caused by a device which may cause risk to health

Written report required within TEN DAYS of removal/correction.

Class III Recalls have recordkeeping but not reporting requirements.

MANDATORY DEVICE RECALL: cease distribution and notification order from FDA if there's a reasonable probability that a device would cause serious adverse health consequences or death.

The order requires mfrs to:
- cease distribution
- notify healthcare professionals and user facilities
- instruct professionals and UFs to cease use.

- If FDA determines a device in distribution poses a risk, FDA may amend order and require a recall.

- FDA requires strategy (depth of recall/public warning/effectiveness checks)

Term

DEVICES: CAPA

Definition

Requires mfrs to establish procedures for:
- analyzing processes, operations, audit reports, quality and service records, complains, returned devices, etc. to identify existing and potential causes of nonconforming product.
- investigating the cause of nonconformities
- identifying action needed to correct and prevent recurrence
- verifying and validating CAPA is effective
- implementing and recording changes in methods and procedures needed to effect CAPA
- telling ppl responsible for ensureing quality about CAPA.

Term

DEVICES: MISBRANDING

Definition

FAILURE TO:
- file 510(k)
- reg+listing
- provide info as required
- have ads approved by FDA
- Comply w/notification or recall order or postmarket surveillance order

MISBRANDING
- false/misleading labeling/ads/promo
- device is dangerous when used as prescribed
- doesn't comply w/color additive provisions
- Failure to comply w/cnotification/reporting/recordkeeping)
- impression of official approval, based on reg + 510(k) clearance.

Term

DEVICES: ADULTERATION

Definition

not mfred under GMPs
contaminated/defective
class III devices for which PMA:
- not filed, not approved, suspended/withdrawn

banned device, low strength, purity, quality, unsafe color additive, failure to comply w/IDE requirements, not in conformance w/performance standard.

Term

DRUGS: NDA/ANDA

Definition

Required for: any new drug or approved drug with a new substance (active ingredient, excipient, carrier, coating, etc.); new combination of already approved drugs; proportion of ingredients changes; new intended use; dosage, method of administration changes.

- ANDA vs NDA: ANDA has no preclinical or clinical data to establish safety and effectiveness.
- NDA & ANDA sections: summary volume/Chem,mfring,controls/ samples/methods validation/labeling/nonclinical pharm+tox/PK&BA/microbiology/clinical*/stats/case reports/patent info+certification/debarment certification/field copy certification/user fee cover sheet/clinicaltrials.gov compliance

Term

DRUGS: eCTD format

Definition

Module 1: regional info/admin
Module 2: TOC/Intro/quality/nonclinical and clinical summary data
Module 4: Nonclinical study reports
Module 5: Clinical study reports

Term

DRUGS: NDA approval criteria, timeframe, possible outcomes

Definition

substantial evidence of S+E.
- Filing review: 60d
- priority NDA: 6 months
- Standard NDA: 10 months

Outcomes:
-Approval
-Complete response letter
-Refusal to file

Term

DRUGS: Application maintenance and changes; reporting/recordkeeping

Definition

NDA Amendment: adds info or modifies a pending app'n
- major amendment could have 180d extension of review period
- minor amendment don't change the review clock

NDA Supplements: submission changes to approved NDA

Manufacturing Supplement/changes:
- Changes requiring Prior Approval (PAS)
- CBE 30, CBE0
- Annual report.

Term

DRUGS: NDA Reporting

Definition

-120 day safety update due after NDA filing.
-postmarket 15 day alert report (for serious and unexpected AEs)
- NDA annual report: w/in 60 d of anniv.of approval; distribution data, labeling, CMC changes, nonclinical and clinical data

NDA field alert: 3 working days for failed batches/mistaken identity/contamination/etc.

Periodic AE Reports: quarterly for 1st 3 years, then annually.

Distribution reports: quantity of product distributed in US - due every 6 months.

Term

DRUGS: clinical (IND)

Definition

Requires: Informed consent/IRB approval of protocol and informed consent/GCP
-IND Required when: new dosage form, route of administration, concentration, new sponsor or mfr, new indication
Investigator IND;
Treatment IND: experimental drugs w/promise for serious or immediately life-threatening conditions

IND Sections - intro/general plan/investigator's brochure/protocol/cmc info/pharm+tox/previous human experience
Emergency use IND:
IND can start within 30 days of submission to FDA

Term

DRUGS: IND Sponsor reports

Definition

IND Information amendments: (new tox, chem, technical information or discontinuance of a clinical investigation - NOT MORE THAN Every 30 days.

IND Safety reports: Telephone report 7 days.
Unexpected fatal or life-threat. AE assoc w/ use of drug - 15d.(serious and unexpected)

IND annual reports - within 60d of anniversary date. - keep 2 years after approval.

Term

DRUGS: AE Reporting: (postmarket)

Definition

Serious AE: death, life threat...
AE: assoc. w/use of drug - overdose, abuse, pharm action, etc.

POSTMARKETING 15day ALERT REPORTS: Required for serious and unexp., can come from anyone.

Periodic reports - quarterly for first 3 years, and then annually.

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