RAC (US) Practice Exam 2015

Your company wishes to seek approval of a combination of individually approved anti-hypertensive and anti-diabetic drugs. However, there is no Reference Listed Drug (RLD) for the proposed combination. Which of the following regulatory pathways is most applicable? A. 505(b)(2) B. 510(k) C. 505(b)(1) D. 505(j)

A. 505(b)(2) Regulatory Reference 21 CFR 314.3, 21 CFR 314.54 Guidance for Industry Applications Covered by Section 505(b)(2) October 1999 Question Feedback A 505(b)2 NDA relies at least in part on data that is not developed by the applicant. Reference listed drug means the listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its abbreviated application. Sec. 314.54 Procedure for submission of an application requiring investigations for approval of a new indication for, or other change from, a listed drug. (4) The applicant shall submit a field copy of the application that contains the technical section described in 314.50(d)(1), a copy of the information required under 314.50(a) and (c), and certification that the field copy is a true copy of the technical section described in 314.50(d)(1) contained in the archival and review copies of the application. (b) An application may not be submitted under this section for a drug product whose only difference from the reference listed drug is that: (1) The extent to which its active ingredient(s) is absorbed or otherwise made available to the site of action is less than that of the reference listed drug; or (2) The rate at which its active ingredient(s) is absorbed or otherwise made available to the site of action is unintentionally less than that of the reference listed drug. Guidance for Industry Applications Covered by Section 505(b)(2) October 1999 Section 505 of the act describes three types of new drug applications: (1) an application that contains full reports of investigations of safety and effectiveness (section 505(b)(1)); (2) 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)); Section 505(b)(2) was added to the act by the Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Amendments). This provision expressly permits FDA to rely, for approval of an NDA, on data not developed by the applicant.

A key parameter for a pharmaceutical product has a specification range of 90-100. Which of the following postmarketing specification changes would require FDA notification prior to making the change? A. 89-100 B.90-99 C. 95 +/- 5 D. 95-100

A. 89-100 Regulatory Reference Guidance for Industry Changes to an Approved NDA or ANDA April 2004 Revision 1 Question Feedback Notification is required when the specification range is widened. VIII. SPECIFICATIONS B. Major Changes (Prior Approval Supplement) The following are examples of changes in specifications considered to have a substantial 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. Relaxing an acceptance criterion except as otherwise provided for in this guidance (e.g., section VIII.C.1.b, VIII.C.1.e). C. Moderate Changes (Supplement - Changes Being Effected) Supplement - Changes Being Effected in 30 Days b. Relaxing an acceptance criterion

An orphan drug product means a product intended for use in a rare disease or condition as defined in FD&C Act Section 526. According to regulations, what constitutes a rare disease or condition? A. A disease or condition which affects fewer than 200,000 people in the US B. A disease or condition which affects fewer than 2% of the population in the US C. A disease or condition identified as rare by the American Medical Association. D. A disease or condition for which the mode of action has not been determined.

A. A disease or condition which affects fewer than 200,000 people in the US Regulatory Reference 21 CFR 316.20(b)(8)(i), FD&C Act Section 526 Question Feedback A disease or condition is considered rare if it affects fewer than 200,000 people in the US or affects more than 200,000 in the US and for which there is no reasonable expectation that the cost of developing and making a drug for such disease or condition available in the US will be recovered from sales of the drug in the US.

While reviewing the 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

A. Annually Regulatory Reference Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs, Frequently Asked Questions—Statement of Investigator (Form FDA 1572) Question Feedback FDA regulations do not require a CV or other statement of qualifications to be updated during a clinical study.

A deficiency letter may be issued to a company during review of a Biologics License Application (BLA) for which of the following? A. Clinical testing did not include enough subjects B. The BLA was not submitted electronically C. The sponsor failed to have a meeting with FDA prior to submitting the BLA to discuss the product and clinical testing plan D. The submission did not include a Drug Master File (DMF) with information about facilities and processes used in manufacturing

A. Clinical testing did not include enough subjects Regulatory Reference 21CFR 601.2 SOPP 8110: Submission of Paper Regulatory Applications to CBER Version #2 (June 3, 2010) SOPP 8101.1: Scheduling and Conduct of Regulatory Review Meetings with Sponsors and Applicants Guidance for Industry: Formal Meetings Between FDA and Sponsors or Applicants, May 2009 21 CFR 600-680 http://www.fda.gov/biologicsbloodvaccines/developmentapprovalprocess/biologicslicenseapplicationsblaprocess/default.htm (http://www.fda.gov/biologicsbloodvaccines/developmentapprovalprocess/biologicslicenseapplicationsblaprocess/default.htm) Question Feedback: Response 1 is correct, as FDA will not approve a BLA if it does not contain adequate clinical data (which may be affected by the number of sites where testing was performed) to demonstrate safety and efficacy. Response 2 is incorrect; although FDAMA originally required all submissions to be electronic by 2002, the implementation of this requirement has been delayed and the extent of electronic information to include in a BLA is still partially at the discretion of the company. Response 3 is incorrect because it is only a recommendation and not a requirement to participate in a meeting with FDA prior to submission of a BLA. Response 4 is incorrect because a DMF is optional in a BLA and pertinent information regarding facilities and processing can be incorporated directly into the BLA; a DMF can be used to submit information from a contract manufacturer without revealing confidential information to the applicant.

FDA has sent a Warning Letter citing mislabeling of a small manufacturer's artificial knee device. The regulatory professional should FIRST 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. Compliance Branch in the appropriate FDA District office Regulatory Reference Inspections, Compliance, Enforcement, and Criminal Investigations: 4-1 - Warning Letters http://www.fda.gov/ICECI/ComplianceManuals/RegulatoryProceduresManual/ucm176870.htm (http://www.fda.gov/ICECI/ComplianceManuals/RegulatoryProceduresManual/ucm176870.htm) Question Feedback This office is the best source for further follow up.

A company has been issued a Complete Response Letter by FDA. 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 that a Class 1 resubmission has a six-month review clock D. Inform the team that a Class 2 resubmission has a three-month review clock

A. Devise a strategy for responding to all deficiencies identified by FDA Regulatory Reference Guidance for Industry: Classifying Resubmission in Response to Action Letters Guidance for Industry: Submitting Separate Marketing Applications and Clinical Data for Purposes of Assessing User Fees PDUFA IV 21 CFR 314.110 Question Feedback Resubmissions purport to answer all of the deficiencies that need to be addressed by the applicant prior to approval of the original application as set forth in a previous action letter.

FDA currently requires all medical device registration and listing information (Annual, Initial or Updates) to be submitted using: A. FDA's Unified Registration and Listing System (FURLS) B. FDA Forms 2891 and 2892 C. FDA Forms 2656 and 2657 D. FDA Form 3356

A. FDA's Unified Registration and Listing System (FURLS) Regulatory Reference FDA website: Medical Devices, How to Register and List Question Feedback: According to the FDA website, the Food and Drug Administration Amendments Act of 2007 requires all registration and listing information (Annual, Initial or Updates) to be submitted electronically unless FDA grants a waiver. Furthermore, registration and listing information needs to be submitted via FDA's Unified Registration and Listing System (FURLS)/Device Registration and Listing Module (DRLM).

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. Filing a new 510(k) documenting changes in product instructions for use Regulatory Reference 21 CFR Part 807 Question Feedback A new intended use requires a 510(k).

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 that the severity grade for this AE is correctly reported 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. 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 Regulatory Reference 21 CFR 312.32 Guidance for Industry and Investigators: Safety Reporting Requirements for INDs and BA/BE Studies Question Feedback Reporting criteria for drug AEs is serious AND unexpected, whereas the reporting criteria for device is only serious.

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

A. Immunizing toxoids Regulatory Reference 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 Question Feedback Monoclonal antibodies for in vivo use were transferred to CDER's Office of New Drugs (OND) effective 30 June 2003.

On Monday, commercial stability batch testing for an approved drug produced results outside the specification. No assignable cause had been identified as of Wednesday. What is the best action for the regulatory professional to take? A. Issue a Field Alert B. Initiate retesting C. Initiate resampling D. Issue an Investigative Protocol

A. Issue a Field Alert Regulatory Reference 21 CFR § 314.81 (b)(1)(ii) Question Feedback Issuance of a Field Alert has a 72-hour (three working day) time limit from the time of confirmed OOS. Note the product must be commercially available for human use. Sec. 314.81 Other postmarketing reports. (b) Reporting requirements. The applicant shall submit to the Food and Drug Administration at the specified times two copies of the following reports: (1) NDA--Field alert report. The applicant shall submit information of the following kinds about distributed drug products and articles to the FDA district office that is responsible for the facility involved within three working days of receipt by the applicant. The information may be provided by telephone or other rapid communication means, with prompt written follow up. The report and its mailing cover should be plainly marked: "NDA--Field Alert Report." (i) Information concerning any incident that causes the drug product or its labeling to be mistaken for, or applied to, another article. (ii) Information concerning any bacteriological contamination, or any significant chemical, physical, or other change or deterioration in the distributed drug product, or any failure of one or more distributed batches of the drug product to meet the specification established for it in the application.

A company is developing a combination product that consists 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. The product is regulated as a drug Regulatory Reference 21 CFR 3.4 is the regulation regarding how FDA designates the review of combination products. 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 classification of products and the roles and responsibilities of the Office of Combination Products. Question Feedback: Primary mode of action is the pain drug and the device is a delivery system.

Which federal law made it illegal for physicians being reimbursed by federally funded programs to prescribe or recommend that the 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. Medicare and Medicaid Patient Protection Act of 1987 Regulatory Reference Medicare and Medicaid Patient Protection Act of 1987 Question Feedback 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.

Distribution records for drug products must reference or contain: A. Name and address of the consignee B. IND Annual Report date C. IND information amendment date D. Route of administration

A. Name and address of the consignee Regulatory Reference 21 CFR 211.196 Question Feedback Distribution records shall contain the name and strength of the product and description of the dosage form, name and address of the consignee, date and quantity shipped, and lot or control number of the drug product. For compressed medical gas products, distribution records are not required to contain lot or control numbers.

The Federal Trade Commission (FTC) has primary authority over which of the following? A. Over-the-counter (OTC) drug advertising B. Prescription drug advertising C. Generic drug advertising D. Restricted medical device advertising

A. Over-the-counter (OTC) drug advertising Regulatory Reference FTC Act Medical Device Amendments of 1976 FD&C Act of 1938 Question Feedback The Federal Trade Commission (FTC) has primary responsibility for the advertising of foods, cosmetics, OTC drugs, nonrestricted medical devices and other products whose safety, efficacy and labeling are regulated by FDA. FDA regulates prescription drug, generic drug, restricted medical devices and veterinary medicines advertising.

A blood center has discovered a unit of packed red blood cells for commercial use previously shipped to a local hospital was stored inappropriately for four days during the manufacturing process. The blood center should: A. Recall the blood product and initiate a blood product deviation report to CBER within 45 calendar days of discovery of the deviation. B. Recall the blood product and initiate a blood product deviation report to CDRH within 45 calendar days of discovery of the deviation. C. Recall the blood product and initiate a blood product deviation report to CBER within 15 calendar days of discovery of the deviation. D. Recall the blood product and initiate a blood product deviation report to CDRH within 15 calendar days of discovery of the deviation.

A. Recall the blood product and initiate a blood product deviation report to CBER within 45 calendar days of discovery of the deviation. Regulatory Reference FDA Guidance for Industry :Biological Product Deviation Reporting for Blood and Plasma Establishments 21 CFR Part 606.171 (c) Question Feedback: The appropriate FDA branch handling biologic products is CBER and the appropriate reporting period is 45 days from discovery of the manufacturing deviation. Under 21 CFR 606.171, a manufacturer is required to report certain events associated with the manufacturing, to include testing, processing, packing, labeling or storage, or with the holding or distribution of blood or a blood component, which may affect the safety, purity or potency of a distributed product. Safety, purity and potency are defined in 21 CFR 600.3(p), (r) and (s). Under 21 CFR 606.171(c), a manufacturer should submit reports as soon as possible, but is required to submit reports at a date not to exceed 45 calendar days from the date of discovery of information reasonably suggesting a reportable event has occurred.

Your company recently had a successful End-of-Phase 2 meeting for a novel drug and would like your regulatory advice on the design for the pivotal Phase 3 study. The clinical compound team wants to use a primary endpoint and unusual design that has never been utilized in the therapeutic area you are studying. Which type of meeting would be the best choice for getting FDA alignment with your pivotal Phase 3 study? A. Request a Special Protocol Assessment Meeting B. Request a Pre-NDA Meeting C. Request a Type C Meeting D. Request a Type A Meeting

A. Request a Special Protocol Assessment Meeting Regulatory Reference Guidance for Industry: Special Protocol Assessment Guidance for Review Staff and Industry: Good Review Management Principles and Practices for PDUFA Products Question Feedback: Based on guidance documents, FDA encouraged the use of the SPA process for trials in which the proposed study design or endpoints are unusual, or for studies that involve an indication or disease for which the FDA has not previously approved a drug or biologic product. Pre-NDA is later, after you would need to discuss the Phase 3 trial design. A Type C Meeting would be better used for general drug development questions. Type A meetings generally are used for dispute resolution; they also are used if a sponsor wants a meeting after receiving comments from FDA on the SPA.

Which of the following is not a responsibility of an investigator? A. Submitting unanticipated adverse event reports to FDA. B. Submitting notices to the IRB of deviations from the investigational plan. C. Maintaining records of receipt, use and disposition of investigational product. D. Reporting to the sponsor withdrawal of IRB approval.

A. Submitting unanticipated adverse event reports to FDA. Regulatory Reference 21 CFR 312.60 21 CFR 812.40 21 CFR 150(a)(1) Question Feedback: It is the sponsor's responsibility to notify FDA once notified by the investigator. The investigator is responsible for notifying both the sponsor and the IRB.

If a device failure is occurring with greater than expected frequency and investigation of the problem implicates improper use by the end user, which of the following should occur? A. The labeling is revised B. The product is recalled C. The product is redesigned D. A "Dear Doctor" letter is issued

A. The labeling is revised Regulatory Reference 21 CFR 801 Question Feedback The labeling should provide appropriate information for proper use of the product.

While reviewing product complaint files for MDR reportability, you noticed a complaint regarding a common failure mode of an implantable screw. There was no patient involvement and no 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 will likely 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. This complaint is reportable; an MDR will be filed with FDA within 30 days Regulatory Reference 21 CFR 803.20(3)(ii) and 21 CFR 803.50(a)(2) Question Feedback: When a recall is initiated for a particular product failure mode, such failure mode is automatically 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.

Which of the following is NOT stipulated by FDA to support product postapproval stability requirements? A. Three batches per year per container/closure system in the stability program B. An adequate number of batches C. An amount that is compliant with the postapproval stability commitment D. Reliable, meaningful and specific test methods .

A. Three batches per year per container/closure system in the stability program Regulatory Reference 21 CFR 211.166(a-b), 21 CFR 314.81(b)(9)(b)(viii) Question Feedback Items 2 and 4 are directly from 21 CFR 211.166 Stability testing. Item 3 is supported by 21 CFR 314.81, A status report is to be included for any chemistry, manufacturing and controls studies the applicant has agreed to perform and for all product stability studies. Sec. 211.166 Stability testing. (a) There shall be a written testing program designed to assess the stability characteristics of drug products. The results of such stability testing shall be used in determining appropriate storage conditions and expiration dates. The written program shall be followed and shall include: (1) Sample size and test intervals based on statistical criteria for each attribute examined to assure valid estimates of stability; (2) Storage conditions for samples retained for testing; (3) Reliable, meaningful, and specific test methods; (4) Testing of the drug product in the same container-closure system as that in which the drug product is marketed; (5) Testing of drug products for reconstitution at the time of dispensing (as directed in the labeling) as well as after they are reconstituted. (b) An adequate number of batches of each drug product shall be tested to determine an appropriate expiration date and a record of such data shall be maintained. Accelerated studies, combined with basic stability information on the components, drug products, and container-closure system, may be used to support tentative expiration dates provided full shelf life studies are not available and are being conducted. Where data from accelerated studies are used to project a tentative expiration date that is beyond a date supported by actual shelf life studies, there must be stability studies conducted, including drug product testing at appropriate intervals, until the tentative expiration date is verified or the appropriate expiration date determined. Sec. 314.81 Other postmarketing reports. (viii) Status of other postmarketing studies. A status report of any postmarketing study not included under paragraph (b)(2)(vii) of this section that is being performed by, or on behalf of, the applicant. A status report is to be included for any chemistry, manufacturing, and controls studies that the applicant has agreed to perform and for all product stability studies

A company plans to develop a new treatment for anemia. The product is a polypeptide fragment of the human protein erythropoietin that has not been approved previously. The company plans to produce the polypeptide by chemical synthesis. To date, other erythropoietins have been approved by FDA, but not the fragment. What is the appropriate pathway by which to seek approval? A. Under Section 505(b)(1) of the FD&C Act B. Under Section 505(b)(2) of the FD&C Act C. Under Section 351(a) of the PHS Act D. Under Section 351(k) of the PHS Act

A. Under Section 505(b)(1) of the FD&C Act Regulatory Reference Section 505(b)(1) of the FD&C Act Question Feedback Although the product is a fragment of a human protein, it will be a chemically synthesized polypeptide and therefore will be regulated under the FD&C Act (not the PHS Act). Because the treatment is a new active ingredient, the sponsor should seek approval via 505(b)(1).

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 submit the Labeling in Structured Product Label (SPL) format upon approval of their product. 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. 14 days Regulatory Reference FDA Guidance for Industry: Providing Regulatory Submissions in Electronic Format—Content of Labeling, April 2005 FDA draft Guidance for Industry: SPL Standard for Content of Labeling—Technical Qs & As, October 2009, Question 13 Question Feedback "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 to submit SPL "As soon as possible, but no later than 14 days from the date of approval letter"

A medical device company is developing a product with drug, biologic and device components. The product and indication have not been classified previously by FDA. What is the most appropriate regulatory pathway? A. An IDE and PMA should be submitted to CDRH, as the company is a medical device company and is most familiar with medical device application regulations B. A Request for Designation (RFD) should be sent to the Office of Combination Products (OCP) at FDA to determine the primary mode of action (PMOA) and assign the center with primary jurisdiction C. An IND and NDA should be submitted to CBER because this is the strictest regulatory pathway D. The company should submit a marketing application to the appropriate FDA center based on the company's determination of primary mode of action (PMOA)

B. A Request for Designation (RFD) should be sent to the Office of Combination Products (OCP) at FDA to determine the primary mode of action (PMOA) and assign the center with primary jurisdiction Regulatory Reference 21 CFR Part 3.7, How to Write a Request for Designation (RFD) Guidance for Industry Question Feedback An unclassified, combination product should be evaluated by OCP through the RFD process to determine the primary mode of action. An RFD also is referred to as an applicant's letter of request (see 21 CFR 3.2(j)). It is a written submission to OCP. RFDs generally request a determination of (1) the regulatory identity or classification of a product as a drug, device, biological product or combination product.

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. A PMA B. A Special 510(k) C. An Individual Device Exemption (IDE) D. An Annual Report for a PMA

B. A Special 510(k) Regulatory Reference The New 510(k) Paradigm—Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications—Final Guidance, March 1998 Question Feedback: The Special 510(k) allows the manufacturer to declare conformance to design controls without providing the data. While the basic content requirements of the 510(k) (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 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. Adulterated Regulatory Reference Section 501 [21 USC §351] of the FD&C Act and 21 CFR 820 Question Feedback A device that fails to comply with the QSR (GMP) regulations set forth in 21 CFR 820 is considered adulterated.

The Food and Drug Administration Modernization Act (FDAMA) established two types of formal early collaboration meetings. Which of the following is one of those meetings? A. PDP meeting B. Agreement Meeting C. Pre-IDE meeting D. Type A meeting

B. Agreement Meeting The Food and Drug Administration Modernization Act of 1997 (FDAMA) (Public Law 105-115) established two types of Formal Early Collaboration meetings ("Determination Meetings" as described in section 513(a)(3)(D) of the Food, Drug, and Cosmetic Act (FD&C Act). "Agreement Meetings," as described in Section 520(g)(7) of the FD&C Act) to provide clear direction for testing and development of devices requiring clinical investigations to support marketing. The Agreement Meeting is a formal meeting to agree on the parameters of the investigational plan. When a meeting request is received by FDA, the meeting will be held within 30 days. The agreements made at the meeting are provided in writing to the sponsor and are binding on FDA.

Company X is planning to conduct a bioequivalence (BE) study for its proposed generic drug product. The clinical protocol requires a multiple-dose study where the total daily dose exceeds that specified in the labeling of the reference approved drug product. As a regulatory professional, which choice below is the correct action concerning this bioequivalence study? A. The bioequivalence study may be started without further FDA action since the drug product is already the subject of an approved NDA. B. An Investigational New Drug Application (IND) must be filed prior to initiating the BE study C. Request a Type B meeting with FDA for protocol review and approval D. Submit a suitability petition requesting the use of the increased dosage range

B. An Investigational New Drug Application (IND) must be filed prior to initiating the BE study Regulatory Reference 21 CFR 320.31(b)(2) Question Feedback As per regulation, an IND application is required for a multiple-dose study in normal subjects or patients where either the single or total daily dose exceeds that specified in the labeling of the drug product that is the subject of an approved NDA or ANDA.

A company has just received FDA approval to market a new drug. When must the drug sponsor submit the content of labeling in structured product labeling (SPL) format using the FDA automated drug registration and listing system? A. As soon as possible, but no later than 30 days in advance of the intended marketing date of the product 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. As soon as possible, but no later than 14 days from the date of the FDA approval letter Regulatory Reference Guidance for Industry SPL Standard for Content of Labeling Technical Qs & As http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072392.pdf (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072392.pdf) Structured Product Labeling Resources www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm (http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm) Question Feedback NDA approval letters say "As soon as possible, but no later than 14 days from the date of this letter..."

During a review of the production records for Batch 1 of Drug Product X, it was discovered the theoretical yield exceeded the maximum percentage established in the master production and control records by 1.5%. The batch has not been distributed. As a regulatory professional, you should recommend the investigation: A. Be extended to only other batches of Drug Product X B. Be extended to other drug products that may have been associated with the discrepancy C. No immediate action is needed but the discrepancy should be noted in the next Annual Report D. Further production should be halted until the reason for the discrepancy is identified

B. Be extended to other drug products that may have been associated with the discrepancy Regulatory Reference 21 CFR 211.192 Production record review Question Feedback: Any unexplained discrepancy (including a percentage of theoretical yield exceeding the maximum or minimum percentages established in master production and control records) or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated, whether or not the batch has already been distributed.

What type of communication will FDA send an applicant when the review division concludes that an NDA or ANDA cannot be approved in its present form and certain additional information or clarifications are needed? A. Non-approvable letter B. Complete response letter C. Non-approval letter D. Approvable letter

B. Complete response letter Regulatory Reference Complete response letter final rule; 21 CFR 314.110 Question Feedback All deficiencies identified by FDA will be in the complete response letter. The letter also will reflect the entire review of the application and/or amendments submitted.

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. Device History Record Regulatory Reference 21 CFR Part 820.184 (Device History Record) Question Feedback 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.

Company X is developing marketing materials for a Class II medical device known as "Y." In one marketing piece, the company talks about the clinical data supporting the marketing of the device. Which of the following statements is illegal and should NOT be included in the marketing materials? A. Company X has conducted clinical studies to demonstrate safety and effectiveness of device Y. B. Device Y is approved for marketing in the US. C. Warning: Device Y is not compatible with MRI equipment. D. Caution: Device Y, when improperly deployed, can cause bleeding.

B. Device Y is approved for marketing in the US. Regulatory Reference 21 CFR 807.97 Question Feedback Class II devices are cleared for marketing in the US by FDA, not approved.

Company X is planning to conduct a clinical investigation for its new oral suspension for a reconstituted drug product. What information related to expiration dating is Company X required to include in the investigational drug product labeling? A. New drug products for investigational use are exempt from expiry dating requirements B. Expiration information for the reconstituted drug product is required C. An expiration date assigned on the basis of stability testing of the new drug product is required D. Expiration for the new drug product and reconstituted drug product are both required

B. Expiration information for the reconstituted drug product is required Regulatory Reference 21 CFR 211.137(g) Question Feedback As per FDA regulation, expiration information for the reconstituted new drug product for investigational use is required.

An important consideration in developing 505(b)(2) products as compared to ANDA products is: A. Lower costs of 505(b)(2) regulated product development and review. B. Extended market exclusivity of 505(b)(2) products. C. Faster FDA processing and approval times for 505(b)(2) products. D. Product development costs and FDA review times for 505(b)(2) products.

B. Extended market exclusivity of 505(b)(2) products. Regulatory Reference Guidance for Industry: Applications Covered by Section 505(b) "The 505 (b) (2) Drug Development Pathway." Kumar M and Jethwani H. Regulatory Focus, April 2010. Question Feedback For 505(b)(2) products, there are three to five years of market exclusivity in the US, depending on the extent of changes to the previously approved drug and the amount of data submitted to FDA. This is an apparent advantage when compared to ANDA approval, where exclusivity can be held for only 180 days and applies only to the first generic product. A 505(b)(2) application may itself be granted three years of Waxman-Hatch exclusivity if one or more of the clinical investigations, other than BA/BE studies, was essential to approval of the application and was conducted or sponsored by the applicant (21 CFR 314.50(j); 314.108(b)(4) and (5)). A 505(b)(2) application also be granted five years of exclusivity if it is for a new chemical entity (21 CFR 314.50(j); 314.108(b)(2)). A 505(b)(2) application also may be eligible for orphan drug exclusivity (21 CFR 314.20- 316.36) or pediatric exclusivity (section 505A of the act).

Which of the following is NOT required in a Biologics License Application (BLA) but is required in a New Drug Application (NDA)? Correct Yours A. FDA form 3397 (user fee cover sheet) B. Field copy certification C. Chemistry section D. Debarment certification

B. Field copy certification Regulatory Reference 21 CFR 601 21 CFR 314 Guidance for Industry: Providing Regulatory Submissions in Electronic Format—NDAs (January 1999) Question Feedback The correct answer is 2. Field copy certification only applies to NDA products, whereas all of the others sections are requirements for both BLAs and NDAs.

The drug substance manufacturing plant is proposing to widen a critical in-process test limit associated with the final intermediate manufacturing process. What will need to be done in order for the plant to implement the change? A. File the change as an annual reportable change and implement the change immediately B. File a Prior Approval Supplement and wait until agency approval to implement C. This type of change cannot be made to an approved drug substance manufacturing process D. File a Changes Being Effected in 30 days and implement after day 30 if the agency has not contacted the company

B. File a Prior Approval Supplement and wait until agency approval to implement Regulatory Reference 21 CFR 314.70 Guidance for Industry: Changes to an Approved NDA or ANDA, Section VIII, B, 1 Question Feedback The widening of acceptance criteria for an in process test performed on the final intermediate would be classified as a Prior Approval Supplement. Therefore, the change would need to be filed with and approved by FDA before implementation.

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 Regulatory Reference 21 CFR 20.101 Administrative enforcement records http://www.fda.gov/ICECI/EnforcementActions/ucm256377.htm (http://www.fda.gov/ICECI/EnforcementActions/ucm256377.htm) Investigations Operations Manual (IOM), Chapter V (Establishment Inspections) http://www.fda.gov/ICECI/Inspections/IOM/default.htm (http://www.fda.gov/ICECI/Inspections/IOM/default.htm) Question Feedback Form FDA 483 is the most correct as 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 when an investigator(s) has observed any conditions that in his or her judgment may constitute violations of the Food, Drug, and Cosmetic Act (FD&C Act) and related acts. FDA Form 483s are discussed with a company's management at the conclusion of the inspection. 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 time frames 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.

A company has submitted its NDA for review. When must additional safety information be submitted to FDA in a safety update report to avoid triggering an extension of the review clock? A. Six months after the initial NDA submission (180 day safety update) B. Four months after the initial NDA submission (120 day safety update) C. Upon initial NDA submission D. After NDA approval

B. Four months after the initial NDA submission (120 day safety update) Regulatory Reference 21 CFR 314.50 (d)(5)(vi)(b) Content and format of an application Clinical data section. Question Feedback: "(vi) A summary and updates of safety information, as follows: (b) The applicant shall, under section 505(i) of the act, update periodically its pending application with new safety information learned about the drug that may reasonably affect the statement of contraindications, warnings, precautions, and adverse reactions in the draft labeling. These "safety update reports" are required to include the same kinds of information (from clinical studies, animal studies, and other sources) and are required to be submitted in the same format as the integrated summary in paragraph (d)(5)(vi)(a) of this section. In addition, the reports are required to include the case report forms for each patient who died during a clinical study or who did not complete the study because of an adverse event (unless this requirement is waived). The applicant shall submit these reports (1) 4 months after the initial submission; (2) following receipt of an approvable letter; and (3) at other times as requested by FDA. Prior to the submission of the first such report, applicants are encouraged to consult with FDA regarding further details on its form and content."

A US medical device contract manufacturer has customers for whom it manufactures medical device components (parts) and finished medical devices. To date, all medical products produced are either parts for Class II medical devices or are Class II finished medical devices. The manager of new business contacts the regulatory manager to assess the impact of possible new business involving a Class III device. What is the first question the regulatory manager should ask to begin to assess the impact of Class III on plant operations? A. Is it a sterile device? B. Is it a component or finished device that would be manufactured? C. Is it an implantable device? D. Is it a single use device?

B. Is it a component or finished device that would be manufactured? Regulatory Reference 21 CFR Part 820.1 (a) the Quality System Regulation (QSR) Question Feedback This regulation does not apply to manufacturers of components or parts of finished devices, but such manufacturers are encouraged to use appropriate provisions of this regulation as guidance. Given the QSR is not mandatory to component (part) manufacturing, if the product is a component, this may eliminate QSR compliance. To assess the regulatory impact one must first know what is to be manufactured at the site, i.e., component or finished device. Many contract device component manufacturers do comply with the QSR; however, in this case, knowing the new business for a Class III device was to manufacture a component only would help determine the applicable regulations. For instance, if the job was to manufacture a component, the need for sterilization might be eliminated because the finished device manufacturer might sterilize the component once it is configured in the finished device. If it were ascertained the new business was to produce the finished product, the QSR and possibly other requirements such as 21CFR Part 821 Medical Device Tracking would apply. Applicability of the QSR The QSR applies to finished device manufacturers that intend to commercially distribute medical devices. A finished device is defined in 21 CFR 820.3(l) as any device or accessory to any device that is suitable for use or capable of functioning, whether or not it is packaged, labeled or sterilized.

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 Regulatory Reference 21 CFR 820.181(d) Question Feedback: Labeling specifications are part of the DMR.

A company is using a clinical research organization (CRO) to develop the protocol and monitor the clinical investigators for the company's clinical trial. The regulatory professional may interact with the CRO in which of the following situations? A. Making presentations to the reviewing IRBs B. Making presentations to the reviewing division at FDA C. Jointly witnessing the signing of patient consent forms D. Arranging for FDA investigators to observe treatment of subjects at clinical sites

B. Making presentations to the reviewing division at FDA Regulatory Reference International Conference on Harmonisation (ICH) Good Clinical Practice (E6), 1996 FDA Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance, 1996. Question Feedback The above FDA guidance identifies the sponsor as "1.53 Sponsor: An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial." Since regulatory professionals are normally not involved in such activities, only answer #2 is correct.

Due to mechanical failure, a product line has remained in process for five days over the time limit established in the company's SOPs. Which of the following should be done first? A. Reject all products in this one line since the time limit has been exceeded. B. Proceed with processing and quarantine the product until QA/QC completes a deviation report and investigation. C. Complete the manufacturing process and proceed to ship the product. D. Review the SOP to determine if the time limitation is appropriate.

B. Proceed with processing and quarantine the product until QA/QC completes a deviation report and investigation. Regulatory Reference 21 CFR 211.100 and 21 CFR 820.90 describe the requirements for control of nonconforming product, nonconformity review and disposition, etc. Question Feedback Quarantine would give the company time to conduct an investigation and determine suitability for release.

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. Products that show evidence of safety and effectiveness in a new subpopulation Regulatory Reference MAPP 5240.3 Review Order of Original ANDAs, Amendments, and Supplements page Definition of ANDA/Generic drug: http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProcedures/UCM407849.pdf (http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProcedures/UCM407849.pdf) Question Feedback 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 following applies to autologous chondrocytes expanded in vitro for the repair of cartilage defects: A. Regulated under Section 351 of the Public Health Service Act and no premarket approval required B. Regulated under Section 351 of the Public Health Service Act and premarket approval required C. Regulated under Section 361 of the Public Health Service Act and no premarket approval required D. Regulated under Section 361 of the Public Health Service Act and premarket approval required

B. Regulated under Section 351 of the Public Health Service Act and premarket approval required Regulatory Reference: 21 CFR 1271.10 and 21 CFR 1271.20 Question Feedback; The product is a HCT/P (human cells, tissues and cellular and tissue-based products). In vitro expansion of cells is considered more than minimal manipulation. The product therefore does not meet the criteria to be subject to regulation under section 361 of the PHS Act (criteria: minimal manipulation; homologous use; not combined with another article; no systemic effect and not dependent on metabolic activity of living cells except if for autologous use, use in a first-degree or second-degree blood relative or for reproductive use) and is regulated under section 351 of the PHS Act and requires a Biologics License Application (BLA)

A drug company's Phase 3 trials will conclude in six months. Members of the statistics team have questions pertaining to the pooling of studies for the statistical analysis in eCTD Module 2. As the regulatory professional, 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. Submit a meeting request to FDA for a Type B meeting Regulatory Reference 21 CFR 312.47 Guidance for Industry Formal Meetings Between the FDA and Sponsors or Applicants Question Feedback Type B meetings include Pre-NDA meetings. A Pre-NDA meeting can be used to discuss appropriate methods for statistical analysis of data in the marketing application.

A pharmaceutical company decides to collaborate with a diagnostic device manufacturer in the development of a new therapeutic drug. The diagnostic device is intended to identify patients who are most likely to benefit from use of the therapeutic product. The device previously has been cleared for a different intended use. What should the diagnostic device manufacturer do prior to commercial distribution of the device for the new intended use? A. Define the patient population identified by the diagnostic device B. Submit a new premarket submission for the device for use with the novel therapeutic product C. Revise the labeling to specify the therapeutic product which the device has been approved or cleared for use D. Identify the therapeutic class of products in which the diagnostic device may be applicable for use

B. Submit a new premarket submission for the device for use with the novel therapeutic product Regulatory Reference Draft Guidance for Industry and FDA Staff: In Vitro Companion Diagnostic Devices 21 CFR 807.81(a)3 Question Feedback The best choice is 2. 1 and 3 alone are not sufficient to legally market a device. A therapeutic class, instead of a specific therapeutic product, should not be claimed unless there is sufficient evidence to support this.

A company is evaluating next steps for a small Phase 1/2 clinical trial. There are four cohorts and the company has just completed enrollment of the third cohort. Efficacy data from immunology testing 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 dose of the drug product and may not be supported nonclinical toxicology studies. The higher dose also will require some additional product development and the time to manufacture is estimated to be approximately 18 months. What is the best regulatory approach? A. Recruitment on the current clinical protocol should be put on hold for two years to wait for the new drug product. B. The current clinical protocol should be terminated and a new clinical protocol written with the new dosing supported by nonclinical studies. C. The clinical protocol should be amended and increased dosing schedule be incorporated into the protocol. D. The clinical protocol should be amended and the dosing of the current drug product increased.

B. The current clinical protocol should be terminated and a new clinical protocol written with the new dosing supported by nonclinical studies. Regulatory Reference 21 CFR 312.45 Question Feedback Trials that are inactive for two years are put on FDA inactive list

Your company recently submitted a Biologics License Application (BLA) to CDER and the review division has notified the company that 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. The product is one in which it has been demonstrated through adequate and well-controlled trials to be less effective than alternative therapies. Regulatory Reference 21 CFR 208.1(c) Medication Guides www.fda.gov/Drugs/DrugSafety/ucm085729.htm (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) Question Feedback: According to 21 CFR 208.1, patient labeling for a drug or biologic 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.

Company Z selected a proprietary name for its new molecular entity, currently in development. The NDA will be submitted in six months. All of the following are Relevant to the proprietary name EXCEPT: A. The request for proprietary name approval may be submitted with the NDA. B. The proprietary name submission package may be Submitted up to one month after NDA submission. C. The request for proprietary name approval may be submitted prior to the NDA. D. FDA will communicate to the applicant a tentative acceptance or non-acceptance of the proposed proprietary name submitted with the NDA within 90 days of the receipt of the complete submission.

B. The proprietary name submission package may be Submitted up to one month after NDA submission. Regulatory Reference 21 CFR Part 314.50 Question Feedback The request for proprietary name approval must be submitted no later than in the NDA. Companies have the option of submitting a proprietary name request prior to NDA submission under the Investigational New Drug application (IND). To meet the review performance goals: The review of a complete submission for a proposed proprietary name submitted during the IND phase must be completed and a tentative acceptance or non-acceptance about the name must be communicated to the sponsor within 180 days of the receipt of the complete submission. The review of a complete submission for a proposed proprietary name submitted with an NDA or BLA or as part of a supplement must be completed and a tentative acceptance or non-acceptance about the name must be communicated to the applicant within 90 days of the receipt of the complete submission.

Which of the following is a requirement for a sponsor to advertise that a prescription drug is safer or more effective than another prescription drug? A. The representation must have been approved as part of the labeling in an initial new drug application or biologic license B. The representation is supported by substantial evidence derived from adequate and well-controlled studies as defined by applicable regulation C. The requirement for adequate and well-controlled studies is waived by regulation D. Peer-reviewed scientific literature in support of the claim must be submitted in a preapproval supplement

B. The representation is supported by substantial evidence derived from adequate and well-controlled studies as defined by applicable regulation Regulatory Reference 21 CFR 202.1 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=202.1 (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=202.1) Question Feedback Peer-reviewed scientific literature in support of the claim is not required to be submitted in a preapproval supplement but should be supplied to the Food and Drug Administration, if requested. Sec. 202.1 Prescription-drug advertisements. (6) An advertisement for a prescription drug is false, lacking in fair balance, or otherwise misleading, or otherwise violative of section 502(n) of the act, among other reasons, if it: (i) Contains a representation or suggestion, not approved or permitted for use in the labeling, that a drug is better, more effective, useful in a broader range of conditions or patients (as used in this section patients means humans and in the case of veterinary drugs, other animals), safer, has fewer, or less incidence of, or less serious side effects or contraindications than has been demonstrated by substantial evidence or substantial clinical experience (as described in paragraphs (e)(4)(ii) (b) and (c) of this section) whether or not such representations are made by comparison with other drugs or treatments, and whether or not such a representation or suggestion is made directly or through use of published or unpublished literature, quotations, or other references

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

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 Regulatory Reference 21 CFR Part 211.170 Question Feedback 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.

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 has since been approved. Subsequently, the 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 that provides the supporting data to justify why the change will not adversely affect the identity, strength, quality, purity and potency of the specific drug product as these factors relate to the product's safety and effectiveness C. Your company may still pursue the change(s) and should submit a CBE-30 that provides the supporting data to justify why the change will not adversely affect the identity, strength, quality, purity and potency of the specific drug product as these factors relate 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. Your company may still pursue the change(s) and should submit a Prior Approval Supplement that provides the supporting data to justify why the change will not adversely affect the identity, strength, quality, purity and potency of the specific drug product as these factors relate to the product's safety and effectiveness Regulatory Reference Draft Guidance for Industry: Comparability Protocols—Chemical, Manufacturing, and Controls Information (2003) Question Feedback 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 won't adversely affect the drug product.

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. 505(b)(2) NDA Regulatory Reference Draft Guidance for Industry: Applications Covered by Section 505(b) "The 505(b)(2) Drug Development Pathway." Kumar M and Jethwani H. Regulatory Focus, April 2010. Question Feedback 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 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 these studies are all 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. 505(b)2 Regulatory Reference FD&C Act Section 505(b)2 21 CFR 314.50 21 CFR 314.54, Guidance for Industry: Applications Covered by Section 505(b)(2) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM079345.pdf (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM079345.pdf) Question Feedback As the drug has been studied and results are published, a comparability study between IV and oral is acceptable under a 505(b)2.

In most cases, the manufacturer of biological products 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. 6 Months Regulatory Reference 21 CFR 600.13 Question Feedback 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.

Which of the following types of drug applications are NOT subject to a one-time FDA user fee upon submission of the application? A. An original NDA containing nonclinical and clinical data that have already been 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 that has not been previously submitted to an IND

C. A supplemental NDA requesting review of new and/or revised manufacturing processes Regulatory Reference FD&C Act, Section 736(c)(1) www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm069943.htm (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm069943.htm) Guidance for Industry: Submitting Separate Marketing Applications and Clinical Data for Purposes of Assessing User Fees Question Feedback Any NDA or SNDA that contains new clinical data must pay a fee to FDA upon submission of the application.

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 the calculation of the yield to be recorded three ways: theoretical yield; actual yield and percentage of theoretical yield. Which of these calculations would you expect to be most impacted 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. Actual yield and percentage of theoretical yield Regulatory Reference 21 CFR Part 210.3 (17),Part 210.3 (18), Part 210.3(19) and 21 CFR Part 211.103 Question Feedback To make the correct selection, one must understand anything that affects 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 defined as a ratio of the actual yield and then expressed as a percentage (see Part 210.3 (19)). Sec. 210.3 Definitions. (17) Theoretical yield means the quantity that would be produced at any appropriate phase of manufacture, processing, or packing of a particular drug product, based upon the quantity of components to be used, in the absence of any loss or error in actual production. (18) Actual yield means the quantity that is actually produced at any appropriate phase of manufacture, processing, or packing of a particular drug product. (19) Percentage of theoretical yield means the ratio of the actual yield (at any appropriate phase of manufacture, processing, or packing 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.

Your company is planning to submit a BLA to CBER. The BLA was pulled together quickly and you are concerned it may not be complete. FDA's initial filing decision could be a Refuse to File (RTF) for all of the reasons below EXCEPT: A. Data tabulations (line listings) or graphic displays cannot be interpreted B. Clear omission of required sections C. An analysis was conducted incorrectly D. Technically deficient electronic submission

C. An analysis was conducted incorrectly Regulatory Reference 21 CFR 601.2 and FDA SOPP 8404 Question Feedback: An RTF is issued when the necessary components of an application are missing or inadequate to be reviewed. A complete response letter (CR) is due to critical omissions of data or analysis as well as adverse judgment about the data, conclusions, rationale, etc., which would include an analysis being conducted incorrectly.

When should the manufacturer of a Class III medical device expect to have an FDA Premarket Approval Inspection? A. Within an IDE application B. After Phase II of the IDE study C. Prior to approval of the PMA D. Within two years following the PMA approval

C. Prior to approval of the PMARegulatory Reference 21CFR814.44(e)(1)(ii) PMA Compliance Program #P91-3 PMA Compliance Program 7383.001 Inspections of Medical Device Manufacturers, C.P. 7382.845 www.fda.gov/MedicalDevices/DeviceRegulationandGuida Question Feedback As a condition of approval, FDA may require an inspection to ensure the manufacturing facilities, methods and controls are in compliance with Part 820 and, if applicable, to verify documents pertinent to the pending PMA.

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 that the lot be released B. Recommend that 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. Assess whether the rework steps are within the regulatory filing and whether there is a potential regulatory impact Regulatory Reference Guidance for Industry: Drug Product: Chemistry, Manufacturing, and Controls Information Guidance for Industry: Immediate Release Solid Oral Dosage Forms SUPAC-IR Questions and Answers about SUPAC-IR Guidance Question Feedback The release and disposition of product 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.

According to the Quality System Regulation, when an investigation of a complaint is conducted, all of the following are requirements for inclusion in the record of the investigation EXCEPT: A. The dates and results of the investigation. B. The nature and details of the complaint. C. Changes in procedures correcting quality problems. D. Any reply to the complainant.

C. Changes in procedures correcting quality problems. Regulatory Reference Complaint files 21 CFR Part 820.198. Question Feedback When an investigation is made conducted this section, a record of the investigation shall be maintained by the formally designated unit identified in paragraph (a) of this section. The record of investigation shall include: (1) The name of the device; (2) The date the complaint was received; (3) Any 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.

Pharmacogenomic testing data results must be submitted to an IND in all the following circumstances EXCEPT when: A. The test results will be used to determine dosing schedule selection in a clinical trial B. The 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. Data were derived from general gene-expression analysis of trial participants Regulatory Reference 21 CFR 312.23 Guidance for Industry: Pharmacogenomic Data Submissions Question Feedback Exploratory data 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).

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. Disposes of unused study medication Regulatory Reference 21 CFR 312.53, 21 CFR 312.60, ICH GCP 4.9, 21 CFR 312.50, ICH GCP 5, 21 CFR 312.66 Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance Question Feedback Investigator is responsible for controlling the study medication during the study, but unused medication is required to be disposed of by the sponsor in a well-documented way. 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/favourable opinion from IRB/IEC and regulatory authority(ies)). 5.14.3 The sponsor should ensure that 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 return of 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.

During the open-label extension phase of a clinical trial for NEWDRUG, some new and different adverse events occurred that could affect the final labeling. The NDA for NEWDRUG 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. Four-month update Regulatory Reference 314.50(d)(5)(vi)(b)(1) Question Feedback Section 505(i) requires an NDA update four months after the initial submission—entitled "safety update report" by the code—which would affect the contraindication, warnings, precautions and adverse reactions sections of the draft labeling.

A company is planning to implement a few minor manufacturing changes for its FDA-approved device. The company is currently conducting a clinical study for a new indication using this device. The correct submission for the regulatory professional to make is the: A. PMA Amendment B. IND Supplement C. IDE 5-day Notice D. CBE-30

C. IDE 5-day Notice Regulatory Reference Changes or Modifications During the Conduct of a Clinical Investigation; Final Guidance for Industry and CDRH Staff (May 2001) Question Feedback IND Supplements and CBE-30 submissions are for drugs. A PMA amendment includes all additional submissions to a PMA or PMA supplement before approval of the PMA or PMA supplement or all additional correspondence after PMA or PMA supplement approval. During the conduct of a clinical study for a device, if minor manufacturing changes are made, these changes can be reported to FDA in an IDE 5-Day Notice.

In order to be approved by FDA, a generic drug must be therapeutically equivalent to the branded product with the exception of: A. Dosage Form B. Route of Administration C. Inactive Ingredient(s) D. Labeling

C. Inactive Ingredient(s) Regulatory Reference 21 CFR 314.92(a)(1) Question Feedback The law requires that generic drugs approved by FDA have the same active ingredient(s), dosage form, strength, route of administration, labeling, and conditions for use as the branded product, and that the generic and branded drug be bioequivalent. The inactive ingredients can be different. Sec. 314.92 Drug products for which abbreviated applications may be submitted. For determining the suitability of an abbreviated new drug application, the term "same as" means identical in active ingredient(s), dosage form, strength, route of administration, and conditions of use, except that conditions of use for which approval cannot be granted because of exclusivity or an existing patent may be omitted.

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 specifications of the foreign purchaser 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. It is labeled on the outside of the shipping package that it is "intended for export only"

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

FDA may refuse to file a PMA for all of the following reasons EXCEPT: Correct Yours 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 review by FDA 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. Major or minor deficiencies are identified with the clinical data after substantive review by FDA Regulatory Reference 21 CFR 814.42(e) Acceptance and Filing Reviews for Premarket Approval Applications (PMAs). Guidance for Industry and Food and Drug Administration Staff. Document issued 31 December 2012: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM313368.pdf (http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM313368.pdf) Question Feedback Substantive review of the PMA submission will begin once FDA determines the submission will not be refused.

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

C. Management Regulatory Reference 21 CFR 820.20(a) Question Feedback Management has the ultimate responsibility to ensure the quality systems are effective and a quality policy is implemented and followed as intended, which assures the integrity of the data and quality of the product.

Devices that are exempt from premarket notification are: A. All Class I devices B. Some Class I devices C. Most Class I devices and some Class II devices D. All Class I devices and some Class II devices

C. Most Class I devices and some Class II devices Regulatory Reference: 21 CFR Parts 862-892 Overview of Device Regulation Medical Device Exemptions 510(k) and GMP Requirements Question Feedback: Most Class I and some Class II devices are exempt from premarket application and FDA clearance before marketing the device in the US. Devices exempt by statute or by regulation from 510(k): 739 Class I (93%), 74 Class II (8%)

Advertising and promotional materials are required to be submitted to FDA at the time of initial dissemination or publication for all products EXCEPT: A. Prescription Drugs B. Biologics C. Non-restricted devices and OTC drugs D. None, all products require submission of advertising and promotional material.

C. Non-restricted devices and OTC drugs Regulatory Reference 21 CFR 314.81(b)(3)(i); 21 CFR 601.12(f)(4); FD&C Act Sections 502(q) and 502(r) Question Feedback Non-restricted medical device and OTC drug advertising is regulated by the Federal Trade Commission (FTC) under the FTC Act.

During a clinical study which is NOT the role of the sponsor? A. Control distribution of drugs B. Monitor studies C. Obtain informed consent D. Submit IND/Protocol to FDA if required

C. Obtain informed consent Regulatory Reference 21 CFR 812.100 Question Feedback It is the investigator's responsibility to obtain the informed consent.

For which device below does the Quality System Regulation require the same procedures for identifying the control number for each unit, lot or batch of finished devices as those mandated by the new UDI Rule? A. Surgical gloves B. X-ray machines C. Pacemakers D. Syringes

C. Pacemakers Regulatory Reference 21 CFR 820.65 Question Feedback According to 21 CFR 820.65,"Each manufacturer of a device that is intended for surgical implant into the body or to support or sustain life and whose failure to perform when properly used in accordance with instructions for use provided in the labeling can be reasonably expected to result in a significant injury to the user shall establish and maintain procedures for identifying with a control number each unit, lot, or batch of finished devices and where appropriate components." The Pacemaker is a Class III implantable device and subject to 21 CFR 820.65. Sec. 820.65 Traceability. Each manufacturer of a device that is intended for surgical implant into the body or to support or sustain life and whose failure to perform when properly used in accordance with instructions for use provided in the labeling can be reasonably expected to result in a significant injury to the user shall establish and maintain procedures for identifying with a control number each unit, lot, or batch of finished devices and where appropriate components. The procedures shall facilitate corrective action. Such identification shall be documented in the DHR.

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. Product recall Regulatory Reference 21 CFR 7.3(j) Question Feedback 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 Sec. 7.3 Definitions. (k) Stock recovery means 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 means 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 means 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.

After product approval, ADE's 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. Quarterly for three years after application approval, annually thereafter, unless alternative reporting is required by FDA. Regulatory Reference 21 CFR 314.80(b)(2) Question Feedback 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.

During the performance of a Class II product recall, additional complaint reports of the same product problem involved in the recall were received for products that were 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. 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 Regulatory Reference Reference: 21 CFR 806.10(d) Question Feedback: 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 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. Release and stability testing of the proposed formulation against the specification established for white tablets Regulatory Reference FDA Guidance for Industry: Immediate Release Solid Oral Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, Manufacturing and Controls, In-Vitro Dissolution Testing and In-Vivo Bioequivalence Documentation Question Feedback Adding a colorant to the tablet film coat is considered a minor change in the drug product formulation. Release and stability data for the proposed formulation meeting a specification established for the current formulation will be sufficient. However, the company should evaluate specificity of HPLC method for impurities and make sure colorants do not interfere with the separation of impurities.

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. Reminder advertisements Regulatory Reference 21 CFR 202.1(e)(2)(i) Question Feedback 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)

You receive an assignment to obtain a Special Protocol Assessment for a Phase 3 clinical trial of an investigational anti-TNF biologic for inflammatory bowel disease. You advise the clinical team and senior management as follows: A. Submit a request to FDA for a Special Protocol Assessment as an amendment to the IND after the clinical trial has started B. It is not possible to request a Special Protocol Assessment for this clinical trial since it is not a Phase 2 clinical trial, stability trial or carcinogenicity trial C. Submit a request to FDA for a Special Protocol Assessment as a separate IND amendment at least 90 days before the clinical trial is scheduled to begin D. Submit a request to FDA for a Special Protocol Assessment as an amendment to the IND and wait 45 days; if FDA does not raise objections, the Special Protocol Assessment status is automatically granted

C. Submit a request to FDA for a Special Protocol Assessment as a separate IND amendment at least 90 days before the clinical trial is scheduled to begin Regulatory Reference FDAMA Section 119(a), amending Section 505(b) of the FD&C Act (21 USC 355(b) (new Section 505(b)(4)(B)) FDA Guidance for Industry: Special Protocol Assessment, May 2002 Question Feedback 90 days should be considered as the minimum time allowed between submission of the SPA and protocol start. Time must be allowed to resolve issues. An SPA will not be awarded by FDA after a study has started. CDER and CBER generally recommend that a sponsor submit a protocol intended for special protocol assessment to the agency at least 90 days prior to the anticipated start of the study.

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, but anticipates the labeling will be identical to that of the RLD. 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. Suitability Petition Regulatory Reference 21 CFR 314.93 Question Feedback 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.

A television advertisement you have been asked to review prior to release discusses the drug's benefits in detail for 25 seconds, and then names all the major side effects associated with the product in the last five seconds. You should advise that: A. The advertisement can be released "as is," since it lists all the major side effects B. The side effects should be presented more slowly, so as to take up equal time with the benefits C. The benefits and side effects of the drug should be presented with the same level of scope, depth and detail D. Information about side effects should be stated earlier in the advertisement

C. The benefits and side effects of the drug should be presented with the same level of scope, depth and deta Regulatory Reference 21 CFR 202.1 Truthful Prescription Drug Advertising and Promotion Question Feedback: An advertisement does not satisfy the requirement that it present a true statement of information if it does not present a fair balance between information relating to effectiveness and information relating to side effects and contraindications. Fair balance means the benefits and risks of a drug must be described with the same scope, depth and detail, not just be given equal time

The supplier of the active drug substance for a company's OTC monograph drug product informs the company that it will be moving its production of the drug substance from the current plant to a new manufacturing plant in another state in six months. The supplier states that all manufacturing processes will remain the same and the specifications will not change. The company intends to qualify the change suitably. How should the company report the change to FDA? A. The change only needs to be reported in an Annual Report because the company will qualify the change and the supplier said the process and specifications will not change B. The change should be reported in a Pre-approval Supplement C. The change would be reported during the annual drug listing process D. An amendment to the OTC monograph should be filed

C. The change would be reported during the annual drug listing process Regulatory Reference 21 CFR 207 Guidance for Industry: Providing Regulatory Submissions in Electronic Format—Drug Establishment Registration and Drug Listing http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072339.pdf (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072339.pdf) Question Feedback Monograph drugs are not subject to Annual Reports or Preapproval Supplements. Nor is the supplier of an active drug substance prescribed by regulation (so a change to the monograph is not warranted). However, because the manufacturing API Drug Establishment number will change, this must be updated with FDA as part of the annual drug listing process.

You are the final distributor for a device manufactured in the US that is subject to device tracking requirements. If you are NOT relabeling, to whom are you required to report information to aid in the tracking the device: A. FDA B. Customs Authorities C. The manufacturer D. The hospital in which the device will be used

C. The manufacturer Regulatory Reference 21 CFR 821.30 b Question Feedback "A final distributor, upon sale or other distribution of a tracked device for use in or by the patient, shall promptly provide the manufacturer tracking the device with the following information..."

Your company is the initial importer of a medical device. Which of the following must be true? A. You must maintain quality assurance files B. You share responsibility for submission with the other distributors C. You must report device malfunctions in an Annual Report D. You must register your company's establishment with FDA

D. You must register your company's establishment with FDA Regulatory Reference 21 CFR 807.20(a)(4) Question Feedback: 21 CFR 807.20(a)(4)—Acts as an initial importer as defined in § 807.3(g), except that initial importers may fulfill their listing obligation for any device for which they did not initiate or develop the specifications for the device or repackage or relabel the device by submitting the name and address of the manufacturer. Initial importers shall also be prepared to submit, when requested by FDA, the proprietary name, if any, and the common or usual name of each device for which they are the initial importer. Amendment published at 77 FR 45941 Aug 2, 2012.

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 intended use of the product 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. The original data are stored in the device design history file. Regulatory Reference 21 CFR 820.30 Design Controls 21 CFR 820.30(e) Design review 21 CFR 820.30(f) Design Verification Question Feedback 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 stages of the device's design development. The purpose of the review is to evaluate the adequacy of the design requirements and the capability of the design to meet these requirements, and to identify problems. The outcome of the design reviews, including identification of the design stage, the date and the individuals involved in the review, should be documented in the Design History File

Which of the following statements is TRUE for Phase 2 clinical investigations of a previously untested drug? 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. They are conducted to determine the common short-term side effects and risks associated with the drug. Regulatory Reference 21 CFR 312.21 Phases of an Investigation Question Feedback: 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.

A manufacturing process requires purified water to produce several finished Class I exempt and Class II 510(k) medical devices. The water is tested monthly by quality control. Since results have consistently 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 determined that QC testing should now 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. This information does not need to be submitted Regulatory Reference CFR 820.70 (b) Question Feedback: 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 choices 1, 2 and 4 cannot be the answer. The best justified answer would be choice 3.

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 the 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. Where is the vendor located? Question Feedback To assess the regulatory impact and filing classification for this change, the answers for questions 1, 2 and 4 are all beneficial to the regulatory professional. Although certain regions of the world have received additional attention from FDA, the location of the vendor is not needed to conduct the analysis.

A clinical trial for a new treatment is recruiting study subjects and wants to use a posting on the company website or other social media such as Facebook or Twitter to solicit participants. Does this information need IRB review? A. No, company websites are not within the jurisdiction of an investigational review board. B. No, not unless it appears after the study has started. C. Yes, advertising that is intended to be seen or heard by prospective subjects to solicit their participation in a study requires IRB approval. D. Yes, but only if it the study is required to appear on the National Cancer Institute's cancer clinical trial listing (PDQ) or the government-sponsored AIDS Clinical Trials Information Services (ACTIS).

C. Yes, advertising that is intended to be seen or heard by prospective subjects to solicit their participation in a study requires IRB approval. Regulatory Reference 21 CFR 56.107(a) & 56.111 IRB is required to ensure that appropriate safeguards exist to protect the rights and welfare of research subjects Recruiting Study Subjects—Information Sheet; Guidance for Institutional Review Boards and Clinical Investigators Question Feedback: FDA considers direct advertising for study subjects to be the start of the Informed Consent and subject selection process, a process for which IRBs have responsibility.

A sponsor intends to submit a Special Protocol Assessment (SPA) request for a clinical trial that will form the primary basis of an efficacy claim in an NDA. Which of the following is TRUE? A. The sponsor should submit the SPA request within 30 days following the start of the trial to expedite FDA feedback B. An SPA provides an opportunity to focus on general drug development issues C. The SPA request will be handled as a request for a Type B meeting D. A sponsor can submit a revised protocol while the agency is reviewing an earlier version of the same protocol

D. A sponsor can submit a revised protocol while the agency is reviewing an earlier version of the same protocol Regulatory Reference-Guidance for Industry: Special Protocol Assessment Question Feedback: The agency can communicate with the sponsor regarding the protocol before issuing a Special Protocol Assessment letter. In such cases, the sponsor can choose to submit a revised protocol. If a sponsor submits a revised protocol, for any reason, while the agency is reviewing an earlier version of the same protocol, FDA ordinarily will not respond to the questions posed about the earlier version of the protocol and will consider the original request withdrawn. The agency will consider a request for a Special Protocol Assessment of a revised protocol to be a new request and will act on the revised protocol within 45 days.

Per 21 CFR 820, a clinical study to establish safety and effectiveness of a device is considered: A. Design verification B. Pivotal C. First in man D. Design validation

D. Design validation Regulatory Reference 21 CFR 820.3(z)(2): definition of design validation Question Feedback The clinical study is objective evidence the device specifications conform with the user needs and intended use.

Senior management at your company 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. Documentation can be provided that the cancer drug meets safety and effectiveness standards required for Fast Track status Regulatory Reference Section 506 [21 USC §356] Fast Track Products (as amended by Section 112 of FDAMA of 1997) FDA Guidance for Industry: Fast Track Drug Development Programs—Designation, Development, and Application Review (January 2006, Procedural, Revision 2) Question Feedback Fast Track status does not comprise or alter the standards for the safety and effectiveness of the drugs that become available through this process.

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 Regulatory Reference 21 CFR 814.3 Question Feedback 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 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. The transfer of the manufacturing process to Facility A is considered a minor change and will only require a notation of the transfer of the manufacturing process 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. The transfer of the process to the older Facility B would be considered a major change and would require prior approval from FDA of the change 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. The move of the manufacturing process to Facility B would be a moderate change and could be filed in a CBE 30.

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. The move of the manufacturing process to Facility B would be a moderate change and could be filed in a CBE 30. Regulatory Reference Guidance for Industry: Changes to an Approved NDA or ANDA Question Feedback The transfer of a drug product manufacturing process to a new facility requires notification of FDA of the change to the process. In reviewing Facilities A and B, the regulatory professional would recognize that 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 a prior approval before drug product manufactured in this location could be placed onto the market. Reporting of this manufacturing change in an Annual Report would be incorrect. The transfer of 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 drug product manufactured on the market.

A subject in a drug clinical trial subject is involved in an automobile accident. As a result, an exploratory laparotomy is performed, that identifies a ruptured spleen. A splenectomy is performed, resulting in patient hospitalization. What, if any, reporting is required? A. The splenectomy should be reported as an adverse event. B. The splenectomy and automobile accident should be reported as an adverse event. C. The hospitalization should be reported. D. No expedited reporting is required and the subject can continue in the study when recovered.

D. No expedited reporting is required and the subject can continue in the study when recovered. Regulatory Reference ICH Guidelines E2A & 21 CFR Part 312.32 Question Feedback The splenectomy is related to the automobile accident, not the drug product being studied. Therefore, no report is required. However, the event resulted in hospitalization (meeting seriousness criteria) and would be captured and reported both within the eventual Clinical Study Report (CSR), and reported in an annual report that summarizes the serious adverse events.

Your company is developing a New Chemical Entity (NCE) drug 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. Request Special Protocol Assessment Regulatory Reference 21 CFR 314.500 Question Feedback A Special Protocol Assessment applies to a Phase 3 study and has to 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.

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. Voluntary registration of clinical trials in FDA database. Regulatory Reference Food and Drug Administration Amendments Act of 2007 (FDAAA) Question Feedback FDAAA established mandatory registration of clinical trials in the ClinicalTrials.gov data bank. Registration is required for trials that meet the FDAAA 801 definition of an "applicable clinical trial" and were either initiated after September 27, 2007 or initiated on or before that date and were still ongoing as of December 26, 2007. "Applicable Clinical Trials" include the following: Trials of drugs and biologics. Controlled clinical investigations, other than phase 1 clinical investigations, of drugs or biological products subject to Food and Drug Administration (FDA) regulation Trials of devices. 1) Controlled trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies, and 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 that meet one of the following conditions: The trial has one or more sites in the United States The trial is conducted under an FDA investigational new drug application or investigational device exemption The trial involves a drug, biologic, or device that is manufactured in the United States or its territories and is exported for research

You have modified your 510(k) cleared device with a special 510(k). In which of the following cases would you need to create a new device listing for the device? A. You have added new sizes and shapes in the product portfolio. B. You have changed the material composition of the device. C. You have changed the package of the device. D. You have added an additional device under a different name with the same intended use and indication for use but with a minor change to its physical characteristics

D. You have added an additional device under a different name with the same intended use and indication for use but with a minor change to its physical characteristics Regulatory Reference 21 CFR 807.22(b) Question Feedback From 21 CFR 807.22(b): (b) Registration and listing updates. Owners or operators shall review and update all of their establishment registration and device listing information that is on file at FDA, documenting any changes that were not previously reported as follows: (1) Annual registration for each fiscal year is required for all establishments. Annual registration shall take place during the period beginning on October 1 and ending on December 31 of each fiscal year; (2) Updates to the registration information as described in 807.25(b) shall be made within 30 days of any change to such information; (3) Every fiscal year, during the period beginning on October 1 and ending on December 31, owners or operators shall review and update all of their device listing information that is on file at FDA, reporting any changes or deletions to listings and any new listings that were not previously reported. The accuracy of all information on file must be confirmed each year regardless of whether any changes were made to the owner or operator's list of devices; and (4) Changes to listing information may also be made at other times, such as when a device is introduced into commercial distribution, when a change is made to a previouslylisted device, or when a previously-listed device is removed from commercial distribution.