RAC Practice exam 2 -HJ

FDA has sent a Warning Letter citing mislabeling of a small manufacturer's artificial knee device. The regulatory professional FIRST should contact the: A. Compliance Branch in the appropriate FDA District Office B. Orthopedic Branch Chief in the CDRH Office of Device Evaluation C. Division of Small Manufacturers, International and Consumer Assistance (DSMICA) in CDRH D. CDRH Ombudsman

A FDA form 483 "Warning letter" - Describes observable violations - FDA district has 15 days to issue a warning letter after an inspection - company has 15 days to respond

Which federal law made it illegal for physicians reimbursed by federally funded programs to prescribe or recommend a patient use a particular manufacturer's medical products when the doctor receives payment from that manufacturer? A. Medicare and Medicaid Patient Protection Act of 1987 B. Food, Drug, and Cosmetic Act of 1938 (FD&C Act) C. Food and Drug Administration Modernization Act of 1997 (FDAMA) D. Food and Drug Administration Amendments Act of 2007 (FDAAA)

A. The Medicare and Medicaid Patient Protection Act of 1987 is also known as the Federal Anti-Kickback Statute and makes it illegal for any person—e.g., healthcare provider, office manager or sales agent—to knowingly and willingly solicit, offer, pay or receive "remuneration" (including kickbacks, bribes, rebates or anything of value) directly or indirectly in cash or in kind to any person to induce or cause that person to prescribe a product for which payment may be made in whole or in part under a federal or federally funded healthcare plan.

How should an NDA holder report a change to aseptic processing filtration parameters (including flow rate, pressure, time or volume, but not filter material or pore size rating). A. Changes Being Effected in 30-Days B. Changes Being Effected in 0-Days C. Prior Approval Supplement D. Annual Report

A. The holder of an approved application under section 505 of the act must assess the effects of the change before distributing a drug product made with a manufacturing change. Examples from Guidance for Industry: Changes to an Approved NDA or ANDA 2004: The following are examples of changes considered to have a moderate potential to have an adverse effect on a drug product's identity, strength, quality, purity or potency as these factors may relate to the product's safety or effectiveness. Additional validation studies for new parameters should be performed for changes to filtration parameters for aseptic processing (including flow rate, pressure, time or volume, but not filter materials or pore size rating).

At what point after a company submits an NDA will FDA provide the applicant with an opportunity to meet with agency reviewers to inform the company of the general progress and status of its application and to advise of deficiencies identified by that time and not already communicated? A. 90-day conference B. 30-day conference C. 60-day conference D. 120-day conference

A. Type C meeting (should be scheduled within 75 days of receipt) Approximately 90 days after the agency receives the application, FDA will provide applicants an opportunity to meet with agency reviewers. The meeting's purpose will be to inform applicants of the general progress and status of their applications, and to advise applicants of deficiencies identified by that time and not communicated already. This meeting will be available on applications for all new chemical entities and major new indications of marketed drugs. Such meetings will be held at the applicant's option, and may be held by telephone, if mutually agreed. Such meetings ordinarily would not be held on abbreviated applications because they are not submitted for new chemical entities or new indications.

FDA is authorized to regulate advertising for what type(s) of medical devices? A. Restricted Devices B. Non-Restricted Devices C. All medical devices D. None, as this is the responsibility of the FTC

A. "Under the FD&C Act, FDA has regulatory authority over the labeling of all medical devices. However, FDA's regulation of medical device advertising is limited to a subset of medical devices. The Federal Trade Commission (FTC) regulates the advertising, as opposed to the labeling, of most medical devices under sections 12-15 of the Federal Trade Commission Act, which prohibit false or misleading advertising of certain products that FDA regulates. (Title 15, United States Code [U.S.C.] section 52-55). Sections 502(q) and 502(r) of the FD&C Act authorize FDA to regulate the advertising of certain devices, which are known as restricted devices (discussed below). Section 502(r) also states that restricted devices are not subject to sections 12-15 of the Federal Trade Commission Act. Thus, FDA regulates the advertising of restricted medical devices while the FTC regulates the advertising of non-restricted devices."

A company is developing a combination product consisting of a device that injects a specially formulated small molecule drug for pain into the muscle tissue. Which of the following describes the best US regulatory path: A. The product is regulated as a drug B. The product is regulated under CDRH C. The company should file a BLA to obtain US marketing approval D. The company should submit a request for designation to OCP

A. 21 CFR 3.4 (http://edocket.access.gpo.gov/cfr_2008/aprqtr/21cfr3.4.htm) is the regulation regarding how FDA designates combination product review. Designation of the lead FDA review center is based on the product's Primary Mode of Action (PMOA). FDA issued a final rule on 25 August 2005 for the definition of PMOA. Statutory provision regarding product classification and the Office of Combination Products' roles and responsibilities can be found in FD&C Act Section 563 (http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCActChapterVDrugsandDevices/ucm110768.htm). Question Feedback Primary mode of action is the pain drug and the device is a delivery system.

A company's competitor is marketing a Class II suture that dissolves during the third week of use. The company's current product has to be removed by a physician. However, a change in weaving configuration gives this product the same dissolving time as the competitor's. What needs to be done for the company to market this new dissolving suture? A. Filing a new 510(k) documenting changes in product instructions for use B. Submission of changes in a periodic report C. After-reporting clinical studies in an Annual Report D. After-submission of labeling change

A. A new intended use requires a 510(k).

Which of the following does NOT describe requirements for reserve samples? A. A reserve sample representative of one lot of shipped product per year must be retained B. The reserve sample should be at least twice the amount required for all tests required to determine whether the active ingredient meets established specifications except for sterility and pyrogen testing C. Reserve samples should be stored under conditions in line with those on the product labeling D. Any evidence of reserve sample deterioration should be investigated and documented

A. 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.

Which of the following is NOT an example of an annual reportable change for a marketed product? A. Deletion of a specification for drug substance B. A change in specification made to comply with an official compendium C. An editorial change to a label D. Tightening of acceptance criteria

A. Deletion of a specification for drug substance requires PAS (major change) Sec. 314.70 Supplements and other changes to an approved application. (b) Changes requiring supplement submission and approval prior to distribution of the product made using the change (major changes) (1) any change in the drug substance, drug product, production process, quality controls, equipment, or facilities that has a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product. (changes in the qualitative or quantitative formulation of the drug product, including inactive ingredients, or in the specifications provided in the approved application)

A company acquired a new US packaging facility to package its pharmaceutical drug products. What must be done for this facility's packaging operation to start up? A. Register the establishment with FDA within five days after beginning the operation B. Contact Dun & Bradstreet to obtain a DUNs number C. Submit supplement to FDA D. Update listing information

A. Drug establishment registration and drug listing requirements are set forth in FD&C Act Section 510, PHS Act Section 351 and 21 CFR Part 207. The owner or operator of an establishment entering into the manufacture, preparation, propagation, compounding or processing (including, among other things, repackaging and relabeling) of a drug or drugs and not exempt under FD&C Act Section 510(g) or 21 CFR Part 207, Subpart B, must register the establishment with FDA within five days after beginning the operation (21 CFR 207.21(a) and 21 CFR 207.3(a)(8)).

Sponsors of a clinical trial must immediately notify FDA and investigators of serious adverse events EXCEPT: A. Temporally associated with the investigational item's use but are not serious and/or unexpected B. Described in the Investigator's Brochure but with greater severity C. Life-threatening or result in inpatient hospitalization D. Findings from animal or in vitro testing that suggest a significant risk in humans exposed to the drug

A. Events that are not undesirable are not adverse events. Events in animals are not reportable. Events of greater severity than described in the Investigator's Brochure are unexpected and therefore reportable. According to 21 CFR 312.32: Answer 2, unexpected fatal or life-threatening suspected adverse reactions, should be reported. The sponsor also must notify FDA of any unexpected fatal or life- threatening suspected adverse reaction as soon as possible, but in no case later than seven calendar days after the sponsor's initial receipt of the information. Additionally, according to the Guidance for Clinical Investigators, Sponsors and IRBs—Adverse Event Reporting to IRBs—Improving Human Subject Protection: An AE that is described or addressed in the Investigator's Brochure, protocol or informed consent documents, but occurs at a specificity or severity inconsistent with prior observations should be reported. According to 21 CFR 312.32, answer ID 3, increased rate of occurrence of serious adverse reaction, should be reported. The sponsor must report any clinically important increase in the rate of a serious suspected adverse reaction over than listed in the protocol or Investigator Brochure. According to 21 CFR 312.32, answer ID 4, iii) findings coming from animal or in vitro testing, also should be reported. The sponsor must report any findings from animal or in vitro testing, whether or not conducted by the sponsor, that suggest a significant risk in humans exposed to the drug, such as mutagenicity, teratogenicity or carcinogenicity reports, or reports of significant organ toxicity at or near the expected human exposure.

A serious adverse event of Grade 4, life-threatening hallucinations is reported by an investigator for an investigational drug in a Phase 3 clinical trial for patients with advanced stage malignant melanoma. Grade 1-3 (mild, moderate, severe) hallucinations have been reported previously in the Investigator's Brochure. You advise the medical monitor to confirm the severity grade for this AE is reported correctly by the investigator. What subsequent reporting should follow? A. If AE is confirmed to be Grade 4, report as a serious and unexpected AE associated with the investigational drug to FDA via phone or facsimile within 7 calendar days, followed by a written report within 8 additional calendar days B. If AE is clarified as Grade 3 not Grade 4, report as a serious and unexpected adverse event to FDA in writing within 15 calendar days C. Regardless of AE severity grade, report as a serious and unexpected AE associated with the investigational drug to FDA in writing within 15 calendar days D. If AE is clarified to be Grade 3 not Grade 4, report as a serious adverse event in the IND annual safety report

A. Reporting criteria for drug AEs is serious AND unexpected, whereas the reporting criteria for device is only serious.

A special control for a medical device may include: A. A black box warning included in the package insert of a new medical device B. Compliance with all current Good Manufacturing Practices C. Listing the device with FDA D. A PMA submission to FDA

A. Special controls may include special labeling requirements, mandatory performance standards and postmarket surveillance. General controls include: 1. Establishment Registration of companies which are required to register under 21 CFR Part 807.20, such as manufacturers, distributors, repackagers and relabelers. 2. Medical Device Listing with FDA of devices to be marketed. 3. Manufacturing devices in accordance with Good Manufacturing Practices (GMP in 21 CFR Part 820. 4. Labeling devices in accordance with labeling regulations in 21 CFR Part 801 or 809. 5. Submission of a premarket notification [510(k)] before marketing a device. Class II—Special Controls Class II devices are those for which general controls alone are insufficient to assure 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.

An investigator wishing to begin a clinical investigation using xenotransplantation must submit the following: A. IND B. 505(b)(2) C. BLA D. INAD

A. The use of xenotransplantation products (cells, tissue and organs derived from animals) in clinical trials in the US is regulated by FDA under both the PHS Act and the FD&C Act. Before use in clinical trials, xenotransplantation products must be reviewed by FDA either as Investigational New Drug (IND) applications for biologics or Investigational Device Exemptions (IDEs) for certain xenotransplantation products that may be regulated as devices. Development of investigational xenotransplantation products must be in compliance with 21 CFR Part 312 for INDs or 21 CFR Part 812 for IDEs. Xenotransplants are biological products regulated by CBER. Xenotransplantation is any procedure that involves the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs.

Which of the following is NOT required for compliance under 21 CFR 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 individuals can use the system, electronically 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 and responsible for actions initiated under their electronic signatures, in order to deter record and signature falsification

A. Time-stamped audit trails must be secure, computer-generated records that independently record the date and time of operator entries and actions that create, modify, or delete electronic records. Manually generated records are NOT acceptable.

All of the following would require a Type B Meeting request EXCEPT: A. Special Protocol Assessment (SPA) B. Pre-IND C. End-of-Phase 2 D. Pre-BLA

A. Type A meetings generally will be reserved for dispute resolution meetings, meetings to discuss clinical holds and Special Protocol Assessment meetings requested by sponsors after FDA's evaluation of protocols (e.g., animal carcinogenicity protocols, final product stability protocols and clinical protocols for Phase 3 trials) in assessment letters. Type B meetings are (1) Pre-IND meetings (21 CFR 312.82), (2) certain End-of-Phase 1 meetings (21 CFR 312.82), (3) End-of-Phase 2/Pre-Phase 3 meetings (21 CFR 312.47) and (4) Pre-NDA/BLA meetings (21 CFR 312.47).

While reviewing product complaint files for MDR reportability, you notice a complaint regarding a common failure mode of an implantable screw. No patient involvement or adverse consequences 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 professional your decision is: A. This complaint is reportable; an MDR will be filed with FDA within 30 days B. A review of the complaint history is needed to see whether such failure mode likely will cause or contribute to death or serious injury C. No MDR is needed as there is no patient involvement and no adverse consequences were reported D. No MDR is needed but you will file this complaint in the recall file

A. When a recall is initiated for a particular product failure mode, such failure mode automatically is MDR-reportable to FDA. Additionally, while the complaint did not report an adverse event, the manufacturer should evaluate the potential to cause an adverse event if the failure mode was to re-occur.

Once an Investigational New Drug (IND) is in effect, an amendment can be submitted for all the following EXCEPT: A. The sponsor intends to conduct a clinical investigation with an exception from Informed Consent for emergency research B. A change in a Phase 3 protocol significantly affecting subjects' safety, the investigation's scope or the study's scientific quality C. Addition of a new investigator to carry out a previously submitted protocol D. Submission of new toxicology, chemistry or other technical information, or a report regarding the discontinuation of a clinical investigation

A. Whenever a sponsor intends to conduct a clinical investigation with an exception from Informed Consent for emergency research as set forth in 21 CFR 50.24, the sponsor shall submit a separate IND to FDA for such investigation. The other choices should be submitted as IND amendments.

Financial disclosure by investigators carrying out the clinical study is required during the period of the study and for one year following its completion if they have: A. Been a prior employee of the sponsor company and own stock worth more than $50,000 (US) B. Been paid $15,000 (US) for conducting clinical trials with the sponsor C. A spouse who had been paid as a consultant by the company before the study began D. Is not a requirement for Phase 2 studies

A. "Compensation affected by the outcome of clinical studies" means compensation that could be higher for a favorable outcome than for an unfavorable outcome, such as compensation that is explicitly greater for a favorable result or compensation to the investigator in the form of an equity interest in the sponsor of a covered study or in the form of compensation tied to sales of the product, such as a royalty interest. (b) "Significant equity interest in the sponsor of a covered study" means any ownership interest, stock options or other financial interest whose value cannot be readily determined through reference to public prices (generally, interests in a non-publicly traded corporation), or any equity interest in a publicly traded corporation that exceeds $50,000 during the time the clinical investigator is carrying out the study and for one year following completion of the study. (c) "Proprietary interest in the tested product" means property or other financial interest in the product including, but not limited to, a patent, trademark, copyright or licensing agreement. (d) "Clinical investigator" means only a listed or identified investigator or subinvestigator who is directly involved in the treatment or evaluation of research subjects. The term also includes the spouse and each dependent child of the investigator. (e) "Covered clinical study" means any study of a drug or device in humans submitted in a marketing application or reclassification petition subject to this part that the applicant or FDA relies on to establish that the product is effective (including studies that show equivalence to an effective product) or any study in which a single investigator makes a significant contribution to the demonstration of safety. This would, in general, not include Phase 1 tolerance studies or pharmacokinetic studies, most clinical pharmacology studies (unless they are critical to an efficacy determination), large open safety studies conducted at multiple sites, treatment protocols, and parallel track protocols. An applicant may consult with FDA as to which clinical studies constitute "covered clinical studies" for purposes of complying with financial disclosure requirements. (f) "Significant payments of other sorts" means payments made by the sponsor of a covered study to the investigator or the institution to support activities of the investigator that have a monetary value of more than $25,000, exclusive of the costs of conducting the clinical study or other clinical studies, (e.g., a grant to fund ongoing research, compensation in the form of equipment or retainers for ongoing consultation or honoraria) during the time the clinical investigator is carrying out the study and for one year following the completion of the study.

During a QSIT audit of a medical device manufacturer, an FDA inspector requests the company's internal audit schedule. While reviewing the documents presented, the inspector discovers an internal audit results and summary report also has been provided, which identifies major quality system deficiencies. The inspector decides to check on the same areas of deficiency as the internal audit and determines the company has not addressed the deficiencies adequately. The inspector ends up issuing a 483. What could have been done by the company to avoid this 483? A. Clearly identify what the inspector was requesting and thoroughly review all documentation before presenting the documentation to the inspector B. The company could have taken the audit results and summary report away from the inspector before he or she completed the review of the documents C. Request the inspector to revise the 483 before he or she leaves because the information was not requested nor intended to be presented to the inspector D. There is no way to avoid a 483 in this situation because the inspector is privy to all internal audit results and reports

A. 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. 72 Sec. 820.22 Quality audit. Each manufacturer shall establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. Quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited. Corrective action(s), including a re-audit of deficient matters, shall be taken when necessary. A report of the results of each quality audit, and re- audit(s) where taken, shall be made and such reports shall be reviewed by management having responsibility for the matters audited. The dates and results of quality audits and re-audits shall be documented. Guidance: Under the law, your firm is responsible for conducting internal self-audits to identify and correct any and all violations of the quality system requirements. FDA Guide to Inspections of Quality Systems August 1999 (Updated 2010) http://www.fda.gov/iceci/inspections/inspectionguides/ucm074883.htm (http://www.fda.gov/iceci/inspections/inspectionguides/ucm074883.htm) Verify quality audits, including re-audits of deficient matters, of the quality system are being conducted. Review the firm's quality audit schedules to ensure quality audits are being conducted with sufficient frequency. It is recommended the time between quality audits not exceed a 12-month period. More frequent audits may be recommended if the firm has a serious Quality System Regulation problem. Evidence of inadequate auditing may exist without gaining access to the written quality audit reports. This evidence may be obtained by relating the audit program to deficiencies observed in other subsystems. If significant quality system problems have existed both before and after the firm's last self-audit, you should critically review the written audit procedures. The audit procedures should cover each quality system and should be specific enough to enable the person conducting the audit to perform an adequate audit. The auditors must be trained adequately. If it is necessary and possible to interview an auditor, ask how the audits are performed; what documents are examined; how long audits take; etc.

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: A. Devise a strategy for responding to all deficiencies identified by FDA B. Devise a strategy to respond to any minor deficiencies in order to restart the review clock C. Inform the team a Class 1 resubmission has a six-month review clock D. Inform the team a Class 2 resubmission has a three-month review clock

A. Resubmissions purport to answer all of the deficiencies needing to be addressed by the applicant prior to the original application's approval as set forth in a previous action letter.

A mid-sized pharmaceutical company negotiated with FDA to submit a draft Package Insert (PI) and patient Medication Guide in annotated Word format for initial FDA review, and committed to submitting the labeling in Structured Product Label (SPL) format upon product approval. What is the preferred timeline for this pharmaceutical company to submit the SPL-formatted labeling upon product approval? A. 7 days B. 14 days C. 30 days D. 60 days

B. "13. If the content of labeling is approved based on the draft SPL, when should the final SPL be submitted after approval? The final SPL should be submitted preferably within 14 calendar days after approval or as soon as possible thereafter." But in practice, FDA stipulates submitting SPL "As soon as possible, but no later than 14 days from the date of approval letter"

The two mechanisms to amend an OTC Monograph are: A. Time & Extent Application (TEA) or Annual Report B. Time & Extent Application (TEA) or Citizen Petition C. Annual Report or Preapproval Supplement D. Citizen Petition or Preapproval Supplement

B. 21 CFR 10.30, 21 CFR 330.14, Regulation of Non-Prescription Drug Products ODE-IV (Slide 23 to 25) located at http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/UCM148055.pdf (http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/UCM148055.pdf) Answer 2, TEA or Citizen Petition, is correct.

A medical device company has received a Warning Letter because mold has been found in two batches of its product. The letter cites that the product is: A. Quarantined B. Adulterated C. Misbranded D. Fraudulent

B. A device failing to comply with the QSR (GMP) regulations set forth in 21 CFR 820 is considered adulterated.

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? A. Changes Being Affected (CBE) Supplement B. Prior Approval Supplement C. Annual Report D. Supplement New Drug Application

B. A. Prior Approval Supplement is required because the manufacturing process is different. B. Major Changes (Prior Approval Supplement) The following are examples of changes considered to have a substantial potential to have an adverse effect on a drug product's identity, strength, quality, purity or potency as these factors may relate to the safety or effectiveness of the drug product. 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 or 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 modified-release solid oral dosage forms, transdermal systems, liposomal drug products, depot drug products, oral and nasal metered-dose inhalers (MDIs), dry powder inhalers (DPIs) 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.

Your company recently submitted a Biologics License Application (BLA) to CDER and the review division has notified the company it must develop and submit a Medication Guide. This request may have resulted from any of the following EXCEPT: A. The product is one for which patient labeling could help prevent serious adverse effects. B. The product is one in which it has been demonstrated through adequate and well-controlled trials to be less effective than alternative therapies. C. The product is one that has serious risk(s) (relative to benefits) of which patients should be made aware because information concerning the risks could affect patients' decision to use, or continue to use, the product. D. The product is important to health and patient adherence to directions for use is crucial to the drug's effectiveness.

B. According to 21 CFR 208.1, drug or biologic patient labeling will be required if FDA determines certain information is necessary to prevent a serious adverse effect, patient decision-making should be informed about a known serious side effect, or patient adherence to directions for use is essential to the its effectiveness. It is not specified in the regulations that a drug that has been shown to be inferior to alternative therapies triggers a requirement for patient labeling.

A " Transfer of Obligations" would occur between which of the following: A. FDA and FTC B. Sponsor and CRO C. Site and Sponsor D. FDA and EPA

B. Some sponsors may not have all the resources needed to conduct a clinical trial. In such a situation, it is common to formally transfer such "obligations" to a CRO for activities such as medical or clinical monitoring, etc., and inform FDA.

Six months after FDA approval of drug "X," your company wishes to make the following labeling changes to the PI: (1) Add an adverse event due to information reported to the agency; and (2) Expand population based on data. Which of the following represents both an accurate statement AND an appropriate regulatory strategy for submission of these changes? A. Adding adverse event information and expanding the population both are major changes. Submit these changes together in a Prior Approval Supplement (PAS). B. Adding adverse event information is a moderate change while expanding population is a major change. Submit these changes together in a PAS. C. Both proposed changes are moderate changes. Submit these changes together as a Changes Being Effected Supplement (CBE). D. Adding adverse event information is a moderate change, while expanding population is a major change. Changes with differing reporting categories cannot be submitted simultaneously. Submit a CBE and PAS separately

B. Adding adverse event information is considered a moderate change, which, by itself, would be submitted as a CBE. Expanding population is considered a major change, which, by itself, would be considered as a PAS. For multiple related changes, where the individual changes' recommended reporting categories differ, CDER recommends the submission be in accordance with the most restrictive category recommended for the individual changes. Therefore, these changes should be submitted together in a Prior Approval Supplement.

You work for a German-based device manufacturer (Company A) that produces a power supply based on a US-based medical device company's (Company B) design. The power supply is imported into your company's US-based manufacturing site (Company C) for further processing and then sent to the US-based medical device company (Company B) for final assembly. Which company needs to register with FDA: A. Company A B. Company B C. Company A &B D. Company A, B &C

B. Company A qualifies as a foreign component manufacturer and as such, does not require establishment registration under 21 CFR 807.65(a). Company C is the initial imported of a component and does not need register under 21 CFR 807.20.

A defective product was released into distribution and has caused patient injuries. The patients 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? A. Class I B. Class II C. ClassIII D. Class IV

B. Exposure to this product may cause temporary or medically reversible adverse health consequences.

Which of the following is NOT true for an FDA inspection of a manufacturing facility? A. A notice of inspection (FDA 482 form) is presented by the FDA investigator on arrival at the facility B. The FDA investigator's credentials can be photocopied for filing at the facility C. The FDA investigator provides inspectional findings on a FDA 483 form D. The FDA investigator provides an FDA 484 form to describe samples taken during the inspection

B. FDA Inspections Operations Manual, Chapter 5 "Establishment Inspections" 5.1.1.2—Credentials Display your credentials to the top management official, be it the owner, operator, or agent in charge. See IOM 5.2.2. NOTE: Although management may examine your credentials and record the number and your name, do not permit your credentials to be photocopied. Federal Law (Title 18, U.S.C. 701) prohibits photographing, counterfeiting, or misuse of official credentials.

The Quality System Regulation calls for finished device manufacturers to carry out all of the following EXCEPT: A. Quality audits conducted by individuals who do not have direct responsibility for the operation being audited B. Annual audits of operations C. Documenting the dates and results of quality audits and re-audits D. Having findings reviewed by management responsible for the matters audited

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

At the completion of a Preapproval Inspection where a deficiency was noted, a meeting is convened to discuss what document? A. Form FDA 482 B. Form FDA 483 C. Form FDA 1572 D. EIR

B. Form FDA 483 is the most correct because an EIR is not written by FDA until the investigators return to their office. An FDA Form 483 is issued to firm management at the conclusion of an inspection if an investigator(s) has observed any conditions that in his or her judgment may constitute violations of the FD&C Act and related acts. FDA Form 483s are discussed with a company's management at the inspection's conclusion. Each observation is read and discussed so there is a full understanding of what the observations are and what they mean. EIRs should be completed and submitted for final classification within a timely manner commensurate with the current regulatory action timeframes for the anticipated regulatory action, but generally not to exceed 30 working days when no further action is expected. Sec. 20.101 Administrative enforcement records.

In the original application for drug "X," your company submitted a comparability protocol outlining a series of proposed, repetitive container closure system changes, the tests and studies that would be used to evaluate the changes and the acceptance criteria that would be met. The application since has been approved. Subsequent comparability test results did not meet some of the predefined acceptance criteria. What regulatory option does your company have in this situation? A. Your company may implement the change(s), but an explanation as to why some of the acceptance criteria were not met must be included within the next Annual Report B. Your company may still pursue the change(s) and should submit a Prior Approval Supplement providing supporting data to justify why the change will not affect the specific drug product's identity, strength, quality, purity and potency adversely as related to the product's safety and effectiveness C. Your company may still pursue the change(s) and should submit a CBE-30 providing supporting data to justify why the change will not affect the specific drug product's identity, strength, quality, purity and potency adversely as related to the product's safety and effectiveness D. There is no further regulatory option; the proposed change(s) cannot be implemented since the predefined acceptance criteria were not met.

B. If test results do not meet the acceptance criteria, the company may elect not to implement the change. However, it still has the option to pursue the change(s) by submitting a Prior Approval Supplement to provide supporting data to justify why the change will not affect the drug product adversely.

Your company is developing a new drug to be developed and used in combination with a cystoscopic light device for the early detection of bladder cancer. You are asked to develop an overall regulatory strategy. The first step you undertake is: A. Submit a Request for Designation to FDA Office of Combination Products for determination of the lead center for primary jurisdiction for the combination product. B. Make a preliminary internal company determination of the combination product's primary mode of action. C. Submit an IND along with a Request for Designation to FDA CDER Office of Oncology Drug Products (OODP). D. Submit a request for designation to FDA CDRH and notify the Office of Combination Products.

B. It is important to determine the primary mode of action first to be able to make a recommendation as to which agency component should have primary jurisdiction, to be followed by a request for designation to FDA OCP if deemed necessary when the product 's classification or the agency center to which it should be assigned in unclear or in dispute.

Which of the following is considered part of the Device Master Record? A. Employee training record B. Labeling specifications C. Design reviews D. Calibration records

B. Labeling specifications are part of the DMR.

Your company is making a change to a specification to comply with an official compendium of an NDA product. How should this change be reported? A. In a CBE-30 due to the moderate potential of the change to have an adverse effect B. As an update in the next Annual Report C. In a new letter of authorization D. There is no need to report this change

B. Minor Changes (Annual Report) The following are examples of changes in specifications considered to have a minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product. Any change in a specification made to comply with an official compendium, except the changes described in section VIII.C.1.e, that is consistent with FDA statutory and regulatory requirements (§ 314.70(d)(2)(i)). http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070621.pdf (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070621.pdf) For compendial drug products approved under an NDA or ANDA, changes made to the specifications in the approved application regarding General Chapter <467> should be in accordance with applicable regulations described in 21 CFR 314.70 and the recommendations in Guidance for Industry Changes to an Approved NDA or ANDA. Generally, an Annual Report, if needed, can be used to report changes such as adding a test to a finished product specification or adding an alternative analytical procedure to a specification to comply with the USP.

A company has just received FDA approval to market a new drug. When must the drug sponsor submit labeling content in structured product labeling (SPL) format using FDA's automated drug registration and listing system? A. As soon as possible, but no later than 30 days in advance of the product's intended marketing date B. As soon as possible, but no later than 14 days from the date of the FDA approval letter C. As soon as possible, but no later than 14 days from the first day the product is marketed D. As soon as possible, but no later than 30 days from the date of the FDA approval letter

B. NDA approval letters say "As soon as possible, but no later than 14 days from the date of this letter..."

What market exclusivity type confers seven years of protection from competitor product marketing application approval? A. New Chemical Entity (NCE) exclusivity B. Orphan Drug Exclusivity C. Pediatric Exclusivity D. Exclusivity granted for an ANDA with Paragraph IV certification

B. Orphan drug exclusivity prevents FDA from approving an application for the same drug for the same condition for seven years. NCE confers five years of exclusivity (does not apply to ANDA/generics). Pediatric exclusivity extends all other exclusivity by six months. Paragraph IV (non-infringement of patent) exclusivity provides 180-day exclusivity to any "first applicant" if all other conditions are met.

An Investigational New Drug Application (IND) was submitted to FDA. A new animal toxicology report is obtained and will be submitted to FDA as an: A. information amendment submitted no more than every 60 days. B. information amendment submitted no more than every 30 days. C. information amendment submitted no more than every 45 days. D. information supplement submitted with the Annual Report.

B. Per 21 CFR 312.31, "a sponsor shall report in an information amendment essential information on the IND that is not within the scope of a protocol amendment, IND safety reports, or annual report. Examples of information requiring an information amendment include: (1) New toxicology, chemistry, or other technical information; or (2) A report regarding the discontinuance of a clinical investigation." Information amendments to the IND should be submitted as necessary but, to the extent feasible, not more than every 30 days. Sec. 312.31 Information amendments. (a) Requirement for information amendment. A sponsor shall report in an information amendment essential information on the IND that is not within the scope of a protocol amendment, IND safety reports, or annual report. Examples of information requiring an information amendment include: (1) New toxicology, chemistry, or other technical information; or (2) A report regarding the discontinuance of a clinical investigation. (b) Content and format of an information amendment. An information amendment is required to bear prominent identification of its contents (e.g., "Information Amendment: Chemistry, Manufacturing, and Control", "Information Amendment: Pharmacology-Toxicology," "Information Amendment: Clinical"), and to contain the following: (1) A statement of the nature and purpose of the amendment. (2) An organized submission of the data in a format appropriate for scientific review. (3) If the sponsor desires FDA to comment on an information amendment, a request for such comment. (c) When submitted. Information amendments to the IND should be submitted as necessary but, to the extent feasible, not more than every 30 days.

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)

B. 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.)

The document required by the Quality System Regulation (QSR) that tracks each device's manufacture by unit, lot and batch is the: A. Device Master Record B. Device History Record C. Design History File D. Device Master File

B. The Device History Record (DHR) 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). Subpart M—Records Sec. 820.184 Device history record. Each manufacturer shall maintain device history records (DHRs). Each manufacturer shall establish and maintain procedures to ensure DHRs for each batch, lot or unit are maintained to demonstrate the device is manufactured in accordance with the DMR and the requirements of this part. The DHR shall include, or refer to the location of, the following information: (a) The dates of manufacture; (b) The quantity manufactured; (c) The quantity released for distribution; (d) The acceptance records which demonstrate the device is manufactured in accordance with the DMR; (e) The primary identification label and labeling used for each production unit; and (f) Any device identification(s) and control number(s) used.

A medical device manufacturer is preparing a submission that requires a Declaration of Conformity with design control requirements. What type of submission is the manufacturer preparing to submit to FDA? A. APMA B. A Special 510(k) C. An Individual Device Exemption (IDE) An D. Annual Report for a PMA

B. The New 510(k) Paradigm—Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications—Final Guidance, March 1998 www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ucm134573.htm#assessment (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ucm134573.htm#assessment) Question Feedback: The Special 510(k) allows the manufacturer to declare conformance to design controls without providing data. While the 510(k) basic content requirements (21 CFR 807.87) remain the same, this type of submission also should reference the cleared 510(k) number and contain a "Declaration of Conformity" with design control requirements. Manufacturers of Class I devices requiring 510(k)s may elect to comply with the design control provision of the Quality System Regulation and submit Special 510(k)s.

A company is developing an (unapproved) drug-device combination product but is not sure to which center it should submit its marketing application. The company should first submit: A. A Request for Determination to the appropriate review division based on the product's primary mode of action B. A Request for Designation to the Office of Combination Products C. A Request for Determination to the Office of Pharmaceutical Science D. A Request for Designation to the Office of New Drug Quality Assessment

B. The Office of Combination Products assigns review responsibility for combination products based on the product's primary mode of action. By submitting a "Request for Designation," a company may obtain a formal agency determination of a combination product's primary mode of action and the lead agency center for the product's premarket review and regulation.

Company X has conducted clinical studies to support drug A's safety and effectiveness. Company X is planning to develop a new drug A dosage formulation and route of administration. This new formulation will rely on previously conducted clinical studies to support drug A's safety and effectiveness. Which of the following should be submitted by Company X? A. A 505(b)(2) application B. An NDA containing full reports of investigations of safety and effectiveness C. A 505(j) application D. An efficacy supplement

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

While seeking a new Class III indication via a 510(k) for a medical device currently on the market as Class II, a company received a vote of "non-approvable" from an FDA Advisory Panel. Possible courses of action include all of the following EXCEPT: A. Continue marketing the device for its Class II indication B. Update the current labeling to include the new indication C. Proceed with a PMA submission to FDA D. Request a face-to-face post-panel meeting with FDA

B. The medical device would be considered misbranded because the agency has not approved the indication and labeling.

A medical device that has just received marketing approval outside the US is to be shipped from the US to a foreign distributor of Company XYZ. Company XYZ contacts the foreign distributor, who confirms the product has not yet been shipped and is still at its warehouse in the US. Company XYZ requests the foreign distributor return the medical device immediately. The enforcement activity described is an example of a: A. Market withdrawal B. Stock recovery C. Class I recall D. Class III recall

B. The product has not been marketed yet, has not been released for sale or use and still is located on premises under the manufacturer's foreign distributor's control. Stock recovery is a firm's removal or correction of a product that has not been marketed or has not left the firm's direct control, i.e., the product is located on premises owned by, or under the control of, the firm and no portion of the lot has been released for sale or use.

A company is evaluating next steps for a small Phase 1/2 clinical trial. Of four cohorts, the company just has completed enrollment of the third. Immunology testing efficacy data have revealed a small signal was detected. Based on these data; the company believes the fourth cohort should be dosed with a higher concentration of drug product. The concentration required is higher than the current drug product dose and may not be supported nonclinical toxicology studies. The higher dose also will require additional product development and the manufacturing time is estimated at approximately 18 months. What is the best regulatory approach? A. Current clinical protocol recruitment should be put on hold for two years to await the new drug product B. The current clinical protocol should be terminated and a new clinical protocol written with new dosing supported by nonclinical studies. C. The clinical protocol should be amended and incorporate the increased dosing schedule D. The clinical protocol should be amended and current drug product dosing increased

B. Trials that are inactive for two years are put on FDA inactive list

A drug company's Phase 3 trials will conclude in six months. Statistics team members have questions pertaining to pooling the studies for the eCTD Module 2 statistical analysis. What is the best course of action: A. Submit a meeting request to FDA for a Type A meeting B. Submit a meeting request to FDA for a Type B meeting C. Submit a meeting request to FDA for a Type C meeting D. Submit a Special Protocol Assessment to review the statistical analysis plan

B. Type B meetings include Pre-NDA meetings. A Pre-NDA meeting can be used to discuss appropriate methods for statistical data analysis in the marketing application.

Your company's commercial product is manufactured by a third-party manufacturer (TPM). The manufacturing 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: A. Recommend the lot be released B. Recommend the lot not be released C. Assess whether the rework steps are within the regulatory filing and whether there is a potential regulatory impact D. If the rework steps are not in the current filing, submit a postapproval change to include the rework steps in order to release the material

C Guidance for Industry: Drug Product: Chemistry, Manufacturing, and Controls Information http://www.fda.gov/OHRMS/DOCKETS/98fr/02d-0525gdl00001.PDF (http://www.fda.gov/OHRMS/DOCKETS/98fr/02d-0525gdl00001.PDF) Guidance for Industry: Immediate Release Solid Oral Dosage Forms http://www.fda.gov/downloads/Drugs/Guidances/UCM070636.pdf (http://www.fda.gov/downloads/Drugs/Guidances/UCM070636.pdf) SUPAC-IR Questions and Answers about SUPAC-IR Guidance http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124826.htm (http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124826.htm) Product release and disposition is a quality responsibility, not regulatory. The regulatory professional is responsible for reviewing the event and assessing whether the additional steps performed in the manufacturing process are allowed within the regulatory filing. The team may decide to include the rework procedure; however, additional data may be needed for the submission. Therefore the recommended first step is response 3.

An IND application is: A. An application requesting an FDA meeting to discuss the sponsor's investigational plan for a compound B. An application requesting permission to start clinical trials in humans C. An application requesting federal exemption from interstate commerce law D. An application requesting permission to start nonclinical research trials in animals

C.

A medical device may be exported under Section 801(e) of the FD&C Act and shall not be deemed to be adulterated or misbranded under the act if all of the following apply for the device EXCEPT: A. It is in accordance with the foreign purchaser's specifications B. It is not in conflict with the laws of the country to which it is intended for export C. It is 510(k)-cleared or PMA-approved D. The outside of the shipping package is labeled "intended for export only"

C. A medical device that would not meet FD&C Act requirements to be sold domestically (i.e., no 510(k) or PMA), may be exported under Section 801(e)(1) of the act provided it is intended solely for export and is: in accordance with the foreign purchaser's specifications not in conflict with the laws of the country to which it is intended for export in a shipping package labeled on the outside "intended for export only" not sold or offered for sale in domestic commerce

A removal of a distributed product involved in a minor violation that would be subject to legal action by FDA is known as: A. Stock recovery B. Market withdrawal C. Product recall D. Corrective action

C. Market withdrawal is not subject to legal action by FDA. PART 7—Enforcement Policy (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=7) Subpart A—General Provisions (k) Stock recovery: 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, i.e., the product is located on premises owned by, or under the control of, the firm and no portion of the lot has been released for sale or use. (j) Market withdrawal: a firm's removal or correction of a distributed product which involves a minor violation that would not be subject to legal action by the Food and Drug Administration or which involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs, etc. (g) Recall: a firm's removal or correction of a marketed product that the Food and Drug Administration considers to be in violation of the laws it administers and against which the agency would initiate legal action, e.g., seizure. Recall does not include a market withdrawal or a stock recovery.

A new device undergoes design review. The review determines current analytical data do not provide enough information to move ahead with human testing. A decision is made to discard the data and begin a new study with a different protocol. This is an acceptable approach if: A. The product's intended use does not change. B. The original data are destroyed before new testing starts. C. The original data are stored in the device Design History File. D. The new study tests three times as many samples as the old one.

C. 21 CFR 820.30 (e) Design review—Each manufacturer shall establish...that formal documented reviews...are planned and conducted. ...the results of the design review, including identification of the design, the date, and the individual(s) performing the review, shall be documented in the design history file. 820.30(f)...The results of the design verification, including identification of the design, method(s), the data, and the individual(s) performing the verification, shall be documented in the Design History File (DHF). Design review refers to formal, systematic (i.e., conducted at planned intervals) reviews of the design verification results conducted at appropriate device design development stages. This review's purpose is to evaluate the design requirements' adequacy and the design's capability to meet these requirements, and to identify problems. The design review outcomes, including identifying the design stage, the date and the individuals involved in the review, should be documented in the Design History File

A company is developing a new device and the classification under which it would fall is unclear. As the regulatory professional, you would submit the following: A. 510(k) Premarket Notification B. Request for Designation C. 513(g) Request for Information D. Type A Meeting Request

C. A 513(g) Request for Information is submitted to ask FDA to determine a device's classification and applicable requirements under the FD&C Act. - A 510(k) submission is filed when a device's classification is known and the device is compared to a predicate device to obtain FDA clearance. - A Request for Designation asks FDA to determine whether a product is a drug, device, biological product or combination product. - A Type A Meeting is needed to help an otherwise stalled product development program proceed.

An important distinction of a Humanitarian Use Device (HUD) according to the Humanitarian Device Exemption (HDE) is that: A. The HDE application must contain the same information as a PMA. B. An HDE application is not required to contain the results of scientifically valid analytical safety studies. C. An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating effectiveness for its intended purpose. D. An HDE application must be submitted within 30 days after marketing begins.

C. A Humanitarian Use Device (HUD) is intended to benefit patients by treating or diagnosing a disease or condition affecting or manifested in fewer than 4,000 individuals in the US per year. An HDE is similar in both form and content to a Premarket Approval (PMA) Application, but is exempt from the PMA effectiveness requirements. An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating the device is effective for its intended purpose. The application, however, must contain sufficient information for FDA to determine the device does not pose an unreasonable or significant risk of illness or injury, and the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.

A sponsor wishes to obtain permission from FDA to submit an ANDA for a drug product that varies from the Reference Listed Drug (RLD) in route of administration, dosage form or strength. What process should be used to apply for that permission from FDA? A. Citizen Petition B. Pre-NDA Meeting C. Suitability Petition D. Notice of Opportunity for Hearing

C. A Suitability Petition is a request for permission to submit an ANDA. Sec. 314.93 Petition to request a change from a listed drug. (b) A person who wants to submit an abbreviated new drug application for a drug product which is not identical to a listed drug in route of administration, dosage form, and strength, or in which one active ingredient is substituted for one of the active ingredients in a listed combination drug, must first obtain permission from FDA to submit such an abbreviated application.

If a company is planning to market a medical device that is substantially equivalent to a device marketed before 1976, which regulatory path would be most appropriate: A. IDE B. PMA C. 510(k) D. Special Assessment Protocol

C. A device legally marketed prior to 28 May 1976 (pre-amendment device) can be used as a predicate device to demonstrate substantial equivalence as part of the Premarket Notification (510(k)).

After product approval, ADEs that do not meet the 15-day reporting requirements should be reported by the company: A. Bi-annually, unless alternative reporting is required by FDA. B. Annually, unless alternative reporting is required by FDA. C. Quarterly for three years after application approval, annually thereafter, unless alternative reporting is required by FDA. D. Quarterly for two years after application approval, annually thereafter, unless alternative reporting is required by FDA.

C. ADEs should be reported quarterly for the first three years and annually thereafter. Sec. 314.80 Postmarketing reporting of adverse drug experiences. (2) Periodic adverse drug experience reports. (i) The applicant shall report each adverse drug experience not reported under paragraph (c)(1)(i) of this section at quarterly intervals, for 3 years from the date of approval of the application, and then at annual intervals.

The following biological products are regulated by CBER EXCEPT: A. Immunizing toxoids B. Monoclonal antibodies for in vitro use C. Monoclonal antibodies for in vivo use D. Infusion of animal sourced cells into a human

C. PHS Act Section 351(a) SOPP 8001.5 Intercenter Consultative/Collaborative Review Process Transfer of Therapeutic Biological Products to the Center for Drug Evaluation and Research http://www.fda.gov/CombinationProducts/JurisdictionalInformation/ucm136265.htm (http://www.fda.gov/CombinationProducts/JurisdictionalInformation/ucm136265.htm) Monoclonal antibodies for in vivo use were transferred to CDER's Office of New Drugs (OND) effective 30 June 2003

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? A. Changes Being Effected (CBE) 0-days B. Changes Being Effected in 30 days (CBE-30) C. Prior Approval Supplement D. Annual Report

C. Prior FDA 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.)

Which of the following is the best regulatory pathway for drugs containing similar active ingredients as a previously approved drug for a new indication? A. 505(j) ANDA B. 505(b)(1) NDA C. 505(b)(2) NDA D. 505(d) Substantial Evidence of Effectiveness

C. An application that contains full reports of investigations of safety and effectiveness but where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference (Section 505(b)(2)); Following are examples of changes to approved drugs for which 505(b)(2) applications should be submitted. Active ingredient. - An application for a change in an active ingredient such as a different salt, ester, complex, chelate, clathrate, racemate or enantiomer of an active ingredient in a listed drug containing the same active moiety. Dosage form. - An application for a change of dosage form, such as a change from a solid oral dosage form to a transdermal patch that relies to some extent upon the agency's finding of safety and/or effectiveness for an approved drug. Strength. - An application for a change to a lower or higher strength. Route of administration. - An application for a change in the route of administration, such as a change from an intravenous to intrathecal route. Substitution of an active ingredient in a combination product. - An application for a change in one of the active ingredients of an approved combination product for another active ingredient that has or has not been previously approved.

A pharmaceutical company received approval of a drug that contains a boxed warning on its labeling. What type(s) of advertisements are NOT permitted? A. Published journals and newspapers B. Radio and television C. Reminder advertisements D. Internet advertisements

C. Answer 3 is correct because reminder advertising is not permitted for drugs with boxed warnings since the boxed warning must be present on all advertising. From FDA: "Reminder ads give the drug's name but not the drug's use. The assumption behind reminder ads is that the audience knows what the drug is for and does not need to be told. A reminder ad does not contain risk information about the drug because the ad does not discuss the condition treated or how well the drug works. Reminder ads are not appropriate for drugs whose labeling has a "boxed warning" (http://www.fda.gov/Drugs/ResourcesForYou/Consumers/PrescriptionDrugAdvertising/ssLINK/ucm072025.htm#boxed_warning) about certain very serious drug risks." http://www.fda.gov/Drugs/ResourcesForYou/Consumers/PrescriptionDrugAdvertising/ucm083573.htm (http://www.fda.gov/Drugs/ResourcesForYou/Consumers/PrescriptionDrugAdvertising/ucm083573.htm)

Which of the following statements is TRUE for Phase 2 clinical investigations of a NCE? A. They are designed to determine the metabolism and pharmacologic actions of the drug in humans. B. They are intended to gather additional information about effectiveness and safety to evaluate the overall benefit-risk of the drug. C. They are conducted to determine the common short-term side effects and risks associated with the drug. D. They are performed to provide an adequate basis for physician labeling.

C. Answer 3 is true for Phase 2 studies, answer 1 is true for Phase 1 studies and answers 2 and 4 are true for Phase 3 studies.

Which of the following drug application types are NOT subject to a one-time FDA user fee upon application submission? A. An original NDA containing nonclinical and clinical data already submitted to an IND B. A supplemental NDA containing previously unsubmitted nonclinical and clinical data C. A supplemental NDA requesting review of new and/or revised manufacturing processes D. An original NDA containing previously submitted nonclinical data and clinical data not previously submitted to an IND

C. Any NDA or SNDA containing new clinical data must pay a fee to FDA upon application submission.

A manufacturing 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 six months, quality test results have been getting closer to the specification limit. Internal review determines QC testing now should take place weekly. This information should be provided to FDA through: A. A postapproval study report B. A medical device report C. This information does not need to be submitted D. An Annual Report

C. As per CFR 820.70 (b), b)Production and process changes. Each manufacturer 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. Therefore answers 1, 2 and 4 are incorrect. The best answer is number 3.

Pharmacogenomic testing data results must be submitted to an IND in all the following circumstances EXCEPT : A. Test results will be used to determine clinical trial dosing schedule selection B. Test results will be used to make decisions in an animal trial used to support safety C. Data were derived from general gene-expression analysis of trial participants D. Test results constitute a known valid biomarker for toxicologic outcomes in humans

C. Exploratory or research data are not required to be submitted, but are welcomed as a voluntary submission of the data in a VGDS (voluntary genomic data submission).

A physician reports to a manufacturer a patient was hospitalized with acute sepsis after treatment with an approved device. This side effect is not listed in the package insert. The manufacturer must report this event to FDA no later than: A. 5 calendar days after receipt or becoming aware of information B. 15 calendar days after receipt or becoming aware of information C. 30 calendar days after receipt or becoming aware of information D. The next quarterly report

C. For medical devices, a serious injury must be reported within 30 days after receipt or becoming aware of information, whether or not it is expected and stated in the IFU.

The basic elements of an IRB-approved Informed Consent Form include the following EXCEPT: A. Description of the foreseeable risks of the study. B. Disclosure about the alternative procedures or treatments available. C. Information about the treatment group to which the patient is assigned. D. Explanation of conditions for any compensation offered.

C. For studies subject to FDA regulations, the Informed Consent documents should meet the requirements of 21 CFR 50.20 and contain the information required by each of the eight basic elements of 21 CFR 50.25(a), and each of the six elements of 21 CFR 50.25(b) appropriate to the study. IRBs have the final authority for ensuring the adequacy of the information in the Informed Consent Form.

A Class II device with electrical components was subjected to extensive standardized testing such as the International Electrotechnical Commission (IEC) series (recognized conformance standard). The tests were conducted by a third party. Which route of submission is the most suitable for this device? A. Traditional 510(k) B. Special 510(k) C. Abbreviated 510(k) D. PMA

C. Regulatory Reference FDA The New 510(k) Paradigm—Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications—Final Guidance How to prepare an Abbreviated 510(k). A manufacturer has the option to submit an Abbreviated 510(k) when FDA has recognized relevant consensus standards applicable to the device. This Abbreviated 510(k) will include a declaration of conformity to the recognized consensus standards, and this declaration, in many cases, should eliminate the need to review actual test data for those aspects of the device addressed by the standards, thus the review will be more efficient. www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ucm134574.htm (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ucm134574.htm) Guidance for Industry: Frequently Asked Questions on the New 510(K) Paradigm www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073946.htm (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073946.htm)

A firm received a raw material for one of its drug products. The raw material was placed in quarantine and sampled appropriately. Sample containers should be identified so the following information can be determined: A. The manufacturer name, lot number, name of person who collected the sample and the date on which the sample was taken. B. The manufacturer name, lot number, the sample attributes, name of person who collected the sample and the date on which the sample was taken. C. The material name, lot number, the container from which the sample was taken, name of person who collected the sample and the date on which the sample was taken. D. The material name, lot number, sample attributes and the date on which the sample was taken.

C. Sample containers shall be identified so the following information can be determined: material name, lot number, the container from which the sample was taken, name of person who collected the sample and the date on which the sample was taken.

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? A. Medwatch form 3500A B. 100 day review C. Four-month update D. Response to FDA request for information

C. 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.

A company has a new oral drug, GOODDRUG, it wishes to market in the US. Studies on intravenous GOODDRUG have been conducted by several academic centers demonstrating safety and efficacy and have been published in peer-reviewed journals. The most-appropriate method to gain approval would be by filing a: A. ANDA B. SNDA C. 505(b)2 D. 505(b)1

C. Since the drug has been studied and those results published, a comparability study between IV and oral dosage forms is acceptable under a 505(b)2.

FDA may refuse to file a PMA for all of the following reasons EXCEPT: A. The application does not contain all the information required under Section 515(c)(1)(A)-(G) 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 21 CFR 54 Financial Disclosure by Clinical Investigators

C. Substantive review of the PMA submission will begin once FDA determines the submission will not be refused.

The responsibilities of an investigator of a clinical study include all of the following EXCEPT: A. Ensures compliant IRB reviews and approves study B. Provides current and updated financial disclosure information C. Disposes of unused study medication D. Obtains informed consent

C. 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 ICH GCP 5.14 Supplying and Handling Investigational Product(s) 5.14.1 The sponsor is responsible for supplying the investigator(s)/institution(s) with the investigational product(s). 5.14.2 The sponsor should not supply an investigator/institution with the investigational product(s) until the sponsor obtains all required documentation (e.g. approval/favorable opinion from IRB/IEC and regulatory authority(ies)). 5.14.3 The sponsor should ensure written procedures include instructions that the investigator/institution should follow for the handling and storage of investigational product(s) for the trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage, dispensing, retrieval of unused product from subjects and returning unused investigational product(s) to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s)). 5.14.4 The sponsor should: (a) Ensure timely delivery of investigational product(s) to the investigator(s). (b) Maintain records that document shipment, receipt, disposition, return, and destruction of the investigational product(s) (see 8. Essential Documents for the Conduct of a Clinical Trial). (c) Maintain a system for retrieving investigational products and documenting this retrieval (e.g. for deficient product recall, reclaim after trial completion, expired product reclaim). (d) Maintain a system for the disposition of unused investigational product(s) and for the documentation of this disposition.

The supply chain organization would like to qualify an alternate vendor for the drug substance utilized to manufacture a drug product. Which question does NOT need to be asked in order to complete a regulatory assessment? A. Are drug substance specifications changing? B. Does the vendor have a US DMF for this material? C. Where is the vendor located? D. Has the site had a satisfactory GMP inspection by FDA?

C. To assess this change's regulatory impact and filing classification, answers to questions 1, 2 and 4 all are beneficial to the regulatory professional. Although certain world regions have received additional FDA attention, the vendor's location is not needed to conduct the analysis.

In most cases, a biological product manufacturer should retain samples for a minimum of what amount of time beyond the expiration date? A. 10 Days B. 30 Days C. 6 Months D. 12 Months

C. Manufacturers shall retain for a period of at least six months after the expiration 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 potency, except Whole Blood, Cryoprecipitated AHF, Platelets, Red Blood Cells, Plasma, and Source Plasma and Allergenic Products prepared to a physician's prescription.

A pharmaceutical manufacturer has a high-volume tablet product that requires the production of about 600 batches per year to meet demand. The batch records are generated from the same Master Production (Batch) Record. Each batch record calls for yield calculation to be recorded three ways: theoretical yield, actual yield and percentage of theoretical yield. Which of these calculations would be impacted most by the amount of waste accumulated during the granulation process? A. All three yield calculations B. Theoretical yield C. Actual yield and percentage of theoretical yield D. None of the three yield calculations

C. To make the correct selection, it is necessary to understand anything affecting the actual yield, e.g., waste, samples pulled, etc., in any part of the process affects the percentage of theoretical yield calculation because the percentage of theoretical yield is a ratio of the actual yield expressed as a percentage (see Part 210.3 (19)). Sec. 210.3 Definitions. (17) Theoretical yield is the quantity that would be produced at any appropriate manufacturing, processing or packing stage of a particular drug product, based on the quantity of components to be used, in the absence of any loss or error in actual production. (18) Actual yield is the quantity actually produced at any appropriate manufacturing, processing or packing phase of a particular drug product. (19) Percentage of theoretical yield is the ratio of the actual yield (at any appropriate manufacturing, processing or packing phase of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage. Sec. 211.103 Calculation of yield. Actual yields and percentages of theoretical yield shall be determined at the conclusion of each appropriate phase of manufacturing, processing, packaging, or holding of the drug product.

According to the Quality System Regulation, when a complaint investigation is conducted, all of the following are required to be included in the record of the investigation A. Investigation dates and results. B. Complaint nature and details. C. Changes in procedures correcting quality problems. D. Any reply to the complainant.

C. When an investigation is conducted, a record of the investigation shall be maintained by a formally designated unit and shall include: (1) The name of the device; (2) The date the complaint was received; (3) Any unique device identifier (UDI) or universal product code (UPC), and any other device identification(s) and control number(s) used; (4) The name, address, and phone number of the complainant; (5) The nature and details of the complaint; (6) The dates and results of the investigation; (7) Any corrective action taken; and (8) Any reply to the complainant. The requirement is for corrective and preventative action and only needed if a corrective action was taken as a result of the investigation.

A company's Phase 3 investigational drug product, available in three different tablet strengths, is a rapidly dissolving, immediate release, white, film-coated tablet. For the commercial drug product, the marketing division proposed distinguishing different strengths by using three different colors. What needs to be done to support this change in the drug product appearance? A. A bioequivalence study B. Multi-point in vitro dissolution profiles C. Release and stability testing of the proposed formulation against the specification established for white tablets D. Formulation changes are not acceptable after Phase 3 studies

C. Adding a colorant to the tablet film coat is considered a minor drug product formulation change. Release and stability data for the proposed formulation meeting a specification established for the current formulation will be sufficient. However, the company should evaluate HPLC method specificity for impurities and ensure colorants do not interfere with impurity separation.

During a Class II product recall, additional complaint reports of the same product problem involved in the recall were received for products not in the date range of the product lots being recalled. What action should the regulatory professional recommend to the company? A. Discontinue the recall until they can determine the actual range of affected product B. Revise the recall scope and notify FDA within two business days about the additional reports and the revised recall scope C. Reassess the root cause analysis, traceability data and rationale for the original recall range to determine why original assumptions were incorrect and notify FDA within 10 working days of the extended recall range D. Provide FDA with a second correction and removal report

C. Corrections and removals - Amendment Reports regarding the extension of the recall range are required to be filed within 10 working days of receiving the additional reports. The manufacturer amends the originally filed report and does not file a new report. 21 CFR 806.10(d): If, after submitting a report under this part, a manufacturer or importer determines that the same correction or removal should be extended to additional lots or batches of the same device, the manufacturer or importer shall within 10-working days of initiating the extension of the correction or removal, amend the report by submitting an amendment citing the original report number assigned according to paragraph (c)(1) of this section, all of the information required by paragraph (c)(2), and any information required by paragraphs (c)(3) through (c)(12) of this section that is different from the information submitted in the original report. The manufacturer or importer shall also provide a statement in accordance with paragraph (c)(13) of this section for any required information that is not readily available.

A Drug Master File may be used for any of the following purposes EXCEPT: A. Supplemental information on the drug product or drug substance B. Supplemental information for any type of submission to the agency C. FDA approval of the Drug Master File D. Incorporation 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

C. FDA does not approve or disapprove Drug Master Files; it only reviews them as supplemental information. Sec. 314.420 Drug master files. FDA ordinarily neither independently reviews Drug Master Files nor approves or disapproves submissions to a drug master file.

Good Manufacturing Practices (GMPs) are NOT applied to the chemical synthesis of an Active Pharmaceutical Ingredient (API) manufacturing process during: A. Intermediate compound drying B. Introduction of the starting material into the process C. Starting material synthesis D. API Packaging

C. For synthetic processes, the introduction of the starting material into the manufacturing process is known as the point at which GMPs are applied in API manufacture. Starting materials synthesis does not have to be completed under GMPs.

In a medical device company, which of the following units has ultimate responsibility for data integrity and product quality: A. Quality Assurance B. Quality Control C. Management D. Regulatory Compliance

C. Management has the ultimate responsibility of ensuring quality systems are effective and a quality policy is implemented and followed as intended, which ensures data integrity and product quality.

A sponsor has an approved product that has been marketed for several years and contains a preservative. However, the product has been reformulated to remove the preservative and the sponsor conducted new clinical trials essential to support approval of the new application. Does the sponsor's product qualify for exclusivity? A. No, the sponsor does not qualify for exclusivity. B. Yes, the sponsor qualifies for 180-day exclusivity. C. Yes, the sponsor qualifies for three-year exclusivity. D. Yes, the sponsor qualifies for five-year exclusivity.

C. New clinical investigation - 3 year exlusivity The Hatch-Waxman Act (Drug Price Competition and Patent Term Restoration Act of 1984) provides for patent term extensions. Under the amendment to the FD&C Act, a sponsor may qualify for three-year exclusivity if the following criteria are met: the active moiety must have been the subject of an approved application, the new application (defined as a full NDA, BLA, 505(b)(2) or a supplement to any application mentioned) must contain new clinical trial data essential to support the new application's approval, and the applicant must conduct the clinical trials.

Your company is developing a New Chemical Entity (NCE) to treat Glioblastoma multiforme, which is the deadliest and most common form of malignant brain tumor. The compound team has designed a pivotal study protocol with a clinically meaningful and well-established primary endpoint. To increase the likelihood FDA will agree with the study design, which of the following regulatory strategies has to occur prior to initiating the pivotal study? A. Request Fast Track designation B. Request priority review C. Request approval under Subpart H, Accelerated Approval of New Drugs for Serious or Life Threatening Illness D. Request Special Protocol Assessment

D. A Special Protocol Assessment applies to a Phase 3 study and must be requested prior to initiating the study, so answer 4 is correct. Fast Track designation can be requested at any time. Priority review is requested prior to filing an NDA, not prior to clinical studies. Answer 3 is not applicable to this case, as Subpart H applies to utilization of surrogate, not well-established endpoints.

In routine stability testing of an NDA drug, a firm discovers a previously unidentified impurity at the 24-month checkpoint. The firm performs a laboratory investigation and the impurity results are confirmed. The drug product has a 36-month shelf life. What should happen next? A. A full investigation into the identification and safety of the impurity should commence. B. A full investigation into the source of the impurity should commence. C. CDER should be notified within 15 working days and a Class III recall should be initiated. D. A field alert report should be submitted to the FDA District Office within three working days of confirmation of the impurity.

D. A field alert report form must be submitted within three working days to the "NDA-Field Alert Report" coordinator in the firm's jurisdictional FDA District Office, who also be available to answer any questions a firm may have regarding the reports.

While reviewing data for an upcoming New Drug Application (NDA) submission, the in-house monitor found the investigator's Curriculum Vitae (CV) has not been updated since it was submitted with the Investigational New Drug (IND) application. According to FDA guidance on Form 1572, how often should the investigator's CV updated? A. Annually B. Every two years C. Every three years D. It does not need to be updated

D. FDA regulations do not require a CV or other statement of qualifications to be updated during a clinical study.

An IVD submission could be submitted as a(n): A. NDA B. BLA C. 510(k) D. BLA or 510(k)

D. IVDs could be submitted as a 510(k) under the FD&C Act or a BLA under the PHS Act. http://www.fda.gov/medicaldevices/deviceregulationandguidance/ivdregulatoryassistance/ucm123682.htm (http://www.fda.gov/medicaldevices/deviceregulationandguidance/ivdregulatoryassistance/ucm123682.htm) Regulatory Authority: IVDs are "medical devices" as defined in Federal Food, Drug, and Cosmetic Act Section 210(h) or biological products subject to Public Health Service Act Section 351.

Five-year exclusivity for a chemical compound, sometimes called New Chemical Entity (NCE) exclusivity, prevents the approval of all of the following for five years EXCEPT: A. A generic application for the approved active ingredient B. A generic application for a salt of the approved active ingredient C. A generic application for an ester of the approved active ingredient D. A Section 505(b)(1) New Drug Application (NDA) for the same drug

D. NCE exclusivity prevents the approval of a generic application for the approved active ingredient or any salt or ester of the approved active ingredient for five years. However, five-year exclusivity does NOT prevent FDA from approving, or a company from submitting, a full Section 505(b)(1) NDA for the same drug. Small Business Assistance: Frequently Asked Questions for New Drug Product Exclusivity (FDA website) http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm069962.htm (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm069962.htm) 1. What is new drug product exclusivity? New Drug Product Exclusivity is provided by the Federal Food, Drug, and Cosmetic Act under section 505(c)(3)(E) and 505(j)(5)(F). Exclusivity provides the holder of an approved new drug application limited protection from new competition in the marketplace for the innovation represented by its approved drug product. This limited protection precludes approval of certain 505(b)(2) applications or certain abbreviated new drug applications (ANDAs) for prescribed periods of time. Some exclusivity provisions also provide protection from competition by delaying the submission of 505(b)(2) applications and ANDAs for certain periods of time. Full new drug applications under 505(b)(1) and 505(b)(2) can receive 5 years of exclusivity for a new chemical entity drug product. A 505(b)(1), 505(b)(2) application or a supplement to a new drug application can receive 3 years of exclusivity. 21 CFR 314.108—New drug product exclusivity. (b) Submission of and effective date of approval of an abbreviated new drug application submitted under section 505(j) of the act or a 505(b)(2) application. (1) [Reserved] (2) If a drug product that contains a new chemical entity was approved after September 24, 1984, in an application submitted under section 505(b) of the act, no person may submit a 505(b)(2) application or abbreviated new drug application under section 505(j) of the act for a drug product that contains the same active moiety as in the new chemical entity for a period of 5 years from the date of approval of the first approved new drug application, except that the 505(b)(2) application or abbreviated application may be submitted after 4 years if it contains a certification of patent invalidity or noninfringement described in § 314.50(i)(1)(i)(A)(4) or § 314.94(a)(12)(i)(A)(4).

Which of the following protocols types would NOT be eligible for a Special Protocol Assessment review process with FDA? A. Animal carcinogenicity protocols B. Stability protocol C. Protocol for Phase 3 trials related to efficacy claim D. Dose ranging protocol

D. Per guidance issued, dose ranging protocols are not to be submitted as an SPA.

All of the following are considered raw data in a preclinical study EXCEPT: A. Final Pathology Report B. Records of quarantine and animal receipt C. Animal data entered into the animal chart D. Computer printout derived from data transferred to computer media from lab data sheets

D. Raw data are defined as "any laboratory worksheets, records, memorandum, notes that are the result of original observations and activities" and are necessary for the reconstruction and evaluation of the report of that study."

A drug manufacturer creates a game-based simulation to assist diabetes patients with management of their blood glucose levels and to motivate them to adhere to their medication schedules. The game will be based on a password protected website that will be made available to patients when an FDA-approved drug is prescribed to them. How will the game most likely be regulated by FDA? A.It should be included as part of the NDA submission B. It will be regulated as a Class I medical device C. It will be regulated as an in vitro diagnostic product D. It will not be an FDA regulated product

D. This type of "advertising" would fall under the category of a "help-seeking" advertisement because the product is not named, although it likely makes recommendations about actions that might be taken based on a particular symptom, i.e., low or elevated glucose levels. Unlike drug and device promotional labeling and prescription drug and restricted device advertising, disease awareness communications are not subject to the requirements of the FD&C Act and FDA regulations.

A manufacturer is closing its current facility for manufacturing an approved drug product. The manufacturer has two other facilities, and has asked regulatory to examine the two locations and develop an appropriate regulatory strategy. Facility A: A large facility being built near the existing facility will have state-of-the-art electronics to monitor the manufacturing process, all new isolated manufacturing areas and all new equipment. The new facility will open one month before the current facility is scheduled to close. This manufacturing process will be the first process moved to this new building. Facility B: A smaller facility 100 miles away from the existing facility has been manufacturing several approved drug products for the same therapeutic purpose for the past 15 years Which is the most accurate analysis/recommendation? A. Transferring the manufacturing process to Facility A is considered a minor change and will only require a notation of the manufacturing process transfer from the current location in the drug product Annual Report. There would be no impact on the manufacturing process or the availability of the drug product. B. Facility A will have a significant positive impact on drug product quality due to the electronic monitoring system and new equipment. The transfer of the manufacturing process to Facility A would be considered a moderate change and could be filed in a CBE 30. C. Transferring the process to the older Facility B would be considered a major change and would require prior FDA approval before the drug product could be placed onto the market. D. Facility B has been manufacturing approved drug products for the same therapeutic purpose for the past 15 years and has been inspected by FDA. Moving the manufacturing process to Facility B would be a moderate change and could be filed in a CBE 30.

D. Transferring a drug product manufacturing process to a new facility requires notifying FDA of the change to the process. In reviewing Facilities A and B, the regulatory professional would recognize Facility A, although new and state-of-the-art, has not been inspected by FDA and would result in a major change to the approved NDA. This major change would require prior approval before drug product manufactured in this location could be placed onto the market. Reporting this manufacturing change in an Annual Report would be incorrect. Transferring the manufacturing process to Facility B, however, would be a moderate change as FDA has inspected it for the other drug products it currently manufactures. This is considered a moderate change and would result in a Changes Being Effected (CBE) 30 notification to FDA prior to placing the manufactured product on the market.

When multiple facilities are involved in a Class III device's design, assembly or processing, the PMA holder should do all of the following EXCEPT: A. Ensure the quality systems in all facilities are in compliance with 21 CFR 820 regulations, as applicable B. Include in the PMA submission a complete description of the device's manufacturing, processing, packing, storage and installation methods C. Provide written authorization to reference the Device Master File information from a contracted facility D. Submit quality system information only for the facility involved in the design of the device

D. When multiple facilities are involved in device design, assembly or processing, the PMA holder should submit applicable quality system information for each facility in separate volumes, clearly identifying the facilities to which they apply.

A company has promising results from preclinical mouse model studies of a biologic agent indicating the agent is effective against a lab-developed strain of pathogen considered to be a potential bioterrorism agent. Infection by the bioterrorism agent is known to cause irreversible morbidity or death. At this point, how should the company proceed? A. Submit an IND and commence clinical studies to demonstrate safety and effectiveness B. Submit an IND and design clinical safety and efficacy studies using a surrogate endpoint for approval of the product under 21 CFR 601 Subpart E C. Submit an IND and design clinical safety and efficacy studies using a surrogate endpoint for approval of the product under 21 CFR 314 Subpart E D. Submit an IND to start clinical safety trials in humans for approval of the product under the Animal Rule (21 CFR 601 Subpart H)

D. Because the drug's target (the biothreat) causes irreversible morbidity or death, clinical efficacy studies in humans are not ethical. This eliminates choices 1, 2 and 3. However, approval under the Animal Rule (21 CFR 601 Subpart H) requires clinical safety data (to be completed in healthy volunteers). Subpart H—Approval of Biological Products When Human Efficacy Studies Are Not Ethical or Feasible §601.90 Scope. This subpart applies to certain biological products that have been studied for their safety and efficacy in ameliorating or preventing serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances. This subpart applies only to those biological products for which: Definitive human efficacy studies cannot be conducted because it would be unethical to deliberately expose healthy human volunteers to a lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substance; and field trials to study the product's efficacy after an accidental or hostile exposure have not been feasible. This subpart does not apply to products that can be approved based on efficacy standards described elsewhere in FDA's regulations (e.g., accelerated approval based on surrogate markers or clinical endpoints other than survival or irreversible morbidity), nor does it address the safety evaluation for the products to which it does apply. §601.91 Approval based on evidence of effectiveness from studies in animals. PART 601 -- LICENSING Subpart E--Accelerated Approval of Biological Products for Serious or Life-Threatening Illnesses Sec. 601.41 Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity. FDA may grant marketing approval for a biological product on the basis of adequate and well-controlled clinical trials establishing that the biological 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. Approval under this section will be subject to the requirement that the applicant study the biological product further, to verify and describe its clinical benefit, where there is uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical benefit to ultimate outcome. Postmarketing studies would usually be studies already underway. When required to be conducted, such studies must also be adequate and well-controlled. The applicant shall carry out any such studies with due diligence.

What is a major difference between an HDE application and a PMA application? A. Application form and content B. Labeling requirements C. Supplemental applications D. Effectiveness requirements

D. Effectiveness requirements are not included in an HDE application. Sec. 814.3 Definitions. (m) HDE means a premarket approval application submitted pursuant to this subpart seeking a humanitarian device exemption from the effectiveness requirements of sections 514 and 515 of the act as authorized by section 520(m)(2) of the act. (e) PMA means any premarket approval application for a class III medical device, including all information submitted with or incorporated by reference therein. "PMA" includes a new drug application for a device under section 520(1) of the act.

A company is developing an unapproved drug-device combination product in which the primary mode of action is the drug. What application type and to which center should the company submit its application for marketing approval? A. Submit a Premarket Application to CDRH B. Submit an Investigational New Drug Application to CDER C. Submit a Premarket Notification application to CDRH D. Submit a New Drug Application to CDER

D. FDA Office of Combination Products website: www.fda.gov/CombinationProducts/RFDProcess/default.htm points (http://www.fda.gov/CombinationProducts/RFDProcess/default.htm) Frequently Asked Questions About Combination Products website: http://www.fda.gov/CombinationProducts/AboutCombinationProducts/ucm101496.htm (http://www.fda.gov/CombinationProducts/AboutCombinationProducts/ucm101496.htm) Final rule, Definition of the Primary Mode of Action of a Combination Product, (25 August 2005), Federal Register, http://edocket.access.gpo.gov/2005/pdf/05-16527.pdf (http://edocket.access.gpo.gov/2005/pdf/05-16527.pdf), 21 CFR 3.4 Designated Agency Component Question Feedback: The primary mode of action determines the center to which a company should submit its application. Because the primary mode of action in this case is a drug, a new drug application should be submitted to CDER.

The Food and Drug Administration Amendments Act of 2007 (FDAAA) established all of the following EXCEPT: A. Expanded FDA authority for postmarket safety of drugs. B. Reauthorization of prescription drug and medical device user fees. C. Incentives to medical device manufacturers to create devices for children. D. Voluntary registration of clinical trials in FDA database.

D. FDAAA established mandatory registration of clinical trials in the ClinicalTrials.gov data bank. Registration is required for trials meeting FDAAA 801's definition of an "applicable clinical trial" and were initiated either after 27 September 2007 or on or before that date and were still ongoing as of 26 December 2007. "Applicable Clinical Trials" include the following: drug and biologics trials—controlled clinical investigations, other than Phase 1 clinical investigations, of drugs or biological products subject to FDA regulation device trials— 1) controlled trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies 2) pediatric postmarket surveillance (http://clinicaltrials.gov/ct2/manage-recs/fdaaa#PediatricPostmarket) required by FDA "Applicable clinical trials" generally include interventional studies (with one or more arms) of FDA-regulated drugs, biological products or devices meeting one of the following conditions: The trial has one or more US sites The trial is conducted under an FDA Investigational New Drug application or Investigational Device Exemption The trial involves a drug, biologic or device manufactured in the US or its territories and is exported for research

Your company's senior management asked you to develop a justification for Fast Track status for an investigational new cancer drug. Which of the following would NOT be an appropriate justification for FDA granting Fast Track status for this investigational new drug? A. Preliminary evidence indicates the new drug may decrease clinically significant toxicity of available treatment B. Cancer is considered by FDA to be a serious disease C. Preliminary evidence indicates the new drug has potential for superior effectiveness compared to available treatment D. Documentation can be provided that the cancer drug meets safety and effectiveness standards required for Fast Track status

D. Fast Track status does not comprise or alter the standards for the drug's safety and effectiveness that become available through this process.